Newer Strategies for the Treatment of Heparin‐Induced Thrombocytopenia

Abstract

Treatment with heparin is associated with two types of thrombocytopenia. One is a mild, transient, nonimmune disorder, generally without adverse clinical consequence. The other, known as heparin-induced thrombocytopenia (HIT), is a potentially serious, immunoglobulin-mediated reaction with a paradoxic high risk of thromboembolic events. Various treatment options for HIT are discussed, with emphasis on pharmacologic approaches that control the increased thrombin generation characteristic of this disorder.

Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia

“…1-3 Procoagulant effects may be associated with formation of platelet-derived microparticles and/or endothelial activation especially in areas of previous endothelial disruption. [1][2][3] The cornerstone of therapy of HITT is the complete elimination of all sources of heparin exposure. Platelet counts begin to rise 24-48 hours after discontinuation with normalization at 4-7 days.…”

“…1-3 Surgery or thrombolytic therapy may be required for limb salvage and other life-threatening situations requiring restoration of blood flow. [1][2][3] Limited pharmacologic treatment options are available and the presence of end-organ dysfunction further increases the complexity and risk of such choices. Warfarin is useful for long-term anticoagulation; however, immediate anticoagulation with warfarin for acute thrombotic events is contraindicated because of an increased risk of thrombosis.…”

“…1 Danaparoid has a long half-life (approximately 25 hours) and its effect on anti-Xa activity is further prolonged with impaired renal function. 3 Danaparoid is further limited by its lack of a reversal agent. 2 Aspirin, dipyridamole, dextran, and glycoprotein IIb/IIIa inhibitors do not offer complete protection against thrombosis and are only considered at best adjunctive agents.…”

“…2 Aspirin, dipyridamole, dextran, and glycoprotein IIb/IIIa inhibitors do not offer complete protection against thrombosis and are only considered at best adjunctive agents. [1][2][3] The most viable options available in the United States today are lepirudin and argatroban. Lepirudin was the first direct thrombin inhibitor shown to be of benefit in the treatment of HITT.…”

Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin

“…Bivalirudin has been successfully used as an alternative anticoagulant to treat patients with HIT. 12,13 Hirudins are proteins 65 amino acids in length and of nonhuman origin (medical leech). Antihirudin antibody formation in patients treated with recombinant hirudins has been demonstrated in several studies.…”