Blood Res.  2016 Jun;51(2):77-87. 10.5045/br.2016.51.2.77.

Dabigatran approaching the realm of heparin-induced thrombocytopenia

• Ho PJ
• Siordia JA

• KMID: 2309208
• DOI: http://doi.org/10.5045/br.2016.51.2.77

Abstract

Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options.

Keyword

Dabigatran; Anticoagulation; Heparin-induced thrombocytopenia

MeSH Terms

Anticoagulants
Antithrombins
Dabigatran*
Heparin, Low-Molecular-Weight
Mortality
Thrombocytopenia*
Thrombosis
Anticoagulants
Antithrombins
Dabigatran
Heparin, Low-Molecular-Weight

Figure

• 

  Fig. 1 Pathophysiology of Heparin-Induced Thrombocytopenia (HIT) and new oral anticoagulants. Heparin-induced thrombocytopenia is an immune-mediated complication of exposure to unfractionated or low-molecular-weight heparin. Platelet factor 4 (PF4) released from α-granule of platelet binds to polyanions such as bacteria and heparin, and exposes previously masked epitope, which leads to formation of anti-PF4-IgG antibodies. These antibodies have ability to bind PF4-heparin complexes, and the PF4-heaprin-IgG immune complex activates platelets through binding to FcγRIIa of the platelets, which in turn activates and aggregates platelets. The release of additional PF4 from activated platelets and thrombin activation lead to increased consumption of platelets and eventually thrombocytopenia. The immune complexes also activate monocytes through binding to FcγRI, which can stimulate production of tissue factors from endothelial cells. Dabigatran, a univalent direct thrombin inhibitor, and the FXa inhibitors such as rivaroxaban and apixaban, could serve as an alternative anticoagulants for HIT and thrombosis prophylaxis. Abbreviations: PF4, platelet factor 4; TF, tissue factor; IIa, thrombin; Va, activated factor V; Xa, activated factor X; VIIIa, activated factor VIII; IXa, activated factor IX; AT, antithrombin.

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