Journal article
Use of Fondaparinux Off-Label or Approved Anticoagulants for Management of Heparin-Induced Thrombocytopenia.
- Schindewolf M 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.
- Steindl J Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany.
- Beyer-Westendorf J 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.
- Schellong S Medical Department II, Municipal Hospital Dresden, Dresden, Germany.
- Dohmen PM Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany; Department of Cardiac Surgery, Heart Center Rostock, University of Rostock, Rostock, Germany.
- Brachmann J Department of Cardiology, II. Medical Clinic, Klinikum Coburg, Coburg, Germany.
- Madlener K Department of Hemostaseology and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany.
- Pötzsch B Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany.
- Klamroth R Department of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain Berlin, Berlin, Germany.
- Hankowitz J Institute of Pharmacology and Preventive Medicine, Munich, Germany.
- Banik N Biostatistics & Epidemiology, GlaxoSmithKline Germany, Munich, Germany; Winicker Norimed Medical Research GmbH, Munich, Germany.
- Eberle S Biostatistics & Epidemiology, GlaxoSmithKline Germany, Munich, Germany; Winicker Norimed Medical Research GmbH, Munich, Germany.
- Müller MM Internal Medicine III, GlaxoSmithKline Germany, Munich, Germany.
- Kropff S Internal Medicine III, GlaxoSmithKline Germany, Munich, Germany; Amgen, Munich, Germany.
- Lindhoff-Last E Department of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany; Cardiovascular Center Bethanien (CCB), Frankfurt am Main, Germany.
- 2017-11-25
Published in:
- Journal of the American College of Cardiology. - 2017
argatroban
danaparoid
fondaparinux
heparin
heparin-induced thrombocytopenia
lepirudin
Anticoagulants
Chondroitin Sulfates
Dermatan Sulfate
Factor Xa Inhibitors
Female
Fondaparinux
Hemorrhage
Heparin
Heparitin Sulfate
Hirudins
Hospital Mortality
Hospitalization
Humans
Male
Necrosis
Off-Label Use
Partial Thromboplastin Time
Patient Safety
Pipecolic Acids
Polysaccharides
Recombinant Proteins
Registries
Retrospective Studies
Thrombocytopenia
Thromboembolism
Treatment Outcome
English
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).
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).
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.jacc.2017.09.1099
- PMID 29169470
- Persistent URL
- https://sonar.ch/global/documents/185052
Statistics
Document views: 56
File downloads: