Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets

Abstract

Platelet microparticles (PMPs) are small vesicles released from blood platelets upon activation. The procoagulant activity of PMPs has been previously mainly characterized by their ability to bind coagulation factors VIII and Va in reconstructed systems. It can be supposed that PMPs can contribute to the development of thrombotic complications in the pathologic states associated with the increase of their blood concentration. In this study, we compared procoagulant properties of calcium ionophore A23187-activated platelets and PMPs using several in-vitro models of hemostasis. Surface densities of phosphatidylserine, CD61, CD62P and factor X bound per surface area unit were determined by flow cytometry. They were 2.7-, 8.4-, 4.3-, and 13-fold higher for PMPs than for activated platelets, respectively. Spatial clot growth rate (V(clot)) in the reaction-diffusion experimental model and endogenous thrombin potential (ETP) were determined in plasma, which was depleted of phospholipid cell surfaces by ultra-centrifugation and supplemented with activated platelets or PMPs at different concentrations. Both V(clot) and ETP rapidly increased with the increase of PMP or platelet concentration until saturation was reached. The plateau values of V(clot) and ETP for activated platelets and PMPs were similar. In both assays, the procoagulant activity of one PMP was almost equal to that of one activated platelet despite at least two-orders-of-magnitude difference in their surface areas. This suggests that the PMP surface is approximately 50- to 100-fold more procoagulant than the surface of activated platelets.

Microparticles impact coagulation after traumatic brain injury

“…Platelet-derived MPs have been shown to be more prothrombotic than platelets themselves [39], and lower circulating PMPs are seen in patients that suffer from hemorrhagic complications after trauma [40]. In parallel with these studies, we noted a relative increase in PMPs 24 h after TBI and an associated increase in clot firmness at this time.…”

Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study: Correlation with coagulopathy

“…They are considered essential for hemostasis, as they expose phospholipids, adhesion receptors, and TF on their surface, providing binding sites for activated clotting factors and thrombin generation [12, 25, 26]. It has been reported that PMPs have 100-fold higher procoagulant activity than platelets [27]. We and others have documented that PMP are the most abundant MP in the healthy population [11, 12].…”

Microvesicles and exosomes: new players in metabolic and cardiovascular disease

“…Despite there being some reports to the contrary (Tushuizen et al 2012), numerous studies have shown that platelet EVs are procoagulant due to the exposure of negatively charged PS which can enhance clot formation (for review see Hargett & Bauer (2013)). Indeed, platelet EVs have more binding sites for the factors involved in the clotting cascade than do activated platelets themselves (Sinauridze et al 2007). More recent studies have revealed the presence of TF on the surface of endothelial-and monocyte-derived EVs (Breitenstein et al 2010), as well as P-selectin glycoprotein ligand-1 which can bind to P-selectin on the surface of activated platelets and become incorporated into the clot (Falati et al 2003).…”