Mechanisms Involved in Heparin-Induced Thrombocytopenia and Associated Thrombosis

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 vicinity complexes can be formed that at the vicinity of pathological sites, large amounts of H-PI, 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.