Acquired hemophilia A associated with Epstein-Barr-virus-associated T/natural killer-cell lymphoproliferative disease: A case report. 2021

Masayo Yamamoto, and Motohiro Shindo, and Chihiro Sumi, and Sho Igarashi, and Takeshi Saito, and Nodoka Tsukada, and Yasumichi Toki, and Mayumi Hatayama, and Junki Inamura, and Kazuya Sato, and Yusuke Mizukami, and Yoshihiro Torimoto, and Toshikatsu Okumura
Department of Medicine, Division of Gastroenterology and Hematology/Oncology, Asahikawa Medical University.

BACKGROUND 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. METHODS 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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007694 Killer Cells, Natural Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type. NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008198 Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymph Node,Node, Lymph,Nodes, Lymph
D008232 Lymphoproliferative Disorders Disorders characterized by proliferation of lymphoid tissue, general or unspecified. Duncan's Syndrome,X-Linked Lymphoproliferative Syndrome,Duncan Disease,Epstein-Barr Virus Infection, Familial Fatal,Epstein-Barr Virus-Induced Lymphoproliferative Disease In Males,Familial Fatal Epstein-Barr Infection,Immunodeficiency 5,Immunodeficiency, X-Linked Progressive Combined Variable,Lymphoproliferative Disease, X-Linked,Lymphoproliferative Syndrome, X-Linked, 1,Purtilo Syndrome,X-Linked Lymphoproliferative Disease,X-Linked Lymphoproliferative Disorder,Disease, Duncan,Disease, X-Linked Lymphoproliferative,Diseases, X-Linked Lymphoproliferative,Disorder, Lymphoproliferative,Disorder, X-Linked Lymphoproliferative,Disorders, Lymphoproliferative,Disorders, X-Linked Lymphoproliferative,Epstein Barr Virus Induced Lymphoproliferative Disease In Males,Epstein Barr Virus Infection, Familial Fatal,Familial Fatal Epstein Barr Infection,Immunodeficiency 5s,Immunodeficiency, X Linked Progressive Combined Variable,Lymphoproliferative Disease, X Linked,Lymphoproliferative Diseases, X-Linked,Lymphoproliferative Disorder,Lymphoproliferative Disorder, X-Linked,Lymphoproliferative Disorders, X-Linked,Lymphoproliferative Syndrome, X-Linked,Lymphoproliferative Syndromes, X-Linked,Purtilo Syndromes,Syndrome, Purtilo,Syndrome, X-Linked Lymphoproliferative,Syndromes, Purtilo,Syndromes, X-Linked Lymphoproliferative,X Linked Lymphoproliferative Disease,X Linked Lymphoproliferative Disorder,X Linked Lymphoproliferative Syndrome,X-Linked Lymphoproliferative Diseases,X-Linked Lymphoproliferative Disorders,X-Linked Lymphoproliferative Syndromes
D008297 Male Males
D010314 Partial Thromboplastin Time The time required for the appearance of FIBRIN strands following the mixing of PLASMA with phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides). It is a test of the intrinsic pathway (factors VIII, IX, XI, and XII) and the common pathway (fibrinogen, prothrombin, factors V and X) of BLOOD COAGULATION. It is used as a screening test and to monitor HEPARIN therapy. Activated Partial Thromboplastin Time,Cephalin-Kaolin Coagulation Time,Kaolin-Cephalin Coagulation Time,Thromboplastin Time, Partial,Coagulation Time, Cephalin-Kaolin,Cephalin Kaolin Coagulation Time,Coagulation Time, Cephalin Kaolin,Coagulation Time, Kaolin-Cephalin,Kaolin Cephalin Coagulation Time
D011239 Prednisolone A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. Di-Adreson-F,Predate,Predonine,Di Adreson F,DiAdresonF
D004279 DNA, Viral Deoxyribonucleic acid that makes up the genetic material of viruses. Viral DNA
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D005169 Factor VIII Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin. Coagulation Factor VIII,Factor VIII Clotting Antigen,Factor VIII Coagulant Antigen,Factor VIII Procoagulant Activity,Thromboplastinogen,Blood Coagulation Factor VIII,F VIII-C,Factor 8,Factor 8 C,Factor Eight,Factor VIIIC,Hyate-C,Hyatt-C,F VIII C,Hyate C,HyateC,Hyatt C,HyattC
D006467 Hemophilia A The classic hemophilia resulting from a deficiency of factor VIII. It is an inherited disorder of blood coagulation characterized by a permanent tendency to hemorrhage. Factor VIII Deficiency,Hemophilia,Autosomal Hemophilia A,Classic Hemophilia,Deficiency, Factor VIII,Factor 8 Deficiency, Congenital,Factor VIII Deficiency, Congenital,Haemophilia,Hemophilia A, Congenital,Hemophilia, Classic,As, Autosomal Hemophilia,Autosomal Hemophilia As,Classic Hemophilias,Congenital Hemophilia A,Congenital Hemophilia As,Hemophilia A, Autosomal,Hemophilia As,Hemophilia As, Autosomal,Hemophilia As, Congenital,Hemophilias, Classic

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