Massive Transfusion Protocols

• TEG Based Protocol
• Another for using FIBTEM for prediction, but Hb and PT seemed as good (Crit Care 2001;15:R265)
• BET for Mass Trans
• Review of 1:1 (Transfusion Medicine Reviews 2009;23(4):255)
• Plasma in patients not massively transfused leads to worse outcome (J Am Coll Surg. 2010 Jun;210(6):957-65. doi: 10.1016/j.jamcollsurg.2010.01.031. Epub 2010 Apr 28. Impact of plasma transfusion in trauma patients who do not require massive transfusion.)

Who needs Massive Transfusion?

In a review of 6 scores, the TASH and the Prince of Wales/Rainer Scores were most accurate; ABC was pretty good (Crit Care 2012;16:r129)

Journal of Trauma and Acute Care Surgery Issue: Volume 74(2), February 2013, p 396–402 When you transfuse your 3rd unit in < 60 minutes, indicator of the need for Massive Trans

Inverse Ratios

Journal of Trauma and Acute Care Surgery Issue: Volume 74(2), February 2013, p 403–410 In pts receiving more than 10 U for vascular trauma increasing ratio of FFP over RBC was assoc with increased survivability

Time-Dependent Study

Study that looks at retrospective ration by time, unfortunately they looked at entirely the wrong time span so negative trial (Crit Care Med 2013;41:1905)

Coagulopathy in Trauma

The mechanism of coagulopathy in trauma is complex and multifactorial: Dilutional coagulopathy results from the dilution of coagulation factors and platelets caused by the infusion of large volumes of crystalloids, colloids, or blood products, which are administered to improve oxygen delivery. The severity of dilutional coagulopathy is determined by both the volume and type of fluids infused. Whereas permissive hypotension and reduced fluid volume in the prehospital setting and early in-hospital treatment may decrease the extent of such coagulopathy, newly developed types of fluids, such as hypertonic saline (with or without dextran), new colloids, and artificial oxygen carriers, may exacerbate it [710]. Hypothermia is a common complication of both civilian and combat injuries, leading to severe coagulation impairment. This is due to the decline in both platelet and coagulation enzyme activities [1113]. These effects are often underestimated as most laboratories re-warm blood samples to 37°C before testing for clotting assays, i.e. PT, PTT. Even if these plasma-clotting assays were performed at the patient’s body temperature, they would still underestimate the magnitude of the coagulopathy, as these assays do not reflect the in vivo coagulation process occurring on cell membranes, such as tissue factor (TF)-bearing cells and activated platelets [14]. Furthermore, platelet functions, which are significantly impaired by hypothermia [15], are not monitored routinely, contributing to the underestimation of the hemostatic defect. Acidosis resulting from decreased perfusion and production of anerobic metabolism leading to the accumulation of lactic acid is common among trauma victims. Even a slight decrease in pH compromises the function of both coagulation enzymes and platelets, particularly in the presence of hypothermia [11]. A decrease in pH from 7.4 to 7 reduces prothrombin (FII) activation by the prothrombinase complex (FXa/FVa) by 70% [15]. Hyperfibrinolysis may be more common in trauma patients than was previously realized. The failure to detect this condition stems from the lack of routine laboratory tests for fibrinolysis. A recent study using rotational thromboelastography (roTEG) has shown that approximately 20% of multi-trauma patients suffering from massive bleeding have marked hyperfibrinolysis (M. Vorweg and M. Doehn, Personal Communication). The reproduction of these findings in larger patient series would support the theory that early administration of antifibrinolytic agents may be beneficial for hemorrhage control in trauma. Treatment with recombinant activated factor VII (rFVIIa), which reduces clot susceptibility to fibrinolysis partly by the induction of thrombin-activated fibrinolytic inhibitor (TAFI), may also be of value in hyperfibrinolysis [16]. Anemia-induced coagulopathy: In addition to their role in oxygen delivery, red blood cells (RBC) provide important mechanical and biochemical functions in the coagulation process. Therefore, anemia causes prolongation of the bleeding time, which can be corrected with a RBC transfusion [1719]. Furthermore, reduction of the hematocrit (Hct) inhibits platelet adhesion and aggregation, e.g. Hct of 20% restricts aggregation to a degree similar to that observed with 20 000 platelets mL1 [20]. Consumption coagulopathy is induced by exposure of TF at the site of injury, leading to activation of the coagulation cascade at this site. Massive injury may cause extensive consumption with depletion of platelets and coagulation factors. This process results in laboratory findings resembling disseminated intravascular coagulation (DIC), such as prolonged PT and aPTT, low levels of platelets and fibrinogen, and high levels of D-dimers and other markers of coagulation and fibrinolysis activation. However, in most cases, these findings do not reflect DIC, as there is no evidence of microthrombi formation and, thus, no intravascular clotting [21].  

hypothermia is an independent risk factor for trauma mortality (J Trauma 2005;59(5):1081)   hypocalcemia is also a cause of coagulopathy increased fibrinolysis as well whole blood is used in iraq Best Review (Brit J Anaes 2005;95(2):130   Acidosis impairs coagulopathy as well (J Trauma 2006;61:624, J Trauma 2003;55:886)   European Surgical Bleeding Guidelines (Management of bleeding following major trauma: a European guideline Critical Care 2007, 11:R17)   Acidosis massively increases risk of coagulopathy, Impairs factor VIIa/tissue factor complex. Clot formation can be normalized with a buffer (J Neurosurg Anesth 2006;18:200)

Massive Transfusion

For every 4 packed cells – 2 FFP For every 8 packed cells and – 4 FFP: 6 Random platelets For every 16PC / 8 FFP – 12 Random platelets plus add a unit of cryoprecipitate   mortality benefit shown (J Trauma 2008;64:1177) It also reduces overall blood usage   Survey of world centers (J Trauma 2006;60:s91)   need plasma coag at least 40% of normal for clotting   >5 units PRBC, you get dilutional coagulopathy need 1:1:1 ratio after ~8 units PRBC At 10 units, you need platelts send fibrinogen levels, may need cryo   can’t clot when acidotic       (Anesth Analg 2007;105:905) fibrinogen is probably the reason for dilutional coagulopathy colloids interfere with clotting by fibrinogen concentration and polymerization blood loss causes fibrinogen to drop first maintaining fibrinogen at at least 150 mg/dL may be the key to trauma bleeding <50 no clot <75 weak clot   linear improvement in clot strength up to 300 OB study with <200 shows 100 % predictive value for postpartum bleeding   Study from Iraq shows 1:1 probably best, but just retrospective. Also has most of the massive transfusion references (J Trauma 2007;63:805)   Two from AAST FFP:PRBC Transfusion Ratio of 1:1 is assoc with sig lower risk of mortality following massive transfusion Early Achievement of a 1:1 ratio of FFP:PRBC reduces mortality in patients receiving massive transfusion   acidosis causes RBC swelling which increases viscosity   Mathematical model of FFP transfusion strategy shows 1:1 is the only way to avoid dilutional coagulopathy (Can J Surg 2005;48(6):470)   We were talking about this yesterday with Peter Shirley who is one of our intensivists and a Royal Air Force anaesthesia/critical care doctor who has recently returned from Camp Bastion in Afghanistan.  The British military have deployed ROTEM for the past 12+ months – initially as a research tool but now used to guide therapy. Peter’s experience is entirely descriptive, but he describes 3 phases of care for the exsanguinating, coagulopathic patient: 1. Identification of active exsanguination, severe shock, Acute Traumatic Coagulopathy (ROTEM 5-minute Clot Amplitude (CA5) less than or equal to 35mm)  = empiric (blind) aggressive transfusion/component therapy.  (Ross Davenport from our unit has done some truly excellent work on ROTEM diagnosis of ATC which was presented at TSIS2010 and is currently in submission) 2. Resuscitation continues, coagulopathy worsens, A ROTEM-guided phase where component therapy is based on clotting profiles 3. Correction of shock state (base deficit normalised) = ROTEM correction may lag behind visible clotting capability and patients have a tendency to overtransfusion if ROTEM is used as a guide in this phase and the “brakes” aren’t put on. There’s no data yet for phase 3 but we’ll see. Note we have presented data to show that a normal CA5 on admission has a 99% negative predictive value for massive transfusion – so ROTEM may be useful to stop massive haemorrhage protocols early and avoid waste / reduce transfusion -related complications. Karim Brohi retrospective support for high plasma rations when >4 <10 units used (J Trauma 2011;70:81)

Prothrombin Complex Concentrate

see also reversal section in Hematology   500 units of Beriplex=2 L of FFP (Eur J of Cardio Surgery 2001;19:219)   Best review (Eur J Anaes 2008;25:784)   New observational trial included 38 patients who got pcc just for bleeding not anti-coagulant (Crit Care)   BJA: British Journal of Anaesthesia Volume 102, Number 3Pp. 345-354  Haemodilution markedly prolonged prothrombin time and reduced peak thrombin generation. PCC, but not FFP, fully reversed those effects. Compared with 15 ml kg–1 FFP, PCC shortened the time to haemostasis after either bone (P=0.001) or spleen (P=0.028) trauma and reduced the volume of blood lost (P<0.001 and P=0.015, respectively). Subsequent to bone injury, PCC also accelerated haemostasis (P=0.003) and diminished blood loss (P=0.006) vs 40 ml kg–1 FFP. Conclusions: PCC was effective in correcting dilutional coagulopathy and controlling bleeding in an in vivo large-animal trauma model. In light of its suitability for more rapid administration than FFP, PCC merits further investigation as a therapy for dilutional coagulopathy in trauma and surgery. Keywords: blood, haemodilution; complications, haemorrhagic disorder; complications, trauma; fresh frozen plasma; prothrombin complex concentrate   FFP compared to PCC and fibrinogen for trauma patients. No mortality benefit. There was morbidity benefit (Injury, Int. J. Care Injured 42 (2011) 697–701)

First trauma study of 3-factor (profilnine SD on average 35 units/kg) showed good reversal of coagulopathy (J Trauma 2012;72(4):828)

Plasma

Type A may be safe regardless of ABO incompatibility (J Trauma 2013;74:69)

Fibrinogen

ABC Score

Abstract from the EAST showed sens 87 spec 85       Case report (anaesthesia 2010;65:199)

European Bleeding in Trauma Guidelines

recommend teg not pt/ptt amongst other good recs

Factor VIIa

If the clot amplitude at 5 minutes is <=35 on rTEG (Crit Care Med 2011;39:2652)

Tranexamic Acid and Hyperfibrinolysis

Crash 2 (Lancet 2011) Review from J Trauma Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study showed mortality benefit, esp in patients who were massively transfused (Morrison Arch Surg 2011)

Lancet 2010

1g tranexamic acid over 10 minutes followed by infusion of 1 g over 8 hours

within 8 hours of injury

sig hemorrhage or predicted sig. hemorrhage (SBP < 90 or HR > 110

1.5% reduction in mortality (all-cause)

Planned reanalysis shows must be given within 3 hours to be effective (Lancet 2011;377:1096)

Review Article (J Trauma 2011;71:S9)

New pre-specified reanalysis shows benefit in all severity classes (BMJ 2012;345:e5839)

TEG Ly30 of > 3% may be the ideal initiation point for starting antifibrinolytics according to this paper ( Journal of Trauma and Acute Care Surgery Issue: Volume 75(6), December 2013, p 961–967)

In AAA

Effect of Early Plasma Transfusion on Mortality in Patients with Ruptured Abdominal Aortic Aneurysm: Well MW, O’Neil AS, Callcut RA, et al. Surgery 2010;148:955–62.

Platelets

Old Platelets are bad from Kenji (Volume 71(6), December 2011, pp 1766-1774)

Early platelets may improve mortality ( Journal of Trauma and Acute Care Surgery Issue: Volume 75(1) Supplement 1, PROMMTT 1, July 2013, p S24–S30)

TRALI

Associated with mass trans but not seemingly with FFP (Journal of Trauma and Acute Care Surgery Issue: Volume 75(1), July 2013, p 32–36)

Crystalloids

Associated with increased mortality during massive transfusion protocols ( Journal of Trauma and Acute Care Surgery Issue: Volume 75(1), July 2013, p 76–82)

Factor Only Massive Transfusion Protocols

Injury 44 (2013) 209–216