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Thromb Haemost 2012; 107(06): 1044-1052
DOI: 10.1160/TH11-10-0689
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles

Grigoris T. Gerotziafas
1   ER2UPMC, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
,
Patrick Van Dreden
3   Research and Development, Diagnostica Stago, Gennevilliers, France
,
Mourad Chaari
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
,
Vassiliki Galea
1   ER2UPMC, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
,
Amir Khaterchi
1   ER2UPMC, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
,
Francois Lionnet
4   Internal Medicine Department, Referral Centre for Adult Sickle Cell Disease, Tenon University Hospital Assistance Public Hospital of Paris, France
,
Katice Stankovic-Stojanovic
4   Internal Medicine Department, Referral Centre for Adult Sickle Cell Disease, Tenon University Hospital Assistance Public Hospital of Paris, France
,
Olivier Blanc-Brude
5   ParCC – Paris Center for Cardiovascular Research Inserm UMRs970, Paris, France
,
Barry Woodhams
3   Research and Development, Diagnostica Stago, Gennevilliers, France
,
Micheline Maier-Redelsperger
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
,
Robert Girot
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
,
Mohamed Hatmi
1   ER2UPMC, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France
6   Département Infection et Epidémiologie, Institut Pasteur, Paris, France
,
Ismail Elalamy
1   ER2UPMC, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, France
2   Service d’Hématologie Biologique Tenon University Hospital, Assistance Publique Hôpitaux de Paris, France
› Author Affiliations
Further Information

Publication History

Received: 08 October 2011

Accepted after major revision: 21 February 2012

Publication Date:
29 November 2017 (online)

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Summary

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.

Keywords

Sickle cell disease - microparticles - thrombin generation - hydroxyurea
 

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