Hemostatic dysfunction in paraproteinemias and amyloidosis

Thrombotic and hemorrhagic complications frequently have been observed in patients with monoclonal gammopathy, Waldenström macroglobulinemia, amyloidosis, multiple myeloma (MM), and myeloma. Chemotherapy in combination with the use of antiangiogenic agents can further enhance the risk of cardiovascular complications. A malignancy-associated thrombophilic state (in particular, cytokine-induced high levels of factor VIII and von Willebrand factor) can also explain the high rate of thrombosis reported in these patients. Impaired fibrinolysis and a transient downregulation of the protein C system are recently discovered pathogenetic mechanisms. At diagnosis, when the highest VTE risk is present, baseline coagulation tests such activated protein C resistance may be helpful to identify patients who can benefit the most from anticoagulation; with the emerging evidence of a positive effect on survival of low molecular weight heparin, prospective trials are needed in this group of diseases.