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 influen ce fibrin assembly in purified systems. Recently fibrin structure has been demonstrated to be a major determinant of fibrinolytic rates. Thi s study examined the effects of purified polyclonal and monoclonal mye loma IgG on fibrin structure and fibrinolysis in plasma clots. Clottin g was initiated by the addition of thrombin (1.0 NIH units/ml) and cal cium (10 mmol/L), Gelation was monitored as a time-dependent increase in optical density (633 nm). Fibrin fiber size (mu = mass-length ratio ) was measured by scanning the gel from 800 to 400 nm, Two preparation s of polyclonal IgG and plasma samples from 10 patients with myeloma w ere studied. Both Sandoglobulin (Sandoz Pharmaceuticals Corp.) and Gam immune (Miles Inc., Cutter Biological) decreased final gel turbidity a s the IgG concentration increased from 0 to 15 mg/ml. Because of its h igh maltose content, Gamimmune produced more-pronounced effects. Over a concentration range of 0 to 15 mg IgG per milliliter, mu decreased f rom 1.25 to 0.59 x 10(13) daltons/cm for Sandoglobulin and from 1.30 t o 0.18 x 10(13) daltons/cm for Gamimmune. Polyclonal IgG at 15 mg/ml p rolonged clot lysis induced by tissue-type plasminogen activator (tPA) from 800 seconds to > 12 hours. Similar effects were noted in myeloma clots, mu values in myeloma clots were significantly smaller than mu values in comparable normal clots, mu became smaller and lysis times b ecame increasingly prolonged as the IgG level increased. High IgG conc entrations induce thin fiber formation and impair fibrinolysis in plas ma gels. These results demonstrate that fibrinolysis is inhibited in m yeloma clots and that the degree of inhibition is correlated with IgG- mediated alterations in fibrin structure. Thin fibrin fibers may contr ibute to thrombotic risk in myeloma.