Heparin-induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune-mediated hypercoagulable disorder caused by antibodies to platelet factor 4 (PF4) and heparin. HIT develops in temporal association with heparin therapy and manifests either as an unexplained thrombocytopenia or thrombocytopenia complicated by thrombosis. The propensity for thrombosis distinguishes HIT from other common drug-induced thrombocytopenias. Diagnosing HIT in hospitalized patients is often challenging because of the frequency of heparin use, occurrence of thrombocytopenia from other causes, and development of asymptomatic PF4/heparin antibodies in patients treated with heparin. This review summarizes our current understanding of the pathogenesis, clinical features, diagnostic criteria, and management approaches in HIT.

Figure 1

Pathogenesis of heparin-induced thrombocytopenia (HIT). (1) Upon activation, platelets release platelet factor 4 (PF4), which can rebind a glycosaminoglycan (GAG) on the platelet surface; or (2) released PF4 binds to endothelial cells, displacing antithrombin bound to heparan sulfate. (3) Administration of heparin leads to displacement of PF4 into circulation, resulting in circulating large multimolecular complexes of PF4/heparin. (4) In 1%–5% of patients, multimolecular complexes of PF4/heparin elicit antibody formation capable of binding Fc receptors on platelets or other cells. (5) Binding of HIT immune complexes (antibody bound to multimolecular complexes) triggers platelet activation and release of procoagulant microparticles.

Figure 2

Diagnostic algorithm for heparin-induced thrombocytopenia (HIT). ^aThrombocytopenia can be absolute (<150,000/μl) or relative (>30% decrease in platelet counts from the highest platelet count prior to initiation of heparin therapy). ^bDecision to initiate alternative anticoagulant therapy should be guided by assessment of patient’s bleeding risk and comorbidities. ^cDecision to continue unfractionated heparin or low-molecular weight heparin (LMWH) should be individualized. ^dFunctional assay recommended, if clinically available. ^eAntibodies with non-PF4/heparin specificity may be causative of disease. ^fDecision to continue alternative anticoagulant therapy should be individualized.