Chapter 109. Disorders of Platelets and Vessel Wall (Part 5)

Laboratory Testing for HIT HIT (antiheparin/PF4) antibodies can be detected using two types of assays. The most widely available is an enzyme-linked immunoassay (ELISA) with PF4/polyanion complex as the antigen. Since many patients develop antibodies but do not develop clinical HIT, the test has a low specificity for the diagnosis of HIT. This is especially true in patients who have undergone cardiopulmonary bypass surgery, where approximately 50% of patients develop these antibodies postoperatively. The other assay is a platelet activation assay that measures the ability of the patients serum to activate platelets in the presence of heparin in a...
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Chapter 109. Disorders of Platelets and Vessel Wall (Part 5) Chapter 109. Disorders of Platelets and Vessel Wall (Part 5) Laboratory Testing for HIT HIT (antiheparin/PF4) antibodies can be detected using two types of assays.The most widely available is an enzyme-linked immunoassay (ELISA) withPF4/polyanion complex as the antigen. Since many patients develop antibodies butdo not develop clinical HIT, the test has a low specificity for the diagnosis of HIT.This is especially true in patients who have undergone cardiopulmonary bypasssurgery, where approximately 50% of patients develop these antibodiespostoperatively. The other assay is a platelet activation assay that measures theability of the patients serum to activate platelets in the presence of heparin in aconcentration-dependent manner. This test has lower sensitivity but higherspecificity than the ELISA. However, HIT remains a clinical diagnosis. The mainvalue in testing is in excluding the diagnosis with negative tests, particularlyELISA. Heparin-Induced Thrombocytopenia: Treatment Early recognition is key in treatment of HIT, with prompt discontinuationof heparin and use of alternative anticoagulants. Thrombosis is a commoncomplication of HIT, even after heparin discontinuation, and can occur in both thevenous and arterial systems. In patients diagnosed with HIT, imaging studies toevaluate the presence of thrombosis (at least lower-extremity duplex dopplers) arerecommended. Patients requiring anticoagulation should be switched from heparinto an alternative anticoagulant. The direct thrombin inhibitors (DTIs) argatrobanand lepirudin are effective in HITT. The DTI bivalirudin and the antithrombin-binding pentasaccharide fondaparinux appear to be effective but are not yetapproved by the U.S. Food and Drug Administration (FDA) for this indication.Danaparoid, a mixture of glycosoaminoglycans with anti-Xa activity, has beenused extensively for the treatment of HITT; it is no longer available in the UnitedStates but is in other countries. HIT antibodies cross-react with LMWH, and thesepreparations should not be used in the treatment of HIT. Because of the high rate of thrombosis in patients with HIT, anticoagulationshould be strongly considered, even in the absence of thrombosis. In patients withthrombosis, patients can be transitioned to warfarin, with treatment usually for 3–6months. In patients without thrombosis, the duration of anticoagulation needed isundefined. An increased risk of thrombosis is present for at least 1 month afterdiagnosis; however, most thromboses occur early, and whether thrombosis occurslater if the patient is initially anticoagulated is unknown. Options includecontinuing anticoagulation until a few days after platelet recovery or for onemonth. Introduction of warfarin alone in the setting of HIT or HITT mayprecipitate thrombosis, particularly venous gangrene, presumably due to clottingactivation and severely reduced levels of proteins C and S. Warfarin should onlybe started after alternative anticoagulation has been given for several days and theprothrombotic state has lessened. Immune Thrombocytopenic Purpura (ITP) Immune thrombocytopenic purpura (ITP; also termed idiopathicthrombocytopenic purpura) is an acquired disorder leading to immune-mediateddestruction of platelets and possibly inhibition of platelet release from themegakaryocyte. In children it is usually an acute disease, most commonlyfollowing an infection, and with a self-limited course. In adults it usually runs amore chronic course. The exact nature of the immune dysfunction is generally notknown. ITP is termed secondary if it is associated with an underlying disorder;autoimmune disorders, particularly systemic lupus erythematosis (SLE), andinfections, such as HIV and hepatitis C, are common causes. The association ofITP with Helicobacter pylori infection is unclear. ITP is characterized by mucocutaneous bleeding and a low, often very low,platelet count, with otherwise normal peripheral blood cells and smear. Patientsusually present either with ecchymoses and petechiae, or with thrombocytopeniaincidentally found on a routine CBC. Mucocutaneous bleeding, such as oralmucosa, gastrointestinal, or heavy menstrual bleeding, may be present. Rarely,life-threatening bleeding, including in the central nervous system, can occur. Wetpurpura (blood blisters in the mouth) and retinal hemorrhages may herald life-threatening bleeding. Laboratory Testing in ITP Laboratory testing for antibodies (serologic testing) is usually not helpfuldue to the low sensitivity and specificity of the tests. Bone marrow examinationcan be reserved for older adults (usually >60 yea ...