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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

1
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: Marc.Schindewolf@insel.ch.
2
Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
3
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.
4
Medical Department II, Municipal Hospital Dresden, Dresden, Germany.
5
Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany; Department of Cardiac Surgery, Heart Center Rostock, University of Rostock, Rostock, Germany.
6
Department of Cardiology, II. Medical Clinic, Klinikum Coburg, Coburg, Germany.
7
Department of Hemostaseology and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany.
8
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany.
9
Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain Berlin, Berlin, Germany.
10
Institute of Pharmacology and Preventive Medicine, Munich, Germany.
11
Biostatistics & Epidemiology, GlaxoSmithKline Germany, Munich, Germany; Winicker Norimed Medical Research GmbH, Munich, Germany.
12
Internal Medicine III, GlaxoSmithKline Germany, Munich, Germany.
13
Internal Medicine III, GlaxoSmithKline Germany, Munich, Germany; Amgen, Munich, Germany.
14
Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; Cardiovascular Center Bethanien (CCB), Frankfurt am Main, Germany.

Abstract

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

KEYWORDS:

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

PMID:
29169470
DOI:
10.1016/j.jacc.2017.09.1099
[Indexed for MEDLINE]
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