Heparin-induced thrombocytopenia type II: Innovations in diagnostics and treatment

Abstract

Heparin-induced thrombocytopenia (HIT) Management of heparin-induced thrombocytopenia (HIT) and treatment options have significantly changed recently. Heparin may induce two types of thrombocytopenia. Type I, occurring earlier with a much higher rate of incidence (5-30%), is characterized by mild thrombocytopenia without significant clinical manifestations. Type II is less frequent (0.5-2%), life threatening immune type, develops following a period of minimum 5-7 days upon introduction of heparin therapy (patients earlier treated with heparin are excluded). Type II heparin-induced thrombocytopenia with severely reduced platelet count may be clinically manifested by thrombosis in 20-50% cases within the period of 30 days. HIT is suspected in persons resistant to heparin with relatively reduced platelet count, though HIT is described in person with normal platelet counts, as well. None of available assays used for HIT detection is completely reliable Sensitivity of a highly specific platelet aggregation assay is only 36% sensitivity and specificity of 14C-serotonin release assays amounts to 95% while ELISA using a heparin/platelet factor-4 target has a sensitivity of 85%. Thus, it is sometimes necessary to combine functional and antigen assays. Furthermore, new classes of antigen assays, like antibody detection tests of complexes between heparin and neutrophil-activating peptide-2 as well as those between heparin and interleukin-8, have been used. Current therapy options Current therapy options exclude formerly applied low-molecular-weight heparins due to the existing cross-reactivity of 80?100%. Danaparoid sodium exhibits in vitro cross-reactivity of 10?61%, clinically manifested in less than 5% of patients. Two drugs are drugs of choice in HIT type II treatment: lepirudin, especially in patients without renal failure and argatroban, particularly in patients with renal failure. The following procedures and agents are also efficient: asmapheresis in the first four days, high-dose intravenous gammaglobulin, antiagregans, especially ADP antagonists, aspirin, dipirydamole, dextran, prostacyclin analogues thrombolytic therapy as well as thromboembolectomy. Oral anticoagulants are not administered in active HIT type II, in deep vein thrombosis with high international normalized ratio (INR) and thrombin-antithrombin complexes, and low protein C levels to avoid the possibility of venous limb gangrene development. They can be administered in a stable phase, when the thrombin generation is controlled by previous administration of one of the above-mentioned alternative anticoagulants.