Platelet Abnormalities in Chronic Kidney Disease and Their Implications for Antiplatelet Therapy

Patients with chronic kidney disease (CKD) display a highly increased 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 hypo-reactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. Here, we summarize the current knowledge on CKD-induced aberrations in hemostasis with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation as well as red blood cell count in CKD may contribute to altered hemostasis in these high-risk patients. Furthermore, with CKD patients commonly receiving anti-platelet therapy to prevent secondary atherothrombotic complications, we discuss anti-platelet treatment strategies and their risk vs. benefit in terms of thrombosis prevention, bleeding and clinical outcome depending on CKD-stage. This reveals a careful consideration of benefits vs. risks of antiplatelet therapy in CKD patients, balancing thrombotic vs. bleeding risk. Nonetheless, despite antiplatelet therapy, CKD patients remain at increased cardiovascular risk. Thus, deep insights into altered platelet activity in CKD as well as underlying mechanisms are important for the optimization and development of current and novel anti-platelet treatment strategies, specifically tailored to these high-risk patients. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and anti-platelet therapy in CKD patients.