Platelet Abnormalities in CKD and Their Implications for Antiplatelet Therapy

Abstract

Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.

Platelet-to-Albumin Ratio: A Novel IgA Nephropathy Prognosis Predictor

“…Although the definite pathogenesis of IgAN is still unclear, most scholars agree that autoimmunity and inflammation play important roles in it ( 2 , 13 ). In recent research, platelet-related parameters have been found to be related to chronic kidney disease (CKD), diabetic nephropathy, sclerosing nephropathy, and some other renal diseases ( 14 , 15 ). Accordingly, it is supposed that platelets might be associated with IgAN.…”

CKD Effects on Platelets: Implications for Cardiovascular Risk

“…The majority of studies of non-dialysis CKD patients revealed decreased platelet aggregation and reduced thromboxane production in CKD 7 , and also a meta-analysis revealed maximal aggregation upon stimulation with collagen to be significantly reduced in patients with CKD 8 . On the other hand, others reported unaltered or increased platelet aggregation responses in CKD 7 . Nonetheless, bleeding time was mostly prolonged in CKD patients 7 .…”

“…Future studies should provide further insights into the source of the high heterogeneity of current findings on platelet responses in CKD, with either CKD etiology, stage, comorbidities or antiplatelet treatment of the investigated patient cohort, as well as differential readouts of platelet activity as potential contributing factors. Also, as recently summarized, the causes of altered platelet activity in CKD are multifactorial and yet incompletely understood, with a suggested role for uremic toxin accumulation, low-grade inflammation, reduced vascular integrity and hypercoagulability in CKD7 . Increased insights into the mechanisms underlying altered platelet responses in CKD may contribute to the optimization of current antiplatelet treatment strategies of CKD patients.Disclosures: C.B.…”

“…Platelet studies in CKD have been performed before, but the results have been highly variable. 7 Most of the studies of nondialysis patients with CKD revealed decreased platelet aggregation and reduced thromboxane production in CKD. 7 A meta-analysis also revealed maximal aggregation upon stimulation with collagen to be significantly reduced in patients with CKD.…”

“… 8 In contrast, others reported unaltered or increased platelet aggregation responses in CKD. 7 Nonetheless, bleeding time was mostly prolonged in patients with CKD. 7 …”