title: Red blood cells from patients with homozygous sickle cell disease provide a catalytic surface for factor Va inactivation by activated protein C.
abstract: The structure of red blood cell (RBC) membranes in homozygous sickle cell disease (SCD) is significantly disturbed, with an increased exposure of aminophospholipids (phosphatidylserine and phosphatidylethanolamine) at the outer surface, responsible for a procoagulant activity of SS RBCs. Aminophospholipids are known not only to promote procoagulant reactions, but also to support inhibition of blood coagulation by the protein C system. The aim of the present study was to examine whether SS RBCs could serve as a catalytic surface for the inactivation of factor Va by activated protein C (APC). Venous blood was obtained from 19 consecutive SS patients and 13 controls (AA). In all SS patients, the amount of phosphatidylserine exposed at the outer surface of RBCs was increased compared with controls, as demonstrated by a prothrombinase assay. In addition, SS RBCs significantly (P < 0.0001) increased the rate of FVa inactivation by APC: the mean values (and ranges) of the factor Va inactivation rates were 30 (0-57) vs 9.5 (0-32) mmol Vai/min/mol APC for SS RBCs and normal RBCs respectively. Our results indicate that SS RBCs provide a catalytic surface for the negative control of blood coagulation, which may partially control the procoagulant activity of these cells.
authors.affiliation: INSERM E9907, Faculté Xavier Bichat, Université Paris 7, 16 Rue Henri Huchard, AP-HP, 75018 Paris, France. annie.bezeaud@bjn.ap-hop-paris.fr
authors.forename: Annie
authors.initials: A
authors.lastname: Bezeaud
authors.forename: Laurence
authors.initials: L
authors.lastname: Venisse
authors.forename: Dominique
authors.initials: D
authors.lastname: Helley
authors.forename: Catherine
authors.initials: C
authors.lastname: Trichet
authors.forename: Robert
authors.initials: R
authors.lastname: Girot
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guillin
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D002648:Child; D004910:Erythrocyte Membrane / Q000378:metabolism*; D015943:Factor Va / Q000378:metabolism*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006720:Homozygote; D006801:Humans; D008297:Male; D011486:Protein C / Q000378:metabolism*; D011516:Prothrombin / Q000032:analysis; D012805:Sickle Cell Trait / Q000097:blood*
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; C036309:fibrin fragment D; D015943:Factor Va; D011516:Prothrombin