Procoagulant Platelets and the Pathways Leading to Cell Death

Abstract

Platelets are critical mediators of thrombosis and hemostasis. In response to agonist, platelets aggregate to form a thrombus via ligand binding of the glycoprotein IIb/IIIa receptor. However, activated platelets are heterogeneous in nature and a subset of platelets stimulated by strong agonists support the assembly of the coagulation complexes. It is proposed that these "procoagulant" platelets have a unique role in hemostasis and thrombosis as the link between primary and secondary hemostasis, localizing the thrombin burst required for fibrin formation to micro-domains within the platelet thrombus. Loss of procoagulant potential leads to bleeding while an increase is linked with propensity to thrombosis. While many features of the procoagulant platelet are known, the exact nature of the procoagulant platelet remains controversial. It is noted that many of the morphological and biochemical features of procoagulant platelets are also features of the cyclophilin D necrosis pathway. This review will focus on the distinct roles of platelet subpopulations, the identity of the procoagulant platelet, and the potential role of the cell death pathways in regulating platelet procoagulant response.

Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol

“…The reduction in PAC-1 binding found on PS-positive platelets has been reported previously and has been described as a down-regulation of the fibrinogen receptor 40 . However, it was recently suggested that this interpretation might need to be revisited 41 , as PS-positive, PAC-1-negative platelets may still bind another conformation-specific antibody, LIBS-6, that also recognize α IIb β 3 when bound to fibrinogen 42 . As PAC-1 has higher affinity for active α IIb β 3 than fibrinogen 14 , 42 and was present during the 10 min activation, PAC-1 should have been able to bind a number of α IIb β 3 receptors whenever these became active.…”

Procoagulant Phosphatidylserine-Exposing Platelets in vitro and in vivo

“…The distinct morphology of procoagulant platelets has led to the terminology of blebbing, balloon(ing), or balloon-like platelets (31)(32)(33)(34)(35). Procoagulant platelets have also been referred to as SCIP (sustained calcium-induced platelet morphology) platelets (36), necrotic/4-[N-(S-glutathionylacetyl)amino]phenylarsonous acid (GSAO)-binding platelets (37)(38)(39), superactivated platelets (40), capped platelets (21,41), and zombie platelets (42). Agbani and Poole (43) recently proposed "procoagulant platelets" as the unifying term for this activated platelet subpopulation.…”

Platelets as Biomarkers of Coronary Artery Disease

“…Furthermore, annexin V is potentially function blocking, which may be a confounder within a flow cytometry based or in vivo experimental methods. 125 Notwithstanding the lack of a universally accepted, sensitive and specific assay for this platelet subset, suitable for whole blood application, several studies, albeit from a single research group, have demonstrated potential utility of the procoagulant platelet subset as a biomarker in CVD. Patients with a higher level of procoagulant platelets following a largeartery stroke had a higher risk of stroke recurrence.…”