Platelet‐ and erythrocyte‐derived microparticles trigger thrombin generation via factor XIIa

Abstract

The procoagulant properties of microparticles (MPs) are due to the of the presence of phosphatidylserine (PS) and tissue factor (TF) on their surface. The latter has been demonstrated especially on MPs derived from monocytes. To investigate the relative contribution of TF and factor (F)XII in initiating coagulation on MPs derived from monocytes, platelets and erythrocytes. Microparticles were isolated from calcium ionophore-stimulated platelets, erythrocytes and monocytic THP-1 cells. MPs were quantified, characterized for cell-specific antigens and analyzed for TF, PS exposure and their thrombin-generating potential. The MP number was not proportional to PS exposure and the majority of the MPs exposed PS. TF activity was undetectable on platelet- and erythrocyte-derived MPs (< 1 fM nM(-1) PS), whereas monocyte-derived MPs exposed TF (32 fM nM(-1) PS). Platelet-, erythrocyte- and monocyte-derived MPs, but not purified phospholipids, initiated thrombin generation in normal plasma in the absence of an external trigger (lag time < 11 min). Deficiency or inhibition of FVII had no effect on thrombin generation induced by platelet- and erythrocyte-derived MPs, but interfered with monocyte MP-triggered coagulation. Platelet- and erythrocyte-derived MPs completely failed to induce thrombin generation in FXII-deficient plasma. In contrast, monocyte-derived MPs induced similar thrombin generation in normal vs. FXII-deficient plasma. MPs from platelets and erythrocytes not only propagate coagulation by exposing PS but also initiate thrombin generation independently of TF in a FXII-dependent manner. In contrast, monocyte-derived MPs trigger coagulation predominantly via TF.