Acquired hemophilia A and plasma cell neoplasms: a case report and review of the literature

Abstract

Background Acquired hemophilia A is a rare autoimmune disease with clinically often significant bleeding diathesis resulting from circulating autoantibodies inhibiting coagulation factor VIII. Half of acquired hemophilia A cases are associated with an underlying disorder, such as autoimmune diseases, cancer, or use of certain drugs, or occur during pregnancy and in the postpartum period. In the other half, no underlying cause is identified. An association of acquired hemophilia A with plasma cell neoplasm seems to be extremely rare. Case presentation We describe a case of a 77-year-old Swiss Caucasian man who was diagnosed with acquired hemophilia A and smoldering multiple myeloma as an underlying cause. Acquired hemophilia A was treated with prednisolone, cyclophosphamide, and immunoadsorption. Extensive workup revealed a plasma cell neoplasm as the only disorder associated with or underlying the acquired hemophilia A. For long-term control of acquired hemophilia A, we considered treatment of the plasma cell neoplasm necessary, and a VRD (bortezomib, lenalidomide, and dexamethasone) regimen was initiated. Due to multiple complications, VRD was reduced to VRD-lite after two cycles. After nine cycles of induction therapy and five cycles of consolidation therapy, the patient is in complete remission of his acquired hemophilia A and very good partial remission of the plasma cell neoplasm. We conducted a literature review to identify additional cases of this rare association and identified 15 other cases. Case descriptions, including the sequence of occurrence of acquired hemophilia A and plasma cell neoplasm , treatment, evolution, and outcome are presented. Discussion and conclusions Our case, together with 15 other cases described in the literature, underscore the possibility of plasma cell neoplasm as an underlying cause of acquired hemophilia A. Physicians should consider including protein electrophoresis, immunofixation, and analysis of free light chains in laboratory diagnostics when treating a patient with acquired hemophilia A. The occurrence of excessive and unexplained bleeding in patients diagnosed with plasma cell neoplasm should raise suspicion of secondary acquired hemophilia A and trigger the request for coagulation tests, particularly in patients treated with immunomodulatory drugs such as thalidomide or lenalidomide. Additionally, early intervention with immunoadsorption can be lifesaving in cases with high-titer factor VIII inhibitors, especially when surgical interventions are necessary.

Autoimmune Complications in Hematologic Neoplasms

“…These cases may confound the initial LPD diagnosis, may be life-threatening (as for cases of catastrophic APS), and may respond to CD and ALL therapies [ 34 , 36 , 38 , 45 , 46 , 47 ]. Finally, several cases of SLE, RA, vasculitis, AH and aVWS complicating MM and amyloidosis have been reported [ 37 , 41 ]. As in LPD, the pathogenic association of MM plasma cells and autoantibody production paved the way to the use of anti-MM agents, including proteasome inhibitors and anti-CD38 antibodies [ 48 , 49 ].…”

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“…The mutation in the family must be known beforehand in order to perform the study. In some cases, it is also possible to perform the genetic study on embryos [20] . A detailed evaluation of the bleeding history of the patient and his family will be an important aid in guiding the correct diagnosis of hemophilia [10] .…”

“…The products can be used on an as-needed basis, when a person has a bleed, or on a regular basis to prevent a bleed from occurring [10] . Today, people with hemophilia and their families can learn how to apply or administer clotting factor at home [20] . Receiving clotting factor at home means that bleeds can be treated more quickly, which means less severe bleeding and side effects.…”

“…There are no restrictions regarding the choice of the type of local anesthetic agent used, although those with vasoconstrictors may provide additional local hemostasis [9] . Dental pain can usually be controlled with a minor analgesic such as paracetamol [20] . Acetylsalicylic acid should not be used because of its inhibitory effect on platelet aggregation.…”

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

“…The described subject achieved simultaneous remission of both disorders after chemotherapy and, experiencing a protein M increase even without myeloma symptoms, he developed an immediate AHA relapse [20]. In the literature, various types of M protein have been described in myeloma patients with AHA [5,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. The most common M protein type is IgG kappa (31%), though some patients have been diagnosed with IgA and light chain disease (LCD), both kappa and lambda (Table I).…”