Heparin-induced thrombocytopenia: natural history, diagnosis, and management

Abstract

Heparin-induced thrombocytopenia (HIT) is an under-recognized, limb-and life-threatening complication of pharmacologic heparin administration. Antibody formation against heparin complexed to platelet factor 4 (PF4) is central to the pathogenesis of HIT. Heparin:PF4 antibodies promote platelet activation and aggregation as well as excess thrombin generation which may lead to clinical thrombosis. HIT should be suspected in patients who develop thrombocytopenia with or without associated arterial or venous thrombosis while on heparin. HIT is a clinical diagnosis. Specialized HIT assays should be interpreted with care. The cornerstone of HIT management is the discontinuation of all forms of heparin exposure and the institution of anticoagulation with an alternative agent. The direct thrombin inhibitors lepirudin and argatroban are currently available and approved for use in patients with HIT.

A prospective study of the prevalence of heparin‐induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis

“…There are two clinically different types of HIT [1][2][3]. Type I is the most common, occurring in 10 to 20% of patients treated with unfractionated heparin.…”

“…Type I is the most common, occurring in 10 to 20% of patients treated with unfractionated heparin. It is characterized by the early onset (usually within 1 to 2 days) of mild thrombocytopenia (platelet counts usually >100,000/mm 3 ), which often resolves completely with no major clinical consequences despite continued heparin treatment [2,3]. In this nonimmune type of HIT, thrombocytopenia results from the direct activation of platelets by heparin [2,3].…”

“…Conversely, type II HIT is immune-mediated, with a delayed onset (typically within 5 to 10 days) and more severe thrombocytopenia (platelet counts often below 100,000/mm 3 ), paradoxically associated with both venous and arterial thrombosis [1][2][3].…”

“…HIT pathogenesis involves antibodies induced by antigenic complexes of heparin with platelet factor 4 (PF4) released by heparin-activated platelets [1][2][3]. The anti-H/PF4 antibodies produced, which are mostly of the IgG class, can activate platelets, endothelial cells, and macrophages, leading to thrombotic events [1][2][3].…”

“…The anti-H/PF4 antibodies produced, which are mostly of the IgG class, can activate platelets, endothelial cells, and macrophages, leading to thrombotic events [1][2][3]. The prevalence of anti-H/PF4 antibodies varies considerably and may exceed 50% in certain populations, but it has been clearly demonstrated that these antibodies do not systematically cause thrombocytopenia or thrombotic complications [1][2][3][4][5]. Indeed, only 1 to 5% of patients receiving unfractionated heparin develop HIT, which is complicated by thrombotic events in 30 to 75% of cases [1][2][3]5].…”