Thrombosis associated with antiphospholipid antibodies cannot be explained by effects on endothelial and platelet prostanoid synthesis.
The effect of 23 antiphospholipid antibody positive SLE sera, 4 antiphospholipid antibody negative SLE sera and 17 control sera on endothelial prostacyclin and platelet thromboxane A2 production was studied. Endothelial cells and platelets were stimulated with different agonists. Depending on the stimulus used, 4-19% of the SLE sera inhibited the prostacyclin release, whereas 4-28% enhanced prostacyclin production. Our data suggest that the pathophysiological mechanisms underlying decreased prostacyclin production are heterogeneous. Follow-up of two patients showed that prostacyclin inhibitory activity was variable in time. Platelet thromboxane production was normal or increased, but never decreased in the presence of the SLE sera. An imbalance in thromboxane A2/prostacyclin ratio was present in some patients, but did not correlate with a history of thrombosis. We conclude that, in general, interference of antiphospholipid antibodies with endothelial or platelet prostanoid synthesis does not explain the occurrence of thromboembolic manifestations in antiphospholipid antibody positive SLE patients.
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D001779:Blood Coagulation Factors / Q000032:analysis / Q000276:immunology*; D001792:Blood Platelets / Q000378:metabolism*; D004727:Endothelium / Q000276:immunology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005227:Fatty Acids / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011466:Prostanoic Acids / Q000096:biosynthesis*; D013927:Thrombosis / Q000209:etiology* / Q000276:immunology; D013928:Thromboxane A2 / Q000096:biosynthesis
D001323:Autoantibodies; D001779:Blood Coagulation Factors; D005227:Fatty Acids; D016682:Lupus Coagulation Inhibitor; D011466:Prostanoic Acids; D013928:Thromboxane A2; D011464:Epoprostenol