Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis.
We have identified an inhibitor of the protein C anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein C and protein S antigen, normal levels of functional protein C, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein C-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein C, since the inhibitor could easily be separated from protein C during fractionation procedures, and did not interfere with the activation of protein C in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein C.
Amer
L
L
Department of Medicine, University of New Mexico School of Medicine, Albuquerque.
Kisiel
W
W
Searles
R P
RP
Williams
R C
RC
D000026:Abortion, Habitual / Q000150:complications; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D001779:Blood Coagulation Factors / Q000276:immunology / Q000378:metabolism; D002308:Cardiolipins / Q000276:immunology*; D005260:Female; D006801:Humans; D016682:Lupus Coagulation Inhibitor; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000150:complications / Q000276:immunology; D011247:Pregnancy; D011486:Protein C / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000150:complications; D013927:Thrombosis / Q000097:blood* / Q000150:complications / Q000276:immunology
D001323:Autoantibodies; D001779:Blood Coagulation Factors; D002308:Cardiolipins; D016682:Lupus Coagulation Inhibitor; D011486:Protein C