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

P Thiagarajan; S S Shapiro; L De Marco

doi:10.1172/JCI109869

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

P Thiagarajan, S S Shapiro, and L De Marco

Published September 1, 1980 - More info

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Abstract

Prolongation of all phospholipid-dependent coagulation tests was found in a patient with macroglobulinemia, despite absence of bleeding manifestations. The purified monoclonal IgM lambda protein and its Fabmu tryptic fragment induced similar changes in normal plasma. Patient IgM and Fabmu completely inhibited Ca++-dependent binding of radiolabeled prothrombin and Factor X to mixed phospholipid micelles. The patient's IgM lambda paraprotein reacted with phosphatidylserine and, to a lesser extent, with phosphatidylinositol and phosphatidic acid, but not with phosphatidylcholine or phosphatidylethanolamine. Prior incubation of phospholipid with patient Fabmu 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.

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