Platelet aggregation and prostaglandin metabolism in uremic patients

Whole Blood Platelet Aggregation and Release Reaction Testing in Uremic Patients

“…The literature has suggested defective prostaglandin synthesis in uremic platelets involving the cyclooxygenase pathway as implied by decreased generation of thromboxane A2 in response to addition of AA, ADP, thrombin, and collagen [19, 28]. Curiously, thromboxane A2 levels normalize or even increase in patients after initiating dialysis [29, 30]. Our study provides evidence that uremia diminishes cyclooxygenase activity.…”

Propyl gallate‐induced platelet aggregation in patients with end‐stage renal disease: The influence of the haemodialysis procedure

“…demonstrated that PG‐induced platelet aggregation and tyrosine phosphorylation of multiple proteins were substantially abolished by aspirin, apyrase and abciximab, suggesting that PG is associated with activation of platelet cyclooxygenase 1, adenosine phosphate receptors and GpIIb/IIIa, respectively 33 . Abnormal function of all these factors has been implicated in platelet dysfunction in HD patients 3–6 . Propyl gallate is possibly a suitable reagent for a global evaluation of platelet aggregation in HD patients, in contrast with other commonly used aggregation reagents like arachidonate, ADP, epinephrine, fibrinogen and others, which are proper for specific, but only partial evaluation of platelet aggregation 34…”

“…The bleeding diathesis observed in HD patients is of multifactorial origin but platelet dysfunction induced by uraemia seems to play a central role. Uraemic thrombocytopathy is attributed to acquired defects in specific receptors that impair platelet binding to fibrinogen and von Willebrand factor, 3,4 lower than normal content of adenosine diphosphate (ADP) and serotonin in platelet α‐granules 5 and impaired arachidonate metabolism 6 . Guanidinosuccinic acid, a low‐molecular‐weight uraemic toxin related with an increase in NO production by uraemic vessels, is implicated in platelet dysfunction 7 …”

“…To the authors’ knowledge this is the first time that PG was used as platelet aggregation agonist in order to evaluate platelet aggregation in HD patients. Impairment in arachidonate metabolism, adenosine phosphate receptors or ADP and glycoprotein IIb/IIIa (GpIIb/IIIa) receptor availability can contribute to platelet dysfunction in HD patients 3–6 . Propyl gallate can concurrently detect disorders in all these factors 33 .…”

PROGRESS IN UREMIC TOXIN RESEARCH: Platelet/Leukocyte Activation, Inflammation, and Uremia

“…In patients with severe renal impairment (creatinine clearance <20 ml ⁄ min or on dialysis), platelet function appears to be defective, resulting in prolonged bleeding time (3). Ultrafiltrates of uremic plasma inhibit platelet-activating factor (PAF) synthesis associated with an inhibition of phospholipase A2 and acetyltransferase activity, enzymes involved in the remodeling pathway for PAF synthesis (4).…”