Acquired hemophilia A associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease: A case report

Abstract

Introduction: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Hematological malignancies, especially lymphoid malignancies, are known to be underlying causes of AHA; however, thus far, there is no report of AHA associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease (EBV-T/NK-LPD). Here, we present a case of AHA that developed during treatment for EBV-T/NK-LPD.

History: A 69-year-old man visited our hospital because of general fatigue. Blood examination showed pancytopenia, and computed tomography revealed whole-body lymphadenopathy, but there were no findings indicating hematological malignancy from bone marrow aspiration and cervical lymph node biopsy. The level of EBV DNA in peripheral blood was extremely high, and he was diagnosed with EBV-T/NK-LPD. EBV-T/NK-LPD improved with prednisolone (PSL) administration. Seventeen months after starting treatment, the patient complained of back and right leg pain. At that time, he had been treated with low-dose PSL, and EBV-T/NK-LPD was well controlled. Imaging revealed hematoma of the right iliopsoas muscle. Prolonged activated partial thromboplastin time (APTT) was the only abnormal finding in a screening coagulation test. FVIII coagulant activity was below detection limit, and FVIII inhibitor level was increased. From these results, he was diagnosed with AHA.A higher dose of PSL was administered, and, after 1 month of treatment, FVIII activity gradually increased, and FVIII inhibitor level became undetectable. APTT also normalized, and complete remission was achieved and maintained for 13 months with low-dose PSL. During treatment, EBV-T/NK-LPD was well controlled.

Conclusion: It is speculated that proliferating lymphocytes interfere with normal immune functions and that abnormal autoantibodies are produced from those lymphocytes in patients with LPD. Therefore, we speculate that EBV-infected and proliferating monoclonal NK cells might have modulated the immune system and produced autoantibodies against FVIII, thus causing AHA in this patient with EBV-T/NK-LPD.

Figure 1

Imaging findings at admission. Enhanced computed tomography (A) showed swelling of the right iliopsoas and iliacus muscles. Magnetic resonance imaging showed an area (white arrows) in the right iliopsoas muscle that had a high signal on T2-weighted images (B), isointense signal on T1-weighted images (C), and without suppression on fat-suppression images (D), from these findings, the patient was diagnosed with hematoma of the right iliopsoas muscle.

Figure 2

Result of mixing test. Activated partial thromboplastin time (APTT) was not corrected by normal plasma, which was clearer after incubation for 2 hours at 37°C than after immediate reaction.

Figure 3

Clinical course from the diagnosis of acquired hemophilia A (AHA). Following diagnosis of AHA, a higher dose of prednisolone (PSL; 1 mg/kg/day) was administered, and eptacog alfa was administered for bleeding. After 1 month of these treatments, factor VIII (FVIII) activity increased gradually, and FVIII inhibitor level became undetectable. Activated partial thromboplastin time (APTT) was also normalized. PSL dose was gradually reduced, and AHA was maintained in complete remission with low-dose PSL (5 mg/day).