Figure 2.

Mechanisms of platelet hyperreactivity in patients with chronic kidney disease. Uremic toxin triggers platelet hyperreactivity, induces release of platelet-derived MPs, results in overexpression of GP IIb/IIIa and P-selectin, and enhances platelet monocyte aggregation. GPIb-V-IX receptors on platelets are involved in platelet adhesion to vWF and collagen, as unveiled on damaged endothelium. Activated platelets recruit other circulating platelets by releasing mediators such as ADP and TXA₂, leading to thrombus formation. The binding of fibrinogen with platelets is mediated by activated GP IIb/IIIa, which induces platelet aggregation. C-reactive protein is associated with increased fibrinogen plasma level. Exposed TF on the disrupted vessel wall triggers thrombin generation, which consequently converts fibrinogen to fibrin to form a stable clot. vWF exhibits a prothrombotic effect by carrying FVIII and facilitating platelet aggregation and adhesion. Reduced NO level induces platelet activation and aggregation. The decreased levels of thrombomodulin and protein C increase the coagulation tendency and thrombotic risk. ADP = adenosine diphosphate; NO = nitric oxide; TF = tissue factor; TXA₂ = thromboxane A₂; vWF = von Willebrand factor; upward black arrow = increase; downward black arrow = decrease.