Author + information
- Received December 12, 2016
- Revision received September 15, 2017
- Accepted September 18, 2017
- Published online November 20, 2017.
- Marc Schindewolf, MDa,b,∗ (, )
- Julia Steindl, MDa,
- Jan Beyer-Westendorf, MDc,d,
- Sebastian Schellong, MDe,
- Pascal Maria Dohmen, MDf,g,
- Johannes Brachmann, MDh,
- Katharina Madlener, MDi,
- Bernd Pötzsch, MDj,
- Robert Klamroth, MDk,
- Johannes Hankowitz, MDl,
- Norbert Banik, PhDm,n,
- Sonja Eberle, PhDm,n,
- Markus Michael Müller, MDo,
- Stefan Kropff, MDo,p and
- Edelgard Lindhoff-Last, MDa,q
- aDepartment of Internal Medicine, Division of Hemostaseology, Goethe University Hospital Frankfurt, Frankfurt am Main, Germany
- bSwiss Cardiovascular Center, Division of Vascular Medicine, University Hospital Bern, Bern, Switzerland
- cThrombosis Research Unit, Department of Medicine 1, Division of Hematology, University Hospital “Carl Gustav Carus” Dresden, Dresden, Germany
- dKing’s Thrombosis Service, Department of Hematology, King’s College London, London, United Kingdom
- eMedical Department II, Municipal Hospital Dresden, Dresden, Germany
- fDepartment of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany
- gDepartment of Cardiac Surgery, Heart Center Rostock, University of Rostock, Rostock, Germany
- hDepartment of Cardiology, II. Medical Clinic, Klinikum Coburg, Coburg, Germany
- iDepartment of Hemostaseology and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany
- jInstitute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
- kDepartment of Internal Medicine, Hemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain Berlin, Berlin, Germany
- lInstitute of Pharmacology and Preventive Medicine, Munich, Germany
- mBiostatistics & Epidemiology, GlaxoSmithKline Germany, Munich, Germany
- nWinicker Norimed Medical Research GmbH, Munich, Germany
- oInternal Medicine III, GlaxoSmithKline Germany, Munich, Germany
- pAmgen, Munich, Germany
- qCardiovascular Center Bethanien (CCB), Frankfurt am Main, Germany
- ↵∗Address for correspondence:
Dr. Marc Schindewolf, Swiss Cardiovascular Center, Division of Vascular Medicine, University Hospital Bern, Freiburgstrasse 4, Building PKT1 C 421, 3010 Bern, Switzerland.
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)
The study was supported by GlaxoSmithKline. The contract research organization and the physicians who were screening the medical records obtained financial compensation for data acquisition and data management from GlaxoSmithKline. The sponsor had no influence on the study design, the collection, the analysis, and the interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication. There were no agreements concerning confidentiality of the data between the sponsor and the authors or the institutions named in the credit lines; all collected data were fully disclosed. Dr. Schindewolf has received speaker fees from Abbott, Aspen, Boston Scientific, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, and Sanofi; travel grants from Bard, Bayer Healthcare, Bristol-Myers Squibb, and Terumo; research grants from Cook, Daiichi-Sankyo, and Terumo; and is a member of the advisory boards of and a consultant for Bayer Healthcare, Bristol-Myers Squibb, Daiichi-Sankyo, and Sanofi. Dr. Beyer-Westendorf has received honoraria from Bayer Healthcare, Boehringer Ingelheim, GlaxoSmithKline, Bristol-Myers Squibb/Pfizer, LEO Pharma, and Mitsubishi Pharma. Dr. Schellong has received speaker fees from Aspen, Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, and Pfizer; has received consulting fees from Aspen; and is on the advisory boards of Bayer Healthcare, Boehringer Ingelheim, Daiichi-Sankyo, GlaxoSmithKline, and Pfizer. Dr. Brachmann has received consultant fees from Biotronik and Medtronic. Dr. Madlener has received lecture fees from Bayer Healthcare, Boehringer Ingelheim, CSL-Behring, GlaxoSmithKline, Mitsubishi Pharma, Roche, Sanofi, Pfizer, and Bristol-Myers Squibb. Dr. Pötzsch has received lecture fees from Amgen, Boehringer Ingelheim, CSL-Behring, and Roche-Diagnostics. Dr. Hankowitz has received consultant fees from Aspen, Bayer Healthcare, Bristol-Myers Squibb, Daiichi-Sankyo, and Sanofi; speaker fees from Sanofi; and has received a research grant from Daiichi-Sankyo. Dr. Müller is an employee of and holds shares in GlaxoSmithKline. Drs. Banik and Eberle are past employees of GlaxoSmithKline. Dr. Kropff is a past employee of and holds shares in GlaxoSmithKline. Dr. Lindhoff-Last has received speakers fees from Bayer Healthcare, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi; and is a member of the advisory boards of Bayer Healthcare, Boehringer, and GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received December 12, 2016.
- Revision received September 15, 2017.
- Accepted September 18, 2017.
- 2017 American College of Cardiology Foundation
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