Tissue Factor-Negative Cell-Derived Microparticles Play a Distinctive Role in Hemostasis: A Viewpoint Review

Abstract

Circulating cell-derived microparticles (MPs) exhibit procoagulant activity and have been investigated for a possible role in some human pathologies. However, their potential role in hemostasis has been neglected and often denied. This review brings to attention a specific body of direct clinical evidence supporting an important but distinctive role of MPs in hemostasis. Evidence for a role of MPs in hemostasis includes: (1) two congenital bleeding disorders attributed to impaired release of MPs; (2) two recent studies of trauma patients relating naturally elevated endogenous MPs at admission to reduced transfusion requirements and better outcomes; (3) a study of coronary surgery patients showing that elevated MP before surgery reduces transfusion requirements during surgery; and (4) a clinical study of patients with immune thrombocytopenia demonstrating that those with high circulating MP have reduced bleeding compared to patients with similar platelet counts but lower MP levels. Mechanisms involving potentiating the contact factor pathway are thought to play a key role and are probably synergistic with polyphosphate released from activated platelets at sites of endothelial injury. Hemostatic defect of patients with deficient MP-mediated coagulation resembles deficiency of FXI (hemophilia C), distinct from hemophilia A or B, so can be termed type C hemostasis. A better understanding of this proposed hemostatic pathway may lead to improved methods for controlling excessive bleeding in surgery, trauma, and other clinical settings.

Extracellular Vesicles in Autologous Cell Salvaged Blood in Orthopedic Surgery

“…By carrying phospholipids and tissue factor, EVs can promote hemostasis, specifically by increasing platelet adhesion, platelet aggregation, and thrombin generation [13][14][15]. Patients with deficient microparticle-mediated coagulation resemble deficiency of factor XI (hemophilia C) [16]. Similarly, microparticles may prevent excessive perioperative bleeding.…”

Platelet, erythrocyte, endothelial, and monocyte microparticles in coagulation activation and propagation

“…Summarizing the results, we can say that MPs derived from different cells play a qualitatively different role in coagulation activation and propagation: TF+ MMPs have a strong activating ability and have a very weak effect on coagulation propagation; on the contrary, contact activation from PMPs and ErMPs in normal plasma is weak, and these MPs, firstly, contribute coagulation propagation. Although an increased concentration of MPs is usually regarded as a risk of thrombosis, MPs that have weak activating capacity but support coagulation propagation in some cases can play a positive role, for example, by reducing blood loss during surgery or mitigating the clinical manifestations of haemophilia [56]. Endothelial MPs, although they have an intermediate activity, are able to make a significant contribution to both the activation and distribution of coagulation.…”

The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles

“…The implications of these findings for in vivo haemostasis is unknown because in that situation both fibroblast damage and EVs generation are likely to occur at the site of vascular injury. However, it has been shown that patients with high levels of circulating EVs did not require transfusions [44]. This will require further investigation.…”