Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function

Schoenwaelder, SM; Yuan, YP; Josefsson, EC; White, MJ; Yao, Y; Mason, KD; O&#39;Reilly, LA; Henley, KJ; Ono, A; Hsiao, S; Willcox, A; Roberts, AW; Huang, DCS; Salem, HH; Kile, BT; Jackson, SP

Author(s): Schoenwaelder, SM; Yuan, YP; Josefsson, EC; White, MJ; Yao, Y; Mason, KD; O'Reilly, LA; Henley, KJ; Ono, A; Hsiao, S; Willcox, A; Roberts, AW; Huang, DCS; Salem, HH; Kile, BT; Jackson, SP;
Details: Publication Year 2009-07-16,Volume 114,Issue #3,Page 663-666
Journal Title: BLOOD
Publication Type: Journal Article
Abstract: Procoagulant platelets exhibit hallmark features of apoptotic cells, including membrane blebbing, microvesiculation, and phosphatidylserine (PS) exposure. Although platelets possess many wellknown apoptotic regulators, their role in regulating the procoagulant function of platelets is unclear. To clarify this, we investigated the consequence of removing the essential mediators of apoptosis, Bak and Bax, or directly inducing apoptosis with the BH3 mimetic compound ABT-737. Treatment of platelets with ABT-737 triggered PS exposure and a marked increase in thrombin generation in vitro. This increase in procoagulant function was Bak/Bax- and caspase-dependent, but it was unaffected by inhibitors of platelet activation or by chelating extracellular calcium. In contrast, agonist-induced platelet procoagulant function was unchanged in Bak(-/-) Bax(-/-) or caspase inhibitor-treated platelets, but it was completely eliminated by extracellular calcium chelators or inhibitors of platelet activation. These studies show the existence of 2 distinct pathways regulating the procoagulant function of platelets. (Blood. 2009; 114: 663-666)
Publisher: AMER SOC HEMATOLOGY
Keywords: PERMEABILITY TRANSITION PORE; APOPTOSIS; ACTIVATION; STORAGE
Publisher's Version: https://doi.org/10.1182/blood-2009-01-200345
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-07-16 12:00:00