Procoagulant platelets: Generation, characteristics, and therapeutic target

Abstract

Platelets play a pivotal role in hemostasis. Activated platelets are classified into two groups, according to their agonist response: aggregating and procoagulant platelets. Aggregating platelets consist of activated integrin αIIbβ3 and stretch out pseudopods to further attract platelets to the site of injury by connecting with fibrinogen. They mainly gather in the core of the thrombus and perform a secretory function, such as releasing adenosine diphosphate (ADP). Procoagulant platelets promote the formation of thrombin and fibrin by interacting with coagulation factors and can thus be considered as the connector between primary and secondary hemostasis. In addition to their functions in blood coagulation, procoagulant platelets play a proinflammatory role by releasing platelet microparticles and inorganic polyphosphate. Considering these important functions of procoagulant platelets, this subpopulation warrants detailed study to analyze their potential in preventing human diseases. This review summarizes the generation and important characteristics of procoagulant platelets, as well as their potential for preventing the adverse effects associated with current antiplatelet therapies.

The Role of NO/sGC/cGMP/PKG Signaling Pathway in Regulation of Platelet Function

“…In pro-coagulant platelets, PS exposure is triggered by activation of calcium dependent scramblase transmembrane protein 16F (TMEM16F), whereas in caspase-dependent apoptotic platelets it is mediated by Xk-related protein family member (Xkr8) [ 140 , 141 ] (summarized in Figure 3 ). Generally, procoagulant platelets are formed during strong activation (usually a combination of thrombin and collagen induces this stage) and triggered by high sustained intracellular calcium level [ 139 , 142 , 143 ]. The frmation of pro-coagulant platelets is an irreversible process which ultimately leads to platelet death and this process is independent from apoptosis and caspase activation pathways [ 139 ].…”

Mechanisms Underlying Dichotomous Procoagulant COAT Platelet Generation—A Conceptual Review Summarizing Current Knowledge

“…Moreover, since Ca 2+ influxes are important to trigger the procoagulant response, physiological levels of Ca 2+ are required in the medium [ 45 , 46 ]. Nowadays, convulxin/thrombin (COAT) dual agonist stimulation in Ca 2+ buffer—generally recognized as standard—is extensively used by many research groups to assess procoagulant function of platelets [ 3 , 4 , 12 , 22 , 47 , 48 , 49 , 50 , 51 ]. Common model such as procoagulant COAT platelets are required in order to compare observations between research groups [ 51 ].…”

“…Aged platelets expose PS through an apoptotic-like mechanism [ 222 , 223 ]. However, platelets appear to become functionally procoagulant only after a necrotic, agonist-induced mechanism [ 4 , 29 , 222 , 223 ]. Indeed, since apoptotic PS-exposing platelets are normally cleared by autophagy before being involved in a procoagulant response, it is unlikely that old cells can support a procoagulant function [ 222 , 224 ].…”

“…Eventually, procoagulant platelets promote the deposition of fibrin in order to stabilize and limit the primary platelet plug, which is composed of aggregating platelets, the main platelet subpopulation [ 2 ]. Hence, balance between platelet aggregation and procoagulant activity in the growing thrombus is a key element of hemostasis [ 3 , 4 , 5 ]. The time-dependent appearance and role of procoagulant platelets are shown in Figure 1 .…”

Coagulopathy in Acute Promyelocytic Leukemia: Can We Go Beyond Supportive Care?

“…Our understanding of the molecular processes that govern hemostasis and thrombosis have significantly improved during the last three decades. To this end, platelets play a central role not only during primary hemostasis but also in the cellular model of secondary hemostasis (16). More so, it is now clear tissue-specific differences in basal fibrinolytic capacity and endothelial cell expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) contribute to different patterns of bleeding and thrombosis (17).…”