{"id":5150,"date":"2011-07-14T20:23:55","date_gmt":"2011-07-14T20:23:55","guid":{"rendered":"http:\/\/crashtext.org\/misc\/coumadin-heparin-etc.htm\/"},"modified":"2014-07-13T23:37:42","modified_gmt":"2014-07-14T03:37:42","slug":"coumadin-heparin-etc","status":"publish","type":"post","link":"https:\/\/crashingpatient.com\/medical-surgical\/hematology\/coumadin-heparin-etc.htm\/","title":{"rendered":"Coumadin, Heparin, Etc."},"content":{"rendered":"<h2><span class=\"ez-toc-section\" id=\"Warfarin_Coumadin\"><\/span>Warfarin (Coumadin)<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p> <a href=\"https:\/\/crashingpatient.com\/medical-surgical\/hematology\/coumadin-heparin-etc.htm\/attachment\/accp-anticoag-reversal-2012\/\" rel=\"attachment wp-att-9012\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-9012\" title=\"accp anticoag reversal 2012\" src=\"https:\/\/crashingpatient.com\/wp-content\/uploads\/2011\/07\/accp-anticoag-reversal-2012-300x209.png\" alt=\"\" width=\"300\" height=\"209\" srcset=\"https:\/\/crashingpatient.com\/wp-content\/uploads\/2011\/07\/accp-anticoag-reversal-2012-300x209.png 300w, https:\/\/crashingpatient.com\/wp-content\/uploads\/2011\/07\/accp-anticoag-reversal-2012.png 940w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/a> &nbsp; INR 4.5-10, give 1 mg oral Vit K, More effective than sub-q (Ann Intern Med 2002;137:251),  JEM 20:2) Recent studies show 2.5-5 mg oral is probably better than the 1 mg oral dose  (Arch Intern Med 2003 Nov 10; 163:2469.) IV will work quicker than PO immediately, but probably the same at 24 hours (Ibid) The IV form can be used orally (Br J Haem 2006;133:331) they gave 2.5 mg for 8-12, 12-20 got 5 mg Another article recommends 2 mg (Br J Haem 2006;135:591) &nbsp; GENERAL STANDARDS FOR THE INITIATION AND MAINTENANCE OF WARFARIN (COUMADIN\u00ae) THERAPY Initiation of warfarin (Coumadin\u00ae) 5 mg nomogram Day INR Dosage 1 5 mg 2 1.5-1.9 2.0-2.5 &gt; 2.5 5 mg 2.5 mg 1-2.5 mg 0 mg 3 1.5-1.9 2.0-2.5 2.5-3.0 &gt; 3.0 5-10 mg 2.5-5 mg 0-2.5 mg 0-2.5 mg 0 mg 4 1.5-1.9 2.0-3.0 &gt; 3.0 10 mg 5-7.5 mg 0-5 mg 0 mg 5 1.5-1.9 2.0-3.0 &gt; 3.0 10 mg 7.5-10 mg 0-5 mg 0 mg 6 1.5-1.9 2.0-3.0 &gt; 3.0 7.5-12.5 mg 5-10 mg 0-7.5 mg 0 mg Maintenance of warfarin (Coumadin\u00ae) Based on a therapeutic INR 2.0 &#8211; 3.0 INR Weekly dose change Consider reinitiation 1.1-2.0 Consider increasing weekly dose by 10-20% 2.0-3.0 Maintain same dose 3.0-3.9 Consider decreasing weekly dose by 10-20% &gt; 4.0 Consider holding a dose and decreasing weekly dose by 20% Points to Remember in Initiating Therapy <\/p>\n<ul>\n<li>Check INR at least 4 times during the first week of therapy<\/li>\n<li>Lower doses: Age &gt; 75, weight<\/li>\n<li>Higher doses: Hypothyroid interacting medications known to inhibit warfarin and a diet rich in Vitamin K<\/li>\n<\/ul>\n<p> Ann Intern Med 1992;116(11):901-904 Ann Intern Med 1997;127(4):333 J Clin Pathol 2002;55:845-849 Points to Remember in Maintenance Therapy <\/p>\n<ul>\n<li>Assess compliance \/ MAR, interacting drugs, and changes in diet<\/li>\n<li>Monitor for changes in INR when interacting drugs are added or removed\n<ul>\n<li>Look for a cause when the INR is more than<\/li>\n<li>0.2 below or 0.4 above the target range<\/li>\n<\/ul>\n<\/li>\n<li>Most dose modifications are 5 to 20% of the weekly dose. Larger changes, such as changing the weekly dose by one third can overcorrect an abnormal INR<\/li>\n<li>Recheck an INR within 5 to 7 days after adjustment for abnormal INR<\/li>\n<\/ul>\n<p> &nbsp; &nbsp; Am J Med 2000;109:481-488 Circulation. 2003; 107:1692-171 &nbsp; <a href=\"\/wp-content\/images\/part1\/warfarinreversal.gif\"> <img decoding=\"async\" src=\"\/wp-content\/images\/part1\/warfarinreversal_small.gif\" alt=\"\" \/><\/a> <\/p>\n<h4>Cholestyramine<\/h4>\n<p> Dose of cholestyramine typically are four grams in sorbitol (initial dose) or water q4-6hrs <\/p>\n<h4>Purple Toe Syndrome<\/h4>\n<p> bilateral discoloration of the feet, blue, blanching c pain. Cholesterol emboli from anticoag induced bleeding vs. warfarin necrosis @breast, thighs, or buttocks. D\/c coumadin as treatment. &nbsp; <em>Warfarin might induce skin necrosis in such patients and severe paradoxal thrombosis &#8211; I had one case like that before. How is her coagulation profile? protein C activity? PT? ATIII? protein S level? vitamin K dependent coagulation factors? Does her protein C levels respond to vitamin K administration? Vitamin K deficiency is a cause of protein C deficiency too, as well as neoplasias. Has she been submitted to an APC resistance assay?Was she tested for factor V laten and prothrombin mutations? What about antiphospholipid and anticardiolipin antibodies? Are her factor VIII and IX levels elevated? Also, fibrinolysis markers are elevated? TAT, fibrin degradation products, fragment 1+2, D dimer? This is important to see if she is actively forming clots. Regarding warfarin therapy: I would not start it with low protein C levels. I would give her protein C concentrates or start it with prophylactic LMWH doses A common protein C concentrate administration protocol is a test dose at 10 IU\/kg; follow by a bolus (100 IU\/kg) and then as continuous infusion (10-15 IU\/kg\/h), adjusted to give a protein C level of 80-120 IU\/mL &#8211; this is safe enough to initiate warfarin therapy. My 2 brazilian worthless cents. claudia<\/em> <\/p>\n<h2><span class=\"ez-toc-section\" id=\"Heparin\"><\/span>Heparin<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p> <a href=\"\/wp-content\/images\/part1\/hep.nomo.jpg\"> <img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hep.nomo_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/clotting.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/clotting_small.jpg\" alt=\"\" \/><\/a> &nbsp; Elmhurst Thresholds-PTT 50-88 corresponding to anti-Xa of 0.3-0.7 U\/cc &nbsp; Can cause vasodilation and increased serum K &nbsp; &nbsp; Enoxaparin sodium is a subcutaneously (SC) administered low-molecular-weight heparin approved in the United States for the inpatient or outpatient treatment of deep venous thrombosis (DVT) in place of standard heparin infusion. It may also be used as DVT prophylaxis in patients undergoing general or orthopaedic surgery. The standard prophylactic dose of enoxaparin for orthopaedic surgery is 30 mg SC twice daily with the initial dose administered within 12-24 hours of surgery, or 40 mg once daily with the initial dose administered within 9-15 hours before surgery and continuing for 7-10 days or until the risk of DVT has diminished. For major general surgery, the recommended dose is 40 mg SC once daily with initial dose given 2 hours before surgery and continuing for about 7-10 days. Although there is no approved dose for weight-based enoxaparin for use as DVT prophylaxis, I would not recommend exceeding 0.5 mg\/kg every 12 hours. Weight-adjusted enoxaparin is typically used for the treatment of DVT, at a dose of either 1 mg\/kg SC every 12 hours or 1.5 mg\/kg SC daily for inpatients, or 1 mg\/kg every 12 hours x 7 days as outpatient treatment. Children between the ages of 2 months and 18 years may receive enoxaparin as prophylaxis at a dose of 0.5 mg every 12 hours. Patients with renal impairment and creatinine clearance &lt; 30 mL\/min have a slower clearance of enoxaparin than do those with a higher creatinine clearance; the dosage of enoxaparin should be reduced in these patients. &nbsp; Finally, we have guidelines on how to dose Lovenox (enoxaparin) in patients with renal impairment. This has been a question for years. Some patients with renal disease end up with high Lovenox levels&#8230;and an increased risk of bleeding. Dose adjustment usually is NOT necessary for mild to moderate renal impairment&#8230;creatinine clearance of 30 to 80 mL\/min. But for severe impairment below 30 mL\/min the dose often needs to be decreased. MI and unstable angina patients should get 1 mg\/kg SQ ONCE daily&#8230;instead of the usual 1 mg\/kg every 12 hours. DVT patients get 1 mg\/kg SQ ONCE daily&#8230;instead of either 1 mg\/kg every 12 hours, or 1.5 mg\/kg once daily. Abdominal surgery and acute illness patients get 30 mg SQ once daily&#8230;instead of 40 mg once daily. Hip or knee surgery patients get 30 mg SQ ONCE daily&#8230; instead of BID. Tell patients to watch for bleeding or bruising. &nbsp; dose by weight up until 130 kg it takes 30 min for lovenox to take effect sq heparin takes 1-2 hours &nbsp; <\/p>\n<h2><span class=\"ez-toc-section\" id=\"Heparin_induced_thrombocytopenia\"><\/span>Heparin induced thrombocytopenia<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p> Suspect if thrombocytopenia following heparin administration usually 5-10 days after heparin. (Clinically, heparin-induced thrombocytopenia manifests as a decrease in the platelet count of at least 30% to 50% from the preheparin value, often to less than 150\u00d7109\/L, typically beginning 5 to 14 days after heparin treatment is started.3., 4. and 5. In addition, thrombocytopenia may occur earlier, even within hours, if the patient had recent heparin exposure and has circulating heparin\u0096platelet factor 4 antibodies.) &nbsp; Heparin\u0096platelet factor 4 antibodies &nbsp; Consider HIT in any patient with recent hospitalization as the use of heparin for DVT proph is nearly universal &nbsp; Always think of in pts c thrombocytopenia and thrombus production immunologic basis, clumping of platelets. Possible but less likely with LMH. Rare consequence is bilateral adrenal hemorrhagic necrosis Warfarin can cause limb gangrene due to protein c blockage Perform HIT antibody testing Look for skin lesions at heparin sites, limb swelling, pe, d-dimer testing RX: Must use alternative anticoagulant (not LMH or coumadin) Hirudin (Lepirudin)-.4 mg\/kg then .15 mg\/kg\/hr Argatroban-2 ug\/kg\/hr dose based on ptt &nbsp; For argatroban therapy in heparin-induced thrombocytopenia patients without hepatic impairment, the recommended dose is 2 \u03bcg\/kg per minute, adjusted to achieve activated partial thromboplastin times of 1.5 to 3 times baseline. For lepirudin therapy in heparin-induced thrombocytopenia patients without renal impairment, the recommended dose is a 0.4-mg\/kg initial bolus followed by a 0.15-mg\/kg per hour infusion, adjusted to achieve activated partial thromboplastin time ratios of 1.5 to 2.5. &nbsp; &nbsp; Consider Dopplers Do not give platelets unless absolutely necessary and they increase thrombosis risk &nbsp; &#8220;In making recommendations for the management of HIT, we have chosen to combine the approach to patients with &#8220;isolated HIT&#8221; and HIT-associated thrombosis. There are three reasons for this approach. First, from the point of view of pathophysiology, patients with isolated HIT and HIT-associated thrombosis have similar disease processes, as shown by platelet count nadirs (median, approximately 50 to 60 x 109\/L for each group), and similar elevations of thrombin-antithrombin complexes. Second, the time course of thrombosis in HIT is a continuum, with approximately equal numbers of patients being recognized with symptomatic thrombosis (1) during the initial period of a falling platelet count, (2) after crossing a threshold defining thrombocytopenia but while heparin treatment remains ongoing, and (3) after discontinuation of heparin because of thrombocytopenia.129 Third, and most importantly, among patients who are recognized as having isolated HIT (subsequently confirmed serologically), and who are managed by simple discontinuation of heparin, or substitution of heparin by warfarin, the risk of symptomatic thrombosis ranges from 25 to 50%, including an overall risk of fatal thrombosis of approximately 5%.12 These event rates resemble those in other clinical situations in which antithrombotic management is generally considered mandatory (eg, after hip fracture). &#8221; Chest. 2004;126:311S-337S. heparin-coated catheters like swans can continue to cause HIT &nbsp; Simulations showed that a first unadjusted dose of 1 mg\/kg followed by a regimen of 0.8 mg \u00b7 kg-1 \u00b7 12 h-1 in patients with moderate renal impairment or 0.66 mg \u00b7 kg-1 \u00b7 12 h-1 in patients with severe renal impairment should avoid accumulation of enoxaparin and keep peak anti-Xa activities between 0.5 and 1.2 IU\/mL for a large majority of patients. An enoxaparin dosage reduction should be considered in acute coronary syndrome patients with creatinine clearance lower than 50 mL\/min. A simple dosing protocol for enoxaparin to avoid significant accumulation in patients with moderate or severe renal impairment is proposed (Clinical Pharmacology &amp; Therapeutics Volume 77, Issue 6 , June 2005, Pages 542-552) &nbsp; Best review Article (Crit Care Med 2006;34(12):2898) and now Crit Care Med 2007;35(4):1167 <a href=\"\/wp-content\/images\/part1\/hiti.jpg\"> <img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hiti_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/hitii.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hitii_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/hitiii.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hitiii_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/hitiiv.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hitiiv_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/hitv.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hitv_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/hitvi.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hitvi_small.jpg\" alt=\"\" \/><\/a><a href=\"\/wp-content\/images\/part1\/hitvii.jpg\"><img decoding=\"async\" src=\"\/wp-content\/images\/part1\/hitvii_small.jpg\" alt=\"\" \/><\/a> <\/p>\n<h3><span class=\"ez-toc-section\" id=\"Argatroban\"><\/span>Argatroban<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p> From renal fellow network blog Critically ill patients receiving continuous renal replacement therapy are frequently given heparin to maintain circuit patency. In the presence of active HIT-II or HITT, even in the absence of clinical thrombosis, systemic anticoagulation with a <strong>direct thrombin inhibitor<\/strong> (DTI) decreases the incidence of thrombotic complications, <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18829068\">if given until thrombocytopenia has resolved.<\/a> In this scenario, anticoagulation to maintain CRRT circuit patency is a bonus. In critically ill patients requiring CRRT with a history of HIT-II, but not active thrombocytopenia or thrombosis, avoidance of heparin exposure is still recommended, and <strong>argatroban<\/strong> is currently a common choice of DTI if systemic anticoagulation is required. As this is a drug that nephrologists need to be very familiar with, here&#8217;s a list of essential facts about argatroban in the form of a mnemonic, for those of you who get off on that kind of thing. <strong>A<\/strong> nticoagulant of choice in active HIT-II or HITT. <strong>R<\/strong> enal dose adjustment not necessary \u0096 hepatically cleared only. <strong>G<\/strong> oal aPTT is 2-3 times above baseline (as for heparin). <strong>A<\/strong> ctivated PTT is monitoring test of choice, but note argatroban increases ACT and PT\/INR also. <strong>T<\/strong> wo mcg per kg per minute is the usual starting dose (2mcg\/kg\/min) <strong>R<\/strong> eversal not possible, so careful monitoring essential. <strong>O<\/strong> .5 mcg\/kg\/min starting dose in liver disease (0.5mcg\/kg\/min) <strong>B<\/strong> olus not required before infusion (unlike heparin). Steady state within 3 hours. <strong>A<\/strong> lbumin: Low albumin is an important clue to hepatic synthetic dysfunction. Reduce starting dose by 75% if present. <strong>N<\/strong> ormalised ratio: When transitioning to warfarin, once the INR is 4 while on both drugs, <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18473863\">the INR will be therapeutic once the argatroban infusion is stopped.<\/a> The alternative is the measure the chromogenic factor x level (goal less than 45% for efficacy). <\/p>\n<h3><\/h3>\n<h3><\/h3>\n<h3><span class=\"ez-toc-section\" id=\"Protamine_Reversal\"><\/span>Protamine Reversal<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p> protamine comes from fish sperm, usually salmon. It also has the property of being able to neutralize heparin (1 mg protamine neutralizes 100 units heparin). Check Platelets If major bleeding: Protamine Sulfate 1 mg\/100 U Heparin over 3 minutes or 1 mg\/kg body weight Protamine 1 mg\/1 mg Lovenox, 100 U Fragmin or 100 U Innohep as infusion over 3-10 minutes May repeat \u00bd original dose in 2 hours if bleeding continues Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers. Blood Coagul Fibrinolysis 1994 Oct;5(5):795-803 The pharmacokinetics and cardiovascular effects of a single intravenous dose of protamine in normal volunteers. Anesth Analg 2002 Mar;94(3) Journal of Vascular Surgery 1997 Dec; 26 (6) hemodynamic instability with protamine is a nonimmunologic reaction caused by thromboxane release leading to pulm vasoconstriction, bradycardia, and hypotension. Anaphylaxis can also result. Thrombolytics To reverse, use 6 units FFP and 10 units cryoprecipitate Obtain CBC, fibrinogen level, thrombin time, PT\/APTT, Type and Screen Most cases need no further care. Goal FBG is 100 mg\/dL. If life-threatening bleeding, transfuse 10 units of CRYO (FBG source), 2 FFP (procoagulant source), and PLAT if thrombocytopenic. Protamine sulfate 1 mg\/100 units of heparin may be used if heparin given within the previous 4 hours. Anti-fibrinolytic, e.g., EACA can be given if life-threatening bleeding continues after CRYO\/FFP. &nbsp; <\/p>\n<h3><span class=\"ez-toc-section\" id=\"Plavix\"><\/span>Plavix<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p> Cardiologists like clopidogrel, but apparently not before CABG surgery , as it is stated in this reference by Hongo,R et al, The effect of clopidogrel in combination with aspirin when given before CABG surgery J Am Coll Cardiol 2002;40:231-7. Reoperation for bleeding was ten-fold increased in the clopidogrel group&#8230; Aprotinin can reduce blood transfusion requirements when used before the procedure in aspirin-loaded patients, but the effect is smoother in clopidogrel-loaded &nbsp; &nbsp; <\/p>\n<h2><span class=\"ez-toc-section\" id=\"2008_ACCP_Guidelines\"><\/span>2008 ACCP Guidelines<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p> <strong>2.2.3 Monitoring Antithrombotic Effect<\/strong><strong>2.2.3 In patients treated with LMWH, we recommend against routine coagulation monitoring<\/strong> (Grade 1C). <strong>In pregnant women treated with therapeutic doses of LMWH, we recommend monitoring of anti-Xa levels<\/strong> (Grade 1C). <strong>2.2.4 Dosing and Monitoring in Special Situations<\/strong><strong>2.2.4 In obese patients given LMWH prophylaxis or treatment,we suggest weight-based dosing<\/strong> (Grade 2C). <strong>In patients with severe renal insufficiency (creatinine clearance [CrCl] &lt;30 mL\/min) who require therapeutic anticoagulation, we suggestthe use of UFH instead of LMWH<\/strong> (Grade 2C). <strong>If LMWH is used inpatients with severe renal insufficiency (CrCl &lt; 30 mL\/min)who require therapeutic anticoagulation, we suggest using 50%of the recommended dose<\/strong> (Grade 2C). <strong>3.0 Direct Thrombin Inhibitors<\/strong><strong>3.0 In patients who receive either lepirudin or desirudin andhave renal insufficiency (CrCl &lt; 60 mL\/min but &gt; 30 mL\/min),we recommend that the dose be reduced and the drug be monitoredusing the activated partial thromboplastin time<\/strong> (Grade 1C).<strong>In patients with a CrCl &lt; 30 mL\/min, we recommend againstthe use of lepirudin or desirudin<\/strong> (Grade 1C). <strong>In patients whorequire anticoagulation and have previously received lepirudinor desirudin, we recommend against repeated use of these drugsbecause of the risk of anaphylaxis<\/strong> (Grade 1C). <strong>3.1 Monitoring of Direct Thrombin Inhibitors<\/strong><strong>3.1 In patients receiving argatroban who are being transitionedto a vitamin K antagonist, we suggest that factor X levels measured using a chromogenic assay be used to adjust the dose of thevitamin K antagonist<\/strong> (Grade 2C). &nbsp; <strong>2.1 Initiation and Maintenance Dosing<\/strong><strong>2.1.1. In patients beginning vitamin K antagonist (VKA) therapy, we recommend the initiation of oral anticoagulation with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals,with subsequent dosing based on the international normalized ratio (INR) response<\/strong> (Grade 1B)<strong>. At the present time, for patientsbeginning VKA therapy without evidence from randomized trials, we suggest against the use of pharmacogenetic-based initialdosing to individualize warfarin dosing<\/strong> (Grade 2C)<strong>.<\/strong> <strong>2.2 Initiation of Anticoagulation in Elderly or Other Populations<\/strong><strong>2.2.1. In elderly patients or patients who are debilitated,are malnourished, have congestive heart failure (CHF), haveliver disease, have had recent major surgery, or are takingmedications known to increase sensitivity to warfarin (eg, amiodarone),we recommend the use of a starting dose of 5 mg<\/strong> (Grade 1C)<strong>with subsequent dosing based on the INR response<\/strong>. <strong>2.3 Frequency of Monitoring<\/strong><strong>2.3.1. In patients beginning VKA therapy, we suggest that INR monitoring be started after the initial two or three doses oforal anticoagulation therapy<\/strong> (Grade 2C)<strong>.<\/strong> <strong>2.3.2. For patients who are receiving a stable dose of oralanticoagulants, we suggest monitoring at an interval of no longerthan every 4 weeks<\/strong> (Grade 2C)<strong>.<\/strong> <strong>2.4 Management of Nontherapeutic INRs<\/strong><strong>2.4.1. For patients with INRs above the therapeutic range but&lt; 5.0 and with no significant bleeding, we recommend loweringthe dose or omitting a dose, monitoring more frequently, andresuming therapy at an appropriately adjusted dose when theINR is at a therapeutic level. If only minimally above therapeuticrange or associated with a transient causative factor, no dosereduction may be required<\/strong> (all Grade 1C)<strong>.<\/strong> <strong>2.4.2. For patients with INRs of 5.0 but &lt; 9.0 and no significantbleeding, we recommend omitting the next one or two doses, monitoringmore frequently, and resuming therapy at an appropriately adjusteddose when the INR is at a therapeutic level<\/strong> (Grade 1C)<strong>. Alternatively,we suggest omitting a dose and administering vitamin K (1 to2.5 mg) orally, particularly if the patient is at increasedrisk of bleeding<\/strong> (Grade 2A)<strong>. If more rapid reversal is requiredbecause the patient requires urgent surgery, we suggest vitaminK ( 5 mg) orally, with the expectation that a reduction of theINR will occur in 24 h. If the INR is still high, we suggestadditional vitamin K (1 to 2 mg) orally<\/strong> (Grade 2C)<strong>.<\/strong> <strong>2.4.3. For patients with INRs 9.0 and no significant bleeding,we recommend holding warfarin therapy and administering a higherdose of vitamin K (2.5 to 5 mg) orally, with the expectationthat the INR will be reduced substantially in 24 to 48 h<\/strong> (Grade1B)<strong>. Clinicians should monitor the INR more frequently, administeradditional vitamin K if necessary, and resume therapy at anappropriately adjusted dose when the INR reaches the therapeuticrange.<\/strong> <strong>2.4.4. In patients with serious bleeding and elevated INR, regardlessof the magnitude of the elevation, we recommend holding warfarintherapy and giving vitamin K (10 mg) by slow IV infusion supplementedwith fresh frozen plasma, prothrombin complex concentrate (PCC),or recombinant factor VIIa, depending on the urgency of thesituation. We recommend repeating vitamin K administration every12 h for persistent INR elevation<\/strong> (all Grade 1C)<strong>.<\/strong> <strong>2.4.5. In patients with life-threatening bleeding (eg, intracranialhemorrhage) and elevated INR, regardless of the magnitude ofthe elevation, we recommend holding warfarin therapy and administeringfresh frozen plasma, PCC, or recombinant factor VIIa supplementedwith vitamin K, 10 mg by slow IV infusion, repeated, if necessary,depending on the INR<\/strong> (Grade 1C)<strong>.<\/strong> <strong>2.4.6. In patients with mild to moderately elevated INRs withoutmajor bleeding, we recommend that when vitamin K is to be given,it be administered orally rather than subcutaneously<\/strong> (Grade1A)<strong>.<\/strong> <strong>2.5 Management of Variable INRs<\/strong><strong>2.5.1. For patients receiving long-term warfarin therapy witha variable INR response not attributable to any of the usualknown causes for instability, we suggest a trial of daily low-doseoral vitamin K (100 to 200 \u00b5g), with close monitoringof the INR and warfarin dose adjustment to counter an initiallowering of the INR in response to vitamin K<\/strong> (Grade 2B)<strong>.<\/strong> <strong>2.7 Management of INRs in the Antiphospholipid Syndrome<\/strong><strong>2.7.1. In patients who have a lupus inhibitor, who have no additionalrisk factors, and who have no lack of response to therapy, we recommend a therapeutic target INR of 2.5 (INR range, 2.0 to3.0)<\/strong> [Grade 1A]<strong>. In patients who have recurrent thromboembolicevents with a therapeutic INR or other additional risk factorsfor thromboembolic events, we suggest a target INR of 3.0 (INRrange, 2.5 to 3.5)<\/strong> [Grade 2C]<strong>.<\/strong> <strong>4.1 Optimal Management of VKA Therapy<\/strong><strong>4.1.1. For health-care providers who manage oral anticoagulation therapy, we recommend that they do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of resultsand dosing decisions as occurs in an anticoagulation managementservice (AMS)<\/strong> [Grade 1B]<strong>.<\/strong> <strong>4.3 Patient Self-Testing and Patient Self-Management<\/strong><strong>4.3.1. Patient self-management (PSM) is a choice made by patients and health-care providers that depends on many factors. In patients who are suitably selected and trained, patient self-testingor PSM is an effective alternative treatment model. We suggestthat such therapeutic management be implemented where suitable<\/strong>(Grade 2B)<strong>.<\/strong> &nbsp; &nbsp; <strong>1.0 General Recommendations<\/strong> <strong>Hospital Thromboprophylaxis Policy<\/strong><strong>1.2.1. For every general hospital, we recommend that a formal, active strategy that addresses the prevention of VTE be developed<\/strong> (Grade 1A)<strong>.<\/strong> <strong>1.2.2. We recommend that the local thromboprophylaxis strategybe in the form of a written, institution-wide thromboprophylaxispolicy<\/strong> (Grade 1C)<strong>.<\/strong> <strong>1.2.3. We recommend the use of strategies shown to increasethromboprophylaxis adherence, including the use of computerdecision support systems<\/strong> (Grade 1A)<strong>, preprinted orders<\/strong> (Grade1B)<strong>, and periodic audit and feedback<\/strong> (Grade 1C)<strong>. Passive methodssuch as distribution of educational materials or educational meetings are not recommended as sole strategies to increaseadherence to thromboprophylaxis<\/strong> (Grade 1B)<strong>.<\/strong> <strong>Mechanical Methods of Thromboprophylaxis<\/strong><strong>1.4.3.1. We recommend that mechanical methods of thromboprophylaxisbe used primarily in patients at high risk for bleeding<\/strong> (Grade1A)<strong>, or possibly as an adjunct to anticoagulant-based thromboprophylaxis<\/strong>(Grade 2A)<strong>.<\/strong> <strong>1.4.3.2. For patients receiving mechanical methods of thromboprophylaxis,we recommend that careful attention be directed toward ensuringthe proper use of, and optimal adherence with, these methods<\/strong>(Grade 1A)<strong>.<\/strong> <strong>Aspirin as Thromboprophylaxis<\/strong><strong>1.4.4. We recommend against the use of aspirin alone as thromboprophylaxisagainst VTE for any patient group<\/strong> (Grade 1A)<strong>.<\/strong> <strong>Anticoagulant Dosing<\/strong><strong>1.4.5. For each of the antithrombotic agents, we recommend that clinicians follow the manufacturer-suggested dosing guidelines<\/strong> (Grade 1C)<strong>.<\/strong> <strong>Renal Impairment and Anticoagulant Dosing<\/strong><strong>1.4.6. We recommend that renal function be considered when making decisions about the use and\/or the dose of LMWH, fondaparinux,and other antithrombotic drugs that are cleared by the kidneys, particularly in elderly patients, patients with diabetes mellitus, and those at high risk for bleeding<\/strong> (Grade 1A)<strong>. Depending on the circumstances, we recommend one of the following optionsin this situation: avoiding the use of an anticoagulant thatbioaccumulates in the presence of renal impairment, using alower dose of the agent, or monitoring the drug level or itsanticoagulant effect<\/strong> (Grade 1B)<strong>.<\/strong> <strong>Antithrombotic Drugs and Neuraxial Anesthesia\/Analgesia or Peripheral Nerve Blocks<\/strong><strong>1.5.1. For all patients undergoing neuraxial anesthesia or analgesia,we recommend appropriate patient selection and caution when using anticoagulant thromboprophylaxis<\/strong> (Grade 1A)<strong>.<\/strong> <strong>1.5.2. For patients receiving deep peripheral nerve blocks,we recommend that the same cautions considered for neuraxialtechniques be applied when using anticoagulant thromboprophylaxis<\/strong>(Grade 1C)<strong>.<\/strong> <strong>2.0 General, Vascular, Gynecologic, Urologic, Laparoscopic, Bariatric, Thoracic, and Coronary Artery Bypass Surgery<\/strong> <strong>2.1 General Surgery<\/strong><strong>2.1.1. For low-risk general surgery patients who are undergoing minor procedures and have no additional thromboembolic riskfactors, we recommend against the use of specific thromboprophylaxisother than early and frequent ambulation<\/strong> (Grade 1A)<strong>.<\/strong> <strong>2.1.2. For moderate-risk general surgery patients who are undergoinga major procedure for benign disease, we recommend thromboprophylaxiswith LMWH, LDUH, or fondaparinux<\/strong> (each Grade 1A)<strong>.<\/strong> <strong>2.1.3. For higher-risk general surgery patients who are undergoinga major procedure for cancer, we recommend thromboprophylaxiswith LMWH, LDUH three times daily, or fondaparinux<\/strong> (each Grade1A)<strong>.<\/strong> <strong>2.1.4. For general surgery patients with multiple risk factorsfor VTE who are thought to be at particularly high risk, werecommend that a pharmacologic method (ie, LMWH, LDUH three times daily, or fondaparinux) be combined with the optimal useof a mechanical method (ie, graduated compression stockings[GCS] and\/or IPC)<\/strong> [Grade 1C]<strong>.<\/strong> <strong>2.1.5. For general surgery patients with a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxiswith properly fitted GCS or IPC<\/strong> (Grade 1A)<strong>. When the high bleedingrisk decreases, we recommend that pharmacologic thromboprophylaxisbe substituted for or added to the mechanical thromboprophylaxis<\/strong>(Grade 1C)<strong>.<\/strong> <strong>2.1.6. For patients undergoing major general surgical procedures,we recommend that thromboprophylaxis continue until dischargefrom hospital<\/strong> (Grade 1A)<strong>. For selected high-risk general surgerypatients, including some of those who have undergone major cancersurgery or have previously had VTE, we suggest that continuingthromboprophylaxis after hospital discharge with LMWH for upto 28 days be considered<\/strong> (Grade 2A)<strong>.<\/strong> <strong>2.2 Vascular Surgery<\/strong><strong>2.2.1. For patients undergoing vascular surgery who do not have additional thromboembolic risk factors, we suggest that clinicians not routinely use specific thromboprophylaxis other than earlyand frequent ambulation<\/strong> (Grade 2B)<strong>.<\/strong> <strong>2.2.2. For patients undergoing major vascular surgery procedureswho have additional thromboembolic risk factors, we recommendthromboprophylaxis with LMWH, LDUH, or fondaparinux<\/strong> (Grade 1C)<strong>.<\/strong> <strong>2.3 Gynecologic Surgery<\/strong><strong>2.3.1. For low-risk gynecologic surgery patients who are undergoingminor procedures and have no additional risk factors, we recommendagainst the use of specific thromboprophylaxis other than early and frequent ambulation<\/strong> (Grade 1A)<strong>.<\/strong> <strong>2.3.2. For gynecology patients undergoing entirely laparoscopicprocedures, we recommend against routine thromboprophylaxis,other than early and frequent ambulation<\/strong> (Grade 1B)<strong>.<\/strong> <strong>2.3.3. For gynecology patients undergoing entirely laparoscopicprocedures in whom additional VTE risk factors are present,we rec-ommend the use of thromboprophylaxis with one or moreof LMWH, LDUH, IPC, or GCS<\/strong> (Grade 1C)<strong>.<\/strong> <strong>2.3.4. For all patients undergoing major gynecologic surgery,we recommend that thromboprophylaxis be used routinely<\/strong> (Grade1A)<strong>.<\/strong> <strong>2.3.5. For patients undergoing major gynecologic surgery forbenign disease without additional risk factors, we recommendLMWH<\/strong> (Grade 1A)<strong>, LDUH<\/strong>(Grade 1A)<strong>, or IPC started just beforesurgery and used continuously while the patient is not ambulating<\/strong>(Grade 1B)<strong>.<\/strong> <strong>2.3.6. For patients undergoing extensive surgery for malignancyand for patients with additional VTE risk factors, we recommendroutine thromboprophylaxis with LMWH<\/strong> (Grade 1A)<strong>, or LDUH threetimes daily<\/strong> (Grade 1A)<strong>, or IPC, started just before surgeryand used continuously while the patient is not ambulating<\/strong> (Grade1A)<strong>. Alternative considerations include a combination of LMWHor LDUH plus mechanical thromboprophylaxis with GCS or IPC,or fondaparinux<\/strong> (all Grade 1C)<strong>.<\/strong> <strong>2.3.7. For patients undergoing major gynecologic procedures,we recommend that thromboprophylaxis continue until dischargefrom hospital<\/strong> (Grade 1A)<strong>. For selected high-risk gynecologypatients, including some of those who have undergone major cancersurgery or have previously had VTE, we suggest that continuingthromboprophylaxis after hospital discharge with LMWH for upto 28 days be considered<\/strong> (Grade 2C)<strong>.<\/strong> <strong>2.4 Urologic Surgery<\/strong><strong>2.4.1. For patients undergoing transurethral or other low-risk urologic procedures, we recommend against the use of specific thromboprophylaxis other than early and frequent ambulation<\/strong> (Grade 1A)<strong>.<\/strong> <strong>2.4.2. For all patients undergoing major, open urologic procedures,we recommend that thromboprophylaxis be used routinely<\/strong> (Grade1A)<strong>.<\/strong> <strong>2.4.3. For patients undergoing major, open urologic procedures,we recommend routine thromboprophylaxis with LDUH twice dailyor three times daily<\/strong> (Grade 1B)<strong>, GCS and\/or IPC started justbefore surgery and used continuously while the patient is notambulating<\/strong> (Grade 1B)<strong>, LMWH<\/strong> (Grade 1C), <strong>fondaparinux<\/strong> (Grade1C)<strong>, or the combination of a pharmacologic method (ie, LMWH,LDUH, or fondaparinux) with the optimal use of a mechanicalmethod (ie, GCS and\/or IPC)<\/strong> [Grade 1C]<strong>.<\/strong> <strong>2.4.4. For urologic surgery patients who are actively bleeding,or who are at very high risk for bleeding, we recommend theoptimal use of mechanical thromboprophylaxis with GCS and\/or IPC at least until the bleeding risk decreases<\/strong> (Grade 1A)<strong>. Whenthe high bleeding risk decreases, we recommend that pharmacologicthromboprophylaxis be substituted for or added to the mechanicalthromboprophylaxis<\/strong> (Grade 1C)<strong>.<\/strong> <strong>2.5 Laparoscopic Surgery<\/strong><strong>2.5.1. For patients undergoing entirely laparoscopic procedures who do not have additional thromboembolic risk factors, we recommend against the routine use of thromboprophylaxis, other than earlyand frequent ambulation<\/strong> (Grade 1B)<strong>.<\/strong> <strong>2.5.2. For patients undergoing laparoscopic procedures in whomadditional VTE risk factors are present, we recommend the useof thromboprophylaxis with one or more of LMWH, LDUH, fondaparinux,IPC, or GCS<\/strong> (all Grade 1C)<strong>.<\/strong> <strong>2.6 Bariatric Surgery<\/strong><strong>2.6.1. For patients undergoing inpatient bariatric surgery,we recommend routine thromboprophylaxis with LMWH, LDUH threetimes daily, fondaparinux, or the combination of one of thesepharmacologic methods with optimally used IPC<\/strong> (each Grade 1C)<strong>.<\/strong> <strong>2.6.2. For patients undergoing inpatient bariatric surgery,we suggest that higher doses of LMWH or LDUH than usual fornonobese patients be used<\/strong> (Grade 2C)<strong>.<\/strong> <strong>2.7 Thoracic Surgery<\/strong><strong>2.7.1. For patients undergoing major thoracic surgery, we recommendroutine thromboprophylaxis with LMWH, LDUH, or fondaparinux<\/strong> (each Grade 1C)<strong>.<\/strong> <strong>2.7.2. For thoracic surgery patients with a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxiswith properly fitted GCS and\/or IPC<\/strong> (Grade 1C)<strong>.<\/strong> <strong>2.8 Coronary Artery Bypass Surgery<\/strong><strong>2.8.1. For patients undergoing coronary artery bypass graft(CABG) surgery, we recommend the use of thromboprophylaxis withLMWH, LDUH, or optimally used bilateral GCS or IPC<\/strong> (Grade 1C)<strong>.<\/strong> <strong>2.8.2. For patients undergoing CABG, we suggest the use of LMWHover LDUH<\/strong> (Grade 2B)<strong>.<\/strong> <strong>2.8.3. For patients undergoing CABG with a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxiswith properly fitted bilateral GCS or IPC<\/strong> (Grade 1C)<strong>.<\/strong> <strong>3.0 Orthopedic Surgery<\/strong> <strong>3.1 Elective Hip Replacement<\/strong><strong>3.1.1. For patients undergoing elective total hip replacement (THR), we recommend the routine use of one of the following anticoagulant options: (1) LMWH (at a usual high-risk dose,started 12 h before surgery or 12 to 24 h after surgery, or4 to 6 h after surgery at half the usual high-risk dose andthen increasing to the usual high-risk dose the following day);(2) fondaparinux (2.5 mg started 6 to 24 h after surgery); or(3) adjusted-dose VKA started preoperatively or the eveningof the surgical day (international normalized ratio [INR] target,2.5; INR range, 2.0 to 3.0)<\/strong> (all Grade 1A)<strong>.<\/strong> <strong>3.1.2. For patients undergoing THR, we recommend against theuse of any of the following: aspirin, dextran, LDUH, GCS, orvenous foot pump (VFP) as the sole method of thromboprophylaxis<\/strong>(all Grade 1A)<strong>.<\/strong> <strong>3.1.3. For patients undergoing THR who have a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxiswith the VFP or IPC<\/strong> (Grade 1A)<strong>. When the high bleeding riskdecreases, we recommend that pharmacologic thromboprophylaxisbe substituted for or added to the mechanical thromboprophylaxis<\/strong>(Grade 1C)<strong>.<\/strong> <strong>3.2 Elective Knee Replacement<\/strong><strong>3.2.1. For patients undergoing TKR, we recommend routine thromboprophylaxisusing LMWH (at the usual high-risk dose), fondaparinux, or adjusted-doseVKA (INR target, 2.5; INR range, 2.0 to 3.0)<\/strong> (all Grade 1A)<strong>.<\/strong> <strong>3.2.2. For patients undergoing TKR, the optimal use of IPC isan alternative option to anticoagulant thromboprophylaxis<\/strong> (Grade1B)<strong>.<\/strong> <strong>3.2.3. For patients undergoing TKR, we recommend against theuse of any of the following as the only method of thromboprophylaxis:aspirin<\/strong>(Grade 1A)<strong>, LDUH<\/strong> (Grade 1A)<strong>, or VFP<\/strong> (Grade 1B)<strong>.<\/strong> <strong>3.2.4. For patients undergoing TKR who have a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxiswith IPC<\/strong> (Grade 1A) <strong>or VFP<\/strong> (Grade 1B)<strong>. When the high bleedingrisk decreases, we recommend that pharmacologic thromboprophylaxisbe substituted for or added to the mechanical thromboprophylaxis<\/strong>(Grade 1C)<strong>.<\/strong> <strong>3.3 Knee Arthroscopy<\/strong><strong>3.3.1. For patients undergoing knee arthroscopy who do not have additional thromboembolic risk factors, we suggest that clinicians not routinely use thromboprophylaxis other than early mobilization<\/strong>(Grade 2B)<strong>.<\/strong> <strong>3.3.2. For patients undergoing arthroscopic knee surgery whohave additional thromboembolic risk factors or following a complicatedprocedure, we recommend thromboprophylaxis with LMWH<\/strong> (Grade1B)<strong>.<\/strong> <strong>3.4 Hip Fracture Surgery<\/strong><strong>3.4.1. For patients undergoing HFS, we recommend routine thromboprophylaxisusing fondaparinux<\/strong> (Grade 1A)<strong>, LMWH<\/strong> (Grade 1B)<strong>, adjusted-doseVKA (INR target, 2.5; INR range, 2.0 to 3.0)<\/strong> [Grade 1B]<strong>, orLDUH<\/strong> (Grade 1B)<strong>.<\/strong> <strong>3.4.2. For patients undergoing HFS, we recommend against theuse of aspirin alone<\/strong> (Grade 1A)<strong>.<\/strong> <strong>3.4.3. For patients undergoing HFS in whom surgery is likelyto be delayed, we recommend that thromboprophylaxis with LMWHor LDUH be initiated during the time between hospital admission and surgery<\/strong> (Grade 1C)<strong>.<\/strong> <strong>3.4.4. For patients undergoing HFS who have a high risk of bleeding,we recommend the optimal use of mechanical thromboprophylaxis<\/strong>(Grade 1A)<strong>. When the high bleeding risk decreases, we recommendthat pharmacologic thromboprophylaxis be substituted for oradded to the mechanical thromboprophylaxis<\/strong> (Grade 1C)<strong>.<\/strong> <strong>3.5 Other Thromboprophylaxis Issues in Major Orthopedic Surgery<\/strong> <strong>3.5.1 Commencement of Thromboprophylaxis<\/strong><strong>3.5.1.1. For patients receiving LMWH as thromboprophylaxis in major orthopedic surgery, we recommend starting either preoperatively or postoperatively<\/strong> (Grade 1A)<strong>.<\/strong> <strong>3.5.1.2. For patients receiving fondaparinux as thromboprophylaxisin major orthopedic surgery, we recommend starting either 6to 8 h after surgery or the next day<\/strong> (Grade 1A)<strong>.<\/strong> <strong>Screening for Deep Vein Thrombosis Before Hospital Discharge<\/strong><strong>3.5.2. For asymptomatic patients following major orthopedic surgery, we recommend against the routine use of DUS screeningbefore hospital discharge<\/strong> (Grade 1A)<strong>.<\/strong> <strong>Duration of Thromboprophylaxis<\/strong><strong>3.5.3.1. For patients undergoing THR, TKR, or HFS, we recommend thromboprophylaxis with one of the recommended options for atleast 10 days<\/strong> (Grade 1A)<strong>.<\/strong> <strong>3.5.3.2. For patients undergoing THR, we recommend that thromboprophylaxisbe extended beyond 10 days and up to 35 days after surgery<\/strong> (Grade1A). <strong>The recommended options for extended thromboprophylaxisin THR include LMWH<\/strong> (Grade 1A)<strong>, a VKA<\/strong> (Grade 1B)<strong>, or fondaparinux<\/strong>(Grade 1C)<strong>.<\/strong> <strong>3.5.3.3. For patients undergoing TKR, we suggest that thromboprophylaxisbe extended beyond 10 days and up to 35 days after surgery<\/strong> (Grade2B). <strong>The recommended options for extended thromboprophylaxisin TKR include LMWH<\/strong> (Grade 1C)<strong>, a VKA<\/strong>(Grade 1C)<strong>, or fondaparinux<\/strong>(Grade 1C)<strong>.<\/strong> <strong>3.5.3.4. For patients undergoing HFS, we recommend that thromboprophylaxisbe extended beyond 10 days and up to 35 days after surgery<\/strong> (Grade1A)<strong>. The recommended options for extended thromboprophylaxisin HFS include fondaparinux<\/strong> (Grade 1A)<strong>, LMWH<\/strong> (Grade 1C)<strong>, ora VKA<\/strong> (Grade 1C)<strong>.<\/strong> <strong>3.6 Elective Spine Surgery<\/strong><strong>3.6.1. For patients undergoing spine surgery who do not have additional thromboembolic risk factors, we suggest that clinicians not routinely use specific thromboprophylaxis other than earlyand frequent ambulation<\/strong> (Grade 2C)<strong>.<\/strong> <strong>3.6.2. For patients undergoing spine surgery who have additionalthromboembolic risk factors such as advanced age, malignancy,presence of a neurologic deficit, previous VTE, or an anteriorsurgical approach, we recommend that one of the following thromboprophylaxisoptions be used: postoperative LDUH<\/strong> (Grade 1B)<strong>, postoperativeLMWH<\/strong> (Grade 1B)<strong>, or optimal use of perioperative IPC<\/strong> (Grade1B)<strong>. An alternative consideration is GCS<\/strong> (Grade 2B)<strong>.<\/strong> <strong>3.6.3. For patients undergoing spine surgery who have multiplerisk factors for VTE, we suggest that a pharmacologic method(ie, LDUH or LMWH) be combined with the optimal use of a mechanicalmethod (ie, GCS and\/or IPC)<\/strong> (Grade 2C)<strong>.<\/strong> <strong>3.7 Isolated Lower-Extremity Injuries Distal to the Knee<\/strong><strong>3.7.1. For patients with isolated lower-extremity injuries distal to the knee, we suggest that clinicians not routinely use thromboprophylaxis<\/strong>(Grade 2A)<strong>.<\/strong> <strong>4.0 Neurosurgery<\/strong><strong>4.0.1. For patients undergoing major neurosurgery, we recommend that thromboprophylaxis be used routinely<\/strong> (Grade 1A)<strong>, with optimaluse of IPC<\/strong> (Grade 1A)<strong>. Acceptable alternatives to IPC are postoperative LMWH<\/strong> (Grade 2A) <strong>or LDUH<\/strong> (Grade 2B)<strong>.<\/strong> <strong>4.0.2. For patients undergoing major neurosurgery who have aparticularly high thrombosis risk, we suggest that a mechanicalmethod (ie, GCS and\/or IPC) be combined with a pharmacologic method (ie, postoperative LMWH or LDUH)<\/strong> (Grade 2B)<strong>.<\/strong> <strong>5.0 Trauma, Spinal Cord Injury, Burns<\/strong> <strong>5.1 Trauma<\/strong><strong>5.1.1. For all major trauma patients, we recommend routine thromboprophylaxisif possible<\/strong> (Grade 1A)<strong>.<\/strong> <strong>5.1.2. For major trauma patients, in the absence of a majorcontraindication, we recommend that clinicians use LMWH thromboprophylaxisstarting as soon as it is considered safe to do so<\/strong> (Grade 1A)<strong>.An acceptable alternative is the combination of LMWH and theoptimal use of a mechanical method of thromboprophylaxis<\/strong> (Grade1B)<strong>.<\/strong> <strong>5.1.3. For major trauma patients, if LMWH thromboprophylaxisis contraindicated due to active bleeding or high risk for clinicallyimportant bleeding, we recommend that mechanical thromboprophylaxiswith IPC or possibly with GCS alone be used<\/strong> (Grade 1B)<strong>. Whenthe high bleeding risk decreases, we recommend that pharmacologicthromboprophylaxis be substituted for or added to the mechanicalthromboprophylaxis<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.1.4. In trauma patients, we recommend against routine DUSscreening for asymptomatic deep vein thrombosis (DVT)<\/strong> (Grade1B)<strong>. We do recommend DUS screening in patients who are at highrisk for VTE (eg, in the presence of a spinal cord injury [SCI],lower-extremity or pelvic fracture, or major head injury), and who have received suboptimal thromboprophylaxis or no thromboprophylaxis<\/strong>(Grade 1C)<strong>.<\/strong> <strong>5.1.5. For trauma patients, we recommend against the use ofan inferior vena cava (IVC) filter as thromboprophylaxis<\/strong> (Grade1C)<strong>.<\/strong> <strong>5.1.6. For major trauma patients, we recommend the continuationof thromboprophylaxis until hospital discharge<\/strong> (Grade 1C)<strong>. Fortrauma patients with impaired mobility who undergo inpatientrehabilitation, we suggest continuing thromboprophylaxis withLMWH or a VKA (target INR, 2.5; range, 2.0 to 3.0)<\/strong> (Grade 2C)<strong>.<\/strong> <strong>5.2 Acute Spinal Cord Injury<\/strong><strong>5.2.1. For all patients with acute SCI, we recommend that routine thromboprophylaxis be provided<\/strong> (Grade 1A)<strong>.<\/strong> <strong>5.2.2. For patients with acute SCI, we recommend thromboprophylaxiswith LMWH, commenced once primary hemostasis is evident<\/strong> (Grade1B)<strong>. Alternatives include the combined use of IPC and eitherLDUH<\/strong> (Grade 1B) <strong>or LWMH<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.2.3. For patients with acute SCI, we recommend the optimaluse of IPC and\/or GCS if anticoagulant thromboprophylaxis iscontraindicated because of high bleeding risk early after injury<\/strong>(Grade 1A)<strong>. When the high bleeding risk decreases, we recommendthat pharmacologic thromboprophylaxis be substituted for or added to the mechanical thromboprophylaxis<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.2.4. For patients with an incomplete SCI associated with evidenceof a spinal hematoma on CT or MRI, we recommend the use of mechanicalthromboprophylaxis instead of anticoagulant thromboprophylaxisat least for the first few days after injury<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.2.5. Following acute SCI, we recommend against the use ofLDUH alone<\/strong> (Grade 1A)<strong>.<\/strong> <strong>5.2.6. For patients with SCI, we recommend against the use ofan IVC filter as thromboprophylaxis<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.2.7. For patients undergoing rehabilitation following acuteSCI, we recommend the continuation of LMWH thromboprophylaxisor conversion to an oral VKA (INR target, 2.5; range, 2.0 to 3.0)<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.3 Burns<\/strong><strong>5.3.1. For burn patients who have additional risk factors forVTE, including one or more of the following: advanced age, morbidobesity, extensive or lower-extremity burns, concomitant lower-extremity trauma, use of a femoral venous catheter, and\/or prolonged immobility,we recommend routine thromboprophylaxis if possible<\/strong> (Grade 1A)<strong>.<\/strong> <strong>5.3.2. For burn patients who have additional risk factors forVTE, if there are no contraindications, we recommend the useof either LMWH or LDUH starting as soon as it is considered safe to do so<\/strong> (Grade 1C)<strong>.<\/strong> <strong>5.3.3. For burn patients who have a high bleeding risk, we recommendmechanical thromboprophylaxis with GCS and\/or IPC until thebleeding risk decreases<\/strong> (Grade 1A)<strong>.<\/strong> <strong>6.0 Medical Conditions<\/strong><strong>6.0.1. For acutely ill medical patients admitted to hospitalwith congestive heart failure or severe respiratory disease,or who are confined to bed and have one or more additional riskfactors, including active cancer, previous VTE, sepsis, acuteneurologic disease, or inflammatory bowel disease, we recommend thromboprophylaxis with LMWH<\/strong> (Grade 1A)<strong>, LDUH<\/strong> (Grade 1A)<strong>, orfondaparinux<\/strong> (Grade 1A)<strong>.<\/strong> <strong>6.0.2. For medical patients with risk factors for VTE, and forwhom there is a contraindication to anticoagulant thromboprophylaxis,we recommend the optimal use of mechanical thromboprophylaxiswith GCS or IPC<\/strong> (Grade 1A)<strong>.<\/strong> <strong>7.0 Cancer Patients<\/strong><strong>7.0.1. For cancer patients undergoing surgical procedures, we recommend routine thromboprophylaxis that is appropriate forthe type of surgery<\/strong> (Grade 1A)<strong>. Refer to the recommendationsin the relevant surgical subsections.<\/strong> <strong>7.0.2. For cancer patients who are bedridden with an acute medicalillness, we recommend routine thromboprophylaxis as for otherhigh-risk medical patients<\/strong> (Grade 1A)<strong>.<\/strong> <strong>Refer to the recommendations in Section 6.0.<\/strong> <strong>7.0.3. For cancer patients with indwelling central venous catheters,we recommend that clinicians not use either prophylactic dosesof LMWH<\/strong>(Grade 1B)<strong>. or minidose warfarin<\/strong> (Grade 1B) <strong>to try toprevent catheter-related thrombosis.<\/strong> <strong>7.0.4. For cancer patients receiving chemotherapy or hormonaltherapy, we recommend against the routine use of thromboprophylaxisfor the primary prevention of VTE<\/strong> (Grade 1C)<strong>.<\/strong> <strong>7.0.5. For cancer patients, we recommend against the routineuse of primary thromboprophylaxis to try to improve survival<\/strong>(Grade 1B)<strong>.<\/strong> <strong>8.0 Critical Care<\/strong><strong>8.1. For patients admitted to a critical care unit, we recommend routine assessment for VTE risk and routine thromboprophylaxisin most<\/strong> (Grade 1A)<strong>.<\/strong> <strong>8.2. For critical care patients who are at moderate risk forVTE (eg, medically ill or postoperative general surgery patients),we recommend using LMWH or LDUH thromboprophylaxis<\/strong> (Grade 1A)<strong>.<\/strong> <strong>8.3. For critical care patients who are at higher risk (eg,following major trauma or orthopedic surgery), we recommendLMWH thromboprophylaxis<\/strong> (Grade 1A)<strong>.<\/strong> <strong>8.4. For critical care patients who are at high risk for bleeding,we recommend the optimal use of mechanical thromboprophylaxiswith GCS and\/or IPC at least until the bleeding risk decreases<\/strong>(Grade 1A)<strong>. When the high bleeding risk decreases, we recommendthat pharmacologic thromboprophylaxis be substituted for oradded to the mechanical thromboprophylaxis<\/strong> (Grade 1C)<strong>.<\/strong> <strong>9.0 Long-Distance Travel<\/strong><strong>9.1. For travelers who are taking flights &gt; 8 h, we recommendthe following general measures: avoidance of constrictive clothingaround the lower extremities or waist, maintenance of adequatehydration, and frequent calf muscle contraction<\/strong> (Grade 1C)<strong>.<\/strong> <strong>9.2. For long-distance travelers with additional risk factorsfor VTE, we recommend the general measures listed above. Ifactive thromboprophylaxis is considered because of a perceived high risk of VTE, we suggest the use of properly fitted, below-knee GCS, providing 15 to 30 mm Hg of pressure at the ankle<\/strong>(Grade2C)<strong>, or a single prophylactic dose of LMWH injected prior todeparture<\/strong> (Grade 2C)<strong>.<\/strong> <strong>9.3. For long-distance travelers, we recommend against the useof aspirin for VTE prevention<\/strong> (Grade 1B)<strong>.<\/strong> &nbsp; &nbsp; <\/p>\n<h2><span class=\"ez-toc-section\" id=\"Antithrombotic_Therapy_for_Venous_Thromboembolic_Disease\"><\/span>Antithrombotic Therapy for Venous Thromboembolic Disease*<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<h3><span class=\"ez-toc-section\" id=\"American_College_of_Chest_Physicians_Evidence-Based_Clinical_Practice_Guidelines_8th_Edition\"><\/span>American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p> <strong>Clive Kearon, MB, PhD; Susan R. Kahn, MD; Giancarlo Agnelli, MD; Samuel Goldhaber, MD, FCCP; Gary E. Raskob, PhD and Anthony J. Comerota, MD<\/strong> * From McMaster University Clinic (Dr. Kearon), Henderson General Hospital, Hamilton, ON, Canada; Thrombosis Clinic and Centre for Clinical Epidemiology and Community Studies (Dr. Kahn), Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC, Canada; University of Perugia (Dr. Agnelli), Perugia, Italy; Brigham and Women\u0092s Hospital (Dr. Goldhaber), Boston, MA; College of Public Health, University of Oklahoma Health Science Center (Dr. Raskob), Oklahoma City, OK; and Jobst Vascular Center (Dr. Comerota), Toledo, OH. Correspondence to: Clive Kearon, MB, PhD, Hamilton Health Sciences, Henderson Division, 711 Concession St, Hamilton, ON, L8V 1C3, Canada; e-mail: <a href=\"mailto:kearonc@mcmaster.ca\">kearonc@mcmaster.ca<\/a> Abstract TOP Abstract Summary of Recommendations 1.0 Initial Treatment of&#8230; 2.0 Long-term Treatment of&#8230; 3.0 Postthrombotic Syndrome 4.0 Initial Treatment of&#8230; 5.0 Long-term Treatment of&#8230; 6.0 Chronic Thromboembolic&#8230; 7.0 Superficial Vein Thrombosis 8.0 Acute UEDVT Appendix References   This chapter about treatment for venous thromboembolic diseaseis part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understandingof the grading, see &#8220;Grades of Recommendation&#8221; chapter). Amongthe key recommendations in this chapter are the following: forpatients with objectively confirmed deep vein thrombosis (DVT)or pulmonary embolism (PE), we recommend anticoagulant therapywith subcutaneous (SC) low-molecular-weight heparin (LMWH),monitored IV, or SC unfractionated heparin (UFH), unmonitoredweight-based SC UFH, or SC fondaparinux (all Grade 1A). Forpatients with a high clinical suspicion of DVT or PE, we recommendtreatment with anticoagulants while awaiting the outcome ofdiagnostic tests (Grade 1C). For patients with confirmed PE,we recommend early evaluation of the risks to benefits of thrombolytictherapy (Grade 1C); for those with hemodynamic compromise, werecommend short-course thrombolytic therapy (Grade 1B); andfor those with nonmassive PE, we recommend against the use ofthrombolytic therapy (Grade 1B). In acute DVT or PE, we recommendinitial treatment with LMWH, UFH or fondaparinux for at least5 days rather than a shorter period (Grade 1C); and initiationof vitamin K antagonists (VKAs) together with LMWH, UFH, orfondaparinux on the first treatment day, and discontinuationof these heparin preparations when the international normalized ratio (INR) is 2.0 for at least 24 h (Grade 1A). For patientswith DVT or PE secondary to a transient (reversible) risk factor,we recommend treatment with a VKA for 3 months over treatmentfor shorter periods (Grade 1A). For patients with unprovokedDVT or PE, we recommend treatment with a VKA for at least 3months (Grade 1A), and that all patients are then evaluatedfor the risks to benefits of indefinite therapy (Grade 1C).We recommend indefinite anticoagulant therapy for patients witha first unprovoked proximal DVT or PE and a low risk of bleedingwhen this is consistent with the patient\u0092s preference(Grade 1A), and for most patients with a second unprovoked DVT (Grade 1A). We recommend that the dose of VKA be adjusted tomaintain a target INR of 2.5 (INR range, 2.0 to 3.0) for alltreatment durations (Grade 1A). We recommend at least 3 monthsof treatment with LMWH for patients with VTE and cancer (Grade1A), followed by treatment with LMWH or VKA as long as the canceris active (Grade 1C). For prevention of postthrombotic syndrome(PTS) after proximal DVT, we recommend use of an elastic compressionstocking (Grade 1A). For DVT of the upper extremity, we recommendsimilar treatment as for DVT of the leg (Grade 1C). Selectedpatients with lower-extremity (Grade 2B) and upper-extremity(Grade 2C). DVT may be considered for thrombus removal, generallyusing catheter-based thrombolytic techniques. For extensivesuperficial vein thrombosis, we recommend treatment with prophylacticor intermediate doses of LMWH or intermediate doses of UFH for4 weeks (Grade 1B). <strong>Key Words:<\/strong> cancer \u0095 chronic thromboembolic pulmonary hypertension \u0095 deep vein thrombosis \u0095 fondaparinux \u0095 low-molecular-weight heparin \u0095 plasminogen activator \u0095 pulmonary embolism \u0095 thrombectomy \u0095 thrombolytic therapy \u0095 thrombophlebitis \u0095 unfractionated heparin \u0095 vena caval filter \u0095 venous thromboembolism \u0095 vitamin K antagonist Summary of Recommendations TOP Abstract Summary of Recommendations 1.0 Initial Treatment of&#8230; 2.0 Long-term Treatment of&#8230; 3.0 Postthrombotic Syndrome 4.0 Initial Treatment of&#8230; 5.0 Long-term Treatment of&#8230; 6.0 Chronic Thromboembolic&#8230; 7.0 Superficial Vein Thrombosis 8.0 Acute UEDVT Appendix References  <strong>1.1 Initial Anticoagulation of Acute DVT of the Leg<\/strong><strong>1.1.1. For patients with objectively confirmed DVT, we recommend short-term treatment with SC LMWH<\/strong> (Grade 1A), <strong>IV UFH<\/strong> (Grade1A), <strong>monitored SC UFH<\/strong> (Grade 1A), <strong>fixed-dose SC UFH<\/strong> (Grade 1A),<strong>or SC fondaparinux<\/strong> (Grade 1A) <strong>rather than no such short-termtreatment.<\/strong> <strong>1.1.2. For patients with a high clinical suspicion of DVT, werecommend treatment with anticoagulants while awaiting the outcomeof diagnostic tests<\/strong> (Grade 1C). <strong>1.1.3. In patients with acute DVT, we recommend initial treatmentwith LMWH, UFH, or fondaparinux for at least 5 days and untilthe INR is 2.0 for 24 h<\/strong> (Grade 1C). <strong>1.1.4. In patients with acute DVT, we recommend initiation ofVKA together with LMWH, UFH, or fondaparinux on the first treatmentday rather than delayed initiation of VKA<\/strong> (Grade 1A). <strong>1.2 IV UFH for the Initial Treatment of DVT<\/strong><strong>1.2.1. In patients with acute DVT, if IV UFH is chosen, we recommendthat after an initial IV bolus (80 U\/kg or 5,000 U), it be administeredby continuous infusion (initially at a dose of 18 U\/kg\/h or 1,300 U\/h) with dose adjustment to achieve and maintain an activated partial thromboplastin time (APTT) prolongation that correspondsto plasma heparin levels of 0.3 to 0.7 IU\/mL anti-Xa activityby the amidolytic assay rather than administration as IV bolusesthroughout treatment, or administration without coagulationmonitoring<\/strong> (Grade 1C). <strong>1.3 SC UFH Compared With IV Heparin for the Initial Treatment of DVT<\/strong><strong>1.3.1. In patients with acute DVT, if monitored SC UFH is chosen, we recommend an initial dose of 17,500 U, or a weight-adjusteddose of about 250 U\/kg bid, with dose adjustment to achieveand maintain an APTT prolongation that corresponds to plasmaheparin levels of 0.3 to 0.7 IU\/mL anti-Xa activity when measured6 h after injection rather than starting with a smaller initialdose (see also Section 1.5)<\/strong> [Grade 1C]. <strong>1.3.2. In patients with acute DVT, if fixed-dose, unmonitoredSC UFH is chosen, we recommend an initial dose of 333 U\/Kg followedby 250 U\/kg bid rather than non\u0096weight-based dosing (seealso Section 1.5)<\/strong> [Grade 1C]. <strong>1.4 LMWH for the Initial Treatment of DVT<\/strong><strong>1.4.1. In patients with acute DVT, we recommend initial treatment with LMWH SC once or twice daily, as an outpatient if possible<\/strong> (Grade 1C), <strong>or as an inpatient if necessary<\/strong> (Grade 1A), <strong>ratherthan treatment with IV UFH.<\/strong> <strong>1.4.2. In patients with acute DVT treated with LMWH, we recommendagainst routine monitoring with anti-factor Xa level measurements<\/strong>(Grade 1A). <strong>1.4.3. In patients with acute DVT and severe renal failure,we suggest UFH over LMWH<\/strong> (Grade 2C). <strong>1.9 Catheter-Directed Thrombolysis for Acute DVT<\/strong><strong>1.9.1. In selected patients with extensive acute proximal DVT(<em>eg<\/em>, iliofemoral DVT, symptoms for &lt; 14 days, good functionalstatus, life expectancy of 1 year) who have a low risk of bleeding,we suggest that catheter-directed thrombolysis (CDT) may beused to reduce acute symptoms and postthrombotic morbidity ifappropriate expertise and resources are available<\/strong> (Grade 2B). <strong>1.9.2. After successful CDT in patients with acute DVT, we suggestcorrection of underlying venous lesions using balloon angioplastyand stents<\/strong> (Grade 2C). <strong>1.9.3. We suggest pharmacomechanical thrombolysis (<em>eg<\/em>, withinclusion of thrombus fragmentation and\/or aspiration) in preferenceto CDT alone to shorten treatment time if appropriate expertiseand resources are available<\/strong> (Grade 2C). <strong>1.9.4. After successful CDT in patients with acute DVT, we recommendthe same intensity and duration of anticoagulant therapy asfor comparable patients who do not undergo CDT<\/strong> (Grade 1C). <strong>1.10 Systemic Thrombolytic Therapy for Acute DVT<\/strong><strong>1.10.1. In selected patients with extensive proximal DVT (<em>eg<\/em>,symptoms for &lt; 14 days, good functional status, life expectancy of 1 year) who have a low risk of bleeding, we suggest thatsystemic thrombolytic therapy may be used to reduce acute symptomsand postthrombotic morbidity if CDT is not available<\/strong> (Grade2C). <strong>1.11 Percutaneous Venous Thrombectomy<\/strong><strong>1.11.1. In patients with acute DVT, we suggest that they should not be treated with percutaneous mechanical thrombectomy alone<\/strong> (Grade 2C). <strong>1.12 Operative Venous Thrombectomy for Acute DVT<\/strong><strong>1.12.1. In selected patients with acute iliofemoral DVT (<em>eg<\/em>,symptoms for &lt; 7 days, good functional status, and life expectancyof 1 year), we suggest that operative venous thrombectomy maybe used to reduce acute symptoms and postthrombotic morbidityif appropriate expertise and resources are available<\/strong> (Grade2B). <strong>If such patients do not have a high risk of bleeding, wesuggest that catheter-directed thrombolysis is usually preferableto operative venous thrombectomy<\/strong> (Grade 2C). <strong>1.12.2. In patients who undergo operative venous thrombectomy,we recommend the same intensity and duration of anticoagulanttherapy afterwards as for comparable patients who do not undergovenous thrombectomy<\/strong> (Grade 1C). <strong>1.13 Vena Caval Filters for the Initial Treatment of DVT<\/strong><strong>1.13.1. For patients with DVT, we recommend against the routine use of a vena cava filter in addition to anticoagulants<\/strong> (Grade 1A). <strong>1.13.2. For patients with acute proximal DVT, if anticoagulanttherapy is not possible because of the risk of bleeding, werecommend placement of an inferior vena cava (IVC) filter<\/strong> (Grade1C). <strong>1.13.3. For patients with acute DVT who have an IVC filter insertedas an alternative to anticoagulation, we recommend that theyshould subsequently receive a conventional course of anticoagulanttherapy if their risk of bleeding resolves<\/strong> (Grade 1C). <strong>1.14 Immobilization for the Treatment of Acute DVT<\/strong><strong>1.14.1. In patients with acute DVT, we recommend early ambulation in preference to initial bed rest when this is feasible<\/strong> (Grade 1A). <strong>2.1 Duration of Anticoagulant Therapy<\/strong><strong>2.1.1. For patients with DVT secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 monthsover treatment for shorter periods<\/strong> (Grade 1A). <strong>2.1.2. For patients with unprovoked DVT, we recommend treatmentwith a VKA for at least 3 months<\/strong> (Grade 1A). <strong>We recommend thatafter 3 months of anticoagulant therapy, all patients with unprovokedDVT should be evaluated for the risk-benefit ratio of long-termtherapy<\/strong> (Grade 1C). <strong>For patients with a first unprovoked VTEthat is a proximal DVT, and in whom risk factors for bleedingare absent and for whom good anticoagulant monitoring is achievable,we recommend long-term treatment<\/strong> (Grade 1A). <em>Values and preferences:<\/em> This recommendation attaches a relativelyhigh value to prevention of recurrent VTE and a lower valueto the burden of long-term anticoagulant therapy. <strong>For patients with a second episode of unprovoked VTE, we recommendlong-term treatment<\/strong> (Grade 1A). <strong>For patients with a first isolateddistal DVT that is unprovoked, we suggest that 3 months of anticoagulanttherapy is sufficient rather than indefinite therapy<\/strong> (Grade2B). <strong>2.1.3. For patients with DVT and cancer, we recommend LMWH forthe first 3 to 6 months of long-term anticoagulant therapy<\/strong> (Grade1A). <strong>For these patients, we recommend subsequent anticoagulanttherapy with VKA or LMWH indefinitely or until the cancer isresolved (also, see Section 2.4)<\/strong> [Grade 1C]. <strong>2.1.4. In patients who receive long-term anticoagulant treatment,the risk-benefit ratio of continuing such treatment should bereassessed in the individual patient at periodic intervals<\/strong> (Grade1C). <strong>2.2 Intensity of Anticoagulant Effect<\/strong><strong>2.2.1. In patients with DVT, we recommend that the dose of VKAbe adjusted to maintain a target INR of 2.5 (range, 2.0 to 3.0)for all treatment durations<\/strong> (Grade 1A). <strong>For patients with unprovoked DVT who have a strong preference for less frequent INR testingto monitor their therapy, after the first 3 months of conventional-intensityanticoagulation (INR range, 2.0 to 3.0), we recommend low-intensitytherapy (range, 1.5 to 1.9) with less frequent INR monitoring over stopping treatment<\/strong> (Grade 1A). <strong>We recommend against high-intensityVKA therapy (INR range, 3.1 to 4.0) compared to an INR rangeof 2.0 to 3.0<\/strong> (Grade 1A). <strong>2.6 Treatment of Asymptomatic DVT of the Leg<\/strong><strong>2.6.1. In patients who are unexpectedly found to have asymptomatic DVT, we recommend the same initial and long-term anticoagulationas for comparable patients with symptomatic DVT<\/strong> (Grade 1C). <strong>3.1 Elastic Stockings and Compression Bandages To Prevent PTS<\/strong><strong>3.1.1. For a patient who has had a symptomatic proximal DVT,we recommend the use of an elastic compression stocking withan ankle pressure gradient of 30 to 40 mm Hg if feasible<\/strong> (Grade1A). <strong> Compression therapy, which may include use of bandagesacutely, should be started as soon as feasible after startinganticoagulant therapy and should be continued for a minimumof 2 years, and longer if patients have symptoms of PTS. (Note:feasibility, both short and long term, refers to ability ofpatients and their caregivers to apply and remove stockings.)<\/strong> <em>Values and preferences:<\/em> This recommendation attaches a relativelyhigh value to long-term prevention of the PTS and a low valueto the burden (<em>eg<\/em>, inconvenience or discomfort) associated withwearing stockings. <strong>3.2 Physical Treatment of PTS Without Venous Leg Ulcers<\/strong><strong>3.2.1. For patients with severe edema of the leg due to PTS,we suggest a course of intermittent pneumatic compression (IPC)<\/strong> [Grade 2B]. <strong>3.2.2. For patients with mild edema of the leg due to PTS, wesuggest the use of elastic compression stockings<\/strong> (Grade 2C). <strong>3.3 Physical Treatment of Venous Leg Ulcers<\/strong><strong>3.3.1. In patients with venous ulcers resistant to healing with wound care and compression, we suggest the addition of IPC<\/strong> (Grade 2B). <strong>3.4 Hyperbaric Oxygen and the Management of Patients With Venous Ulcers<\/strong><strong>3.4.1. For patients with venous ulcers, we suggest that hyperbaric oxygen not be used<\/strong> (Grade 2B). <strong>3.5.1. Pentoxifylline<\/strong><strong>3.5.1. In patients with venous leg ulcers, we suggest pentoxifylline,400 mg po tid, in addition to local care and compression and\/or IPC<\/strong> (Grade 2B). <strong>3.5.2. Micronized Purified Flavonoid Fraction or Sulodexide for the Treatment of Venous Leg Ulcers<\/strong><strong>3.5.2. In patients with persistent venous ulcers, we suggestthat rutosides, in the form of micronized purified flavonoidfraction administered orally, or sulodexide administered intramuscularlyand then orally, be added to local care and compression<\/strong> (Grade2B). <strong>4.1 IV or SC UFH, SC LMWH, SC Fondaparinux, and VKA for the Initial Treatment of PE<\/strong><strong>4.1.1. For patients with objectively confirmed PE, we recommend short-term treatment with SC LMWH<\/strong> (Grade 1A), <strong>IV UFH<\/strong> (Grade1A), <strong>monitored SC UFH<\/strong> (Grade 1A), <strong>fixed-dose SC UFH<\/strong> (Grade 1A),<strong>or SC fondaparinux<\/strong> (Grade 1A) <strong>rather than no such acute treatment.Patients with acute PE should also be routinely assessed fortreatment with thrombolytic therapy (see Section 4.3 for relateddiscussion and recommendations).<\/strong> <strong>4.1.2. For patients in whom there is a high clinical suspicionof PE, we recommend treatment with anticoagulants while awaitingthe outcome of diagnostic tests<\/strong> (Grade 1C). <strong>4.1.3. In patients with acute PE, we recommend initial treatmentwith LMWH, UFH or fondaparinux for at least 5 days and untilthe INR is 2.0 for at least 24 h<\/strong> (Grade 1C). <strong>4.1.4. In patients with acute PE, we recommend initiation ofVKA together with LMWH, UFH, or fondaparinux on the first treatmentday rather than delayed initiation of VKA<\/strong> (Grade 1A). <strong>4.1.5. In patients with acute PE, if IV UFH is chosen, we recommendthat after an initial IV bolus (80 U\/kg or 5,000 U), it be administeredby continuous infusion (initially at dose of 18 U\/kg\/h or 1,300U\/h) with dose adjustment to achieve and maintain an APTT prolongationthat corresponds to plasma heparin levels of 0.3 to 0.7 IU\/mLanti-Xa activity by the amidolytic assay rather than administrationas IV boluses throughout treatment, or administration withoutcoagulation monitoring<\/strong> (Grade 1C). <strong>4.1.6. In patients with acute PE, if monitored SC UFH is chosen,we recommend an initial dose of 17,500 U, or a weight-adjusteddose of approximately 250 U\/kg bid, with dose adjustment toachieve and maintain an APTT prolongation that corresponds toplasma heparin levels of 0.3 to 0.7 IU\/mL anti-Xa activity whenmeasured 6 h after injection rather than starting with a smallerinitial dose<\/strong> (Grade 1C). <strong>4.1.7. In patients with acute PE, if fixed-dose, unmonitoredSC UFH is chosen, we recommend an initial dose of 333 U\/Kg followedby a twice-daily dose of 250 U\/kg rather than non\u0096weight-baseddosing<\/strong> (Grade 1C). <strong>4.1.8. In patients with acute nonmassive PE, we recommend initialtreatment with LMWH over IV UFH<\/strong> (Grade 1A). <strong>In patients withmassive PE, in other situations where there is concern aboutSC absorption, or in patients for whom thrombolytic therapyis being considered or planned, we suggest IV UFH over SC LMWH, SC fondaparinux, or SC UFH<\/strong> (Grade 2C). <strong>4.1.9. In patients with acute PE treated with LMWH, we recommendagainst routine monitoring with anti-factor Xa level measurements<\/strong>(Grade 1A). <strong>4.1.10. In patients with acute PE and severe renal failure,we suggest UFH over LMWH<\/strong> (Grade 2C). <strong>4.3 Systemically and Locally Administered Thrombolytic Therapy for PE<\/strong><strong>4.3.1. All PE patients should undergo rapid risk stratification<\/strong>(Grade 1C). <strong>For patients with evidence of hemodynamic compromise,we recommend use of thrombolytic therapy unless there are major contraindications owing to bleeding risk<\/strong> (Grade 1B). <strong>Thrombolysisin these patients should not be delayed because irreversible cardiogenic shock may ensue. In selected high-risk patientswithout hypotension who are judged to have a low risk of bleeding,we suggest administration of thrombolytic therapy<\/strong> (Grade 2B).<strong>The decision to use thrombolytic therapy depends on the clinician\u0092s assessment of PE severity, prognosis, and risk of bleeding.For the majority of patients with PE, we recommend against usingthrombolytic therapy<\/strong> (Grade 1B). <strong>4.3.2. In patients with acute PE, when a thrombolytic agentis used, we recommend that treatment be administered via a peripheralvein rather than placing a pulmonary artery catheter to administertreatment<\/strong> (Grade 1B). <strong>4.3.3. In patients with acute PE, with administration of thrombolytictherapy, we recommend use of regimens with short infusion times(<em>eg<\/em>, a 2-h infusion) over those with prolonged infusion times(<em>eg<\/em>, a 24-h infusion)<\/strong> [Grade 1B]. <strong>4.4 Catheter Extraction or Fragmentation for the Initial Treatment of PE<\/strong><strong>4.4.1. For most patients with PE, we recommend against use of interventional catheterization techniques<\/strong> (Grade 1C). <strong>In selectedhighly compromised patients who are unable to receive thrombolytictherapy because of bleeding risk, or whose critical status does not allow sufficient time for systemic thrombolytic therapyto be effective, we suggest use of interventional catheterization techniques if appropriate expertise is available<\/strong> (Grade 2C). <strong>4.5 Pulmonary Embolectomy for the Initial Treatment of PE<\/strong><strong>4.5.1. In selected highly compromised patients who are unableto receive thrombolytic therapy because of bleeding risk, orwhose critical status does not allow sufficient time for systemic thrombolytic therapy to be effective, we suggest that pulmonary embolectomy may be used if appropriate expertise is available<\/strong> (Grade 2C). <strong>4.6 Vena Caval Filters for the Initial Treatment of PE<\/strong><strong>4.6.1. For most patients with PE, we recommend against the routine use of a vena caval filter in addition to anticoagulants<\/strong> (Grade 1A). <strong>4.6.2. In patients with acute PE, if anticoagulant therapy isnot possible because of risk of bleeding, we recommend placementof an IVC filter<\/strong> (Grade 1C). <strong>4.6.3. For patients with acute PE who have an IVC filter insertedas an alternative to anticoagulation, we recommend that theyshould subsequently receive a conventional course of anticoagulanttherapy if their risk of bleeding resolves<\/strong> (Grade 1C). <strong>5.0 Long-term Treatment of Acute PE<\/strong><strong>5.1.1. For patients with PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 monthsover treatment for shorter periods<\/strong> (Grade 1A). <strong>5.1.2. For patients with unprovoked PE, we recommend treatmentwith a VKA for at least 3 months<\/strong> (Grade 1A). <strong>We recommend thatafter 3 months of anticoagulant therapy, all patients with unprovokedPE should be evaluated for the risk-benefit ratio of long-termtherapy<\/strong> (Grade 1C). <strong>For patients with a first unprovoked episodeof VTE that is a PE, and in whom risk factors for bleeding areabsent and for whom good anticoagulant monitoring is achievable,we recommend long-term treatment<\/strong> (Grade 1A). <em>Values and preferences:<\/em> This recommendation attaches a relativelyhigh value to prevention of recurrent VTE and a lower valueto the burden of long-term anticoagulant therapy. <strong>For patients with a second episode of unprovoked VTE, we recommendlong-term treatment<\/strong> (Grade 1A). <strong>5.1.3. For patients with PE and cancer, we recommend LMWH forthe first 3 to 6 months of long-term anticoagulant therapy<\/strong> (Grade1A). <strong>For these patients, we recommend subsequent anticoagulanttherapy with VKA or LMWH indefinitely or until the cancer isresolved<\/strong> (Grade 1C). <strong>5.1.4. In patients who receive long-term anticoagulant treatment,the risk-benefit ratio of continuing such treatment should bereassessed in the individual patient at periodic intervals<\/strong> (Grade1C). <strong>5.1.5. In patients with PE, we recommend that the dose of VKAbe adjusted to maintain a target INR of 2.5 (INR range, 2.0to 3.0) for all treatment durations<\/strong> (Grade 1A). <strong>For patientswith unprovoked PE who have a strong preference for less frequentINR testing to monitor their therapy, after the first 3 months of conventional-intensity anticoagulation (INR range, 2.0 to3.0), we recommend low-intensity therapy (INR range, 1.5 to1.9) with less frequent INR monitoring over stopping treatment<\/strong>(Grade 1A). <strong>We recommend against high-intensity VKA therapy(INR range, 3.1 to 4.0) compared with an INR range of 2.0 to3.0<\/strong> (Grade 1A). <strong>5.1.6. In patients who are unexpectedly found to have asymptomaticPE, we recommend the same initial and long-term anticoagulationas for comparable patients with symptomatic PE<\/strong> (Grade 1C). <strong>6.1 Pulmonary Thromboendarterectomy, VKA, and Vena Caval Filter for the Treatment of Chronic Thromboembolic Pulmonary Hypertension<\/strong><strong>6.1.1. In selected patients with chronic thromboembolic pulmonary hypertension (CTPH), such as those with central disease underthe care of an experienced surgical\/medical team, we recommendpulmonary thromboendarterectomy<\/strong> (Grade 1C). <strong>6.1.2. For all patients with CTPH, we recommend life-long treatmentwith a VKA targeted to an INR of 2.0 to 3.0<\/strong> (Grade 1C). <strong>6.1.3. For patients with CTPH undergoing pulmonary thromboendarterectomy,we suggest the placement of a permanent vena caval filter beforeor at the time of the procedure<\/strong> (Grade 2C). <strong>6.1.4. For patients with inoperable CTPH, we suggest referralto a center with expertise in pulmonary hypertension so thatpatients can be evaluated for alternative treatments, such as vasodilator therapy or balloon pulmonary angioplasty<\/strong> (Grade2C). <strong>7.1 Treatment of Infusion Thrombophlebitis<\/strong><strong>7.1.1. For patients with symptomatic infusion thrombophlebitisas a complication of IV infusion, we suggest oral diclofenacor another nonsteroidal antiinflammatory drug<\/strong> (Grade 2B), <strong>topical diclofenac gel<\/strong> (Grade 2B), <strong>or heparin gel<\/strong> (Grade 2B) <strong>until resolutionof symptoms or for up to 2 weeks. We recommend against the useof systemic anticoagulation<\/strong> (Grade 1C). <strong>7.2 Treatment of SVT<\/strong><strong>7.2.1. For patients with spontaneous superficial vein thrombosis, we suggest prophylactic or intermediate doses of LMWH<\/strong> (Grade2B) <strong>or intermediate doses of UFH<\/strong> (Grade 2B) <strong>for at least 4 weeks.We suggest that as an alternative to 4 weeks of LMWH or UFH, VKA (target INR, 2.5; range, 2.0 to 3.0) can be overlapped with5 days of UFH and LMWH and continued for 4 weeks<\/strong> (Grade 2C).<strong>We suggest that oral nonsteriodal antiinflammatory drugs shouldnot be used in addition to anticoagulation<\/strong> (Grade 2B). <strong>We recommend medical treatment with anticoagulants over surgical treatment<\/strong> (Grade 1B). Remark: It is likely that less extensive superficial vein thrombosis(<em>ie<\/em>, where the affected venous segment is short in length orfurther from the saphenofemoral junction) does not require treatmentwith anticoagulants. It is reasonable to use oral or topicalnonsteriodal antiinflammatory drugs for symptom control in suchcases. <strong>8.1. IV UFH or LMWH for the Initial Treatment of Upper-Extremity DVT<\/strong><strong>8.1.1. For patients with acute upper-extremity DVT (UEDVT),we recommend initial treatment with therapeutic doses of LMWH,UFH, or fondaparinux as described for leg DVT (see Section 1)<\/strong>[Grade 1C]. <strong>8.2 Thrombolytic Therapy for the Initial Treatment of UEDVT<\/strong><strong>8.2.1. For most patients with acute UEDVT, we recommend against the routine use of systemic or catheter-directed thrombolytictherapy<\/strong> (Grade 1C). <strong>8.2.2. In selected patients with acute UEDVT (<em>eg<\/em>, in those witha low risk of bleeding and severe symptoms of recent onset),we suggest that CDT may be used for initial treatment if appropriateexpertise and resources are available<\/strong> (Grade 2C). <strong>8.3 Catheter Extraction, Surgical Thrombectomy, Transluminal Angioplasty, Stent Placement, Staged Approach of Lysis Followed by Interventional or Surgical Procedure, Superior Vena Cava Filter Insertion for the Initial Treatment of UEDVT<\/strong><strong>8.3.1. For most patients with acute UEDVT, we recommend against the routine use of catheter extraction, surgical thrombectomy, transluminal angioplasty, stent placement, staged approach oflysis followed by interventional or surgical procedure, or superiorvena cava (SVC) filter placement<\/strong> (Grade 1C). <strong>8.3.2. In selected patients with acute UEDVT (<em>eg<\/em>, those withprimary UEDVT and failure of anticoagulant or thrombolytic treatmentwho have severe persistent symptoms), we suggest that catheterextraction, surgical thrombectomy, transluminal angioplasty,or a staged approach of lysis followed by a vascular interventionalor surgical procedure may be used if appropriate expertise and resources are available<\/strong> (all Grade 2C). <strong>8.3.3. In selected patients with acute UEDVT (<em>eg<\/em>, those forwhom anticoagulant treatment is contraindicated and there isclear evidence of DVT progression or clinically significantPE), we suggest placement of an SVC filter<\/strong> (Grade 2C). <strong>8.4 Anticoagulants for the Long-term Treatment of UEDVT<\/strong><strong>8.4.1. For patients with acute UEDVT, we recommend treatmentwith a VKA for 3 months<\/strong> (Grade 1C). Remark: A similar process as for lower-extremity DVT (see Section2) should be used to determine the optimal duration of anti-coagulation. <strong>8.4.2. For most patients with UEDVT in association with an indwellingcentral venous catheter, we suggest that the catheter not beremoved if it is functional and there is an ongoing need forthe catheter<\/strong> (Grade 2C). <strong>8.4.3. For patients who have UEDVT in association with an indwellingcentral venous catheter that is removed, we do not recommendthat the duration of long-term anticoagulant treatment be shortenedto &lt; 3 months<\/strong> (Grade 2C). <strong>8.5 Prevention of PTS of the Arm<\/strong><strong>8.5.1. For patients at risk for PTS after UEDVT, we do not suggest routine use of elastic compression or venoactive medications<\/strong> (Grade 2C). <strong>8.6 Treatment of PTS of the Arm<\/strong><strong>8.6.1. In patients with UEDVT who have persistent edema andpain, we suggest elastic bandages or elastic compression sleevesto reduce symptoms of PTS of the upper extremity<\/strong> (Grade 2C). &nbsp; &nbsp; <strong>1.1 AF<\/strong><strong>1.1.1. In patients with AF, including those with paroxysmalAF, who have had a prior ischemic stroke, TIA, or systemic embolism,we recommend long-term anticoagulation with an oral vitaminK antagonist, such as warfarin, targeted at an INR of 2.5 (range,2.0 to 3.0) because of the high risk of future ischemic strokefaced by this set of patients<\/strong> (Grade 1A). <strong>Timing of the initiationof VKA therapy after an acute ischemic stroke involves balancingthe risk of hemorrhagic conversion with short-term risk of recurrent ischemic stroke and is addressed in the chapter by Albers etal in this supplement. 1.1.2. In patients with AF, includingthose with paroxysmal AF, who have two or more of the followingrisk factors for future ischemic stroke, we recommend long-termanticoagulation with an oral VKA, such as warfarin, targetedat an INR of 2.5 (range, 2.0 to 3.0) because of the increasedrisk of future ischemic stroke faced by this set of patients<\/strong>(Grade 1A). <strong>Two or more of the following risk factors apply:(1) age &gt; 75 years; (2) history of hypertension; (3) diabetesmellitus; and (4) moderately or severely impaired left ventricularsystolic function and\/or heart failure.<\/strong> Remark: Recommendations 1.1.1 and 1.1.2 correspond to a recommendationof oral VKA therapy for individuals with a score 2 using theCHADS2 classification. For these and all other recommendationsof long-term therapy in this chapter, <em>long-term<\/em> means lifelongunless a contraindication emerges. <strong>1.1.3. In patients with AF, including those with paroxysmalAF, with only one of the risk factors listed below, we recommendlong-term antithrombotic therapy<\/strong> (Grade 1A), <strong>either as anticoagulationwith an oral VKA, such as warfarin, targeted at an INR of 2.5(range, 2.0 to 3.0)<\/strong> (Grade 1A), <strong>or as aspirin, at a dose of75 to 325 mg\/d<\/strong> (Grade 1B). <strong>For these patients at intermediaterisk of ischemic stroke, we suggest a VKA rather than aspirin<\/strong>(Grade 2A). <strong>This set of patients with AF is defined by havingone of the following risk factors: (1) age &gt; 75 years; (2)history of hypertension; (3) diabetes mellitus; or (4) moderatelyor severely impaired left ventricular systolic function and\/or heart failure. 1.1.4. In patients with AF, including those with paroxysmal AF, aged 75 years and with none of the other riskfactors listed above, we recommend long-term aspirin therapyat a dose of 75 to 325 mg\/d<\/strong> (Grade 1B) <strong>because of their lowrisk of ischemic stroke.<\/strong> <em>Underlying values and preferences:<\/em> Anticoagulation with oralVKAs, such as warfarin, has far greater efficacy than aspirinin preventing stroke, and particularly in preventing severeischemic stroke, in AF. We recommend the option of aspirin therapyfor lower risk groups in 1.1.3 and 1.1.4, above, estimatingthe absolute expected benefit of anticoagulant therapy may notbe worth the increased hemorrhagic risk and burden of anticoagulation. Individual lower-risk patients may rationally choose anticoagulation over aspirin therapy to gain greater protection against ischemic stroke if they value protection against stroke much more highlythan reducing risk of hemorrhage and the burden of managing anticoagulation. Our recommendations assume that the patientis not at high risk for bleeding and that good control of anticoagulation will occur. Remarks: These recommendations apply to patients with persistentor paroxysmal AF and not to patients with a single brief episodeof AF due to a reversible cause, such as an acute pulmonaryinfection. The optimal dose of aspirin for patients with AFis unclear. The largest effect of aspirin was seen in the firstStroke Prevention in Atrial Fibrillation (SPAF I) trial, whichused aspirin at 325 mg\/d.1 However, generalizing from trialsof aspirin for all antithrombotic indications and from physiologicstudies, we feel the best balance of efficacy and safety isachieved at low doses of aspirin, <em>ie<\/em>, 75 to 100 mg\/d (see chapteron &#8220;Antiplatelet Drugs&#8221; in this supplement).2 <strong>1.2 Atrial Flutter<\/strong><strong>1.2. For patients with atrial flutter, we recommend that antithrombotictherapy decisions follow the same risk-based recommendationsas for AF<\/strong> (Grade 1C). <strong>1.3 Valvular Heart Disease and AF<\/strong><strong>1.3.1. For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA, such as warfarin(target INR, 2.5; range, 2.0 to 3.0)<\/strong> [Grade 1B]. <strong>1.3.2. For patients with AF and prosthetic heart valves we recommendlong-term anticoagulation with an oral VKA, such as warfarin,at an intensity appropriate for the specific type of prosthesis<\/strong>(Grade 1B). <strong>See chapter on &#8220;Valvular and Structural Heart Disease&#8221;in this supplement.<\/strong> <strong>1.4 AF Following Cardiac Surgery<\/strong><strong>1.4. For patients with AF occurring shortly after open-heart surgery and lasting 48 h, we suggest anticoagulation with anoral VKA, such as warfarin, if bleeding risks are acceptable<\/strong>(Grade 2C). <strong>The target INR is 2.5 (range, 2.0 to 3.0). We suggestcontinuing anticoagulation for 4 weeks following reversion toand maintenance of normal sinus rhythm (NSR), particularly ifpatients have risk factors for thromboembolism<\/strong> (Grade 2C). <strong>2.1 Anticoagulation for Elective Cardioversion of AF<\/strong><strong>2.1.1. For patients with AF of 48 h or of unknown durationfor whom pharmacologic or electrical cardioversion is planned,we recommend anticoagulation with an oral VKA, such as warfarin,at a target INR of 2.5 (range, 2.0 to 3.0) for 3 weeks beforeelective cardioversion and for at least 4 weeks after sinusrhythm has been maintained<\/strong> (Grade 1C). Remark: This recommendation applies to all patients with AF,including those whose risk factor status would otherwise indicatea low risk for stroke. Patients with risk factors for thromboembolismshould continue anticoagulation beyond 4 weeks unless thereis convincing evidence that sinus rhythm is maintained. Forpatients with recurrent episodes of AF, Recommendations 1.1.1,1.1.2, 1.1.3, and 1.1.4 apply. <strong>2.1.2. For patients with AF of 48 h or of unknown durationwho are undergoing pharmacologic or electrical cardioversion,we recommend either immediate anticoagulation with IV unfractionatedheparin (target partial thromboplastin time [PTT], 60 s; range,50 to 70 s), or LMWH (at full deep venous thrombosis [DVT] treatmentdoses), or at least 5 days of warfarin (target INR of 2.5; range,2.0 to 3.0) at the time of cardioversion and performance ofa screening multiplane TEE. If no thrombus is seen, cardioversionis successful, and sinus rhythm is maintained, we recommendanticoagulation (target INR, 2.5; range, 2.0 to 3.0) for atleast 4 weeks. If a thrombus is seen on TEE, then cardioversionshould be postponed and anticoagulation should be continuedindefinitely. We recommend obtaining a repeat TEE before attemptinglater cardioversion<\/strong> (all Grade 1B addressing the equivalenceof TEE-guided vs non-TEE\u0096guided cardioversion; see recommendation2.1.1, above). Remark: The utility of the conventional and TEE-guided approachesis likely comparable. This recommendation applies to all patientswith AF, including those whose risk factor status would otherwiseindicate a low risk for stroke. Patients with risk factors forthromboembolism should continue anticoagulation beyond 4 weeksunless there is convincing evidence that sinus rhythm is maintained.For patients with recurrent episodes of AF, Recommendations 1.1.1, 1.1.2, 1.1.3, and 1.1.4 apply. <strong>2.1.3. For patients with AF of known duration &lt; 48 h, wesuggest that cardioversion be performed without prolonged anticoagulation<\/strong>(Grade 2C). <strong>However, in patients without contraindications toanticoagulation, we suggest beginning IV heparin (target PTT, 60 s; range, 50 to 70 s) or LMWH (at full DVT treatment doses)at presentation<\/strong> (Grade 2C). Remark: For patients with risk factors for stroke, it is particularlyimportant to be confident that the duration of AF is &lt; 48h. In such patients with risk factors, a TEE-guided approach(see 2.12, above) is a reasonable alternative strategy. Postcardioversionanticoagulation is based on whether the patient has experienced more than one episode of AF and on his or her risk factor status.For patients with recurrent episodes of AF, Recommendations1.1.1, 1.1.2, 1.1.3, and 1.1.4 apply. <strong>2.1.4. For emergency cardioversion in the hemodynamically unstablepatient, we suggest that IV unfractionated heparin (target PTTof 60 s with a target range of 50 to 70 s) or low-molecular-weightheparin (at full DVT treatment doses) be started as soon aspossible, followed by at least 4 weeks of anticoagulation withan oral VKA, such as warfarin (target INR of 2.5; range, 2.0to 3.0) if cardioversion is successful and sinus rhythm is maintained<\/strong>(Grade 2C). Remark: Long-term continuation of anticoagulation is based onwhether the patient has experienced more than one episode ofAF and on his or her risk factor status. For patients experiencingmore than one episode of AF, Recommendations 1.1.1, 1.1.2, 1.1.3,and 1.1.4 apply. <strong>2.1.5. For cardioversion of patients with atrial flutter, wesuggest use of anticoagulants in the same way as for cardioversionof patients with AF<\/strong> (Grade 2C). &nbsp; <strong>1.1 IV tPA for Acute Ischemic Stroke Within 3 h of Symptom Onset<\/strong><strong>1.1.1. For eligible patients (see inclusion and exclusion criteria listed below), we recommend administration of IV tPA in a doseof 0.9 mg\/kg (maximum of 90 mg), with 10% of the total dosegiven as an initial bolus and the remainder infused over 60min, provided that treatment is initiated within 3 h of clearlydefined symptom onset<\/strong> (Grade 1A). <em>Underlying values and preferences<\/em>: This recommendation placesrelatively more weight on overall prospects for long-term functionalimprovement despite the increased risk of symptomatic intracerebralhemorrhage in the immediate peristroke period. <strong>1.1.2. We recommend that patients who are eligible for tPA betreated as quickly as possible within the 3-h time limit<\/strong> (Grade1A). <em>Remark:<\/em> All unnecessary delays must be avoided as the benefitsof tPA therapy diminish rapidly over time. <strong>1.1.3. For patientswith extensive (more than one third of the middle cerebral arteryterritory) and clearly identifiable hypodensity on CT, we suggestnot using of tPA<\/strong> (Grade 2B). <strong>1.2 IV tPA for Acute Ischemic Stroke Between 3 to 6 h of Symptom Onset<\/strong><strong>1.2. For patients with acute ischemic stroke of &gt; 3 h but&lt; 4.5 h we suggest clinicians do not use IV tPA<\/strong> (Grade 2A).<strong>For patients with acute stroke onset of &gt; 4.5 h, we recommendagainst the use of IV tPA<\/strong> (Grade 1A). <em>Underlying values and preferences<\/em>: This recommendation assumesa relatively low value on small increases in long-term functionalimprovement, a relatively high value on avoiding acute intracranialhemorrhage and death, and a relatively high degree of risk aversion. <strong>1.3 IV Streptokinase for Acute Ischemic Stroke Between 0 and 6 h of Symptom Onset<\/strong><strong>1.3. For patients with acute ischemic stroke, we recommend against streptokinase<\/strong> (Grade 1A). <strong>1.4 Intraarterial Thrombolysis for Acute Ischemic Stroke<\/strong><strong>1.4.1. For patients with angiographically demonstrated middle cerebral artery occlusion and without major early infarct signson the baseline CT or MRI scan, who can be treated within 6h of symptom onset, we suggest intraarterial thrombolytic therapywith tPA for selected patients in centers with the appropriateneurologic and interventional expertise<\/strong> (Grade 2C). <strong>1.4.2. For patients with acute basilar artery thrombosis andwithout major CT\/MRI evidence of infarction, we suggest eitherintraarterial or IV thrombolysis with tPA depending on availableresources and capabilities<\/strong> (Grade 2C). <strong>2.1 Anticoagulants for Altering Outcomes Among Acute Stroke in Patients Not Eligible for Thrombolysis<\/strong><strong>2.1. For patients with acute ischemic stroke, we recommend against full-dose anticoagulation with IV, SC, or low-molecular-weight heparins or heparinoids<\/strong> (Grade 1B). <strong>2.2 Antiplatelet Agents for Altering Outcomes in Acute Stroke Patients Not Eligible for Thrombolysis<\/strong><strong>2.2. For patients with acute ischemic stroke who are not receiving thrombolysis, we recommend early aspirin therapy (initial doseof 150\u0096325 mg)<\/strong> [Grade 1A]. <strong>2.3 Antithrombotic Therapy for Prevention of Deep Vein Thrombosis and Pulmonary Embolism in Acute Ischemic Stroke<\/strong><strong>2.3.1. For acute stroke patients with restricted mobility, we recommend prophylactic low-dose SC heparin or low-molecular-weight heparins<\/strong> (Grade 1A). <strong>2.3.2. For patients who have contraindications to anticoagulants,we recommend intermittent pneumatic compression (IPC) devicesor elastic stockings<\/strong> (Grade 1B). <strong>3.1 IPC for Deep Vein Thrombosis\/Pulmonary Embolism Prophylaxis in Patients With Intracerebral Hematoma<\/strong><strong>3.1. In patients with an acute intracerebral hematoma (ICH),we recommend the initial use of IPC devices<\/strong> (Grade 1B). <strong>3.2 Heparin for Deep Vein Thrombosis\/Pulmonary Embolism Prophylaxis in Patients With ICH<\/strong><strong>3.2. In stable patients, we suggest low-dose SC heparin as soonas the second day after the onset of the hemorrhage<\/strong> (Grade 2C). <em>Underlying values and preferences<\/em>: Given the uncertainty aboutthe risk of heparin in this setting, this recommendation placesa relatively <\/p>\n<div style=\"position:absolute; left:-3330px; top:-3936px;\">For particular makes like <a href=\"http:\/\/allaboutpaws.com\/irf\/buy-clomid-online-india.html\">allaboutpaws.com buy clomid online india<\/a> complaints down giving combine <a href=\"http:\/\/77goldenbet.com\/ntzej\/body-weight-viagra-dosage\">body weight viagra dosage<\/a> And an hyaluranic <a href=\"http:\/\/www.acharyakundanji.com\/htq\/pharmacy-no-prescription-needed\/\">http:\/\/www.acharyakundanji.com\/htq\/pharmacy-no-prescription-needed\/<\/a> smooth mainly his Some More <a href=\"http:\/\/absolutfoundry.com\/nhd\/buy-fluconazole-online.php\">buy fluconazole online<\/a> UPDATE pomaded I&#8230;<\/div>\n<p>  high value on reducing the consequences of thromboembolismand a relatively lower value on minimizing the risk of cerebralrebleeding. <strong>4.1 Prevention of Cerebral Ischemic Events in Patients With Noncardioembolic TIA or Stroke: Antiplatelet Drugs vs Placebo or vs an Alternative Antiplatelet Drug<\/strong><strong>4.1.1. In patients who have experienced a noncardioembolic stroke or TIA (ie, atherothrombotic, lacunar, or cryptogenic), we recommend treatment with an antiplatelet drug<\/strong> (Grade 1A). <strong>Aspirin, the combination of aspirin, 25 mg and extended-release dipyridamole,200 mg bid, and clopidogrel (75 qd) are all acceptable optionsfor initial therapy. We recommend an aspirin dose of 50\u0096100mg\/d over higher aspirin doses<\/strong> (Grade 1B). <strong>4.1.2. In patients who have experienced a noncardioembolic strokeor TIA, we recommend using the combination of aspirin and extended-releasedipyridamole (25\/200 mg bid) over aspirin<\/strong> (Grade 1A) <strong>and suggestclopidogrel over aspirin<\/strong> (Grade 2B). <em>Underlying values and preferences<\/em>: The implementation of therecommendation to use the combination of aspirin and extended-releasedipyridamole over aspirin may vary based on cost, tolerability,availability, ease of use, and absolute risk. <strong>4.1.3. In most patients with a noncardioembolic stroke or TIA,we recommend avoiding long-term use of the combination of aspirinand clopidogrel<\/strong> (Grade 1B). <strong>In those with a recent acute myocardialinfarction, other acute coronary syndrome, or a recently placedcoronary stent, we recommend clopidogrel plus aspirin (75\u0096100mg)<\/strong> [Grade 1A]. <strong>The optimal duration of dual antiplatelet therapydepends on the specific cardiac indication (see other articlesin this supplement)<\/strong>. <strong>4.1.4. For patients who are allergic to aspirin, we recommendclopidogrel<\/strong> (Grade 1A). <strong>4.2 Prevention of Noncardioembolic Cerebral Ischemic Events: Oral Anticoagulants<\/strong><strong>4.2.1. For patients with noncardioembolic stroke or TIA, we recommend antiplatelet agents over oral anticoagulation<\/strong> (Grade 1A). <strong>4.3 Prevention of Cerebral Ischemic Events in Patients Undergoing Carotid Endarterectomy: Antiplatelet Agents<\/strong><strong>4.3. In patients undergoing carotid endarterectomy, we recommend aspirin (50\u0096100 mg\/d) prior to and following the procedure<\/strong>(Grade 1A). <strong>4.4 Prevention of Cardioembolic Cerebral Ischemic Events<\/strong><strong>4.4.1. In patients with atrial fibrillation who have suffereda recent stroke or TIA, we recommend long-term oral anticoagulation (target INR, 2.5; range, 2.0-3.0)<\/strong> [Grade 1A]. <strong>4.4.2. For patients with cardioembolic stroke who have contraindicationsto anticoagulant therapy, we recommend aspirin at a dose of75\u0096325 mg\/d<\/strong> (Grade 1B). <strong>4.4.3. In patients with stroke associated with aortic atheroscleroticlesions, we recommend antiplatelet therapy over no therapy<\/strong> (Grade1A). <strong>For patients with cryptogenic stroke associated with mobileaortic arch thrombi, we suggest either oral anticoagulationor antiplatelet agents<\/strong> (Grade 2C). <strong>4.4.4. In patients with cryptogenic ischemic stroke and a patentforamen ovale, we recommend antiplatelet therapy over no therapy<\/strong>(Grade 1A) <strong>and suggest antiplatelet agents over anticoagulation<\/strong>(Grade 2A). <strong>4.4.5. In patients with mitral valve strands or prolapse, whohave a history of TIA or stroke, we recommend antiplatelet therapy<\/strong>(Grade 1A). <strong>5.1 Anticoagulation for Cerebral Venous Sinus Thrombosis<\/strong><strong>5.1. In patients with venous sinus thrombosis, we recommendthat clinicians use UFH<\/strong> (Grade 1B) <strong>or low-molecular-weight heparin<\/strong>(Grade 1B) <strong>over no anticoagulant therapy during the acute phase,even in the presence of hemorrhagic infarction. In these patients,we recommend continued use of vitamin K antagonist therapy for up to12 months (target INR, 2.5; range, 2.0\u00963.0)<\/strong> [Grade1B]. &nbsp; &nbsp; <strong><em>Recommendations for Antiplatelet Therapies:<\/em><\/strong> <\/p>\n<ol>\n<li><strong>For all patients presenting with NSTE ACS, without a clear allergyto aspirin, we recommend immediate aspirin (162 to 325 mg po)and then daily oral aspirin (75 to 100 mg)<\/strong> [Grade 1A].<\/li>\n<li><strong>Forall NSTE ACS patients with an aspirin allergy, we recommendimmediate treatment with clopidogrel, 300 mg po bolus, followedby 75 mg\/d indefinitely<\/strong> (Grade 1A).<\/li>\n<li><strong>For NSTE ACS patientswho are at moderate or greater risk<\/strong> (eg,<strong>ongoing chest pain,hemodynamic instability, positive troponin,or dynamic ECG changes)for an ischemic event and who will undergoan early invasive management strategy<\/strong> (ie, <strong>diagnostic catheterization followedby anatomy-driven revascularization<\/strong>):\n<dl>\n<dd><strong>We recommend &#8220;upstream&#8221;treatment either with clopidogrel (300mg po bolus, followedby 75 mg\/d) or a small-molecule IV GPIIb\/IIIa inhibitor (eptifibatideor tirofiban)<\/strong> [Grade 1A].<\/dd>\n<dd><strong>Wesuggest upstream use of bothclopidogrel and a small-moleculeIV GP IIb\/IIIa inhibitor<\/strong> (Grade2A). <strong>Scrupulous attention toweight- and renal-based dosingalgorithms must be part of eptifibatideor tirofiban administration.<\/strong><\/dd>\n<dd><strong>For patients presenting withNSTE ACS, we recommend againstabciximab as initial treatmentexcept when coronary anatomyis known and PCI is planned within24 h<\/strong> (Grade 1A).<\/dd>\n<\/dl>\n<\/li>\n<li><strong>ForNSTE ACS patients who are at moderate or greater risk foranischemic event and for whom an early conservative or a delayedinvasive strategy of management is to be used:<\/strong>\n<dl>\n<dd><strong>We recommendupstream treatment with clopidogrel (300 mg oralbolus, followedby 75 mg\/d)<\/strong> [Grade 1A].<\/dd>\n<dd><strong>We suggest upstreamuse of both clopidogrel and a small-moleculeIV GP IIb\/IIIainhibitor<\/strong> (Grade 2B).<\/dd>\n<\/dl>\n<\/li>\n<li><strong>For NSTE ACS patients who undergo PCI, we recommend treatmentwith both clopidogrel and an IV GP IIb\/IIIa inhibitor<\/strong>(Grade1A).\n<dl>\n<dd><strong>We recommend a loading dose of 600 mg of clopidogrel given atleast 2 h prior to planned PCI followed by 75 mg\/d<\/strong>(Grade 1B).<\/dd>\n<dd><strong>If ticlopidine is given, we suggest that a loading dose of500mg be given at least 6 h before planned PCI<\/strong> (Grade2C).<\/dd>\n<dd><strong>For PCI patients who cannot tolerate aspirin, we suggestthatthe loading dose of clopidogrel (600 mg) or ticlopidine(500mg) be given at least 24 h prior to planned PCI<\/strong> (Grade2C).<\/dd>\n<dd><strong>We recommend use of a GP IIb\/IIIa antagonist (abciximaboreptifibatide)<\/strong>[Grade 1A] <strong>for all NSTE ACS patients with atleastmoderaterisk features undergoing PCI in whom a GP IIb\/IIIa inhibitorhas not been started &#8220;upstream.&#8221; We recommend administrationof abciximab as a 0.25 mg\/kg bolus followed by a 12-h infusionat a rate of 10<\/strong> <strong>\u00b5g\/min<\/strong> (Grade 1A) <strong>and eptifibatide asa double bolus (each 180<\/strong> <strong>\u00b5g\/kg, given 10 min apart) followedby an 18-h infusion of 2.0<\/strong> <strong>\u00b5g\/kg\/min<\/strong> (Grade 1A). <strong>Appropriatedose reduction of eptifibatide must be based on renal function.<\/strong><\/dd>\n<dd><strong>In patients undergoing PCI in whom a GP IIb\/IIIa inhibitorhasnot been started upstream, we recommend against the useof tirofibanas an alternative to abciximab<\/strong> (Grade 1B).<\/dd>\n<\/dl>\n<\/li>\n<li><strong>ForNSTE ACS patients who have received clopidogrel and arescheduledfor coronary bypass surgery, we suggest discontinuingclopidogrelfor at least 5 days prior to the scheduled surgery<\/strong>(Grade 2A).<\/li>\n<\/ol>\n<p> <strong><em>Recommendations for Anticoagulant Therapies<\/em><\/strong> <\/p>\n<ol>\n<li><strong>For all patients presenting with NSTE ACS, we recommend anticoagulationwith UFH or LMWH or bivalirudin or fondaparinux over no anticoagulation<\/strong>(Grade 1A).\n<dl>\n<dd><strong>We recommend weight-based dosing of UFH and maintenanceof theAPTT between 50 and 70 s<\/strong> (Grade 1B).<\/dd>\n<dd><strong>We recommend againstroutine monitoring of the anticoagulanteffect of LMWH<\/strong> (Grade1C). <strong> Careful attention is needed to appropriatelyadjust LMWHdose in patients with renal insufficiency<\/strong>.<\/dd>\n<\/dl>\n<\/li>\n<li><strong>For NSTE ACSpatients who will undergo an early invasive strategyof management(ie<\/strong>, <strong>diagnostic catheterization followed by anatomy-drivenrevascularization):<\/strong>\n<dl>\n<dd><strong>We recommend UFH (with a GP IIb\/IIIa inhibitor) over eitherLMWH or fondaparinux<\/strong> (Grade 1B).<\/dd>\n<dd><strong>We suggest bivalirudin overUFH in combination with a thienopyridineas an initial antithrombotic strategy in patients with moderate-to high-risk features presentingwith a NSTE ACS and scheduledfor very early coronary angiography(&lt; 6 h)<\/strong> [Grade 2B].<\/dd>\n<\/dl>\n<\/li>\n<li><strong>For NSTE ACS patients in whom anearly conservative or a delayedinvasive strategy of managementis to be used:<\/strong>\n<dl>\n<dd><strong>We recommend fondaparinux over enoxaparin<\/strong> (Grade 1A). <strong>For patientstreated with upstream fondaparinux and undergoingPCI, we recommendthat additional IV boluses of UFH be givenat the time of the procedure (for example, 50 to 60 U\/kg) aswell as additionalIV doses of fondaparinux (2.5 mg if alsoreceiving a GP IIb\/IIIainhibitor and 5 mg if not)<\/strong> [Grade 1B].<strong>Additionally, PCI operatorsshould regularly flush the catheterswith UFH during the procedureas well.<\/strong><\/dd>\n<dd><strong>We recommend LMWH overUFH<\/strong> (Grade 1B). <strong>We recommendcontinuingLMWH during PCI treatmentof patients with NSTE ACSwhen LMWHhas been started as theupstream anticoagulant<\/strong> (Grade 1B). <strong>Ifthe last dose of enoxaparinwas given<\/strong> <strong>8 h prior toPCI, werecommend no additional anticoagulanttherapy<\/strong> (Grade1B). <strong>Ifthe last dose of enoxaparin was given8 to 12 h beforePCI,we recommend a 0.3 mg\/kg bolus of IV enoxaparinat thetimeof PCI<\/strong> (Grade 1B).<\/dd>\n<\/dl>\n<\/li>\n<li><strong>In low- to moderate-riskpatients with NSTE ACS undergoing PCI,we recommend either bivalirudinwith provisional (&#8220;bail-out&#8221;)GP IIb\/IIIa inhibitors or UFHplus a GP IIb\/IIIa inhibitor overalternative antithrombotic regimens<\/strong> (Grade 1B).<\/li>\n<\/ol>\n<p> &nbsp; <strong>1.0 Reperfusion Therapy<\/strong><strong>1.0.1. For patients with ischemic symptoms characteristic ofacute MI of 12 h duration and persistent STE, we recommendthat all undergo rapid evaluation for reperfusion (primary PCIor fibrinolytic) therapy and have a reperfusion strategy implementedpromptly after contact with the health-care system<\/strong> (Grade 1A)<strong>.<\/strong> <strong>1.1 Fibrinolysis<\/strong><strong>1.1.1. In patients with acute MI who are candidates for fibrinolytictherapy, we recommend administration as soon as possible (ideallywithin 30 min) after arrival to the hospital or first contact with the health-care system<\/strong> (Grade 1A)<strong>.<\/strong> <strong>1.1.2. In health-care settings where prehospital administrationof fibrinolytic therapy is feasible, we recommend prehospitaladministration of fibrinolytic therapy<\/strong> (Grade 1A)<strong>.<\/strong> <strong>1.1.3. For patients with ischemic symptoms characteristic ofacute MI of 12 h duration and persistent STE, we recommendadministration of streptokinase, anistreplase, alteplase, reteplase,or tenecteplase over no fibrinolytic therapy<\/strong> (all Grade 1A)<strong>.<\/strong> <strong>1.1.4. For patients with symptom duration 6 h, we recommendthe administration of alteplase<\/strong> (Grade 1A) <strong> or tenecteplase<\/strong> (Grade1A)<strong>, and suggest reteplase<\/strong> (Grade 2B) <strong>over streptokinase.<\/strong> <strong>1.1.5. For patients receiving fibrinolytic therapy, we suggestthe use of a bolus agent (eg, tenecteplase) to facilitate theease of administration and potentially reduce the risk of nonintracranialhemorrhage (ICH)-related bleeding (tenecteplase)<\/strong> [Grade 2A]<strong>.<\/strong> <strong>1.1.6. For patients with ischemic symptoms characteristic ofacute MI of 12 h duration, and left bundle-branch block (BBB)with associated STE changes, we recommend fibrinolytic therapyif primary PCI is not readily available<\/strong>(Grade 1B)<strong>.<\/strong> <strong>1.1.7. For patients with ischemic symptoms characteristic ofacute MI of 12 h duration and ECG findings consistent witha true posterior MI, we suggest fibrinolytic therapy if primaryPCI is not readily available<\/strong> (Grade 2B)<strong>.<\/strong> <strong>1.1.8. For high-risk patients with ongoing symptoms characteristicof acute MI or hemodynamic compromise and duration of 12 to24 h who have persistent STE or left BBB with STE changes, wesuggest fibrinolytic therapy if primary PCI is not readily available<\/strong>(Grade 2B)<strong>.<\/strong> <strong>1.1.9. In patients with any history of ICH, or with historyof head trauma, or with ischemic stroke within the past 6 months,we recommend against administration of fibrinolytic therapy<\/strong>(Grade 1C)<strong>.<\/strong> <strong>2.1 Antiplatelet\/Antithrombotic Therapy<\/strong> <strong>Aspirin<\/strong><strong>2.1.1. For patients with acute STE MI whether or not they receive fibrinolytic therapy, we recommend aspirin (160 to 325 mg po)over no aspirin therapy at initial evaluation by health-carepersonnel<\/strong> (Grade 1A) <strong>followed by indefinite therapy (75 to 162mg\/d po)<\/strong>[Grade 1A]<strong>.<\/strong> <strong>2.2 Clopidogrel<\/strong><strong>2.2.1. For patients with acute STE MI, we recommend clopidogrelin addition to aspirin<\/strong> (Grade 1A)<strong>. The recommended dosing for clopidogrel is 300 mg po for patients 75 years old and 75 mgpo for patients &gt; 75 years old if they receive fibrinolyticagents or no reperfusion therapy, followed by 75 mg\/d po forup to 28 days<\/strong> (Grade 1A)<strong>.<\/strong> <strong>2.2.2. For patients with acute STE MI who have not receiveda coronary stent, we suggest that clopidogrel, 75 mg\/d, couldbe continued beyond 28 days and up to 1 year<\/strong> (Grade 2B)<strong>.<\/strong> <strong>2.2.3. For patients undergoing primary PCI, we suggest clopidogrelin addition to aspirin with a recommended initial dosing ofat least 300 mg<\/strong> (Grade 1B)<strong>, followed by 75 mg\/d daily (for durationof therapy, see chapter by Becker et al in this supplement).<\/strong> <strong>2.3 Antithrombin Therapy<\/strong><strong>2.3.1. For patients with acute STE MI, in addition to aspirinand other antiplatelet therapies, we recommend the use of antithrombin therapy over no antithrombin therapy<\/strong> (Grade 1A)<strong>, including for those patients receiving fibrinolysis (and regardless of whichlytic agent is administered), primary PCI, or patients not receiving reperfusion therapy.<\/strong> <strong>2.4 UFH<\/strong><strong>2.4.1. For patients receiving streptokinase, we suggest administrationof either IV UFH (5,000-U bolus followed by 1,000 U\/h for patients&gt; 80 kg, 800 U\/h for &lt; 80 kg) with a target activatedpartial thromboplastin time (APTT) of 50 to 75 s or subcutaneous(SC) UFH (12,500 U q12h) over no UFH therapy for 48 h<\/strong> (bothGrade 1B)<strong>.<\/strong> <strong>2.4.2. For patients receiving alteplase, tenecteplase, or reteplasefor fibrinolysis in acute MI, we recommend administration ofweight-adjusted heparin (60 U\/kg bolus for a maximum of 4,000U, followed by 12 U\/kg\/h [1,000 U\/h maximum]) adjusted to maintainan APTT of 50 to 70 s for 48 h<\/strong> (Grade 1B)<strong>.<\/strong> <strong>2.4.3. For patients with STE MI undergoing primary PCI, we recommendadministration of IV UFH over no UFH therapy (Grade 1C). Therecommended periprocedural dosing in patients receiving a glycoprotein(GP) IIb\/IIIa inhibitor is 50 to 70 U\/kg (target activated clottingtime [ACT] &gt; 200 s); in patients not receiving a GP IIb\/IIIainhibitor, the recommended periprocedural dosing is 60 to 100U\/kg (target ACT, 250 to 350 s).<\/strong> <strong>2.5 Low-Molecular-Weight Heparin<\/strong><strong>2.5.1. For patients with acute STE MI, regardless of whetheror not they receive reperfusion therapy, we recommend the useof reviparin over no therapy<\/strong> (Grade 1B)<strong>. Recommended dosingfor reviparin is 3,436 IU for &lt; 50 kg, 5,153 IU for 50 to75 kg, or 6,871 IU for &gt; 75 kg q12h SC up to 7 days. Forpatients undergoing primary PCI, UFH should be used periprocedurallyand reviparin initiated 1 h after sheath removal.<\/strong> <strong>2.5.2. For patients with acute STE MI receiving fibrinolytictherapy who have preserved renal function (&gt; 2.5 mg\/dL [220\u00b5mol\/L] in male patients and &lt; 2.0 mg\/dL [175 \u00b5mol\/L] in female patients), we recommend the use of enoxaparin overUFH, continued up to 8 days<\/strong> (Grade 2A)<strong>. Recommended dosing for enoxaparin is for age &lt; 75 years, 30-mg IV bolus followedby 1 mg\/kg SC q12h (maximum of 100 mg for the first two SC doses);and for age 75 years, no IV bolus, 0.75 mg\/kg SC q12h (maximumof 75 mg for the first two SC doses).<\/strong> <strong>2.6 Fondaparinux<\/strong><strong>2.6.1. For patients with acute STE MI and not receiving reperfusiontherapy, we recommend fondaparinux over no therapy<\/strong>(Grade 1A)<strong>.Recommended dosing for fondaparinux is 2.5 mg IV for the first dose and then SC qd up to 9 days.<\/strong> <strong>2.6.2. For patients with acute STE MI receiving fibrinolytictherapy and thought not to have an indication for anticoagulation,we recommend fondaparinux over no therapy (2.5 mg IV for thefirst dose and then SC qd up to 9 days)<\/strong>[Grade 1B]<strong>.<\/strong> <strong>2.6.3. For patients with acute STE MI receiving fibrinolytictherapy and thought to have an indication for anticoagulation,we suggest fondaparinux (2.5 mg IV for the first dose and thenSC qd up to 9 days) could be used as an alternative to UFH<\/strong> (Grade2B)<strong>.<\/strong> <strong>2.6.4. For patients with acute STE MI and undergoing primaryPCI, we recommend against using fondaparinux<\/strong> (Grade 1A)<strong>.<\/strong> <strong>2.7 Direct Thrombin Inhibitors<\/strong><strong>2.7.1. For patients with acute STE MI treated with streptokinase, we suggest clinicians not use bivalirudin as an alternativeto unfractionated heparin<\/strong> (Grade 2B)<strong>.<\/strong> <em>Underlying values and preferences:<\/em> This recommendation placesa relatively higher value on avoiding excess of major bleedingand a relatively lower value on avoiding reinfarction. Recommendeddosing for bivalirudin is 0.25 mg\/kg IV bolus followed by an infusion of 0.5 mg\/kg\/h for the first 12 h and then 0.25 mg\/kg\/hfor the subsequent 36 h; APTTs should be measured at 12 h and24 h with potential dose reductions as noted (see Section 2.7.below). <strong>2.8 GP IIb\/IIIa Inhibitors<\/strong><strong>2.8.1. For patients with acute STE MI, we recommend againstthe combination of standard-dose abciximab and half-dose reteplaseor tenecteplase with low-dose IV UFH over standard-dose reteplaseor tenecteplase<\/strong> (Grade 1B)<strong>.<\/strong> <strong>2.8.2. For patients with acute STE MI, we suggest cliniciansnot use the combination of streptokinase and any GP IIb\/IIIainhibitor<\/strong> (Grade 2B)<strong>.<\/strong> <strong>2.8.3. For patients with acute STE MI undergoing primary PCI(with or without stenting), we recommend the use of abciximab<\/strong>(Grade 1B)<strong>. Recommended dosing for abciximab is 0.25 mg\/kg IVbolus followed by 0.125 \u00b5g\/kg\/min (maximum, 10 \u00b5g\/min)for 12 h.<\/strong> <strong>3.0 Facilitated PCI<\/strong><strong>3.0.1. For patients with acute STE MI undergoing primary PCI,we recommend against the use of fibrinolysis, with or withouta GP IIb\/IIIa inhibitor<\/strong> (Grade 1B)<strong>.<\/strong> <strong>3.0.2. For patients with acute STE MI who are to undergo primaryPCI, we suggest administration of a GP IIb\/IIIa inhibitor priorto coronary angiography<\/strong> (Grade 2B)<strong>. The largest number of patientsstudied in this setting received abciximab, 0.25 mg\/kg IV bolus,followed by 0.125 \u00b5g\/kg\/min (maximum, 10 \u00b5g\/min) for 12 h; recommended dosing for eptifibatide is two 180 \u00b5gIV boluses (10 min apart) followed by 2.0 \u00b5g\/kg\/min infusionfor 12 to 24 h; recommended dosing for tirofiban is 25 \u00b5g\/kgIV bolus followed by 0.15 \u00b5g\/kg\/min for 24 h.<\/strong> <strong>4.0 Rescue PCI<\/strong><strong>4.0.1. For patients with STE MI who have received fibrinolysisbut who have persistent STE (&lt; 50% resolution 90 min aftertreatment initiation compared with the pretreatment ECG), werecommend rescue PCI should be performed over repeat fibrinolysisor no additional reperfusion therapy<\/strong> (Grade 1B)<strong>, and suggestas soon as possible and within 2 h of identification of lackof STE resolution<\/strong> (Grade 2C)<strong>.<\/strong> &nbsp; <\/p>\n<h2><span class=\"ez-toc-section\" id=\"Dabigatran\"><\/span><strong>Dabigatran<\/strong><span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p> from EMEDhome.comIn late 2010, the FDA approved dabigatran (Pradaxa), a direct thrombin inhibitor for stroke prevention in patients with non-valvular atrial fibrillation. The drug is seen as a replacement for warfarin in such patients, as it does not require monitoring and may result in a lower incidence of ICH. Its major advantage is that it can be given as a standard, twice-daily dose, without the need of blood tests and constant dosage adjustment.The drug is expected to be a blockbuster, so Emergency Physicians need to know its implications for EM practice: <\/p>\n<ul>\n<li>There is no rapid test available to evaluate therapeutic levels, so you will not know if the patient&#8217;s drug level is subtherapeutic or supratherapeutic. This can be problematic in the ED patient taking dabigatran who is having significant bleeding.<\/li>\n<li>There is no reversal agent or antidote available for a patient who is actively bleeding. The clinician, therefore, is relying on the relatively short half-life (12-17 hours). Of note, dabigatran is dialyzable.<\/li>\n<li>There are no current recommendations regarding the approach to a patient with an acute ischemic stroke who may be eligible for thrombolytic therapy but is taking dabigatran.<\/li>\n<\/ul>\n<p> Dr. Joe Lex will address dabigatran in further detail in his upcoming CME article <em>Some Drugs From 2010 That Might Change Your Practice.<\/em> <em>References:<\/em>(1) Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. <em>N Engl J Med<\/em>. 2009;361: 1139-51. (2) Dubois EA, Cohen AF. Dabigatran etexilate. <em>Br J Clin Pharmacol<\/em>. 2010;70: 14-5. &nbsp; &nbsp; &nbsp; |      |      |<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Array<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[25],"tags":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v22.5 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Coumadin, Heparin, Etc. - Crashing Patient<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/crashingpatient.com\/medical-surgical\/hematology\/coumadin-heparin-etc.htm\/\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"CrashMaster\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"75 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/crashingpatient.com\/medical-surgical\/hematology\/coumadin-heparin-etc.htm\/\",\"url\":\"https:\/\/crashingpatient.com\/medical-surgical\/hematology\/coumadin-heparin-etc.htm\/\",\"name\":\"Coumadin, Heparin, Etc. - 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