Agents for the treatment of heparin-induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect characterized by platelet activation, hypercoagulability, and increased risk of thrombosis, both venous and arterial. A diagnosis of HIT usually signifies that heparin products, including unfractionated and low-molecular-weight heparin, are contraindicated. Although it is uncertain whether heparin continuation really worsens clinical outcomes, it is clear that vitamin K antagonists such as warfarin do worsen outcomes, as they promote microvascular thrombosis, with the potential for limb amputation (venous limb gangrene). Thus, alternative nonheparin anticoagulants are at the forefront of HIT therapy. This review proposes that alternative anticoagulants (danaparoid, fondaparinux) that share certain properties of heparin-namely its irreversible antithrombin-mediated inhibition of factor Xa-and that have relatively long half-lives, have several advantages in the therapy for HIT over short-acting agents that inhibit thrombin directly (recombinant hirudin, argatroban, and bivalirudin).