Anemia
W/U-cbc, T+C, PT/PTT, Lytes, UA, Retic, IFTs, B12/Folate, LDH, Haptoglobin, Plasma Hb, LFTs (Save a lav and red for hematology consult)
Decreased Production:
Low retic count (corrected retic=% retic x crit/45 % normal is 1-3%)
¯ MCH=hypochromia
Use RDW to differentiate Iron defic from thal
Microcytic-defic or iron, globin (thal), or porphyrin (sideroblastic or lead poison)
Thal-¯ synthesis of globin chains, beta minor mcv<80
Sideroblastic-¯ porphyrin production. Increased serum iron. Can be idiopathic in the elderly try giving B6. Preleukemic state. Lead poisoning (basophilic stippling)
Normocytic-chronic disease or active loss
Macrocytic-
B12 Deficiency
Pernicious anemia
can be exacerbated by nitrous oxide (J Neurol Neurosurg Psychiatry 1998;64:563-564 Subacute combined degeneration of the spinal cord after nitrous oxide anaesthesia: role of magnetic resonance imaging)
takes 4 years to develop, paresthesias, propio or vibratory
Folate
Aplastic-myelophthisic (marrow replaced by tumor, etc.)
Increased Destruction
Intravascular-schizocyte
Extravascular-spherocyte
ferrous sulfate does not require vitamin c, only ferric
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Anemia and Iron Deficiency in Critical Illness
Back to topHemolysis
Direct antiglobulin test (DAT) and indirect antiglobulin test (IAT). AHG = antihuman globulin. A. The DAT reflects in vivo antibody sensitization of erythrocytes. Erythrocytes are washed to remove any unbound antibodies, and anti-IgG AHG reagent is then added. IgG antibodies cannot cause direct erythrocyte agglutination, but if the erythrocytes are coated with IgG antibodies, the AHG reagent will cause them to agglutinate. This test can also be performed using anti-complement AHG reagent. If IgG antibodies are present, they can be eluted off the erythrocytes for specificity determination. B. The IAT is used to detect the presence of IgG antibodies in serum (in vitro sensitization). Reagent erythrocytes are incubated in the presence of serum that potentially contains antibodies. If antibodies are present, they bind to their target antigens on the reagent erythrocytes. After the incubation period the erythrocytes are washed to remove unbound antibodies. Anti-IgG AHG reagent is added and will cause IgG-coated erythrocytes to agglutinate.
The indirect antiglobulin test and its clinical applications
The IAT is used by the blood bank to detect unexpected erythrocyte antibodies in the patient’s serum or plasma. The IAT is thefinal phase of the antibody screen and serologic crossmatchprocedures. In an antibody screen the recipient’s serum is incubatedwith 2 or 3 different type O erythrocytes that express clinicallysignificant antigens. This erythrocyte and serum mixture isthen incubated with anti-IgG AHG and observed for agglutination.If agglutination occurs, the screen is considered positive,and further testing is performed to determine the specificityof the IgG antibody. The serologic crossmatch procedure is alsoan IAT procedure and is performed on patients with unexpectederythrocyte antibodies to verify that the potential donor erythrocyteunit lacks the antigen corresponding to the recipient’s antibody.In this procedure, the patient’s serum is incubated with erythrocytesfrom a potential erythrocyte donor unit, and anti-IgG reagentis added. Agglutination would indicate an incompatibility betweenthe donor erythrocytes and the recipient’s IgG antibody. Thusthe results of the IAT reflect in vitro erythrocyte sensitization.The anti-complement AHG reagent is generally not used in antibodyscreening or crossmatch procedures.
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Sickle Cell Anemia
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Polycythemia
Crit>60%, start to worry about viscosity induced problems
Itching after baths
Back to topWBC Disorders
African Americans have decreased white counts
Chapter 121-Disorders of Hemostasis
Thrombin Sensitive-I,V,VIII,XIII
K Sensitive-II, VII, IX, X
Heparin Sensitive-Iia, Ixa, Xa, Platelet Factor 3
Platelet Disorders-ptechiae and mucosal bleeding
Coag Disorders-joint or muscle bleeding
Bleeding Time-tests just platelet function
PT-extrinsic and common, PTT-intrinsic and common
Neutrophilia
Because glucocorticoids induce prompt eosinopenia and basophilopenia, these cells are almost universally absent in the blood of the acutely injured or infected patient. Thus, their presence should indicate that (1) the acutely ill patient may have concomitant adrenocortical insufficiency, (2) the neutrophilia derives from the inappropriate production of GM-CSF (e.g., by malignant cells), or (3) the neutrophilia is one manifestation of a hematopoietic neoplasm (a chronic myeloproliferative disorder, myelodysplastic syndrome, lymphoma, or acute nonlymphocytic leukemias associated with eosinophilia).
Back to topAcute Intermittent Porphyria
(AIP)
Get single void urine and have lab check for porphobilinogen, preferably using Trace PBG Kit. Must eliminate comperting substances like urobilinogen before using Ehrlich’s reagent. (Ann Intern Med 2005;142(6):439)
AIP is an autosomal dominant disorder that results from an approximately 50% deficiency of Porphobilinogen deaminase (PBG).
The majority of subjects with PBG deaminase deficiency remain asymptomatic.
Most drugs that are harmful in AIP induce hepatic ALA synthase and cytochrome P-450 enzymes. Sulfonamide antibiotics are not inducers and may inhibit PBG deaminase. Reduced caloric and carbohydrate intake enhances the induction of ALA synthase in animals and in AIP can increase ALA and PBG and precipitate symptoms. Administration of carbohydrate can reduce hepatic ALA synthase and P-450 enzymes.
The mechanism of neural damage in AIP is unknown. Porphyrias and related disorders associated with increased ALA have similar neurologic manifestations. ALA is structurally analogous to gamma-aminobutyric acid (GABA) and can interact with GABA receptors. However, ALA and other products of the heme pathway have not been convincingly shown to be neurotoxic. The suggestion that heme deficiency may occur in nervous tissue in these disorders is also unproved.
Symptoms rarely occur before puberty and seldom if ever recur throughout adult life. Characteristically, attacks last for several days or longer, often require hospitalization, and are followed by complete recovery.
Abdominal pain is the most common symptom, is usually steady and poorly localized, but may be cramping.
Tachycardia, hypertension, restlessness, fine tremors, and excess sweating may be due to sympathetic overactivity.
Other manifestations include nausea and vomiting; constipation; pain in the limbs, head, neck, or chest; muscle weakness; and sensory loss. Ileus with distention and decreased bowel sounds is common. However, increased bowel sounds and diarrhea may be seen. Because the abdominal symptoms are neurologic rather than inflammatory, tenderness, fever, and leukocytosis are generally absent or mild. Dysuria and bladder dysfunction may occur. Recurrent attacks tend to be similar in a given patient.
Peripheral neuropathy in AIP is primarily motor, results from axonal degeneration, and does not develop in all patients with acute attacks, even when abdominal symptoms are severe. Rarely, neuropathy develops apart from abdominal symptoms. Weakness most commonly begins in proximal muscles (often requiring a careful examination to detect) and more often in the arms than the legs. It can be asymmetric and focal. Tendon reflexes may be little affected or hyperactive in the early stages but are usually decreased or absent with advanced neuropathy. Cranial and sensory nerves can be affected. Progression to respiratory and bulbar paralysis and death seldom occurs unless the porphyria is not recognized, the use of harmful drugs is not discontinued, and appropriate treatment is not instituted. Sudden death, presumably from cardiac arrhythmia, may also occur.
The central nervous system can be involved. Anxiety, insomnia, depression, disorientation, hallucinations, and paranoia, which can be especially severe during acute attacks, may suggest a primary mental disorder or hysteria.
Seizures may occur as an acute neurologic manifestation of AIP, as a result of hyponatremia, or secondary
to causes unrelated to porphyria. Hyponatremia may be due to hypothalamic involvement and inappropriate antidiuretic hormone secretion; vomiting, diarrhea, and poor intake; or excess renal sodium loss.
After several days, an attack may resolve quite rapidly, with abdominal pain disappearing within a few hours and paresis within a few days. Attacks during the luteal phase of the menstrual cycle usually resolve with the onset of menses. Even advanced neuropathy is potentially reversible. Pain, depression, and other symptoms are sometimes chronic.
Chronic hepatic abnormalities are common in AIP, and affected patients have an increased risk of hepatocellular carcinoma (apparently not associated with hepatitis B or C). AIP may predispose to chronic hypertension and be associated with impaired renal function. The mechanisms of these associations are unknown.
Barbiturates and sulfonamides are the most notorious drugs to induce an attack
Reduced caloric intake is also a common cause
Heme therapy and carbohydrate loading are specific therapies because they repress hepatic ALA synthase and overproduction of ALA and PBG. Heme therapy is most effective in this regard and should be initiated early, but only after the diagnosis of a porphyric attack is confirmed by a marked increase in urinary PBG. Diagnosis is more difficult after heme therapy, which can at least transiently normalize ALA and PBG.
The standard regimen for heme therapy is 3-4 mg heme per kilogram body weight infused intravenously once daily for 4 days. A longer course of treatment is seldom necessary if treatment is started early. Efficacy is reduced and recovery less rapid when treatment is delayed and neuronal damage is more advanced. It is not effective for chronic symptoms of AIP. A lyophilized hematin (hydroxyheme) preparation is available in the United States. The manufacturer recommends reconstitution with sterile water. However, the product is unstable and degradation products adhere to endothelial cells, platelets, and coagulation factors and cause a transient anticoagulant effect and phlebitis at the site of infusion. Reconstitution with human albumin enhances the stability of hematin and prevents these side effects. Heme arginate, which is available in Europe and South Africa, is much more stable than hematin and also does not have these side effects. It is an investigational drug in the United States.
Carbohydrate loading may suffice for mild attacks and can be given orally as sucrose, glucose polymers, or carbohydrate-rich foods. If oral intake is poorly tolerated or is contraindicated by distention and ileus, intravenous administration of glucose (at least 300 g daily) is usually indicated. A central venous line facilitates more complete parenteral nutrition support and avoids excess fluid volumes. Parenteral nutrition support may be indicated in some patients who require heme therapy.
Treatment of seizures is problematic because almost all antiseizure drugs can exacerbate AIP. Bromides, gabapentin, and probably vigabatrin can be given safely. beta-Adrenergic blocking agents may control tachycardia and hypertension in acute attacks of porphyria, but they may be hazardous in patients with hypovolemia, in whom increased catecholamine secretion may be an important compensatory mechanism. Numerous other therapies have been tried in this disease but have not been consistently useful.