Use of Fondaparinux Off-Label or Approved Anticoagulants for Management of Heparin-Induced Thrombocytopenia

作者：Schindewolf Marc^*; Steindl Julia; Beyer Westendorf Jan; Schellong Sebastian; Dohmen Pascal Maria; Brachmann Johannes; Madlener Katharina; Poetzsch Bernd; Klamroth Robert; Hankowitz Johannes; Banik Norbert; Eberle Sonja; Mueller Markus Michael; Kropff Stefan; Lindhoff Last Edelgard

来源：Journal of the American College of Cardiology, 2017, 70(21): 2636-2648.

DOI：10.1016/j.jacc.2017.09.1099

• argatroban
• danaparoid
• fondaparinux
• heparin
• heparin-induced thrombocytopenia
• lepirudin

BACKGROUND Life-threatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoagulants argatroban, lepirudin, or danaparoid. Frequently, the pentasaccharide fondaparinux is used off-label.
OBJECTIVES The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.
METHODS In a national, multicenter registry study, hospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts score >= 4 points), and received treatment with >= 1 dose of the aforementioned anticoagulants were included. Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arterial events, amputations, recurrent/persistent thrombocytopenia, skin lesions) and bleedings.
RESULTS Of 195 patients, 46 (23.6%), 4 (2.1%), 61 (31.3%), and 84 (43.1%) had been treated first-line with argatroban, lepirudin, danaparoid, and fondaparinux, respectively. The composite endpoint of HIT-specific complications (thromboembolic events, amputation, skin necrosis) occurred in 11.7% of patients treated with approved alternative anticoagulation and in 0.0% of fondaparinux-treated patients. The all-cause in-hospital mortality rates were 14.4% during approved alternative anticoagulation and 0.0% during fondaparinux treatment. Bleeding complications occurred in alternatively anticoagulated patients and in fondaparinux-treated patients in 6.3% and 4.8%, respectively. Post hoc analysis of clinical and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47.3%) were treated with fondaparinux.
CONCLUSIONS Fondaparinux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-treated patients, even among those with a high clinical HIT probability. Further data from randomized controlled trials are urgently needed because lepirudin was recalled from the market; danaparoid access has been limited and is not approved in the United States; and argatroban is contraindicated in patients with impaired liver function, and activated partial thromboplastin time monitoring.

• 出版日期2017-11-28