As hematoma volume correlates with mortality in spontaneous intracerebral hemorrhage (sICH) survivors, limiting hematoma expansion appears to be an effective therapeutic strategy. However, currently utilized hemostatic agents have complications that outweigh their benefits. In contrast, red cell-derived microparticles (RMPs) are universal hemostatic agents with an excellent safety profile as based on earlier studies. However, the mechanism of action of RMPs is not known. In this study, we investigated how RMPs influence secondary hemostasis. To evaluate this, we examined clotting in human plasma deficient in coagulation factors VII, VIII, IX, XI, and XII in the presence of RMPs. Pooled plasma and factor-deficient plasma were mixed to generate plasma that is 85%, 92.5% and 96.25% deficient in each of the factors, and R-times (clotting times) were determined with thromboelastography. We found that RMP treatment decreased R-times in 96.25% and 92.5% deficiency, but not 85% deficiency of factor VII. For factor VIII-deficient plasma, RMPs reduced R-times in 92.5%, but not 96.25% or 85% deficiency. For factor IX-deficient plasma and factor XI-deficient plasma, RMP treatment reduced R-times in all tested degrees of deficiency. RMP treatment did not decrease R-times for factor XII in all three degrees of deficiency. Overall, we found that RMPs significantly (p< 0.05, n=3 each) reduced R-times for plasma deficient in factors VII, VIII, IX, XI but not XII. Our results indicate that RMPs limit hematoma expansion in sICH by enhancing secondary hemostasis through both intrinsic and extrinsic pathways.
