今日の臨床サポート

後天性血友病

著者: 得平道英 埼玉医科大学総合医療センター 血液内科

監修: 木崎昌弘 埼玉医科大学総合医療センター

著者校正/監修レビュー済:2018/04/18
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 後天性血友病は、これまで出血の既往歴がなく、後天的に第Ⅷ因子自己抗体(インヒビター)が出現し、第Ⅷ因子が低下し重篤な出血症状を呈する疾患である。ときに致死的な臨床経過をたどる。出血症状に対する治療の第1選択はバイパス治療である。
  1. 後天性血友病は1年あたり、100万人に1人程度の発症率を有するまれな疾患である。
 
診断:
  1. 著明な出血症状が急激に全身に出現するため、その鑑別診断が必要となる。先天性および後天性凝固異常症、血小板異常症、薬剤性などを念頭に置いた問診が重要である。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
得平道英 : 未申告[2021年]
監修:木崎昌弘 : 講演料(ブリストル・マイヤーズスクイブ,ヤンセンファーマ,ノバルティスファーマ,セルジーン,MSD,小野薬品,武田薬品,大日本住友製薬),研究費・助成金など(武田薬品),奨学(奨励)寄付など(協和キリン,中外製薬,武田薬品,小野薬品,第一三共)[2021年]

改訂のポイント
  1. 後天性血友病A診療ガイドライン2011
に基づき改訂を行った。

病態・疫学・診察

疾患情報  
  1. 後天性血友病は1年あたり、100万人に1人程度の発症率を有するまれな疾患である[1][2][3]。その基本病態は第Ⅷ凝固因子に対する自己抗体であり、出血傾向を来し、ときに致死的な臨床経過をたどる。そのトリガーとなる基礎病態には自己免疫性疾患、薬剤性、癌、血液疾患、外科的手術後、分娩後などがあり、原因が同定できない特発性も存在する。<図表>
  1. 検査値では血小板数正常、aPTT延長、PT正常を呈し、第Ⅷ因子活性の著明低下および第Ⅷ因子インヒビターが検出される。<図表>アルゴリズム
  1. 治療は急性期には活性型プロトロンビン複合体濃縮製剤(活性型第Ⅶ、第Ⅸおよび第Ⅹ因子を含むファイバなど)や遺伝子組換え活性型第Ⅶ因子製剤(注射用ノボセブン)を用いるとともに( エビデンス )、免疫抑制薬の併用および原疾患の治療を考慮する。 エビデンス 
問診・診察のポイント  
  1. 著明な出血症状が急激に全身に出現するため、その鑑別診断が必要となる。先天性および後天性凝固異常症、血小板異常症、薬剤性などを念頭に置いた問診が重要である。特に家族歴および既往における出血のエピソード、出血傾向を呈した直前の原因となり得るエピソードの聴取を行う。後天性血友病ではさまざまな要因がきっかけとなって出現することより、注意深い問診が大切となる。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Shrimati Shetty, Manali Bhave, Kanjaksha Ghosh
雑誌名: Autoimmun Rev. 2011 Apr;10(6):311-6. doi: 10.1016/j.autrev.2010.11.005. Epub 2010 Nov 27.
Abstract/Text Acquired hemophilia A (AHA) is a rare disorder with an incidence of approximately 1 per million/year with a high mortality rate of more than 20%. The disease occurs due to autoantibodies against coagulation factor VIII (FVIII) which neutralize its procoagulant function and result in severe, often life-threatening bleeding. The antibodies arise in individuals with no prior history of hemophilia A. AHA may be associated with pregnancy, autoimmune diseases, malignancy, infections or medication and occurs most commonly in the elderly. Approximately 50% of the patients remain idiopathic with no known underlying pathological condition. Clinical manifestations include spontaneous hemorrhages into the skin, muscles or soft tissues or excessive bleeding during surgery. Hemarthrosis which is the hallmark of congenital severe hemophilia A seldom occurs in AHA. The diagnosis of AHA is based on the isolated prolongation of activated partial thromboplastin time (APTT) which does not normalize after the addition of normal plasma along with reduced FVIII levels. The treatment involves two aspects-eradication of antibodies and maintaining effective hemostasis during a bleeding episode. The protocols for eradication of antibodies include immunoadsorption, immunosuppression or immune tolerance induction (ITI). The treatment of acute bleeding episodes involves use of different bypassing agents like recombinant activated factor VIIa (rFVIIa, NovoSeven®) and activated prothrombin complex concentrate (aPCC, (FEIBA®) in case of patients with high titer inhibitors or with antifibrinolytics,1-deamino-8-D-arginine vasopressin (DDAVP) or FVIII concentrates in low titer inhibitor patients. The anti CD20 monoclonal antibody, rituximab, has shown very good results either singly or in combination with immunosuppressive regimens in patients who do not respond to standard immunosuppressors. The present review summarizes the diagnostic, aetiological, clinical and treatment aspects of AHA focusing on the recent advances in this area.

Copyright © 2010 Elsevier B.V. All rights reserved.
PMID 21115138  Autoimmun Rev. 2011 Apr;10(6):311-6. doi: 10.1016/j.aut・・・
著者: L Rochanda, G J Del Zoppo, D I Feinstein, H A Liebman
雑誌名: Haemophilia. 2012 Jan;18(1):102-7. doi: 10.1111/j.1365-2516.2011.02553.x. Epub 2011 Jun 27.
Abstract/Text Bleeding disorders secondary to acquired non-inhibitory antibodies directed against vitamin K-dependent coagulation proteins are rare. In this report, the authors describe a patient with a low grade lymphoma who presented with a fatal acquired bleeding manifestation and abnormal hemostatic studies resulting from deficiencies in both prothrombin and factor X. Patient plasma samples were collected and studied for the presence of an acquired inhibitor. Levels of plasma coagulation proteins were measured using immunoassay. Patient anti-prothrombin immunoglobulin G was isolated and binding to prothrombin, prothrombin F1.2, factors IX and X was evaluated using immunoblots and competition immunoassay. Prolongation in the prothrombin time and activated partial thromboplastin time suggested a factor deficiency in the common pathway of coagulation. Functional and antigenic levels of both prothrombin and factor X were decreased. An IgG subtype-4 antibody was isolated from patient plasma using affinity chromatography on prothrombin-sepharose. This antibody was found to bind to a common metal-ion-dependent conformational epitope found on the γ-carboxyglutamic acid (Gla) domain of prothrombin, factor X and factor IX. This report represents the first description of an acquired bleeding disorder resulting from a unique cross-reactive auto-antibody against a common metal-ion-dependent antigenic structure on the Gla-domain of the vitamin K-dependent proteins.

© 2011 Blackwell Publishing Ltd.
PMID 21707870  Haemophilia. 2012 Jan;18(1):102-7. doi: 10.1111/j.1365-・・・
著者: Julio Delgado, Victor Jimenez-Yuste, Fernando Hernandez-Navarro, Ana Villar
雑誌名: Br J Haematol. 2003 Apr;121(1):21-35.
Abstract/Text
PMID 12670328  Br J Haematol. 2003 Apr;121(1):21-35.
著者: Pier Mannuccio Mannucci, Flora Peyvandi
雑誌名: Haematologica. 2009 Apr;94(4):459-61. doi: 10.3324/haematol.2009.005777.
Abstract/Text
PMID 19336750  Haematologica. 2009 Apr;94(4):459-61. doi: 10.3324/haem・・・
著者: S Sallah
雑誌名: Haemophilia. 2004 Mar;10(2):169-73.
Abstract/Text Haemorrhagic manifestations in patients with acquired haemophilia can be fatal if not recognized and treated appropriately. A retrospective analysis of the efficacy of factor eight inhibitor bypassing activity (FEIBA) in patients with acquired haemophilia treated in three medical centres in the past 10 years was conducted. The median inhibitor titre at treatment was 128 Bethesda Units (BU) in patients with severe and 34 BU in patients with moderate bleeding; P = 0.001. The majority of patients received FEIBA at a dose of 75 u kg-1 every 8-12 h. The number of FEIBA doses administered was higher in patients with severe compared with moderate haemorrhage, 10 vs. 6 doses per bleeding episode; P = 0.001. Complete response (CR) was achieved in 76% of severe and 100% of moderate bleeding episodes with a total CR of 86%. When compared with patients with human inhibitor titre <50 BU, those with titre >51 BU at treatment had lower median porcine titre, 1 vs. 9.5 BU; P < 0.05, fewer doses of FEIBA, 6 vs. 8.5 doses; P < 0.05, and shorter time to CR, 29 vs. 42 h; P < 0.05. Patients exposed to factor VIII concentrates prior to FEIBA had significantly higher maximum recorded human inhibitor titre compared with patients without such exposure, 273 vs. 38 BU; P = 0.0001. Treatment with FEIBA was very well tolerated and with very few side effects. This study provides evidence that FEIBA is an effective agent in acquired haemophilia and suitable for all types of patients regardless of severity of haemorrhage, underlying disease or inhibitor titre.

PMID 14962206  Haemophilia. 2004 Mar;10(2):169-73.
著者: M J Sumner, B D Geldziler, M Pedersen, S Seremetis
雑誌名: Haemophilia. 2007 Sep;13(5):451-61. doi: 10.1111/j.1365-2516.2007.01474.x.
Abstract/Text Acquired haemophilia is a rare bleeding disorder usually caused by the spontaneous formation of inhibitory antibodies to coagulation FVIII. The disease occurs most commonly in the elderly, and although acquired haemophilia may be associated with a variety of underlying conditions, up to 50% of reported cases are idiopathic. Treatment options have traditionally involved human FVIII or FIX replacement therapy (if the inhibitor titre allows), porcine FVIII or the use of activated pro-thrombin complex concentrates. Recombinant activated coagulation FVII (rFVIIa) was available on an emergency and compassionate use basis from 1988 to 1999 at sites in Europe and North America. It has been registered in Europe for use in treating acquired haemophilia since 1996 and has recently been licensed for this indication in the United States. By directly activating FX on the surface of activated platelets at the site of injury (thereby bypassing FVIII and FIX), rFVIIa can circumvent the actions of inhibitory antibodies present in acquired haemophilia patients. This paper provides an overview of experiences with rFVIIa for the treatment of acquired haemophilia from the NovoSeven compassionate and emergency use programmes (1989-1999), the Hemophilia and Thrombosis Research Society Registry, and independent published reports from January 1999 to September 2005. rFVIIa has been reported to provide safe and effective haemostasis as a first line therapy in patients of all ages for a variety of surgical and non-surgical bleeding situations.

PMID 17880429  Haemophilia. 2007 Sep;13(5):451-61. doi: 10.1111/j.1365・・・
著者: C R Hay, J N Lozier, C A Lee, M Lafan, H Tradati, E Santagostino, N Ciavarella, M Schiavoni, H Fukui, A Yoshioka
雑誌名: Semin Hematol. 1994 Apr;31(2 Suppl 4):20-5.
Abstract/Text
PMID 7939768  Semin Hematol. 1994 Apr;31(2 Suppl 4):20-5.
著者: Heike Zeitler, Gudrun Ulrich-Merzenich, Lothar Hess, Eligius Konsek, Christoph Unkrig, Peter Walger, Hans Vetter, Hans-Hermann Brackmann
雑誌名: Blood. 2005 Mar 15;105(6):2287-93. doi: 10.1182/blood-2004-05-1811. Epub 2004 Nov 12.
Abstract/Text Acquired hemophilia (AH) is an extremely rare condition in which autoantibodies (inhibitors) against clotting factor VIII induce acute and life-threatening hemorrhagic diathesis because of abnormal blood clotting. The mortality rate of AH is as high as 16%, and current treatment options are associated with adverse side effects. We investigated a therapeutic approach for AH called the modified Bonn-Malmo Protocol (MBMP). The aims of MBMP include suppression of bleeding, permanent elimination of inhibitors, and development of immune tolerance, thereby avoiding long-term reliance on coagulation products. The protocol included immunoadsorption for inhibitor elimination, factor VIII substitution, intravenous immunoglobulin, and immunosuppression. Thirty-five high-titer patients with critical bleeding who underwent MBMP were evaluated. Bleeding was rapidly controlled during 1 or 2 apheresis sessions, and no subsequent bleeding episodes occurred. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% confidence interval [95% CI], 2-4 days), factor substitution was stopped within a median of 12 days (95% CI, 11-17 days), and treatment was completed within a median of 14 days (95% CI, 12-17 days). Long-term follow-up (7 months-7 years) showed an overall response rate of 88% for complete remission (CR). When cancer patients were excluded, the CR rate was 97%.

PMID 15542586  Blood. 2005 Mar 15;105(6):2287-93. doi: 10.1182/blood-2・・・
著者: S Schulman
雑誌名: Haemophilia. 1998 Jul;4(4):564-7.
Abstract/Text Continuous infusion with coagulation factor concentrates has only been widely adopted during the last decade and with recombinant activated factor VII (rFVIIa) only during the last 2 years. Still the accumulated number of days on continuous infusion with this product amounts by now to more than one year, 35 patients and 26 surgical procedures. The experience is reviewed here and compared with data from the conventional bolus dose regimen.

PMID 9873795  Haemophilia. 1998 Jul;4(4):564-7.
著者: E Zanon, F Martinelli, C Bacci, P Zerbinati, A Girolami
雑誌名: Haemophilia. 2000 Sep;6(5):533-6.
Abstract/Text We found no case-control studies on dental extraction in haemophilia patients in the literature even though the use of antifibrinolytic agents following a single infusion of factor VIII or IX has been accompanied by a lower number of bleeding complications in dental extractions. In this study we verified the incidence of bleeding complications after dental extraction in a group of 77 haemophilia patients. One hundred and eighty-four male patients requiring dental extraction represented the control group. All haemophilia patients received 20 mg kg-1 of tranexamic acid and a single infusion of factor VIII or IX to achieve a peak level about 30% of factor VIII or IX in vivo prior to dental extraction. Forty-five of 98 (45.9%) dental extractions in haemophilia patients and 110 of 239 (46%) dental extractions in the control group were surgical ones. We registered two bleeding complications in the group of haemophilia patients (one late bleeding and one haematoma in the site of the anaesthetic injection) and one (a late bleeding) in the control group. The difference of bleeding complications in the two groups of patients were not statistically significant (P=0.2; OR 0.2; CI 0.01-2.22). The protocol proposed in this study, characterized by the feasibility and the number of haemorrhagic complications not different from normal population, make dental extractions in haemophilia patients possible on an out-patient basis with a cost reduction for the community and minor discomfort for the patients.

PMID 11012698  Haemophilia. 2000 Sep;6(5):533-6.
著者: B de la Fuente, S Panek, L W Hoyer
雑誌名: Br J Haematol. 1985 Jan;59(1):127-31.
Abstract/Text DDAVP (1-deamino 8 D-arginine vasopressin) was administered on two occasions to a patient with an acquired factor VIII inhibitor. Because the patient's autoantibody was low titre (1.8 Bethesda units) and had type II kinetic properties, it was expected that endogenous factor VIII/VWF released by DDAVP would be inactivated at a slow enough rate to permit satisfactory haemostasis during dental procedures. In both instances there was a 7-9-fold increase in factor VIII above the baseline level (13 units/dl), and factor VIII activity remained above 35 units/dl for 5 h after the infusion. The inhibitor could not be detected in his plasma during this period and the activated PTT was shortened into the normal range. Our experience with this patient suggests that DDAVP has a role in the management of some patients with low titre autoantibodies that inactivate factor VIII.

PMID 3918556  Br J Haematol. 1985 Jan;59(1):127-31.
著者: M Muhm, N Grois, P Kier, A Stümpflen, P Kyrle, I Pabinger, P Bettelheim, W Hinterberger, K Lechner
雑誌名: Haemostasis. 1990;20(1):15-20.
Abstract/Text 1-Deamino-8-D-arginine vasopressin (DDAVP) was administered to 3 patients with spontaneous factor VIII inhibitors. In 2 patients with baseline factor VIII levels above 1%, a marked increase of factor VIII activity after DDAVP infusion could be observed. No rise of factor VIII activity after DDAVP was seen in the 3rd patient with a baseline factor VIII level of less than 1%. Daily infusion of DDAVP resulted in a reduction of the efficacy, but the full effect could be retained when DDAVP was given at 48-hour intervals. The effect of DDAVP infusion on factor VIII levels in the 2 responding patients was superior to the treatment with 30 U/kg factor VIII concentrate and approximately equivalent to infusion of 45 U/kg factor VIII concentrate. DDAVP may be a useful and less expensive treatment for patients with acquired factor VIII inhibitors and a baseline factor VIII level of more than 1%.

PMID 2108912  Haemostasis. 1990;20(1):15-20.
著者: D Green, A W Rademaker, E Briët
雑誌名: Thromb Haemost. 1993 Nov 15;70(5):753-7.
Abstract/Text Thirty-one non-hemophilic patients with acquired antibodies to factor VIII were entered into a prospective, randomized, multi-institutional trial to determine the safety and efficacy of prednisone (P), cyclophosphamide (C), or the combination in the treatment of this disorder. Patients were eligible if they had antibody demonstrated by the Bethesda assay, had not received these agents previously, and gave informed consent. All patients were treated initially with P, 1 mg/kg, for 3 weeks. If the antibody persisted and there was no rise in factor VIII activity, patients were randomized to either continue P for an additional 6 weeks; taper P and begin C, 2 mg per kg; or continue P and add C. Antibody disappeared in 10 during the initial P therapy, and in three of four others randomized to continue on P; one patient was discontinued because of an herpetic infection. Antibody disappeared in three of six patients treated with C alone, and five of ten given C and P. The titer of antibody was significantly lower in responders than in non-responders (p = 0.003), but seven patients with titers of more than five Bethesda units had complete remissions. There was no difference in antibody titers between those responding to P and those responding to C. We conclude that all patients with acquired antibodies to factor VIII should receive initial management with P, and that C is effective as second-line therapy for many of those who are steroid-resistant.

PMID 8128430  Thromb Haemost. 1993 Nov 15;70(5):753-7.
著者: Eric C-Y Lian, Mary Jo Villar, Lionel I Noy, Zoneddy Ruiz-Dayao
雑誌名: Am J Hematol. 2002 Apr;69(4):294-5.
Abstract/Text Life-threatening bleeding can occur in non-hemophiliacs with factor VIII inhibitor and is difficult to control. Various methods have been used to suppress the inhibitor. Since 1993 we treated 6 non-hemophilic patients with factor VIII inhibitor with cyclophosphamide, vincristine, and prednisone (CVP) every 3-4 weeks. Five had complete response with disappearance of factor VIII inhibitor and normalization of factor VIII after 1 to 7 cycles of CVP. One patient did not respond after 4 cycles of CVP; mitoxantrone was added to additional two cycles of CVP, and the inhibitor disappeared.

Copyright 2002 Wiley-Liss, Inc.
PMID 11921026  Am J Hematol. 2002 Apr;69(4):294-5.
著者: A G Brox, H Laryea, M Pelletier
雑誌名: Am J Hematol. 1998 Jan;57(1):87-8.
Abstract/Text The treatment of Factor VIII inhibitors remains controversial and no standard therapy exists. We describe in this report two consecutive patients with this inhibitor that responded to cyclosporin. Clinical improvement of the bleeding diathesis, a return to normal of the PTT, a decrease in the level of the inhibitor, and a return to normal of the factor VIII level followed use of this drug. We believe that cyclosporin is effective in the treatment of factor VIII inhibitors and deserves further investigation.

PMID 9423825  Am J Hematol. 1998 Jan;57(1):87-8.
著者: M Petrovic, E Derom, G Baele
雑誌名: Haematologica. 2000 Aug;85(8):895-6.
Abstract/Text
PMID 10942956  Haematologica. 2000 Aug;85(8):895-6.
著者: Roberto Stasi, Maurizio Brunetti, Elisa Stipa, Sergio Amadori
雑誌名: Blood. 2004 Jun 15;103(12):4424-8. doi: 10.1182/blood-2003-11-4075. Epub 2004 Mar 2.
Abstract/Text The activity and safety profile of selective B-cell depletion with rituximab, an anti-CD20 monoclonal antibody, were evaluated in 10 patients with acquired hemophilia. Rituximab was given intravenously at the dose of 375 mg/m(2) once weekly for 4 consecutive weeks. Infusion-related side effects were observed in 3 patients but were of mild intensity and did not require discontinuation of treatment. Eight patients with Factor VIII (FVIII) inhibitor titers between 4 and 96 Bethesda units per milliliter (BU/mL) achieved a complete remission, which was defined as a return to normal FVIII activity and undetectable FVIII inhibitor titers. Two more patients with inhibitor levels greater than 100 BU/mL experienced only a partial transient decrease of the inhibitor after rituximab alone, but they achieved a complete response after being challenged with a combination of rituximab plus pulse intravenous cyclophosphamide. With a median follow-up of 28.5 months (range, 12-41 months), 3 patients have thus far relapsed. Retreatment with the monoclonal antibody at the same dose and schedule resulted in a new sustained response in all these patients. In conclusion, rituximab appears an effective and well-tolerated treatment for patients with acquired hemophilia and low inhibitor titers. A reinforcement of therapy with other agents seems to be required to achieve a full and durable response in those patients with high inhibitor levels.

PMID 14996701  Blood. 2004 Jun 15;103(12):4424-8. doi: 10.1182/blood-2・・・
著者: Angela Huth-Kühne, Francesco Baudo, Peter Collins, Jørgen Ingerslev, Craig M Kessler, Hervé Lévesque, Maria Eva Mingot Castellano, Midori Shima, Jean St-Louis
雑誌名: Haematologica. 2009 Apr;94(4):566-75. doi: 10.3324/haematol.2008.001743.
Abstract/Text Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies directed against circulating coagulation factor (F) VIII. Typically, patients with no prior history of a bleeding disorder present with spontaneous bleeding and an isolated prolonged aPTT. AHA may, however, present without any bleeding symptoms, therefore an isolated prolonged aPTT should always be investigated further irrespective of the clinical findings. Control of acute bleeding is the first priority, and we recommend first-line therapy with bypassing agents such as recombinant activated FVII or activated prothrombin complex concentrate. Once the diagnosis has been achieved, immediate autoantibody eradication to reduce subsequent bleeding risk should be performed. We recommend initial treatment with corticosteroids or combination therapy with corticosteroids and cyclophosphamide and suggest second-line therapy with rituximab if first-line therapy fails or is contraindicated. In contrast to congenital hemophilia, no comparative studies exist to support treatment recommendations for patients with AHA, therefore treatment guidance must rely on the expertise and clinical experience of specialists in the field. The aim of this document is to provide a set of international practice guidelines based on our collective clinical experience in treating patients with AHA and contribute to improved care for this patient group.

PMID 19336751  Haematologica. 2009 Apr;94(4):566-75. doi: 10.3324/haem・・・
著者: Peter W Collins, Sybil Hirsch, Trevor P Baglin, Gerard Dolan, John Hanley, Michael Makris, David M Keeling, Ri Liesner, Simon A Brown, Charles R M Hay, UK Haemophilia Centre Doctors' Organisation
雑誌名: Blood. 2007 Mar 1;109(5):1870-7. doi: 10.1182/blood-2006-06-029850. Epub 2006 Oct 17.
Abstract/Text Acquired hemophilia A is a severe bleeding disorder caused by an autoantibody to factor VIII. Previous reports have focused on referral center patients and it is unclear whether these findings are generally applicable. To improve understanding of the disease, a 2-year observational study was established to identify and characterize the presenting features and outcome of all patients with acquired hemophilia A in the United Kingdom. This allowed a consecutive cohort of patients, unbiased by referral or reporting practice, to be studied. A total of 172 patients with a median age of 78 years were identified, an incidence of 1.48/million/y. The cohort was significantly older than previously reported series, but bleeding manifestations and underlying diseases were similar. Bleeding was the cause of death in 9% of the cohort and remained a risk until the inhibitor had been eradicated. There was no difference in inhibitor eradication or mortality between patients treated with steroids alone and a combination of steroids and cytotoxic agents. Relapse of the inhibitor was observed in 20% of the patients who had attained first complete remission. The data provide the most complete description of acquired hemophilia A available and are applicable to patients presenting to all centers.

PMID 17047148  Blood. 2007 Mar 1;109(5):1870-7. doi: 10.1182/blood-200・・・

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