Rituximab and intravenous immunoglobulin (IVIG) for the management of acquired factor VIII inhibitor in multiple myeloma: case report and review of literature

Abstract

Acquired factor VIII inhibitor (AFI) is a rare disorder and is even more uncommon in multiple myeloma patients, with only five cases reported in literature. Solid and hematologic malignancies, autoimmune conditions, drugs, and infections are the conditions commonly associated with the development of this condition, with mucocutaneous bleeding being the most common presenting sign. Diagnosis is usually made with the laboratory finding of an elevated partial thromboplastin time aPTT that cannot be corrected by plasma mixing, and further confirmed by low factor VIII activity/antigen levels along with elevated factor VIII inhibitor levels using the Bethesda assay. Treatment is usually based on the clinical picture with factor VIII inhibitor bypass activity (FEIBA) and recombinant factor VIIa (rFVIIa) employed to control acute bleeding; steroids and cyclophosphamide to suppress the inhibitor with Rituximab, in combination with other immunosuppressants in cases not suitable for steroids, and finally wherever possible, to remove the offending drug or control the underlying pathology that might predispose to the development of this condition. This case report highlights the successful management of a myeloma patient who presented with life-threatening hemorrhagic pericardial effusion and hemarthrosis. The patient was treated with FEIBA to control the acute bleeding and then received Rituximab in combination with intravenous immunoglobulin to suppress the AFI.

Practice parameter for the diagnosis and management of primary immunodeficiency

“…552,555,556,763,767 High-dose/ immunomodulatory therapy with IgG could be considered because it has been effective for therapy of other disorders caused by autoantibodies to humoral components, such as clotting factors. 768 However, to our knowledge, this has not yet been reported for the treatment of cytokine autoantibody-mediated disorders.…”

Teaching tolerance

“…Tolerance can be induced with non-depleting anti-CD4 antibodies 25 , 26 and with AAV vector-mediated expression of antigens in the liver, 27 including rhGAA 28 - 30 . IVIg, a source of Tregitopes, induces tolerance in a number of different settings such as solid organ transplant, 31 eradication of FVIII and FIX inhibitory antibodies in hemophilia patients, 32 - 34 and autoimmune diseases such as systemic lupus erythematosus (SLE 35 ), idiopathic thrombocytopenic purpura (ITP) and chronic inflammatory demyelinating polyneuropathy (CIDP) 36 - 41 . Of relevance to the goal of inducing tolerance to rhGAA, IVIg has been used to reduce ADA in Pompe patients undergoing Myozyme treatment 9 .…”

A Case of an Acquired Factor VIII Inhibitor Complicated by Multiple Treatment-Related Opportunistic Infections and Review of the Literature

“…This condition is generally diagnosed after detection of an isolated prolonged activated partial thromboplastin time (APTT), with failure to correct on mixing studies, and subsequent identification of reduced FVIII levels and presence of FVIII inhibitor. Most cases of acquired FVIII inhibitor are idiopathic, but up to 50% are associated with autoimmune diseases, malignancies, medications, or the postpartum period [2, 3]. …”

“…Current first-line treatment for eradication of FVIII inhibitor is oral corticosteroid [3, 4]; this may be combined with cyclophosphamide [3]. Although combination with cyclophosphamide results in a greater remission rate than steroid alone, the increased rate of neutropenia-related infection means that the overall mortality rate is unchanged [4].…”

“…Although combination with cyclophosphamide results in a greater remission rate than steroid alone, the increased rate of neutropenia-related infection means that the overall mortality rate is unchanged [4]. There is increasing evidence for the efficacy of rituximab (RTX) in those who fail first-line treatment or as first-line treatment for patients in whom corticosteroids and chemotherapeutic agents are contraindicated [3, 5–7]. RTX is a chimeric anti-CD20 monoclonal antibody widely used in the treatment of autoimmune disorders.…”