Figure 3.

Mechanism of platelet dysfunction in patients with chronic kidney disease. Uremic toxins impair the binding of platelets to endothelial cells via the vWF–GPIb-IX-V receptor complex. The high production of PGI₂ causes the inhibition of platelet aggregation. In this condition, the numbers and functions of GP IIb/IIIa receptors decline, and reduced production of TXA₂ and ADP occurs. The carbamylation of GP IIb/IIIa inhibits the binding of fibrinogen with platelets, thereby inducing bleeding. The increased level of GDF-15 is associated with major bleeding. The elevated thrombomodulin level is involved in clot dissolution, with subsequent bleeding risk. The increased plasma NO level in CKD patients decreases platelet aggregation. The synergistic effect of anemia and CKD imposes a worsening effect with regard to platelets abnormalities. ADP = adenosine diphosphate; GDF-15 = growth differentiation factor 15; NO = nitric oxide; PGI₂ = prostacyclin; TXA₂ = thromboxane A₂; vWF = von Willebrand factor; upward black arrow = increase; downward black arrow = decrease.