Pharmacy & Therapeutics - November 2008 - (Page 644)

Heparin-Induced Thrombocytopenia ticularly important when patients have multiple medical conditions and are taking medications that can confound the presentation and the diagnosis of HIT. Thrombocytopenia can result from many causes, such as disease processes (infection, bone-marrow disease, infection, disseminated intravascular coagulation, splenomegaly) or drugs (chemotherapeutic agents, antibiotics, anticonvulsants) (Table 3).18–22 platelet aggregation assay and the much more sensitive test used today, the SRA. Despite the widespread use of the platelet aggregation test, attributable to its simplicity, inexpensiveness, and the ability to yield results in two to three hours, its comparatively low sensitivity (30% to 50%) brings into question its clinical utility.19 The SRA is the gold standard for laboratory confirmation of HIT. Normal donor platelets are radiolabeled with serotonin and are then “washed,” making them very sensitive to activation by HIT serum. The patient’s serum, as well as therapeutic (0.1 U/mL) and high (100 U/mL) concentrations of heparin, is added. A positive result occurs with significant activation at therapeutic levels and an absence of significant effect at high levels. SRA has high sensitivity (90% to 98%) and specificity (above 95% in early phases and 80% to 97% for late-phase platelet declines). Nevertheless, SRA is technically demanding, timeconsuming, and not readily available at most institutions.11,18 ELISA. For the solid-phase ELISA, complexes of PF4 with either heparin or polyvinyl sulfonate (depending on the test used) are coated on a microtiter plate. The patient’s serum is then added. If antibodies against the PF4 complex are present, they bind; this can be confirmed by adding a second antibody. A negative result strongly rules out the diagnosis of HIT, whereas a positive result should be confirmed with a functional assay. Sensitivity has been noted at greater than 90% and specificity at 95% in early platelet decline and at 50% to 93% in late platelet decline.18 A potential drawback, however, is that antigen assays are likely to detect the presence of clinically insignificant HIT antibodies, which do not have platelet-activating LABORATORY CONFIRMATION In many instances, the results from highly specific assays used in the laboratory confirmation of HIT lag behind the diagnosis, which is made primarily on clinical grounds. In these cases, decisions are made based on the pretest probability of HIT. In fact, routine testing for HIT antibodies in the absence of clinical features of HIT, such as thrombocytopenia, thrombosis, or heparin-induced skin lesions, is not recommended. Given the often transient nature of HIT antibodies, acute serum or plasma should be used in assays.10 Two fundamental types of assays are used: • functional: platelet activation or a serotonin-release assay (SRA) • antigenic: the enzyme-linked immunosorbent assay (ELISA) Even though no assay has complete 100% sensitivity or specificity, functional and antigenic assays should serve as complementary tests in the diagnosis of HIT.18 Functional assay. Platelet-activation assays include the Table 3 Factors Complicating the Diagnosis of Heparin-Induced Thrombocytopenia (HIT): Differential Diagnosis Causes of Drug-Induced Thrombocytopenia Bone marrow suppression • Cytotoxic chemotherapeutic agents (carboplatin, alkylating agents, anthracyclines antimetabolites) • Ethanol • Chloramphenicol Immune mechanisms • Anti-inflammatory drugs (aspirin, paracetamol) • Sedatives, anticonvulsants (diazepam, valproate, phenytoin, carbamazepine) • Antibiotics (sulfonamides, penicillins, cephalosporins, trimethoprim) • Heparin • Antidiabetic agents (chlorpropamide, tolbutamide) • Cardiovascular agents (thiazide diuretics, digoxin, quinidine, methyldopa) Disorders Resembling HIT (Thrombocytopenia Complicated by Thrombosis) but Negative for HIT Antibodies • • • • • • • • • Adenocarcinoma Pulmonary embolism Diabetic ketoacidosis Antiphospholipid antibody syndrome Thrombolytic therapy Septicemia-associated disseminated intravascular coagulation, purpura fulminans Infective endocarditis Paroxysmal nocturnal hemoglobinuria Post-transfusion purpura Data from Warkentin TE. Arch Pathol Lab Med 2002;126(11):1415–1423;18 Brieger DB, et al. J Am Coll Cardiol 1998;31(7):1449–1459;19 Hoffbrand AV et al., eds. Essential Hematology, 5th ed., 2006;20 Shinton NK, ed. Desk Reference for Hematology, 2nd ed. 2008;21 and Hanin RI. In: Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine, 16th ed., 2005.22 continued on page 647 644 P&T® • November 2008 • Vol. 33 No. 11

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Pharmacy & Therapeutics - November 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Heparin-Induced Thrombocytopenia Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched From Fixed-Dose to Free-Combination Antihypertensive Therapy European Society for Medical Oncology and Association for the Study of Bone and Mineral Research Pharmaceutical Approval Update

Pharmacy & Therapeutics - November 2008

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