Inhibition of Fibrin Monomer Polymerization by Lambda Myeloma Globulins

Blood obtained from seven patients with lambda type myeloma proteins showed evidence of gelatinous bulky clots, impaired clot retraction, and circulating anticoagulant activity associated with interference of fibrin monomer polymerization. Five patients had γG₁ and two had γA₁ myeloma proteins. The pathologic plasmas and isolated myeloma proteins had anticoagulant activity that prolonged both thrombin and reptilase times, that was not absorbed by BaSO₄ or neutralized by protamine sulfate, and that resisted heating to 56°C for 10 min. Addition of excess calcium partially corrected the anticoagulant effect. The anticoagulant activity of the isolated whole myeloma proteins, the enzymatic fragments, and polypeptide chains was measured by a thrombin time assay and a spectophotometric system with fibrin monomer. Low concentrations of the isolated IgGL proteins inhibited fibrin polymerization. The IgAL proteins did not demonstrate this activity at low concentrations but were active at concentrations comparable to in vivo levels. F(ab')₂ and Fab fragments produced from the IgG proteins by enzymatic digestion possessed full inhibitory activity of the native intact proteins. Fc fragments and isolated polypeptide chains did not display significant anticoagulant activity. The results suggest that the Fab sites of certain lambda myeloma proteins may bind to fibrin during clotting and fibrin polymerization.