Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation

We determined the numbers, cellular origin and thrombin-generating properti es of microparticles in healthy individuals (n = 15). Microparticles, isola ted from fresh blood samples and identified by flow cytometry, originated f rom platelets [237 x 10(6)/L (median; range 116-565)], erythrocytes (28 x 1 0(6)/L; 13-46), granulocytes (46 x 10(6)/L; 16-94) and endothelial cells (6 4 x 10(6)/L; 16-136). They bound annexin V, indicating surface exposure of phosphatidylserine, and supported coagulation in vitro. Interestingly, coag ulation occurred via tissue factor (TF)-independent pathways, because antib odies against TF or factor (F)VII were ineffective. In contrast, in our in vitro experiments coagulation was partially inhibited by antibodies against FXII (12%, p = 0.006) FXI (36%, p <0.001), FIX (28%, p <0.001) or FVIII (3 2%, p <0.001). Both the number of annexin V-positive microparticles present in plasma and the thrombin-generating capacity inversely correlated to the plasma concentrations of thrombin-antithrombin complex (r = -0.49, p = 0.0 72 and r = -0.77, p = 0.001, respectively), but did not correlate to prothr ombin fragment F1+2 (r = -0.002, p = 0.99). The inverse correlations betwee n the number of microparticles and their thrombin-forming capacity and the levels of thrombin-antithrombin complex in plasma may indicate that micropa rticles present in the circulation of healthy individuals have an anticoagu lant function by promoting the generation of low amounts of thrombin that a ctivate protein C. We conclude that microparticles in blood from healthy in dividuals support thrombin generation via TF- and FVII-independent pathways , and which may have an anticoagulant function.