Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is 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.

The 4Ts score is commonly used to determine the clinical probability of HIT.

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 a patient has suspected HIT and at least an intermediate-probability 4Ts score, all sources of heparin (including low molecular weight heparin) must be discontinued and a nonheparin anticoagulant should be initiated.

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.[1]Warkentin T, Chong B, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost. 1998 Jan;79(1):1-7. http://www.ncbi.nlm.nih.gov/pubmed/9459312?tool=bestpractice.com 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 risk of inducing HIT. Despite rare reports of fondaparinux-induced HIT, observational studies report the successful use of fondaparinux to treat HIT, and it is considered to be a nonheparin anticoagulant.[2]Warkentin TE. Fondaparinux: does it cause HIT? Can it treat HIT? Expert Rev Hematol. 2010 Oct;3(5):567-81. http://www.ncbi.nlm.nih.gov/pubmed/21083474?tool=bestpractice.com [3]Kang M, Alahmadi M, Sawh S, et al. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. http://www.ncbi.nlm.nih.gov/pubmed/25515959?tool=bestpractice.com