Send to

Choose Destination
J Am Coll Cardiol. 2017 Nov 28;70(21):2636-2648. doi: 10.1016/j.jacc.2017.09.1099.

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

Author information

Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; Swiss Cardiovascular Center, Division of Vascular Medicine, University Hospital Bern, Bern, Switzerland. Electronic address:
Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
Thrombosis Research Unit, Department of Medicine 1, Division of Hematology, University Hospital "Carl Gustav Carus" Dresden, Dresden, Germany; King's Thrombosis Service, Department of Hematology, King's College London, London, United Kingdom.
Medical Department II, Municipal Hospital Dresden, Dresden, Germany.
Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany; Department of Cardiac Surgery, Heart Center Rostock, University of Rostock, Rostock, Germany.
Department of Cardiology, II. Medical Clinic, Klinikum Coburg, Coburg, Germany.
Department of Hemostaseology and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany.
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany.
Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain Berlin, Berlin, Germany.
Institute of Pharmacology and Preventive Medicine, Munich, Germany.
Biostatistics & Epidemiology, GlaxoSmithKline Germany, Munich, Germany; Winicker Norimed Medical Research GmbH, Munich, Germany.
Internal Medicine III, GlaxoSmithKline Germany, Munich, Germany.
Internal Medicine III, GlaxoSmithKline Germany, Munich, Germany; Amgen, Munich, Germany.
Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; Cardiovascular Center Bethanien (CCB), Frankfurt am Main, Germany.



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.


The authors sought to investigate the safety and efficacy of the different anticoagulants for treating HIT.


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.


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.


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 confounding may interfere with monitoring. (Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II; NCT01304238).


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

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center