A severe drug reaction to heparin that can lead to life- and limb-threatening venous and/or arterial thromboembolism.
Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin-dependent platelet-activating HIT antibodies.
Neither discontinuation of heparin alone nor initiation of a vitamin K antagonist alone (e.g., warfarin) is sufficient to stop the development of thrombosis in a patient with acute HIT.
If clinical suspicion for HIT is at least moderate, all sources of heparin must be discontinued and initiation of treatment with a nonheparin anticoagulant considered.
Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome that occurs when heparin-dependent, IgG antibodies bind to heparin/platelet factor 4 (PF4) complexes to activate platelets and produce a hypercoagulable state. This results in thrombocytopenia and/or thrombosis in temporal relationship to a preceding immunizing exposure to heparin.  HIT typically develops 5 to 10 days after exposure to heparin (range of 4-15 days) and can occur with unfractionated heparin, low molecular weight heparin, or, more rarely, fondaparinux. The presence of heparin-dependent antibodies alone, without any clinical manifestations, is insufficient for a diagnosis of HIT.
Fondaparinux, a pentasaccharide anticoagulant, does not usually promote antibody binding to PF4, despite its structural similarity to heparin, owing to absent/weak cross-reactivity. Therefore, it has a very low, but not zero, risk of inducing HIT. Despite rare reports of fondaparinux-induced HIT, it has been used to successfully treat HIT in case series, and is considered to be a nonheparin anticoagulant. 
Department of Medicine
Juravinski Hospital and Cancer Centre
LL is an author of several references cited in this monograph. LL has also been reimbursed for educational lectures for Pfizer Canada (Fragmin; dalteparin) and has received lecture honoraria and research funding from Bayer, Inc (Xarelto; rivaroxaban).
Assistant Clinical Professor of Medicine
Acting Associate Chair of the Division of Hematology and Medical Oncology
University of Connecticut School of Medicine
JSW declares that he has no competing interests.
Aberdeen Royal Infirmary
Foresterhill Health Campus
HW declares that he has no competing interests.
Royal Brompton Hospital
Honorary Clinical Lecturer
Imperial College London
SD is a consultant for Mitsubishi Pharma, the manufacturer of argatroban.
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