An IgM lupus anticoagulant that neutralizes the enhancing effect of phospholipid on purified endothelial thrombomodulin activity--a mechanism for thrombosis.
An anticoagulant activity was isolated from the plasma of a patient with a strong lupus-like anticoagulant using gel filtration by high performance liquid chromatography. IgM were detected in this anticoagulant fraction which exhibited specificity towards 50% phosphatidylcholine - 50% phosphatidylserine vesicles and cardiolipin. These phospholipids were able to produce an apparent 3-fold enhancement of purified human protein C activation by human alpha-thrombin in the presence of purified human placenta thrombomodulin. In the absence of phospholipid, the anticoagulant fraction had no effect on thrombomodulin activity. The anticoagulant fraction could neutralize the enhancement of thrombomodulin activity by phospholipid in a dose-dependent manner. This study suggests that the neutralization of phospholipid might result in a reduced activation of protein C which could be responsible for the occurrence of thrombotic complications in a proportion of patients with lupus anticoagulants.
D000368:Aged; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D004727:Endothelium / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000302:isolation & purification*; D066298:In Vitro Techniques; D016682:Lupus Coagulation Inhibitor; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology; D008297:Male; D010743:Phospholipids / Q000494:pharmacology; D011486:Protein C; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018179:Receptors, Thrombin; D013927:Thrombosis / Q000209:etiology*
D001779:Blood Coagulation Factors; D006023:Glycoproteins; D007075:Immunoglobulin M; D016682:Lupus Coagulation Inhibitor; D010743:Phospholipids; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin