Monoclonal immunoglobulin Mλ coagulation inhibitor with phospholipid specificity. Mechanism of a lupus anticoagulant

Abstract

Prolongation of all phospholipid dependent coagulation tests was found in a patient with macroglobulinemia, despite absence of bleeding manifestations. The purifed monoclonal IgMλ protein and its Fab(μ) tryptic fragment induced similar changes in normal plasma. Patient IgM and Fab(μ) completely inhibited Ca++ -dependent binding of radiolabeled prothrombin and Factor X to mixed phospholipid micelles. The patient's IgM(λ) paraprotein reacted with phosphatidylserine and, to a lesser extent, with phosphatidylinositol or phosphatidylethanolamine. Prior incubation of phospholipid with patient Fab(μ) blocked the positive reactions. Substitution of washed platelets for phospholipid led to normalization of patient coagulation tests and corrected all abnormalities produced in normal plasma by patient IgM. Furthermore, binding of 125I-factor Xa to thrombin-treated platelets was entirely normal in the presence of patient IgM. These studies support the concept that platelets, rather than phospholipid micelles, are the primary locus of prothrombin and Factor X activation in normal hemostasis.