In the present study we examined if, among other mechanisms, the abnormal exposure of phosphatidylserine at the surface of sickle red blood cells (RBCs) contributes to the hypercoagulability which characterizes homozygous sickle cell disease (SCD). The question was addressed by comparison of the procoagulant properties of RBCs from subjects with various phenotypes (SS, SC and AS) that differ in clinical presentation. As previously reported, SS‐RBCs accelerated the prothrombin activation by factor Xa, by decreasing the K m of the reaction compared to normal RBCs. SC‐RBCs and AS‐RBCs also promoted prothrombin activation although their procoagulant properties were milder compared to SS‐RBCs. A significant increase of the thrombin–antithrombin complexes was observed in SS subjects. Prothrombin fragment 1+2 (F1+2) was elevated in half of the SS subjects, but the difference with controls did not reach significance. Elevated levels of thrombin–antithrombin complexes were observed in a number of SC (4/11) and AS (3/12) subjects, but the difference with controls was not significant. A significant correlation was observed between the plasma levels of thrombin–antithrombin complexes in the subjects with SS, AS and AA phenotypes, and the procoagulant properties of RBCs. Our results strongly suggest that the procoagulant properties which characterize SS‐RBCs also affect SC‐RBCs and AS‐RBCs, and that exposure of phosphatidylserine by RBCs contributes to the hypercoagulable state observed in SCD.
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.
