Successful Bortezomib Salvage Therapy for Acquired Hemophilia

Case Report

Ann Hematol Oncol. 2018; 5(2): 1195.

Successful Bortezomib Salvage Therapy for Acquired Hemophilia

Schmälter AK¹*, Zimmermann C² and Rank A¹

¹Department of Hematology and Oncology, Klinikum Augsburg, Germany

²Department of Trauma, Plastic and Hand Surgery, Klinikum Augsburg, Germany

*Corresponding author: Schmälter AK, Department of Hematology and Oncology, Klinikum Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany

Received: March 15, 2018; Accepted: April 17, 2018; Published: May 04, 2018


This case report is about a patient with acquired hemophilia in which standard therapy with corticosteroids, cyclophosphamide and rituximab failed in an active bleeding incident. In our patient the coagulation factor VIII activity was below the detection limit of 0.25%, the autoantibody inhibitor titer was increased to 63 Bethesda units. An initial substitution with recombinant porcine factor VIII increased factor VIII activity insignificantly. A long-term application of activated recombinant human factor VII was necessary to control the bleeding situation. No cause could be found for the acquired hemophilia. Finally, a salvage therapy with the proteasome inhibitor bortezomib resulted in a continuous increase in factor VIII activity. In theory the effectiveness is due to the elimination of CD20 negative plasma cells which produce the autoantibodies against coagulation factor VIII.

Keywords: Hemophilia, Coagulation factor VIII, Bortezomib


Acquired hemophilia has an incidence rate of 1 person/1000000/ year and is therefore a rare autoimmune disease associated with the occurrence of life-threatening bleeding [1]. In this hemorrhagic diathesis autoantibodies of the IgG class are secreted by plasma cells and are directed against coagulation factor VIII. Acquired hemophilia occurs mainly in patients over 50 years of age and is idiopathic in 50% of cases. Causes may include pregnancy, underlying autoimmune diseases such as systemic lupus erythematosus or malignant neoplasms [2]. Subcutaneous hemorrhage is most common, followed by muscle and gastrointestinal bleeding, which may also occur simultaneously [3].

Basic principles of treatment are firstly the control of acute bleeding, secondly the elimination of the inhibitor to restore normal hemostasis and, thirdly, the treatment of existing causes. For acute hemostasis, replacement therapy with recombinant porcine factor VIII can be attempted. Alternatively, recombinant activated factor VII (raFVII) or prothrombin complex concentrate can be administered. The first-line therapy for eliminating the inhibitor is immunosuppression with corticosteroids. If this is not effective, the therapy can be supplemented with cyclophosphamide or rituximab [4]. To monitor the response to therapy, factor VIII activity is used.

Patient information and diagnostics

A 77-year-old Caucasian patient was admitted to trauma surgery for treatment of wound healing disorders following rotator cuff reconstruction. Peri-and postoperatively bleeding complications occurred. The cause of the new bleeding tendency was acquired hemophilia, the factor VIII level was less than 0.25% (reference values 70-150%). The patient received a transient substitution with raFVII and prednisolone, which led to a slight increase in factor VIII activity.

The patient has been wheelchair-bound for more than 50 years due to a spastic paresis of both legs. Otherwise, type 2 diabetes mellitus, arterial hypertension and moderate aortic stenosis are known.

Two months later, the patient was admitted to vascular surgery for an urgent revision of a Type III endoleak after implantation of an aorto-biiliac stent graft in an abdominal aortic aneurysm five years ago (Figure 1). However, prior to the planned surgery, a prolonged PTT to 123 s (reference 26-36 s) and large hematomas on the right lateral thoracic wall had been noted. After reduction of the immunosuppression the factor VIII activity was again below the detection limit of 0.25%, so the revision of the endoleak was not feasible. The Bethesda essay for determining the inhibitor titer showed an increase to 63 Bethesda units (reference values 0-0.5). Imaging, laboratory and clinical diagnostics revealed no evidence of neoplasia, other underlying autoimmune diseases or an infectious cause of the acquired hemophilia.

Citation: Schmälter AK, Zimmermann C and Rank A. Successful Bortezomib Salvage Therapy for Acquired Hemophilia. Ann Hematol Oncol. 2018; 5(2): 1195.