Effects of the lupus anticoagulant in patients with systemic lupus erythematosus on endothelial cell prostacyclin release and procoagulant activity.
A disturbance in endothelial cell (EC) function may be pathogenetic in the thrombotic tendency of patients with the lupus anticoagulant (LA). The ability of serum from normal subjects and patients with systemic lupus erythematosus (SLE), with and without the LA, to modulate the release of prostacyclin (PGI2) and the expression of procoagulant activity by cultured human EC was investigated. Only the 10% and 20% serum concentrations from patients with SLE-LA produced a significantly greater inhibition of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) release (the stable metabolite of PGI2) than control serum. However, when patients with SLE-LA having Raynaud's phenomenon were excluded from this group, there was then no significant difference between the effect of the patient and control serum. Serum from patients with SLE +/- LA caused a significant increase in EC procoagulant activity compared to healthy controls. The two-stage partial thromboplastin time expressed in seconds decreased from 66 (normal) to 34 (SLE - LA) and 31 (SLE + LA), but there was no significant difference between the patients with and without the LA. The significantly increased EC procoagulant activity induced by serum from patients with SLE +/- LA may account for the observed increased incidence of thrombotic events in patients with SLE. Our data suggest that factors other than decreased prostacyclin release are responsible for the altered hemostasis observed in patients with SLE + LA.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D001779:Blood Coagulation Factors / Q000276:immunology* / Q000494:pharmacology / Q000502:physiology*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013925:Thromboplastin
D001779:Blood Coagulation Factors; D016682:Lupus Coagulation Inhibitor; C053675:endothelial cell procoagulant activity; D015121:6-Ketoprostaglandin F1 alpha; D013925:Thromboplastin; D011464:Epoprostenol