Heparin-induced thrombocytopenia: an update

Abstract

Heparin-induced thrombocytopenia (HIT) is the most important and most frequent drug-induced, immune-mediated type of thrombocytopenia. It is associated with significant morbidity and mortality if unrecognized. In this review, we briefly discuss the main features of heparin-induced thrombocytopenia, particularly analyzing the most recent advances in the pathophysiology, diagnosis and treatment of this syndrome.

Deep Vein Thrombosis, Ecythyma Gangrenosum and Heparin-Induced Thrombocytopenia Occurring in a Man with a Heterozygous Factor V Leiden Mutation

“…12,13 It occurs within five days of heparin therapy, the thrombocytopenia is mild and there is no associated risk of thrombosis. 12,13 Type II occurs when an antibody reacts with a complex formed between PF 4 and heparin. 12–14 producing PF4/H/IgG complexes that bind to platelet Fc receptors.…”

“…Activation of platelets and intrinsic tissue factor and increased thrombin generation result, leading to a hypercoagulable state and thrombosis. 13 The acute arterial or venous occlusion occurs because of intravascular platelet aggregation. Cutaneous necrosis can occur, usually 6 to 13 days after onset of therapy.…”

Heparin-induced thrombocytopenia and recent advances in its therapy

“…The principal antigen involved is a complex of heparin and PF4 (22). Patients with HIT produce IgG antibodies against these complexes of PF4 and heparin.…”

“…The PF4 is a small positively charged peptide molecule stored within the alpha granules of platelets, which is released into the circulation when platelets are activated (5,23). Heparin binds to the PF4 molecules because of opposite charges, thereby exposing neoepitopes that act as immunogens leading to antibody production (22). The IgG antibody produced binds to the complex on the platelet surface through the Fab region to form IgG antibody-heparin-PF4 immunocomplex (24).…”

“…This triggers the activation and aggregation of the platelets in a cyclical manner. The activation of platelets leads to the release of PF4 and possibly contributes to the thrombotic complications (4)(5)(6)22). A simple diagrammatic illustration of the pathogenesis of HIT is shown in Fig.…”