Titre of anti-heparin/PF4-antibodies and extent of in vivo activation of the coagulation and fibrinolytic systems.

Details

Serval ID
serval:BIB_E0D907F5436C
Type
Article: article from journal or magazin.
Collection
Publications
Title
Titre of anti-heparin/PF4-antibodies and extent of in vivo activation of the coagulation and fibrinolytic systems.
Journal
Thrombosis and Haemostasis
Author(s)
Chilver-Stainer L., Lämmle B., Alberio L.
ISSN
0340-6245 (Print)
ISSN-L
0340-6245
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
91
Number
2
Pages
276-282
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Heparin-induced thrombocytopenia (HIT) is mediated by antibodies directed against the heparin/platelet factor 4 (PF4) complex. Our aim was to investigate whether the antibody titre is associated with the degree of in vivo thrombin generation. We measured the anti-heparin/PF4-antibody titre, prothrombin fragments F1+2, thrombin-antithrombin (TAT) complexes and D-dimers in plasma samples from 225 patients with suspected HIT. Antibody titres as detected by a particle gel immunoassay strongly correlated with optical density values measured by ELISA (r=0.84, p<0.0001). Patients with titres > or =4 (n=44) had significantly higher median levels of F1+2 (2.49 nmol/l), TAT (13.01 microg/l) and D-dimers (3340 microg/l) compared to patients with undetectable antibodies (n=148; F1+2 1.61 nmol/l, TAT 4.95 micro g/l, D-dimers 1911 micro g/l; p<0.0001 for all comparisons) or patients with titres of 1-2 (n=33; F1+2 1.44 nmol/l, p=0.0014; TAT 4.37 microg/l, p=0.0018; D-dimers 2231 microg/l, p=0.0016). Multivariate analysis indicated the anti-heparin/PF4-antibody titre as an independent predictor for F1+2 (p=0.0036), TAT (p=0.0176) and D-dimer (p=0.0003) levels. This relationship remained statistically significant after exclusion of patients with concomitant prothrombotic conditions and/or thromboembolic complications during heparin treatment. These data demonstrate that high anti-heparin/PF4-antibody titres are independently associated with an increased in vivo thrombin generation. Rapid determination of the anti-heparin/PF4-antibody titre could help guide clinical management, identifying a subset of HIT-patients who are at high risk of developing thromboembolic complications and possibly require alternative anticoagulation in therapeutic dosage even in the context of isolated HIT.
Keywords
Antibodies/blood, Biological Markers/blood, Blood Coagulation, Fibrinolysis, Heparin/adverse effects, Heparin/immunology, Humans, Immunoassay, Multivariate Analysis, Platelet Factor 4/immunology, Predictive Value of Tests, Thrombin/biosynthesis, Thrombocytopenia/blood, Thrombocytopenia/immunology
Pubmed
Web of science
Create date
10/02/2015 11:00
Last modification date
20/08/2019 16:05
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