Lupus anticoagulant induces a selective defect in thrombin-mediated endothelial prostacyclin release and platelet aggregation.
A patient with microvascular thrombosis and thrombocytopenia was found to have a high-titre lupus anticoagulant. The biological effects of the patient's lupus anticoagulant were studied using whole patient serum and plasma. Staph Protein A eluate, and affinity-purified lupus anticoagulant. The latter was isolated by immunoadsorption of serum onto cardiolipin/phosphatidylserine/cholesterol liposomes. Each source of lupus anticoagulant demonstrated 'anticoagulant' activity, defined as prolongation of a modified kaolin clotting time, and contained antibody which bound to endothelial monolayers. Each interfered with thrombin-mediated prostacyclin release from endothelial cells, but had no effect on arachidonate-induced prostacyclin release. In addition, the lupus anticoagulant selectively blocked platelet aggregation in response to thrombin, but not in response to arachidonate, ADP or epinephrine. Lupus anticoagulant also reduced thrombin-stimulated shifts in cytosolic calcium. Thrombin-mediated membrane inositol metabolism and total thrombin binding to endothelium were unaffected by lupus anticoagulant, and another endothelial anticoagulant function related thrombin binding. Protein C activation by thrombomodulin, was not altered. We conclude that the binding of lupus anticoagulant to endothelial cells and platelets does not prevent all thrombin signalling events, but does interrupt prostacyclin production.
Schorer
A E
AE
Department of Medicine, Minneapolis Veterans Administration Medical Center, MN 55417.
Wickham
N W
NW
Watson
K V
KV
D001323:Autoantibodies / Q000276:immunology; D001779:Blood Coagulation Factors / Q000276:immunology* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D006801:Humans; D016682:Lupus Coagulation Inhibitor; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010974:Platelet Aggregation; D013917:Thrombin / Q000502:physiology*; D013921:Thrombocytopenia / Q000276:immunology / Q000503:physiopathology; D013927:Thrombosis / Q000276:immunology / Q000503:physiopathology
D001323:Autoantibodies; D001779:Blood Coagulation Factors; D016682:Lupus Coagulation Inhibitor; D010716:Phosphatidylinositols; D010743:Phospholipids; D011464:Epoprostenol; D013917:Thrombin; D002118:Calcium