Marc Schindewolf1, Julia Steindl2, Jan Beyer-Westendorf3, Sebastian Schellong4, Pascal Maria Dohmen5, Johannes Brachmann6, Katharina Madlener7, Bernd Pötzsch8, Robert Klamroth9, Johannes Hankowitz10, Norbert Banik11, Sonja Eberle11, Stefan Kropff12, Markus Michael Müller12, Edelgard Lindhoff-Last2. 1. Department of Internal Medicine, Division of Vascular Medicine/Haemostaseology, Goethe University Hospital, Frankfurt/M., Germany. Electronic address: marc.schindewolf@kgu.de. 2. Department of Internal Medicine, Division of Vascular Medicine/Haemostaseology, Goethe University Hospital, Frankfurt/M., Germany. 3. Department of Medicine III, Division of Angiology, University Hospital Carl Gustav Carus Dresden, Dresden, Germany. 4. Medical Department II, Municipal Hospital Dresden Friedrichstadt, Dresden, Germany. 5. Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany. 6. II. Medical Clinic, Department of Cardiology, Klinikum Coburg, Coburg, Germany. 7. Department of Haemostaseology and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany. 8. Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany. 9. Department of Internal Medicine, Haemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain Berlin, Berlin, Germany. 10. Institute of Pharmacology and Preventive Medicine, München, Germany. 11. GlaxoSmithKline, Biostatistics & Epidemiology, München, Germany. 12. GlaxoSmithKline, Cardiovascular and Antithrombotics, München, Germany.
Abstract
INTRODUCTION: In life-threatening immune heparin-induced thrombocytopenia (HIT), treatment with an approved non-heparin anticoagulant is essential. However, off-label use with fondaparinux has been reported in the literature. The study aim was to collect data on "real-life" management of patients with suspected acute HIT regarding diagnostic and therapeutic strategies. PATIENTS AND METHODS: In a national multi-centre registry study, patients with a 4T's HIT-probability score of ≥ 4 points and treatment with at least one dose of (A)rgatroban, (L)epirudin, (D)anaparoid, or (F)ondaparinux were retrospectively evaluated. RESULTS: Of 195 patients, the 4T's scores were 4/5/6/7/8 points in 46 (23.6%)/50 (25.6%)/74 (38.0%)/13 (6.7%)/7 (3.6%) patients, respectively. During heparin therapy, 47 (24.1%) thromboembolic events, 5 (2.6%) skin lesions, 1 (0.5%) amputation, 24 (12.3%) Hb-relevant bleedings, and 2 (1.0%) fatalities occurred. A functional heparin-induced platelet activation assay was performed in 96.9%, a platelet factor 4/heparin-dependent enzyme immunoassay in 89.2%, a particle gel immunoassay in 12.3%, and a serotonin-release assay in none of the patients. Argatroban was used in 16.4%, lepirudin in 2.1%, danaparoid in 23.6%, fondaparinux in 40.0% of the patients; the sequential therapy strata were: AF (5.6%), DA (5.6%), DF (2.6%), DL (2.1%), ADF (1.5%), and DFL (0.5%). CONCLUSIONS: The current diagnostic laboratory strategy for suspected HIT is mostly (>96%) based on the recommended 2-step strategy (immunoassay plus functional assay). However, there is a wide fondaparinux off-label use (up to 50.3%) for suspected HIT, even in those patients with a high clinical pretest probability. Efficacy and safety of fondaparinux for HIT-treatment require further evaluation.
INTRODUCTION: In life-threatening immune heparin-induced thrombocytopenia (HIT), treatment with an approved non-heparin anticoagulant is essential. However, off-label use with fondaparinux has been reported in the literature. The study aim was to collect data on "real-life" management of patients with suspected acute HIT regarding diagnostic and therapeutic strategies. PATIENTS AND METHODS: In a national multi-centre registry study, patients with a 4T's HIT-probability score of ≥ 4 points and treatment with at least one dose of (A)rgatroban, (L)epirudin, (D)anaparoid, or (F)ondaparinux were retrospectively evaluated. RESULTS: Of 195 patients, the 4T's scores were 4/5/6/7/8 points in 46 (23.6%)/50 (25.6%)/74 (38.0%)/13 (6.7%)/7 (3.6%) patients, respectively. During heparin therapy, 47 (24.1%) thromboembolic events, 5 (2.6%) skin lesions, 1 (0.5%) amputation, 24 (12.3%) Hb-relevant bleedings, and 2 (1.0%) fatalities occurred. A functional heparin-induced platelet activation assay was performed in 96.9%, a platelet factor 4/heparin-dependent enzyme immunoassay in 89.2%, a particle gel immunoassay in 12.3%, and a serotonin-release assay in none of the patients. Argatroban was used in 16.4%, lepirudin in 2.1%, danaparoid in 23.6%, fondaparinux in 40.0% of the patients; the sequential therapy strata were: AF (5.6%), DA (5.6%), DF (2.6%), DL (2.1%), ADF (1.5%), and DFL (0.5%). CONCLUSIONS: The current diagnostic laboratory strategy for suspected HIT is mostly (>96%) based on the recommended 2-step strategy (immunoassay plus functional assay). However, there is a wide fondaparinux off-label use (up to 50.3%) for suspected HIT, even in those patients with a high clinical pretest probability. Efficacy and safety of fondaparinux for HIT-treatment require further evaluation.
Authors: Allyson M Pishko; Daniel S Lefler; Phyllis Gimotty; Koosha Paydary; Sara Fardin; Gowthami M Arepally; Mark Crowther; Lawrence Rice; Rolando Vega; Douglas B Cines; James P Guevara; Adam Cuker Journal: J Thromb Haemost Date: 2019-08-12 Impact factor: 5.824
Authors: Maureen A Smythe; Jennifer Priziola; Paul P Dobesh; Diane Wirth; Adam Cuker; Ann K Wittkowsky Journal: J Thromb Thrombolysis Date: 2016-01 Impact factor: 2.300