Bleeding disorder associated with albumin-dependent partial deficiency in platelet thromboxane production. Effect of albumin on arachidonate metabolism in platelets.
The authors describe a patient with a longstanding bleeding disorder associated with impaired platelet aggregation and secretion despite normal granule contents. Thrombin-induced platelet thromboxane A2 production, measured using a radioimmunoassay for thromboxane B2, was markedly decreased or undetectable in platelet-rich plasma and whole blood serum. However, significant amounts of thromboxane B2 were detected on thrombin stimulation of platelets suspended in albumin-free salt medium. Malondialdehyde and 14C-hydroxyheptadecatrienoic acid production was undetectable in the patient's platelets. Liberation of free 14C-arachidonic acid from phospholipids during stimulation of prelabeled platelets was normal, indicating normal phospholipase activity. These observations indicate an albumin-dependent partial deficiency in thromboxane production resulting from a defect either in cyclooxygenase or thromboxane synthetase. Further, the authors studied the effect of albumin on arachidonic acid metabolism in normal platelets. These studies indicate that albumin enhances liberation of arachidonic acid from phospholipids but has an overall inhibitory effect on thromboxane synthesis.
D000328:Adult; D000418:Albumins / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001760:Bleeding Time; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002850:Chromatography, Gel; D005260:Female; D006474:Hemorrhagic Disorders / Q000097:blood*; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D010314:Partial Thromboplastin Time; D010743:Phospholipids / Q000378:metabolism; D010974:Platelet Aggregation; D010976:Platelet Count; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000096:biosynthesis*
D000418:Albumins; D001095:Arachidonic Acids; D010743:Phospholipids; D013931:Thromboxanes; D016718:Arachidonic Acid; D012701:Serotonin; D008315:Malondialdehyde; D013929:Thromboxane B2; D013928:Thromboxane A2; D013917:Thrombin