Frequent off-label use of fondaparinux in patients with suspected acute heparin-induced thrombocytopenia (HIT)--findings from the GerHIT multi-centre registry study.
BACKGROUND
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.


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.
Department of Internal Medicine, Division of Vascular Medicine/Haemostaseology, Goethe University Hospital, Frankfurt/M., Germany. Electronic address: marc.schindewolf@kgu.de.
Marc
M
Schindewolf
Department of Internal Medicine, Division of Vascular Medicine/Haemostaseology, Goethe University Hospital, Frankfurt/M., Germany.
Julia
J
Steindl
Department of Medicine III, Division of Angiology, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
Jan
J
Beyer-Westendorf
Medical Department II, Municipal Hospital Dresden Friedrichstadt, Dresden, Germany.
Sebastian
S
Schellong
Department of Cardiovascular Surgery, Charité Hospital, Medical University Berlin, Berlin, Germany.
Pascal Maria
PM
Dohmen
II. Medical Clinic, Department of Cardiology, Klinikum Coburg, Coburg, Germany.
Johannes
J
Brachmann
Department of Haemostaseology and Transfusion Medicine, Kerckhoff-Klinik, Bad Nauheim, Germany.
Katharina
K
Madlener
Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany.
Bernd
B
Pötzsch
Department of Internal Medicine, Haemophilia Treatment Centre, Vivantes Klinikum im Friedrichshain Berlin, Berlin, Germany.
Robert
R
Klamroth
Institute of Pharmacology and Preventive Medicine, München, Germany.
Johannes
J
Hankowitz
GlaxoSmithKline, Biostatistics & Epidemiology, München, Germany.
Norbert
N
Banik
GlaxoSmithKline, Biostatistics & Epidemiology, München, Germany.
Sonja
S
Eberle
GlaxoSmithKline, Cardiovascular and Antithrombotics, München, Germany.
Stefan
S
Kropff
GlaxoSmithKline, Cardiovascular and Antithrombotics, München, Germany.
Markus Michael
MM
Müller
Department of Internal Medicine, Division of Vascular Medicine/Haemostaseology, Goethe University Hospital, Frankfurt/M., Germany.
Edelgard
E
Lindhoff-Last
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D000077425:Fondaparinux; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D011134:Polysaccharides / Q000627:therapeutic use*; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy*; D055815:Young Adult
D000925:Anticoagulants; D011134:Polysaccharides; D006493:Heparin; D000077425:Fondaparinux
Argatroban; Danaparoid; Fondaparinux; Heparin; Heparin-induced thrombocytopenia; Lepirudin