American Society of Hematology

Figure 1.

$Figure 1. Hemostatic and prothrombotic function of platelets under flow. (A) Platelet adhesion mechanisms operating under arterial flow. After disruption of the endothelium, platelets are rapidly recruited from flowing blood via a tethering mechanism dependent on the interaction of platelet GPIb-V-IX and VWF. This adhesive bond has a rapid dissociation rate, resulting in platelet translocation on the vessel wall. (B) Platelet firm adhesion and aggregation. Translocating platelets engage collagen in the vessel wall through their adhesion receptors GPVI and α2β1. GPVI is the major collagen receptor inducing intracellular calcium flux necessary for stable platelet adhesion, cytoskeletal reorganization, αIIbβ3 activation, and the release of the soluble agonists (ADP and TxA2). These agonists act through specific G-protein–coupled receptors to amplify the platelet activation response. TxA2 is derived from the metabolism of arachidonic acid via the COX-1 pathway, whereas ADP is released from platelet-dense granules. Locally generated thrombin also enhances platelet activation through proteolytic cleavage and activation of PARs. Activated platelets form stable aggregates through αIIbβ3 engagement of VWF and fibrinogen. These molecular pathways of amplification of platelet activation are the target of both clinically available and experimental therapeutic interventions in the treatment of atherothrombotic disease. (C) Stabilization of the platelet thrombus. The primary hemostatic plug is consolidated by fibrin generation at the site of injury and throughout the developing thrombus. α-Thrombin generation at the injured vessel wall is critically dependent on TF, whereas thrombin generation on the surface of activated platelets is likely to evolve both TF and contact factor–dependent activation of blood coagulation. UHF indicates unfractionated heparin; LMWH, low-molecular-weight heparin; VKA, vitamin K antagonist; PGH2, prostaglandin H2; AA, arachidonic acid, PLA2, phospholipase A2; IP3R, inositol trisphosphate receptor; ITAM, immunoreceptor tyrosine-based activation motif; FcRγ, Fc receptor gamma.$

Hemostatic and prothrombotic function of platelets under flow. (A) Platelet adhesion mechanisms operating under arterial flow. After disruption of the endothelium, platelets are rapidly recruited from flowing blood via a tethering mechanism dependent on the interaction of platelet GPIb-V-IX and VWF. This adhesive bond has a rapid dissociation rate, resulting in platelet translocation on the vessel wall. (B) Platelet firm adhesion and aggregation. Translocating platelets engage collagen in the vessel wall through their adhesion receptors GPVI and α₂β₁. GPVI is the major collagen receptor inducing intracellular calcium flux necessary for stable platelet adhesion, cytoskeletal reorganization, α_IIbβ₃ activation, and the release of the soluble agonists (ADP and TxA₂). These agonists act through specific G-protein–coupled receptors to amplify the platelet activation response. TxA₂ is derived from the metabolism of arachidonic acid via the COX-1 pathway, whereas ADP is released from platelet-dense granules. Locally generated thrombin also enhances platelet activation through proteolytic cleavage and activation of PARs. Activated platelets form stable aggregates through α_IIbβ₃ engagement of VWF and fibrinogen. These molecular pathways of amplification of platelet activation are the target of both clinically available and experimental therapeutic interventions in the treatment of atherothrombotic disease. (C) Stabilization of the platelet thrombus. The primary hemostatic plug is consolidated by fibrin generation at the site of injury and throughout the developing thrombus. α-Thrombin generation at the injured vessel wall is critically dependent on TF, whereas thrombin generation on the surface of activated platelets is likely to evolve both TF and contact factor–dependent activation of blood coagulation. UHF indicates unfractionated heparin; LMWH, low-molecular-weight heparin; VKA, vitamin K antagonist; PGH₂, prostaglandin H₂; AA, arachidonic acid, PLA₂, phospholipase A₂; IP₃R, inositol trisphosphate receptor; ITAM, immunoreceptor tyrosine-based activation motif; FcRγ, Fc receptor gamma.

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