Platelet Dysfunction in Renal Failure

Abstract

Patients with end-stage renal disease suffer from complex hemostatic disorders. Uremic patients show a bleeding diathesis that is mainly due to abnormalities of primary hemostasis; in particular, platelet dysfunction and impaired platelet-vessel wall interaction. However, despite decreased platelet function, these patients have a high prevalence of cardiovascular and thrombotic complications. Platelet dysfunction in uremic patients is partially due to uremic toxins present in circulating blood. Dialysis improves platelet abnormalities and reduces, but does not eliminate, the risk of hemorrhage. Hemodialysis can even contribute to the bleeding through the continuous platelet activation induced by the interaction between blood and artificial surfaces. Thrombocytopenia, glomerular thrombosis, and thrombi in small arteries and glomerular capillaries are common pathological features in many renal diseases. Platelets are also involved directly in the pathogenesis of glomerular diseases through a variety of mechanisms, including release of active molecules, by enhancing immune complex deposition, and by altering glomerular permeability.

Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor

“…These massive amounts of CXCL4 are deemed to be necessary to trigger the initial phase of hemostasis (24); yet, CXCL4 also exerts immunomodulatory and proinflammatory effects, especially by promoting monocyte activation and differentiation (32). These properties of CXCL4 may be of particular clinical relevance when platelets are abnormally activated in the course of inflammatory processes (13)(14)(15)(16) including HIV-1 infection where a variety of platelet anomalies have been described associated with sustained platelet activation and increased tendency toward thrombosis (17)(18)(19)(20)(21)(22). Thus, CXCL4 may play a dual role in the pathogenesis of HIV-1 disease, on one side by suppressing HIV-1 replication but on the other by fostering immunologic activation, inflammation, and coagulation abnormalities.…”

“…The latter are specialized anucleated cells that store in their α-granules large amounts of CCL5, CXCL4 (PF-4), and the CXCL7 (NAP-2) precursor, β-thromboglobulin (12). Besides their classic role in hemostasis, platelets also participate in the inductive phase of inflammatory responses (13,14), and it has been suggested that they play a key role in the pathogenesis of certain inflammatory disorders such as hepatitis (15) and renal glomerular disease (16).…”

Renal Function and the Risk of Stroke and Bleeding in Patients With Atrial Fibrillation

“…15,16 On the contrary, kidney dysfunction is associated with hemostatic dysfunction, including decreased levels of glycoprotein IIb and IIIa, decreased activity of von Willebrand Factor and altered arachidonic acid metabolism. 17,18 Results from other cohorts have raised safety concerns on the use of warfarin in patients with severely reduced renal function. 3 A recent cohort study by Jun et al 3 reported gradually higher crude rates of bleeding associated with reduced renal function in patients with AF who received warfarin; however, after adjustment for relevant risk factors, this association was only significant among patients with eGFR<15 mL/min per 1.73 m 2 .…”

Effect of erythropoietin use on mean platelet volume in children undergoing chronic dialysis

“…KBH olan olgularda damar duvarında-ki hasara karşı oluşan trombosit cevabı bozulmuş olup aynı zamanda, hemodiyaliz tedavisi ile kanın diyaliz membranlarına teması ile oluşan "kronik trombosit aktivasyonu" sonucu tromboz gelişimine yatkınlık oluşmaktadır [17,18].…”