Blood Res 2016; 51(2):
Published online June 23, 2016
https://doi.org/10.5045/br.2016.51.2.77
© The Korean Society of Hematology
Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
Correspondence to : Correspondence to Juan A Siordia, M.D. Department of Surgery, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA. jas@email.arizona.edu
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords Dabigatran, Anticoagulation, Heparin-induced thrombocytopenia
Blood Res 2016; 51(2): 77-87
Published online June 23, 2016 https://doi.org/10.5045/br.2016.51.2.77
Copyright © The Korean Society of Hematology.
Patricia J Ho, and Juan A Siordia*
Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
Correspondence to: Correspondence to Juan A Siordia, M.D. Department of Surgery, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA. jas@email.arizona.edu
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Dabigatran, Anticoagulation, Heparin-induced thrombocytopenia
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.
Abbreviations: CrCl, creatinine clearance; BID, twice daily; OD, once daily; D1, first day; P-gp, P-glycoprotein; AF, atrial fibrillation; DVT, deep vein thrombosis; PE, pulmonary embolism..
a)History of prior exposure. b)Due to persistent thrombocytopenia..
Abbreviatrions: Tx, Treatment; Cx, complications; NR, not reported; AT, Arterial thrombosis; DVT, deep vein thrombosis; VT, venous thrombosis; PE, pulmonary embolism; UFH, unfractionated heparin; LMWH, low-molecular-weight heparin; VTE, venous thromboembolism; HIT, heparin-induced thrombocytopenia; ET, essential thrombocytopenia; ESRD, end stage renal failure; LA, lupus anticoagulant; AF, atrial fibrillation; CABG, coronary artery bypass graft..
a)Includes additional events identified post-publication, which did not alter conclusions. b)Per-protocol, as-treated population..
Abbreviations: BID, twice daily; OD, once daily; AF, atrial fibrillation; SE, systemic embolism..
Sang Hyuk Park, Seongsoo Jang, Hyoeun Shim, Geum-Borae Park, Chan-Jeoung Park, Hyun-Sook Chi, and Sang-Bum Hong
Korean J Hematol 2012; 47(1): 39-43
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.