Platelet function as an assay for uremic toxins.
The nature of the toxins responsible for the uremic syndrome remains a mystery. There is current interest, however, in the possible role of middle molecular weight (500-3000 daltons) retention products and elevated hormonal factors, e.g., parathormone, as such toxins. Clinical studies of the uremic platelet defect suggest that this defect is due to a dialysable platelet inhibitor perhaps within the middle molecular weight range. An in vitro test system has been developed using the response of platelets in plasma, or in buffer following separation by gel-filtration, to release 14C labelled serotonin by graded doses of particulate collagen. This can demonstrate reversible and irreversible platelet inhibition by exogenous factors such as drugs, and in addition, demonstrates a reversible platelet inhibitor in uremic patients. It is suggested, therefore, this gel-filtered platelet preparation may be useful to study, biologically, the toxicity of middle molecules and other factors. Preliminary experimental work demonstrates that following the fractionation of an ultrafiltrate from uremic serum an inhibitor of platelet release is found in two cases: (1) in those fractions containing substances in the middle molecular range; and (2) in association with those fractions where the salt peak exists. In fractions obtained from ultrafiltrates of normal serum, platelet toxicity only coincides with the salt peak. These experiments do, indeed, support a toxic role for middle molecules but, in addition, indicate some of the problems of bioassays and the need for careful controls.
D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D012016:Reference Values; D012701:Serotonin / Q000097:blood; D014118:Toxins, Biological / Q000097:blood* / Q000494:pharmacology; D014511:Uremia / Q000503:physiopathology
D014118:Toxins, Biological; C026865:uremia middle molecule toxins; D012701:Serotonin; D006493:Heparin; D003094:Collagen; D003404:Creatinine