Mechanisms Involved in Heparin-Induced Thrombocytopenia and Associated Thrombosis

ABSTRACT

Heparin-induced thrombocytopenia (HIT), sometimes complicated by the occurrence of thrombosis (HITT), is a rare but severe complication of heparin therapy (both unfractionated and low molecular weight heparin). It is induced by the generation of antibodies targeted to complexes of platelet factor (PF) 4 and heparin (H), mainly IgG isotypes with the highest avidity. Laboratory studies and clinical surveys help elucidate the mechanisms of HIT/HITT. The presence of stoichiometric complexes of H-PF4 is probably the immunogenic stimulus that induces the generation of antibodies, via a T-cell response. In pathologies, where a large extent of platelet activation occurs, especially at the vicinity of pathological sites, large amounts of H-PF4 complexes can be formed that bind to platelet surfaces (mainly activated platelets), but also to endothelial cells and other blood cells such as monocytes. This induces cell–cell interactions and the release of microparticles, which can amplify to a hypercoagulable state resulting from release of tissue factor, microparticles, and expression of procoagulant phospholipids. The clinical consequence is the development of thrombocytopenia, which can be complicated by a rapid evolution to thrombosis that becomes life threatening. The present understanding of the mechanisms of HIT/HITT, the advances in clinical investigations, and the availability of alternative anticoagulants have progressively introduced new tools for a better diagnosis and management of patients with this disease.

KEYWORDS

Heparin-induced thrombocytopenia - platelet factor 4-heparin complexes - mechanisms - antibodies - thrombosis

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