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1 2017; 28 3 : 自己免疫性出血病 FXIII/13 診療ガイド Guidance on Diagnosis and Management of Autoimmune Hemorrhaphilia FXIII/13(AHFXIII/13) FXIII/
2 394 Contents I CQ 398 II COI II 402 III AHFXIII/ Q & A III 406 IV Q & A IV Q & A IV Q & A IV Q & A IV V 417 Q & A V FXIII/
3 395 I 100 CQ 1 1 AHFXIII/13 FXIII FXIII FXIII 2 AHFXIII/13 FXIII FXIII PT APTT 3 AHFXIII/ AHFXIII/13 5 AHFXIII/13 6 AHFXIII/13 FXIII/13 III FXIII 1-C 3 FXIII 1-D FXIII 4 FXIII 2-D 5 2-D 6 FXIII FXIII D IV D 8 1-D 28 3
4 VII 1-D 10 IV A mg/kg/ 1-C 13 1-C 1000 mg/ C 1 2 mg/kg mg/ 2-C 3 5 mg/kg/ mg/ 2-C 14 2-C 15 FXIII FXIII 16 1 mg/kg/ 4 6 FXIII FXIII 1-A 17 1-A IV FXIII 30
5
6 FXIII 1-C V CQ Q1 AHFXIII/13 Q2 AHFXIII/13 Q3 AHFXIII/13 Q4 AHFXIII/13 Q5 AHFXIII/13 Q6 AHFXIII/13 Q7 AHFXIII/13 Q8 FXIII Q9 FXIII Q10 FXIII Q11 FFP PC Q12 Q13 Q14 Q15 VII/7 FVII Q16 Q17 Q18 PSL Q19 Q20 Q21 Q22 Q23 Q24 Q25 Q26 Q27 Q28
7 399 II XIII/13 FXIII FXIII FXIII/13 Autoimmune Hemorrhaphilia FXIII/13 1 AHFXIII/13 1 FXIII FXIII FXIII-A FXIII-A FXIII-B FXIII-B A 2 B 2 FXIII AHFXIII/13 2, 3 AHFXIII/13 AHFXIII/13 4 FXIII/13 5 AHFXIII/13 FXIII/13 AHFXIII/ AHFXIII/ Evidence-Based Medicine EBM 28 3
8 400 1 A 1 Minds Minds B Pubmed database (((((factor XIII) OR fibrin stabilizing factor) OR fibrin stabilising factor)) AND ((((((inhibitor) OR inhibitors) OR antibody) OR antibodies) OR autoantibody) OR autoantibodies)) NOT (((hereditary) OR inherited) OR congenital) 958 C XIII or or and or or 147 D ISTH ASH E Pubmed database (((((factor XIII) OR fibrin stabilizing factor) OR fibrin stabilising factor) OR plasma transglutaminase)) AND ((((((antibody) OR antibodies) OR autoantibody) OR autoantibodies) OR inhibitor) OR inhibitors) ((((((factor XIII) OR fibrin stabilizing factor) OR fibrin stabilising factor) OR plasma transglutaminase)) AND ((((((antibody) OR antibodies) OR autoantibody) OR autoantibodies) OR inhibitor) OR inhibitors)) NOT (((congenital) OR hereditary) OR inherited) F 28 5 AHXIII/ Minds
9 A B RCT C D F XIII/ F XIII/
10 AHFXIII/ XIII COI COI 9 AHFXIII/13 II 1 Ichinose A; Japanese Collaborative Research Group (JCRG) on AH13 Hemorrhagic Acquired Coagulopathies: Inhibitors of Factor XIII/13 in older patients. Semin Thromb Hemost 40: , Lorand L. Acquired Inhibitors of Fibrin Stabilization: A Class of Hemorrhagic Disorders of Diverse Origins. In: Green D ed. Anticoagulants Physiologic, Pathologic, and Pharmacologic. CRC Press , Egbring R, Kröniger A, Seitz R: Erworbene inhibitoren gegen Faktor XIII. Hämostaseologie 16: , XIII Kenkoukyoku/ pdf FXIII/13 FXIII/13 26: , 2015.
11 403 III AHFXIII/13 Q1 AHFXIII/13 A1 AHFXIII/13 FXIII FXIII FXIII Q2 AHFXIII/13 A2 FXIII FXIII PT APTT FXIII 1 Q3 AHFXIII/13 A , 3 4 Q4 AHFXIII/13 A4 FXIII 2 1, 4 Q5 AHFXIII/13 A5 AHFXIII/13 FXIII-A FXIII-B 4,
12 404 1, 4 2 AHFXIII/13 1 SLE RA MGUS 5INH Bleeding Assessment Tools ver , 8 3 9, 10 3 Q6 AHFXIII/13 A6 FXIII/13 FXIII/13 1 AHFXIII/13 4 FXIII FXIII FXIII FXIII FXIII FXIII FXIII FXIII AHFXIII/13 FXIII 5 11
13 405 図3 表3 出血評価票 AHFXIII/13 の重症度分類 2014 Schulman S et al., ; Baudo F et al., の重症出血の定義を改変 1 重症出血 1 致命的な出血 2 重要部位 重要臓器の出血 例えば 頭蓋内 脊髄内 眼球内 気管内 胸腔内 腹腔内 後腹膜 関節内 心囊内 コンパートメント症候群を伴う筋肉内出血など 3 Hb 値 8 g/dl 以下の貧血 あるいは 2 g/dl 以上の急速な Hb 値低下をもたらす出血 4 24 時間以内に 2 単位以上の赤血球輸血を必要とする出血 2 軽症出血 上記以外の全ての出血 日本語版出血評価票 JBAT も参考にすることを推奨 多発性および有痛性の出血は 重症度に準じて止血治療を考慮すべき 文献 1 の表を一部修正 第 28 巻 第 3 号
14 406 4 FXIII/13 AHFXIII/ definite probable possible AHFXIII/ XIII FXIII FXIII 50 probable FXIII 37 2 definite FXIII ELISA XIII/13 FXIII 2 FXIII FXIII/13 Autoimmune Hemorrhaphilia FXIII/13; AHFXIII/13 5 FXIII 1 DIC III 1 FXIII/13 FXIII/13 26: , Ichinose A, Souri M; Japanese collaborative research group on Acquired haemorrha-philia due to factor XIII deficiency : As many as 12 cases with haemorrhagic acquired factor XIII deficiency due to its inhibitors were recently found in Japan. Thromb Haemost 105: , Ichinose A, Osaki T, Souri M; Japanese Collaborative Research Group (JCRG) on AH13 (supported by the Japanese Ministry of Health, Labor, and Welfare): Clinical features of 32 new Japanese cases with autoimmune haemorrha-philia due to anti-factor XIII antibodies. Haemophilia 21: , Ichinose A; Japanese Collaborative Research Group on AH13: Autoimmune acquired factor XIII deficiency due to anti-factor XIII/13 antibodies: A summary of 93 patients. Blood Rev 31: 37 45, Souri M, Osaki T, Ichinose A: Anti-factor XIII A subunit (FXIII-A) autoantibodies block FXIII-A2 B2 assembly and steal FXIII-A from native FXIII-A2 B2. J Thromb Haemost 13: , Rodeghiero F, Tosetto A, Abshire T, Arnold DM, Coller B, James P, Neunert C, Lillicrap D; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group: ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 8: , Ichinose A; Japanese Collaborative Research Group (JCRG) on AH13 Hemorrhagic Acquired Coagulopathies: Inhibitors of Factor XIII/13 in older patients. Semin Thromb Hemost 40: , Factor XIII 25: , Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis: Definition of major bleeding in clinical investigations of antihemostatic medicinal products in
15 407 non-surgical patients. J Thromb Haemost 3: , Baudo F, Collins P, Huth-Kühne A, Lévesque H, Marco P, Nemes L, Pellegrini F, Tengborn L, Knoebl P; EACH2 registry contributors: Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood 120: 39 46, Kohler HP, Ichinose A, Seitz R, Ariens RAS, Muszbek L; Factor XIII and Fibrinogen SSC Subcommittee of the ISTH: Diagnosis and classification of factor XIII deficiencies. J Thromb Haemost 9: , Lewis JH, Szeto IL, Ellis LD, Bayer WL: An acquired inhibitor to coagulation factor 13. Johns Hopkins Med J 120: , Lorand L, Jacobsen A, Bruner-Lorand J: A pathological inhibitor of fibrin cross-linking. J Clin Invest 47: , Otis PT, Feinstein DI, Rapaport SI, Patch MJ: An acquired inhibitor of fibrin stabilization associated with isoniazid therapy: clinical and biochemical observations. Blood 44: , Fear JD, Miloszewski KJ, Losowsky MS: An acquired inhibitor of factor XIII with a qualitative abnormality of fibrin cross-linking. Acta Haematol 71: , IV 1 Q7 AHFXIII/13 A7 1-A 1 1-A 1-A 1-A 1 1 FXIII FXIII FXIII FXIII 70 6 FXIII 2 3 FXIII Hb Bleeding Assessment Tool ver JBAT 3 BS 28 3
16 408 4 FXIII 2 5 FFP PC IV 1 1 Factor XIII 25: , Kojima M, Ichinose A, Souri M, Osaki T, Kawai H, Amaki J, Numata H, Miyamoto M, Ogiya D, Tsuboi K, Ogawa Y, Ozawa S, Ando K: Successful bypass surgery for esophageal carcinoma under adequate factor XIII/13 replacement therapy in a case of intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies. Int J Hematol 103: , Q8 FXIII A8 1-C 1, 2 FXIII FXIII 25 /kg 50 /kg FXIII 6 FXIII 6 3 FXIII P 240 ml FXIII 4 ml 4 FXIII 2500 FXIII A 2,500 IU 3.2 ml 5 Q9 FXIII A9 FXIII 1-D FXIII 1, 3 FXIII 2 FXIII- B FXIII FXIII-B FXIII- A 2 B 2 FXIII FXIII
17 409 Q10 FXIII A10 FXIII 2-D FXIII FXIII 6 3 AHFXIII/13 FXIII FXIII 1 Q11 FFP PC A11 2-D FXIII FFP PC 2-D FFP FXIII FFP FXIII FFP FXIII FFP FXIII FXIII 3 FFP PC 6 FXIII FFP PT-INR 2.0 APTT 2 PC 5 /μl Q12 A12 FXIII 2-D FXIII 1, 7 FXIII IV 2 1 XIII/13 56: , FXIII/13 FXIII/13 26: ,
18 410 3 Factor XIII 25: , P 5 XIII DIC DIC 20: , Kojima M, Ichinose A, Souri M, Osaki T, Kawai H, Amaki J, Numata H, Miyamoto M, Ogiya D, Tsuboi K, Ogawa Y, Ozawa S, Ando K: Successful bypass surgery for esophageal carcinoma under adequate factor XIII/13 replacement therapy in a case of intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies. Int J Hematol 103: , Q13 A13 2-D FXIII 1 2 α FXIII g 1 2 Q14 A14 1-D AHFXIII/13 Q15 VII/7 FVII A15 AHFXIII/13 1-D VIII/8 FVIII FVII FVII FVII IX/9 X/10 FVIII 3 AHFXIII/13 FXIII Q16 A16 1-A 3
19 411 4 IV DIC DIC 20: , A A 22: , Factor XIII 25: , Q17 A17 FXIII/13 1-A FXIII-A FXIII-B FXIII FXIII 2 FXIII 3, 4 5, 6 FXIII Q18 PSL A18 1-C 1-C PSL 1 mg/kg/ mg/kg/ mg/
20 412 PSL 8 PSL PSL PSL PSL 3 PSL 8 1, 7 PSL PSL A AHA ITP 9, 10 PSL 1 PSL PSL 9 1 ITP 80 PSL PSL PSL PSL A PSL Q19 A19 1-C PSL PSL PSL PSL 11 13
21 413 PSL 1 mg/kg/ 4 FXIII 14 Q20 A20 1-C CY 2-C IVCY 2-C 2-C SLE SLE IVCY 1-C CY 1 2 mg/kg/ mg/ IVCY bi-weekly IVCY mg/body monthly IVCY mg/m mg/kg/ mg/m C Y mg/kg CY 15, 16 IVCY ACR 17 bi-weekly IVCY monthly IVCY ng/ ml ng/ml
22 infusion reaction 19 B JC 19 1, A PSL+CY 9, 20, 21 CY 1 50 mg CY IVCY IVCY SLE ACR 17 bi-weekly IVCY monthly IVCY AHA International recommendation 20 Consensus recommendation 21 SLE Q21 A21 2-C FXIII FXIII FXIII L = kg 1/13 1 Ht/100
23 415 Q22 A22 FXIII FXIII 1-A FXIII FXIII 1-A II 2 I FXIII 3 FXIII FXIII FXIII 11 FXIII FXIII FXIII FXIII FXIII FXIII 4 1 FXIII FXIII I FXIII FXIII 2 Q23 A FXIII FXIII 1-A PSL 1 mg/kg/ 4 6 FXIII FXIII FXIII FXIII 2 I FXIII 3 II FXIII
24 416 PSL 1 PSL Q24 A24 FXIII FXIII 1-A PSL 4 FXIII FXIII PSL FXIII FXIII PSL mg/ I 7 2 FXIII PSL FXIII FXIII FXIII PSL IV 4 1 Ichinose A, Osaki T, Souri M; Japanese Collaborative Research Group (JCRG) on AH13 (supported by the Japanese Ministry of Health, Labor, and Welfare): Clinical features of 32 new Japanese cases with autoimmune haemorrha-philia due to anti-factor XIII antibodies. Haemophilia 21: , Factor XIII 25: , Lewis JH, Szeto IL, Ellis LD, Bayer WL: An acquired inhibitor to coagulation factor 13. Johns Hopkins Med J 120: , Lorand L, Jacobsen A, Bruner-Lorand J: A pathological inhibitor of fibrin cross-linking. J Clin Invest 47: , Otis PT, Feinstein DI, Rapaport SI, Patch MJ: An acquired inhibitor of fibrin stabilization associated with isoniazid therapy: clinical and biochemical observations. Blood 44: , Fear JD, Miloszewski KJ, Losowsky MS: An acquired inhibitor of factor XIII with a qualitative abnormality of fibrin cross-linking. Acta Haematol 71: , Ichinose A; Japanese Collaborative Research Group on AH13: Autoimmune acquired factor XIII deficiency due to anti-factor XIII/13 antibodies: A summary of 93 patients. Blood Rev 31: 37 45, mg 9 A A 22: , ITP : , Ogawa Y, Mihara M, Souri M, Yanagisawa K, Hayashi T, Kobayashi N, Shimizu H, Iriuchishima H, Ishizaki T, Handa H, Osaki T, Nojima Y, Ichinose A: Complete remission achieved by steroid pulse therapy following rituximab treatment in a case with autoimmune haemorrhaphilia due to anti-factor XIII antibodies. Thromb Haemost 112: , 2014.
25 Kotake T, Souri M, Takada K, Kosugi S, Nakata S, Ichinose A: Report of a patient with chronic intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies who died of hemorrhage after sustained clinical remission for 3 years. Int J Hematol 101: , Kojima M, Ichinose A, Souri M, Osaki T, Kawai H, Amaki J, Numata H, Miyamoto M, Ogiya D, Tsuboi K, Ogawa Y, Ozawa S, Ando K: Successful bypass surgery for esophageal carcinoma under adequate factor XIII/13 replacement therapy in a case of intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies. Int J Hematol 103: , XIII/13 56: , mg mg 17 Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM; American College of Rheumatology: American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 64: , mg/mL 20 Huth-Kühne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Lévesque H, Castellano ME, Shima M, St-Louis J: International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 94: , Collins P, Baudo F, Huth-Kühne A, Ingerslev J, Kessler CM, Castellano ME, Shima M, St-Louis J, Lévesque H: Consensus recommendations for the diagnosis and treatment of acquired hemophilia A. BMC Res Notes 3: , Franchini M, Lippi G: Acquired factor VIII inhibitors. Blood 112: , V Q25 A FXIII FXIII FXIII FXIII FXIII 3 FXIII ELISA AHFXIII/ AHA 8 1, FXIII 1 1 FXIII 28 3
26 FXIII FXIII Q26 A26 FXIII 1-A FXIII FXIII FXIII 30 8 Q27 A27 AHFXIII/ FXIII Q28 A28 FXIII 1-C FXIII
27 V 1 Factor XIII 25: , Kotake T, Souri M, Takada K, Kosugi S, Nakata S, Ichinose A: Report of a patient with chronic intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies who died of hemorrhage after sustained clinical remission for 3 years. Int J Hematol 101: , Souri M, Osaki T, Ichinose A: Anti-factor XIII A subunit (FXIII-A) autoantibodies block FXIII-A2 B2 assembly and steal FXIII-A from native FXIII-A2 B2. J Thromb Haemost 13: , Osaki T, Sugiyama D, Magari Y, Souri M, Ichinose A: Rapid immunochromatographic test for detection of anti-factor XIII A subunit antibodies can diagnose 90 % of cases with autoimmune haemorrhaphilia XIII/13. Thromb Haemost 113: , Kotake T, Souri M, Takada K, Kosugi S, Nakata S, Ichinose A: Report of a patient with chronic intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies who died of hemorrhage after sustained clinical remission for 3 years. Int J Hematol 101: , Huth-Kühne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Lévesque H, Castellano ME, Shima M, St-Louis J: International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 94: , Ishida F, Okubo K, Ito T, Okumura N, Souri M, Ichinose A: Spontaneous regression of the inhibitor against the coagulation factor XIII A subunit in acquired factor XIII deficiency. Thromb Haemost 104: , Peyvandi F, Palla R, Menegatti M, Siboni SM, Halimeh S, Faeser B, Pergantou H, Platokouki H, Giangrande P, Peerlinck K, Celkan T, Ozdemir N, Bidlingmaier C, Ingerslev J, Giansily-Blaizot M, Schved JF, Gilmore R, Gadisseur A, Benedik-Dolni ar M, Kitanovski L, Mikovic D, Musallam KM, Rosendaal FR; European Network of Rare Bleeding Disorders Group: Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 10: , Sugiyama H, Uesugi H, Suzuki S, Tanaka K, Souri M, Ichinose A: Aggressive fatal case of autoimmune hemorrhaphilia resulting from anti-factor XIII antibodies. Blood Coagul Fibrinolysis 24: 85 89, Ichinose A, Osaki T, Souri M; Japanese Collaborative Research Group (JCRG) on AH13 (supported by the Japanese Ministry of Health, Labor, and Welfare): Clinical features of 32 new Japanese cases with autoimmune haemorrha-philia due to anti-factor XIII antibodies. Haemophilia 21: , Kojima M, Ichinose A, Souri M, Osaki T, Kawai H, Amaki J, Numata H, Miyamoto M, Ogiya D, Tsuboi K, Ogawa Y, Ozawa S, Ando K: Successful bypass surgery for esophageal carcinoma under adequate factor XIII/13 replacement therapy in a case of intractable autoimmune hemorrhaphilia due to anti-factor XIII/13 antibodies. Int J Hematol 103: , Lim W, Moffat K, Hayward CP: Prophylactic and perioperative replacement therapy for acquired factor XIII deficiency. J Thromb Haemost 2: , Miesbach W: Rituximab in the treatment of factor XIII inhibitor possibly caused by Ciprofloxacin. Thromb Haemost 93: , Boehlen F, Casini A, Chizzolini C, Mansouri B, Kohler HP, Schroeder V, Reber G, de Moerloose P: Acquired factor XIII deficiency: a therapeutic challenge. Thromb Haemost 109: ,
28 420 1 FXIII AHFXIII/13 FXIII-A FXIII-B EBM PT APTT SLE RA INH JBAT ELISA FFP PC FVIII FVII PSL AHA factor XIII XIII/13 autoimmune hemorrhaphilia FXIII/13 FXIII/13 FXIII-A subunit FXIII-A FXIII-B subunit FXIII-B Evidence-Based Medicine prothrombin time activated partial thromboplastin time systemic lupus erythematosus rheumatoid arthritis isoniazid Japanese Bleeding Assessment Tools enzyme-linked immunosorbent assay fresh frozen plasma platelet concentrate factor VIII VIII/8 factor VII VII/7 prednisolone acquired hemophilia A A 2 FXIII FXIII FXIII PT APTT FXIII FXIII FXIII A B FXIII FXIII FXIII FXIII FXIII
DocHdl1OnPRS1tmpTarget
2015; 26 6 : 658-668 自己免疫性出血病 FXIII/13 診断ガイド Guidance on Diagnostic Criteria for Autoimmune Hemorrhaphilia FXIII/13(AHFXIII/13) FXIII/13 659 Contents 1 660 2 660 3 660 4 661 5 661 6 661 7 661 8 661 9 662
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診断 治療 技術講座 2018; 29 4 : 413-420 APTT 波形解析 APTT waveform Hideo WADA Key words: APTT, waveform, hemophilia, anticoagulant therapy 1978 1982 1982 1983 1985 NIH 1985 2000 / 2008 1 activated partial thromboplastin
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特集 : 自己抗体による出血 血栓 : 基礎と臨床の現状 2018; 29 3 : 273-280 後天性フォンヴィレブランド症候群 Acquired von Willebrand Syndrome (AvWS) Nobuaki SUZUKI 要約 :von Willebrand Factor VWF Acquired von Willebrand Syndrome AvWS 1968 SLE 50
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日本血栓止血学会サイトお役立ちリンク集 日本血栓止血学会サイトに掲載しているおすすめコンテンツのリンクをご紹介します 診療ガイドライン 研修医のお役立ち論文コンテンツ 用語集 本編は次ページより掲載しております
日本血栓止血学会サイトお役立ちリンク集 日本血栓止血学会サイトに掲載しているおすすめコンテンツのリンクをご紹介します 診療ガイドライン 研修医のお役立ち論文コンテンツ 用語集 本編は次ページより掲載しております トピックス 2016; 27 5 : 553-556 補体関連 TMA( 非定型 HUS) Complement-mediated TMA (atypical HUS) Masanori MATSUMOTO
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