Evidence against a platelet cyclooxygenase defect in uraemic subjects on chronic haemodialysis.
Defective platelet thromboxane synthesis has been described in uraemia and attributed to a 'functional cyclooxygenase defect'. We have studied platelet aggregation and generation of immunoreactive thromboxane B2 (TXB2) in 11 subjects on a chronic haemodialysis programme. The platelet function abnormality of uraemia was confirmed, maximal aggregation in response to collagen (2 and 4 micrograms/ml) and sodium arachidonate (1.5 and 3.0 mM) being significantly depressed. However, increased platelet aggregation in response to sodium arachidonate 0.75 mM was noted. Due to the reduced haematocrit, the platelet concentration in platelet-rich plasma (PRP) of uraemic subjects was significantly lower than that of controls; when TXB2 generation in PRP adjusted to 200 X 10(9) platelets/l was assessed, no evidence for a defect of cyclooxygenase was found, although reduced synthesis of TXB2 in response to thrombin was noted. Furthermore, increased thromboxane generation by uraemic PRP in response to sodium arachidonate 0.75 mM was detected. We conclude that the mild platelet abnormality in uraemic subjects treated by haemodialysis is not explained by a 'functional cyclooxygenase defect', although an abnormality of thrombin-induced thromboxane synthesis may be present. Furthermore, the tendency to increased aggregation and thromboxane synthesis in response to a low concentration of arachidonic acid may contribute to the thrombotic tendency which is also described in such subjects.
Bloom
A
A
Greaves
M
M
Preston
F E
FE
Brown
C B
CB
D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects; D002908:Chronic Disease; D003094:Collagen / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D006435:Renal Dialysis; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood*; D014511:Uremia / Q000097:blood*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D003094:Collagen; D011451:Prostaglandin-Endoperoxide Synthases; D013917:Thrombin