Abnormal fibrin structure and inhibition of fibrinolysis in patients with multiple myeloma

Abnormal clot structures have been reported in patients with multiple myeloma, and purified immunoglobulin G (IgG) has been shown to influence fibrin assembly in purified systems. Recently fibrin structure has been demonstrated to be a major determinant of fibrinolytic rates. This study examined the effects of purified polyclonal and monoclonal myeloma IgG on fibrin structure and fibrinolysis in plasma clots. Clotting was initiated by the addition of thrombin (1.0 NIH units/ml) and calcium (10 mmol/L). Gelation was monitored as a time-dependent increase in optical density (633 nm). Fibrin fiber size (μ = mass-length ratio) was measured by scanning the gel from 800 to 400 nm. Two preparations of polyclonal IgG and plasma samples from 10 patients with myeloma were studied. Both Sandoglobulin (Sandoz Pharmaceuticals Corp.) and Gamimmune (Miles Inc., Cutter Biological) decreased final gel turbidity as the IgG concentration increased from 0 to 15 mg/ml. Because of its high maltose content, Gamimmune produced more-pronounced effects. Over a concentration range of 0 to 15 mg IgG per milliliter, μ decreased from 1.25 to 0.59 × 10 13 daltons/cm for Sandoglobulin and from 1.30 to 0.18 × 10 13 daltons/cm for Gamimmune. Polyclonal IgG at 15 mg/ml prolonged clot lysis induced by tissue-type plasminogen activator (tPA) from 800 seconds to > 12 hours. Similar effects were noted in myeloma clots. μ values in myeloma clots were significantly smaller than μ values in comparable normal clots. μ became smaller and lysis times became increasingly prolonged as the IgG level increased. High IgG concentrations induce thin fiber formation and impair fibrinolysis in plasma gels. These results demonstrate that fibrinolysis is inhibited in myeloma clots and that the degree of inhibition is correlated with IgG-mediated alterations in fibrin structure. Thin fibrin fibers may contribute to thrombotic risk in myeloma.