Disturbances of anticoagulation and fibrinolytic systems in monoclonal gammopathies-another mechanism of M-protein interference with hemostasis.

Monoclonal gammopathies (MG) may be associated with unique monoclonal immunoglobulin (MIg)-induced disturbances of either primary hemostasis or plasma coagulation. We have investigated the possible interference of MIg with antithrombotic systems in 49 patients with MG. Although an increase of tissue-type plasminogen activator (t-PA) activity was the most frequent abnormality in our group, defect of anticoagulation factors was found in 26.5% of patients. The relationship between MIg type and concentration and frequency of antithrombotic factor abnormalities was not found. The risk of venous thrombosis was higher in patients with the defect in comparison with the unaffected group (46% vs. 22%), but the difference was not statistically significant. Bleeding complications were markedly less frequent in the group of patients with defect of anticoagulation mechanisms (0% vs. 17%). In conclusion, we have found abnormalities in anticoagulation and/or fibrinolytic system, analogous to well-known disturbances of hemostatic mechanisms, in more than a quarter of patients with MG. The interference of M-protein with antithrombotic pathways is supposed to be another mechanism of secondary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen and APC resistance. Together with other factors, it could contribute to higher risk of thromboembolism in myeloma patients.

Oxidative stress and platelet function in multiple myeloma and renal insufficiency: clinical relations of different tests.

Hemorrhagic tendency is frequent in uremic patients and is often associated with prolonged bleeding time and decreased platelet functions in vitro. Similarly, in multiple myeloma, platelet functions are affected, mainly by the inhibitory effect of paraprotein. We have studied patients with renal insufficiency and multiple myeloma to investigate the possible relation of oxidative stress to platelet functions, adhesion and aggregation activity. We observed diminished platelet aggregation response to collagen, ADP and thrombin receptor-activating peptide (TRAP) in both groups of patients as compared with normals. The adhesion of platelets to fibrin dimers was also diminished. Malondialdehyde concentration as a criterion of oxidative stress was significantly enhanced in both groups of patients together with increased concentrations of vitamins A and E. It seems to be possible that oxidative stress contributes to modification of adhesion proteins and fibrinogen and, thus, augments the observed inhibitory influence of vitamin E on platelet aggregation and adhesion. In conclusion, the concerted influence of both malondialdehyde and vitamins A and E can contribute to diminished platelet functions in renal insufficiency and augment the inhibitory influence of paraprotein on platelet functions in multiple myeloma.