A new molecular link between coagulation and platelet activation. Emphasis is on the novel pathway. Platelet activation on subendothelial collagens is mediated by GPVI and leads to release of inorganic polyphosphates (PolyP) and surface exposure of procoagulant phosphatidylserine (PS). PolyP-triggerd FXII activation (intrinsic coagulation pathway) and tissue factor (TF)/FVIIa (extrinsic coagulation pathway) lead to activation of FX and finally thrombin (Thr) generation. Al-Tamimi and coworkers1 now demonstrate that FXa also directly or indirectly activates ADAM10 (and possibly other metalloproteinases) on the platelet surface leading to ectodomain shedding of GPVI, which may limit further activation of adherent platelets and/or reduce reactivity of circulating platelets.

A new molecular link between coagulation and platelet activation. Emphasis is on the novel pathway. Platelet activation on subendothelial collagens is mediated by GPVI and leads to release of inorganic polyphosphates (PolyP) and surface exposure of procoagulant phosphatidylserine (PS). PolyP-triggerd FXII activation (intrinsic coagulation pathway) and tissue factor (TF)/FVIIa (extrinsic coagulation pathway) lead to activation of FX and finally thrombin (Thr) generation. Al-Tamimi and coworkers now demonstrate that FXa also directly or indirectly activates ADAM10 (and possibly other metalloproteinases) on the platelet surface leading to ectodomain shedding of GPVI, which may limit further activation of adherent platelets and/or reduce reactivity of circulating platelets.

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