Clinical challenge of managing patients with multiple myeloma and acquired hemophilia A with risk of both thrombosis and bleeding: a narrative review

Abstract

Acquired hemophilia A (AHA) is a rare bleeding disorder, caused by the development of autoantibodies (inhibitor) against endogenous clotting factor VIII (FVIII). A common clinical manifestation is subcutaneous bleeding, but soft tissue hematomas and excessive post-operative hemorrhages may also occur. A diagnosis of AHA is made in patients presenting with an isolated prolonged activated partial thromboplastin time without correction in a mixed plasma study, and decreased FVIII activity. Multiple myeloma (MM) is a hematological malignancy of terminally differentiated plasma cells producing monoclonal protein (M protein). Although malignancy is found as an underlying disorder in 6–18% of AHA cases, MM seems to be a very rare cause of AHA. MM is associated with an increased risk of thrombotic complications, while AHA leads to bleeding in up to 95% of cases (although one third of patients do not require hemostatic treatment) and therefore management of patients with concomitant AHA and MM is a clinical challenge. For bleeding control and therapy of AHA, the by-passing agents activated prothrombin complex concentrate and recombinant activated factor VII, as well as porcine recombinant factor VIII, are efficient. However, for inhibitor eradication, immunosuppressive treatment can beinsufficient, and therefore intensive myeloma-aimed treatment is required. Disease- and therapy-related coagulation alterations in MM patients carry the risk of both thrombosis and bleeding, complicating the treatment of AHA in this group of patients.