Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis.
In an attempt to elucidate the nature of the bleeding tendency in uremia, some in vitro functions of platelets from eight patients undergoing long-term hemodialysis were studied. None of the patients had diabetes. All had bleeding times longer than eight minutes. Threshold aggregating concentrations for collagen, adenosine diphosphate, and epinephrine, when used singly or in pairs, were two to three times higher than normal in platelet-rich plasmas from these patients. In contrast, those for arachidonic acid and U-46619, a cyclic endoperoxide/thromboxane A2 analogue, were within the normal ranges. Thromboxane B2 formation was normal in response to arachidonic acid (0.2 to 1 mM), whereas it was decreased by 30 to 50 percent in response to thrombin (0.5 to 10 units/ml), collagen (0.5 to 10 micrograms/ml), and the combination of collagen with adenosine diphosphate or epinephrine. There was a partial (about 35 percent) reduction of the platelet granular content of adenosine diphosphate. Secretion of adenosine triphosphate by 5 units/ml of thrombin was 25 to 50 percent less than in normal subjects. Thus, there was a storage pool defect as well. Similar but less severe defects were found in platelets from uremic patients who had never undergone hemodialysis. Partial correction of aggregation and thromboxane B2 formation was seen after dialysis, although platelet adenosine diphosphate content did not increase. It is concluded that the platelet dysfunction in uremia is multifaceted. There appears to be an aggregation and secretion defect related to impaired arachidonic acid release from platelet phospholipids as well as a storage pool defect. The first is improved with dialysis; the second is not.
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000209:etiology / Q000628:therapy; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D006435:Renal Dialysis; D013929:Thromboxane B2 / Q000096:biosynthesis; D014511:Uremia / Q000097:blood* / Q000150:complications / Q000503:physiopathology
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen; D004837:Epinephrine