From the Guidelines
Platelet dysfunction in chronic kidney disease (CKD) is primarily caused by the accumulation of uremic toxins, which impair platelet adhesion, aggregation, and secretion by interfering with glycoprotein receptor function and intracellular signaling pathways. This is supported by a study published in the Journal of the American College of Cardiology in 2019 1, which highlights the factors contributing to a pro-hemorrhagic state in CKD, including alterations in platelet synthesis, composition, and activation, as well as dysfunctional platelet-vessel wall interactions. Some key factors contributing to platelet dysfunction in CKD include:
- Alterations in platelet synthesis, composition, and activation, including decreased synthesis of platelet activating factor and altered arachidonic acid metabolism 1
- Dysfunctional platelet-vessel wall interactions, including decreased platelet-vessel wall interaction and reduced platelet aggregation 1
- Anemia, which reduces the rheological forces that normally push platelets toward vessel walls, further compromising platelet-vessel wall interactions 1
- Increased oxidative stress, which damages platelet membranes and impairs platelet function 1
- Abnormal von Willebrand factor multimers and decreased platelet ADP content, contributing to impaired aggregation 1
- Medications commonly used in CKD management, such as antiplatelet agents and certain antibiotics, which can worsen platelet dysfunction 1 Overall, the etiology of platelet dysfunction in CKD is complex and multifactorial, involving the interplay of various factors that impair platelet function and increase the risk of bleeding and thrombotic complications.
From the Research
Etiology of Platelet Dysfunction in Chronic Kidney Disease
The etiology of platelet dysfunction in patients with chronic kidney disease (CKD) is complex and multifactorial. Several studies have investigated the effects of uremic toxins on platelet function, with varying findings.
- Uremic toxins have been shown to have both platelet-stimulatory and inhibitory effects 2, 3.
- The accumulation of uremic toxins in the circulation and in tissues is associated with the progression of CKD and its co-morbidities, including cardiovascular disease (CVD) 4.
- Platelet dysfunction in CKD patients may be due to alterations in the platelet transcriptome, including changes in messenger RNA (mRNA) and microRNA levels 5.
Role of Uremic Toxins
Uremic toxins play a key role in the development of platelet dysfunction in CKD patients.
- Protein-bound uremic toxins (PBUTs) seem to have an important pathophysiologic role in CKD, inducing various cardiovascular complications 6.
- The removal of uremic toxins from the blood with dialytic techniques represents a proven approach to limit CKD-related complications 6.
- However, conventional dialysis mainly focuses on the removal of water-soluble compounds of low and middle molecular weight, whereas PBUTs are strongly protein-bound, thus not efficiently eliminated 6.
Platelet Abnormalities in CKD
Platelet abnormalities in CKD patients are inconsistent, but most studies report impaired platelet function.
- Bleeding time is mostly prolonged and platelet adhesion is mainly reduced in CKD patients 2.
- Maximal platelet aggregation is significantly reduced in patients with CKD upon collagen stimulation 2.
- Platelet hyporeactivity mediated by uremic toxins and anemia contributes to the increased bleeding risk in advanced CKD 3.