Abstract
Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation. We investigated if MPs improve hemostasis in HA plasma models. MPs isolated from pooled normal human plasma were added to severe, moderate and mild HA plasma models (0%, 2.5%, 20% FVIII). The MPs’ effect on hemostasis was evaluated by calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP) assays, while fibrin structure was imaged by standard confocal, stimulated emission depletion (STED) microscopy and scanning electron microscopy (SEM). MPs partially restored thrombin generation and fibrin formation in all HA plasma models. The procoagulant effect of MPs requires PS exposure, to a less extent of contact pathway activation, but not tissue factor exposure or in vitro stimulation of MPs. MPs partially normalized the fibrin structure, and using super-resolution STED, MPs attached to fibrin were clearly resolved. In summary, our results demonstrate that PS positive MPs could improve hemostasis in HA plasma models.
Highlights
Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation
We investigated the role of MPs in improving hemostasis in in vitro Hemophilia A (HA) plasma models using global hemostatic assays and imaging techniques
We found that MPs partially increased thrombin generation, and improved fibrin formation and clot stability in a dose-dependent manner in the severe HA plasma model
Summary
Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation. MPs partially restored thrombin generation and fibrin formation in all HA plasma models. One previous clinical study of plasma from on-demand-treated severe HA patients showed that the level of MPs decreased after FVIII treatment, and was inversely correlated with thrombin generation and fibrin formation. These findings suggest that MPs may participate www.nature.com/scientificreports in the formation of hemostatic clots in severe HA patients[12]. This study was aimed at investigating the contribution of MPs isolated from pooled normal human plasma (PNP) in improving hemostasis in in vitro HA models. Stimulated emission depletion (STED) microscopy was used to gain insight into the incorporation of MPs in fibrin networks
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