Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

被引：252

作者：

Collins, Peter ^{[1
,123
]}

Baudo, Francesco ^{[2
,52
]}

Knoebl, Paul ^{[3
]}

Levesque, Herve ^{[4
]}

Nemes, Laszlo ^{[5
,6
]}

Pellegrini, Fabio ^{[7
]}

Marco, Pascual ^{[8
,110
]}

Tengborn, Lilian ^{[9
,119
]}

Huth-Kuehne, Angela ^{[10
,11
]}

Aspoeck, Gerold ^{[12
]}

Heistinger, Max ^{[13
]}

Knobl, Paul ^{[14
]}

Makipernaa, Anne ^{[15
]}

Andre, Helene ^{[16
]}

Aouba, A. ^{[17
]}

Bellucci, Sylvia ^{[18
]}

Beurrier, Philippe ^{[19
]}

Borg, Jeanne Yvonne ^{[20
]}

Darnige, Luc ^{[21
]}

Devignes, Jean ^{[22
]}

d'Oiron, Roseline ^{[23
]}

Gautier, Philippe ^{[24
]}

Gay, Valerie ^{[25
]}

Girault, Stephane ^{[26
]}

Gruel, Yves ^{[27
]}

Guerin, Viviane ^{[28
]}

Hezard, Nathalie ^{[29
]}

Khellaf, Mehdi ^{[30
]}

Koenig, Martial ^{[31
]}

Lifermann, Francois ^{[32
]}

Marlu, Raphael ^{[33
]}

Ninet, J. ^{[34
]}

Peynet, Jocelyne ^{[35
]}

Quemeneur, Thomas ^{[36
]}

Rothschild, Chantal ^{[37
]}

Schleinitz, Nicolas ^{[38
]}

Sigaud, Marianne ^{[39
]}

Trouillier, Sebastien ^{[40
]}

Voisin, Sophie ^{[41
]}

Giebl, Andreas ^{[42
]}

Holstein, Katharina ^{[43
]}

Huth-Kuhne, Angela ^{[44
]}

Loreth, Ralph M. ^{[45
]}

Steigerwald, Udo ^{[46
]}

Tiede, Andreas ^{[47
]}

Theodossiades, George ^{[48
]}

Radvanyi, Gaspar ^{[49
]}

Schlammadinger, Agota ^{[50
]}

Barillari, Giovanni ^{[51
]}

Pasca, Samantha ^{[51
]}

机构：

[1] Cardiff Univ, Sch Med, Univ Wales Hosp, Arthur Bloom Haemophilia Ctr, Cardiff CF14 4XN, S Glam, Wales

[2] Osped Niguarda Ca Granda, Ctr Emofilia, Milan, Italy

[3] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostasis, Vienna, Austria

[4] Rouen Univ Hosp, Dept Internal Med, Rouen, France

[5] Natl Hemophilia Ctr, Budapest, Hungary

[6] State Hlth Ctr, Hemostasis Dept, Budapest, Hungary

[7] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Biostat Unit, I-66030 Santa Maria Imbaro, Italy

[8] Hosp Gen Univ, Serv Hematol, Unidad Hemostasia & Trombosis, Alicante, Spain

[9] Skane Univ Hosp, Clin Coagulat Res Unit, Malmo, Sweden

[10] Stiftung Rehabil Kurpfalzkrankenhaus Heidelberg, Heidelberg, Germany

[11] Hemophilia Ctr, Heidelberg, Germany

[12] Inst Med & Chem Labordiagnost 2, Klinikum Wels Grieskirchen, A-4600 Wels, Austria

[13] LKH Klagenfurt, Med Abt 1, A-9020 Klagenfurt, Austria

[14] Med Univ Wien, Klin Innere Med 1, Abt Hamatol & Hamostaseol, A-1090 Vienna, Austria

[15] Helsinki Univ Hosp, Dept Haematol Coagulation Disorders, SF-00029 Helsinki, Finland

[16] Hop Europeen Georges Pompidou, Serv Med Interne, F-75015 Paris, France

[17] Hop Necker Enfants Malad, Dept Haematol, F-75015 Paris, France

[18] Hop Lariboisiere, Serv Hematol Biol, F-75015 Paris, France

[19] CHU Angers, Ctr Traitement Hemophilie, F-49933 Angers, France

[20] Rouen Univ Hosp, Haematol Lab, F-76031 Rouen, France

[21] Hop Europeen Georges Pompidou, Serv Hematol Biol, F-75908 Paris, France

[22] Ctr Hosp Univ Nancy, Serv Hematol Biol Hemostase, F-545111 Nancy, France

[23] APHP Bicetre Univ Hosp, Hemophilia Ctr, F-94270 Le Kremlin Bicetre, France

[24] CHU, Lab Hematol, CRTH, F-14033 Caen, France

[25] Hop Chambrey, Serv Hemovigilance, Chambery, France

[26] CHU Dupuytren, F-87000 Limoges, France

[27] Univ Hosp Tours, F-37044 Tours, France

[28] Hop Pellegrin, Lab Hematol, Bordeaux, France

[29] CHU Robert Debre, Lab Hematol, F-51092 Reims, France

[30] CHU Henri Mondor, Serv Med Interne, F-94010 Creteil, France

[31] CHU St Etienne, Med Interne, F-42055 St Etienne, France

[32] Ctr Hosp Gen, Dept Med Interne, F-40100 Dax, France

[33] CHU Grenoble, Lab Hematol, F-38700 La Tronche, France

[34] Hop Edouard Herriot, Serv Med Interne, F-69437 Lyon, France

[35] Ctr Hosp de Versailles, Ctr Traitement Hemophilie, F-78157 Le Chesnay, France

[36] Ctr Hosp, SCE Med Interne & Nephrol, F-59322 Valenciennes, France

[37] Hop Necker Enfants Malad, Hemophilia Ctr, F-75015 Paris, France

[38] CHU Conception, Serv Med Interne, F-13385 Marseille, France

[39] CHU Nantes, Ctr Traitement Hemophilie, Lab Hematol, F-44 Nantes, France

[40] CHU Gabriel Montpied, Serv Med Interne, F-63000 Clermont Ferrand, France

[41] Hop Rangueil, Lab Hematol, F-31059 Toulouse 9, France

[42] Klinikum Univ Munchen, Klinik fur Anastheseol, D-81366 Munich, Germany

[43] Univ Krankenhaus Hamburg Eppendorf, D-20246 Hamburg, Germany

[44] SRH Kurpfalzkrankenhaus Heidelberg, Innere Medizin Hamophiliezentrum, D-69123 Heidelberg, Germany

[45] Westpfalz-Klinikum GmbH, Medizinische Klinik 3 Klinische Hamostaseol, D-67655 Kaiserslautern, Germany

[46] Univ Klinikum Wurzburg, Zentrallabor Gerinnungsambulanz, D-97080 Wurzburg, Germany

[47] Hannover Med Sch, Hamatol Onkol, D-30625 Hannover, Germany

[48] Hippocration Hosp, Haemophilia Ctr, GR-11527 Athens, Greece

[49] Semmelweis Hosp, Hematol, H-3529 Miskolc, Hungary

[50] Univ Debrecen, Dept Med 2, H-4032 Debrecen, Hungary

来源：

BLOOD | 2012年 / 120卷 / 01期

关键词：

FACTOR-VIII INHIBITORS; UNITED-KINGDOM; RITUXIMAB; DISCRIMINATION; MANAGEMENT; DIAGNOSIS;

D O I：

10.1182/blood-2012-02-409185

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclo-phosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first- line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level. (Blood. 2012;120(1):47-55)

引用

页码：47 / 55

页数：9

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