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The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles.
MedLine Citation:
PMID:  22535498     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Sickle cell disease (SCD) is linked to hypercoagulability and is characterised by high concentrations of erythrocyte-derived microparticles (Ed-MPs). However, the impact of procoagulant cell-derived microparticles on the thrombin generation process remains unclear. We analysed the alterations of each phase of thrombin generation (TG) in relation to the concentration of erythrocyte- or platelet-derived microparticles (Ed-MPs and Pd-MPs) in a cohort of patients with steady-state SCD. We studied 92 steady-state SCD patients, 19 of which were under treatment with hydroxyurea, and 30 healthy age- and sex-matched individuals. TG was assessed by calibrated automated thrombogram. Ed-MP and Pd-MP expressing or not phosphatidylserine (PS) were determined by means of flow cytometry. Procoagulant phospholipid-dependent activity in the plasma was evaluated by the Procoag-PPL assay. Levels of thrombomodulin and haemoglobin in the plasma as well as red blood cell and reticulocyte counts were measured. SCD patients, independently of the administration of hydroxyurea, were marked by a significant acceleration in the propagation phase of TG which correlated with the Ed-MP/PS+ concentration. TG was significantly attenuated in hydroxyurea-treated patients. In conclusion, the acceleration of the propagation phase of TG, driven by Ed-MP/PS+, is a major functional alteration in blood coagulation in patients with steady-state SCD. Treatment with hydroxyurea, in addition to the regulation of haemolysis, lowers Ed-MPs and attenuates thrombin generation. The thrombogram could be a useful tool for the diagnosis of hypercoagulability and optimisation of the treatment in patients with SCD.
Authors:
G T Gerotziafas; P Van Dreden; M Chaari; V Galea; A Khaterchi; F Lionnet; K Stankovic-Stojanovic; O Blanc-Brude; B Woodhams; M Maier-Redelsperger; R Girot; M Hatmi; I Elalamy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-26
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  107     ISSN:  0340-6245     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Grigoris T. Gerotziafas, Service d'Hématologie Biologique, Hôpital Tenon, 4, rue de la Chine, 75020, Paris, Cedex 20, France, Tel.: +33156018063, Fax: +33156016044, E-mail: grigoris.gerotziafas@tnn.aphp.fr.
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