The molecular localization of the ability of certain monoclonal immunoglobulins to interfere with fibrin polymerization.

When a purified myeloma protein with the ability to inhibit fibrin polymerization was preincubated with sheep anti-human F(ab')2 antibodies, there was a marked reduction of the ability to prolong the thrombin clotting time, while anti-Fc antibodies had only a slight effect. A monoclonal immunoglobulin which shortens the thrombin time was uninfluenced by anti-F (ab')2 as well as by anti-Fc antibodies. Partial reduction and alkylation of the immunoglobulins did not modify their effect on the thrombin time. None of the immunoglobulins bound to fibrinogen or fibrin monomer that had been linked to CNBr-activated agarose. Myeloma proteins may interfere with fibrin polymerization in two ways: some proteins inhibit polymerization in a reaction that depends on the Fab (antigen binding) part of the molecule; however, antibody binding activity against fibrinogen or fibrin monomer has not been demonstrated. Other (rare) myeloma proteins accelerate fibrin polymerization; this effect cannot be ascribed to any particular portion of the molecule and is probably of an unspecific nature.