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1. Demographic and clinical data in acquired hemophilia A

Author

Knoebl, P, Marco, P, Baudo, F, Collins, P, Huth Kühne, A, Nemes, L, Pellegrini, F, Tengborn, L, Lévesque, H, Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, D'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lévesque H, Lifermann F, Marlu R, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Huth Kühne A, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Nemes L, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Baudo F, Caimi T, Contino L, Di Minno G, Cerbone AM, Di Minno D, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, POGLIANI, ENRICO MARIA, Carpenedo M, Remiddi C, Santagostino E, Santoro R, Papaleo G, Schinco P, Borchiellini A, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Sartori R, Tagariello G, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Brandolini B, Hamulyák K, Kamphuisen P, Laros van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez Yuste V, Jose Felix L, Pascual M, Mingot ME, Perez Garrido R, Perez Gonzale Nz, Prieto Garcia M, Rodriguez Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Tengborn L, Boehlen F, Korte W, Chowdary P, Collins P, Evans G, Pavord S, Rangarajan S, Wilde J., Knoebl, P, Marco, P, Baudo, F, Collins, P, Huth Kühne, A, Nemes, L, Pellegrini, F, Tengborn, L, Lévesque, H, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lifermann, F, Marlu, R, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Caimi, T, Contino, L, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, matteo nicola dario, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Sartori, R, Tagariello, G, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Pascual, M, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Boehlen, F, Korte, W, Chowdary, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., Aspoeck, G, Borg, JY, Huth-Kühne, A, Loreth, RM, Di Minno, G, Cerbone, AM, Di Minno, D, D'incà, M, Mazzucconi, MG, Scortechini, AR, Tagliaferri, AR, Rivolta, GF, Laros-van Gorkom, B, Leebeek, FW, van der Linden, PW, Gutiérrez Pimentel, MJ Jiménez-Yuste, V, Jose-Felix, L, Pascual, M, Mingot, ME, Rodriguez-Huerta, AM, Wilde, J, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Huth Kühne, A, Lévesque, H, Borg, J, Loreth, R, Cerbone, A, Mazzucconi, M, Scortechini, A, Tagliaferri, A, Rivolta, G, Brandolini, B, Leebeek, F, van der Linden, P, Gutiérrez Pimentel, M, Mingot, M, Perez Gonzale, N, Rodriguez Huerta, A, and Other departments

Subjects
Registrie, Male, Pediatrics, diagnosis, medicine.medical_treatment, Hemostatic Technique, Kaplan-Meier Estimate, registry, THERAPY, Settore MED/15 - Malattie Del Sangue, Immunosuppressive Agent, IMMUNOADSORPTION, Risk Factors, Pregnancy, 80 and over, Prospective Studies, Registries, Prospective cohort study, health care economics and organizations, Aged, 80 and over, treatment, Immunosuppression, Hematology, Middle Aged, FACTOR-VIII INHIBITOR, Acquired hemophilia, Demographics, Diagnosis, Outcome, Registry, Treatment, Aged, Autoantibodies, Chi-Square Distribution, Europe, Factor VIII, Female, Hemostatic Techniques, Humans, Immunosuppressive Agents, Risk Assessment, Treatment Outcome, Hemophilia A, Hemorrhage, Autoantibodie, acquired hemophilia, demographics, outcome, INTRAVENOUS GAMMA-GLOBULIN, Human, medicine.medical_specialty, Malignancy, hemophilia, registry, medicine, METAANALYSIS, Autoimmune disease, business.industry, Risk Factor, Autoantibody, medicine.disease, Surgery, Prospective Studie, Hemostasis, business, Chi-squared distribution
Abstract

Summary. Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. Objectives: The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Results: Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. Conclusions: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.

Published
2012
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2. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Author

Collins, Peter, Baudo, Francesco, Knoebl, Paul, Lévesque, Hervé, Nemes, László, Pellegrini, Fabio, Marco, Pascual, Tengborn, Lilian, Huth Kühne, Angela, Group Author: Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, d'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lévesque H, Lifermann F, Marlu R, Ninet J, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Huth Kühne A, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Nemes L, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Baudo F, Caimi T, Contino L, D'Angelo Armando CL, Fattorini A, Cerbone AM, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, Pogliani E, Carpenedo M, Remiddi C, Santagostino E, Mancuso ME, Santoro R, Papaleo G, Schinco P, Borchiellini A, Valeri F, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Tagariello G, Sartori R, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Brandolin B, Hamulyák K, Kamphuisen P, Laros van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez Yuste V, Jose Felix L, Marco P, Mingot ME, Perez Garrido R, Perez Gonzale NZ, Prieto Garcia M, Rodriguez Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Tengborn L, Boehlen F, Korte W, Chowdary P, Collins P, Evans G, Pavord S, Rangarajan S, Wilde J., DI MINNO, GIOVANNI, DI MINNO, MATTEO, Interne Geneeskunde, Foundations and methods of Law, RS: CARIM School for Cardiovascular Diseases, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Collins, Peter, Baudo, Francesco, Knoebl, Paul, Lévesque, Hervé, Nemes, László, Pellegrini, Fabio, Marco, Pascual, Tengborn, Lilian, Huth Kühne, Angela, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, Matteo, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Brandolin, B, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Tengborn, L, Boehlen, F, Korte, W, Chowdary, P, Collins, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., and Other departments

Subjects
Registrie, Male, Clinical Trials and Observations, medicine.medical_treatment, THERAPY, Biochemistry, Gastroenterology, Immunosuppressive Agent, Antibodies, Monoclonal, Murine-Derived, Adult, Aged, Aged, 80 and over, Autoantibodies, Cyclophosphamide, Cyclosporine, Europe, Factor VIII, Female, Follow-Up Studies, Hemophilia A, Humans, Immunosuppressive Agents, Middle Aged, Registries, Rituximab, Secondary Prevention, Steroids, Treatment Outcome, FACTOR-VIII INHIBITORS, Monoclonal, 80 and over, UNITED-KINGDOM, Hematology, RECLASSIFICATION, Immunosuppression, Autoantibodie, Human, medicine.drug, Murine-Derived, medicine.medical_specialty, Immunology, DIAGNOSIS, Antibodies, Follow-Up Studie, Internal medicine, MANAGEMENT, medicine, Steroid, Autoimmune disease, business.industry, Settore MED/09 - MEDICINA INTERNA, Autoantibody, Cell Biology, Odds ratio, CENTER DOCTORS ORGANIZATION, medicine.disease, Surgery, DISCRIMINATION, Etiology, business
Abstract

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 cyclophosphamide; 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.

Published
2012

3. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry

Author

Baudo, Francesco, Collins, Peter, Huth Kühne, Angela, Lévesque, Hervé, Marco, Pascual, Nemes, László, Pellegrini, Fabio, Tengborn, Lilian, Knoebl, Paul, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, Cerbone, Am, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Brandolin, B, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Tengborn, L, Boehlen, F, Korte, W, Chowdary, P, Collins, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., DI MINNO, GIOVANNI, DI MINNO, MATTEO, Other departments, Baudo, Francesco, Collins, Peter, Huth Kühne, Angela, Lévesque, Hervé, Marco, Pascual, Nemes, László, Pellegrini, Fabio, Tengborn, Lilian, Knoebl, Paul, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, Matteo, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Brandolin, B, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Tengborn, L, Boehlen, F, Korte, W, Chowdary, P, Collins, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Huth Kühne, A, Lévesque, H, Pellegrini, F, Knoebl, P, Aspoeck, G, Borg, J, Loreth, R, D'Angelo Armando, C, Di Minno, G, Cerbone, A, Di Minno, D, Mazzucconi, M, Mancuso, M, Scortechini, A, Tagliaferri, A, Rivolta, G, Leebeek, F, van der Linden, P, Gutiérrez Pimentel, M, Mingot, M, Perez Gonzale, N, Rodriguez Huerta, A, and Wilde, J

Subjects
Registrie, Male, SURGERY, Biochemistry, THERAPY, Hemostatics, Hemostatic, FACTOR-VIII INHIBITORS, 80 and over, Deamino Arginine Vasopressin, Registries, Desmopressin, UNITED-KINGDOM, Factor IX, Aged, 80 and over, Hematology, biology, Incidence, FEIBA, Recombinant Protein, Middle Aged, Blood Coagulation Factors, Recombinant Proteins, Europe, Treatment Outcome, Coagulation, Female, medicine.drug, Blood Coagulation Factor, Human, Adult, medicine.medical_specialty, Adolescent, Immunology, Aged, Factor VIII, Factor VIIa, Hemophilia A, Hemorrhage, Humans, Young Adult, DIAGNOSIS, Internal medicine, BYPASSING ACTIVITY, medicine, business.industry, Settore MED/09 - MEDICINA INTERNA, RECOMBINANT FACTOR VIIA, Retrospective cohort study, Cell Biology, FACTOR-IX, CENTER DOCTORS ORGANIZATION, Surgery, Recombinant factor VIIa, Propensity score matching, biology.protein, business
Abstract

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Published
2012

4. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry

Author

Tengborn L, Baudo F, Huth-Kühne A, Knoebl P, Lévesque H, Marco P, Pellegrini F, Nemes L, Collins P, EACH2 registry contributors, Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, d'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lifermann F, Marlu R, Ninet J, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Caimi T, Contino L, D'Angelo Armando CL, Fattorini A, Di Minno G, Cerbone AM, Di Minno D, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, Pogliani E, Carpenedo M, Remiddi C, Santagostino E, Mancuso ME, Santoro R, Papaleo G, Schinco P, Borchiellini A, Valeri F, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Tagariello G, Sartori R, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Hamulyák K, Kamphuisen P, Laros-van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez-Yuste V, Jose-Felix L, Mingot ME, Perez Garrido R, Perez Gonzale NZ, Prieto Garcia M, Rodriguez-Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Boehlen F, Korte W, Chowdary P, Evans G, Pavord S, Rangarajan S, Wilde J, Tengborn, L, Baudo, F, Huth-Kühne, A, Knoebl, P, Lévesque, H, Marco, P, Pellegrini, F, Nemes, L, Collins, P, EACH2 registry, C, Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, J, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Loreth, R, Steigerwald, U, Tiede, A, Theodossiades, G, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Caimi, T, Contino, L, D'Angelo Armando, C, Fattorini, A, Di Minno, G, Cerbone, A, Di Minno, D, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, M, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, M, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, A, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, A, Di Perna, C, Rivolta, G, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Hamulyák, K, Kamphuisen, P, Laros-van Gorkom, B, Leebeek, F, Marten, N, Novakova, I, Schutgens, R, van der Linden, P, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, M, Jiménez-Yuste, V, Jose-Felix, L, Mingot, M, Perez Garrido, R, Perez Gonzale, N, Prieto Garcia, M, Rodriguez-Huerta, A, Sedano, C, Tolosa Munoz, A, Baghaei, F, Boehlen, F, Korte, W, Chowdary, P, Evans, G, Pavord, S, Rangarajan, S, and Wilde, J

Subjects
Adult, Acquired haemophilia A, diagnosis, pregnancy, treatment, Antifibrinolytic Agents, Blood Coagulation Factors, Drug Therapy, Combination, Europe, Factor VIIa, Female, Follow-Up Studies, Hemostatics, Humans, Immunosuppressive Agents, Kaplan-Meier Estimate, Pregnancy, Prospective Studies, Recombinant Proteins, Registries, Treatment Outcome, Hemophilia A, Pregnancy Complications, Hematologic, Drug Therapy, Hematologic, Acquired Haemophilia, Pregnancy, Pregnancy Complications, Combination
Abstract

Objective The European Acquired Haemophilia registry (EACH2) collected data on the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcome of women with acquired haemophilia A (AHA), a rare and often severe bleeding disorder caused by autoantibodies directed against coagulation factor VIII. Design Prospective, multi-centre, large-scale, pan-European registry. Setting A total of 117 haemophilia centres in 13 European countries. Population Pregnancy-associated AHA. Methods Data were reported using a web-based electronic case report form. Diagnosis was based on the presence of a prolonged activated partial thromboplastin time, reduced coagulation Factor VIII level and positive inhibitor assay. Main outcome measures Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome. Results The EACH2 registry (n = 501) documented 42 (8.4%) cases of AHA associated with the peripartum period, a median Factor VIII level at diagnosis of 2.5 (range 0-25) IU/dl and inhibitor titre of 7.8 (range 0.7-348) BU/ml. Antepartum inhibitors were evident in eight women. Time to diagnosis of AHA after delivery was 89 (range 21-120) days. First-line haemostatic treatment was successful in 20/23 (87%) women treated. Bleeding episodes resolved in 17/18 (94%) women treated with a bypassing agent and 29/39 (74%) women achieved complete remission with first-line immunosuppressive treatment. Two babies experienced postnatal bleeding, suggesting transplacental transfer of the antibody. All women were alive at last follow-up. Conclusions Although rare, pregnancy-associated AHA may cause severe bleeding-related morbidity. Once diagnosed, women respond well to haemostatic treatment with bypassing agents and immunosuppression. Awareness of peripartum AHA requires improvement to facilitate rapid and appropriate management.

Published
2012

5. Pregnancy-associated acquired haemophilia A: Results from the European Acquired Haemophilia (EACH2) registry

Author

Tengborn, L, Baudo, F., Huth Kühne, A., Knoebl, P., Lévesque, H., Marco, P., Pellegrini, F., Nemes, L., Collins, P, Group Author: Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, d'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lévesque H, Lifermann F, Marlu R, Ninet J, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Huth Kühne A, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Nemes L, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Baudo F, Caimi T, Contino L, D'Angelo Armando CL, Fattorini A, Cerbone AM, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, Pogliani E, Carpenedo M, Remiddi C, Santagostino E, Mancuso ME, Santoro R, Papaleo G, Schinco P, Borchiellini A, Valeri F, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Tagariello G, Sartori R, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Hamulyák K, Kamphuisen P, Laros van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez Yuste V, Jose Felix L, Marco P, Mingot ME, Perez Garrido R, Perez Gonzale NZ, Prieto Garcia M, Rodriguez Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Tengborn L, Boehlen F, Korte W, Chowdary P, Collins P, Evans G, Pavord S, Rangarajan S, Wilde J., DI MINNO, GIOVANNI, DI MINNO, MATTEO, Tengborn, L, Baudo, F., Huth Kühne, A., Knoebl, P., Lévesque, H., Marco, P., Pellegrini, F., Nemes, L., Collins, P, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, Matteo, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Boehlen, F, Korte, W, Chowdary, P, Evans, G, Pavord, S, Rangarajan, S, and Wilde, J.

Subjects
Adult, Registrie, treatment, Pregnancy Complications, Hematologic, Obstetrics and Gynecology, Factor VIIa, Kaplan-Meier Estimate, Recombinant Protein, Antifibrinolytic Agent, Hemophilia A, Follow-Up Studie, Europe, diagnosi, Immunosuppressive Agent, Prospective Studie, Hemostatic, Treatment Outcome, Pregnancy, Drug Therapy, Combination, Female, Acquired haemophilia A, Blood Coagulation Factor, Human
Published
2012

6. Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Author

Lodi, Sara, Del Amo, Julia, Moreno, Santiago, Bucher, H. C., Furrer, Hansjakob, Logan, Roger, Sterne, Jonathan, Pérez-Hoyos, Santiago, Jarrín, Inma, Phillips, Andrew, Olson, Ashley, Van Sighem, Ard, Reiss, Peter, Sabin, C., Jose, Sophie, Justice, Amy, Goulet, Joseph, Miró, José M., Ferrer, Elena, Meyer, Laurence, Seng, Rémonie, Vourli, Georgia, Antoniadou, Anastasia, Dabis, Francois, Vandenhede, Mari Anne, Costagliola, Dominique, Abgrall, S., Hernán, Miguel A., Hernan, Miguel, Bansi, L., Hill, T., Dunn, D., Porter, K., Glabay, A., Orkin, C., Thomas, R., Jones, K., Fisher, M., Perry, N., Pullin, A., Churchill, D., Gazzard, B., Nelson, M., Asboe, D., Bulbeck, S., Mandalia, S., Clarke, J., Delpech, V., Anderson, J., Munshi, S., Post, F., Easterbrook, P., Khan, Y., Patel, P., Karim, F., Duffell, S., Gilson, R., Man, S. L., Williams, I., Gompels, M., Dooley, D., Schwenk, A., Ainsworth, J., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Ismajani Puradiredja, D., Phillips, A., Walsh, J., Weber, J., Kemble, C., Mackie, N., Winston, A., Leen, C., Wilson, A., Bezemer, D. O., Gras, L. A.J., Kesselring, A. M., Van Sighem, A. I., Zaheri, S., Van Twillert, G., Kortmann, W., Branger, J., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., Van Der Meer, J. T.M., Wit, F. W.M.N., Godfried, M. H., Reiss, P., Van Der Poll, T., Nellen, F. J.B., Lange, J. M.A., Geerlings, S. E., Van Vugt, M., Pajkrt, D., Bos, J. C., Van Der Valk, M., Grijsen, M. L., Wiersinga, W. J., Brinkman, K., Blok, W. L., Frissen, P. H.J., Schouten, W. E.M., Van Den Berk, G. E.L., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M.E., Lauw, F. N., Van Eeden, A., Verhagen, D. W.M., Van Agtmael, M. A., Perenboom, R. M., Claessen, F. A.P., Bomers, M., Peters, E. J.G., Richter, C., Van Der Berg, J. P., Gisolf, E. H., Schippers, E. F., Van Nieuwkoop, C., Van Elzakker, E. P., Leyten, E. M.S., Gelinck, L. B.S., Pronk, M. J.H., Bravenboer, B., Kootstra, G. J., Delsing, C. E., Sprenger, H. G., Doedens, R., Scholvinck, E. H., Van Assen, S., Bierman, W. F.W., Soetekouw, R., Ten Kate, R. W., Van Vonderen, M. G.A., Van Houte, D. P.F., Kroon, F. P., Van Dissel, J. T., Arend, S. M., De Boer, M. G.J., Jolink, H., Ter Vollaard, H. J.M., Bauer, M. P., Weijer, S., El Moussaoui, R., Lowe, S., Schreij, G., Oude Lashof, A., Posthouwer, D., Koopmans, P. P., Keuter, M., Van Der Ven, A. J.A.M., Ter Hofstede, H. J.M., Dofferhoff, A. S.M., Warris, A., Van Crevel, R., Van Der Ende, M. E., De Vries-Sluijs, T. E.M.S., Schurink, C. A.M., Nouwen, J. L., Nispen Tot Pannerden, M. H., Verbon, A., Rijnders, B. J.A., Van Gorp, E. C.M., Hassing, R. J., Smeulders, A. W.M., Hartwig, N. G., Driessen, G. J.A., Den Hollander, J. G., Pogany, K., Juttmann, J. R., Van Kasteren, M. E.E., Hoepelman, A. I.M., Mudrikova, T., Schneider, M. M.E., Jaspers, C. A.J.J., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W.M., Barth, R. E., Geelen, S. P.M., Wolfs, T. F.W., Bont, L. J., Van Den Berge, M., Stegeman, A., Groeneveld, P. H.P., Alleman, M. A., Bouwhuis, J. W., Barin, F., Burty, C., Duvivier, C., Enel, P., Fredouille-Heripret, L., Gasnault, J., Khuong, M. A., Mahamat, A., Pilorgé, F., Tattevin, P., Salomon, Valérie, Jacquemet, N., Costagliola, D., Grabar, S., Guiguet, M., Lanoy, E., Lièvre, L., Mary-Krause, M., Selinger-Leneman, H., Lacombe, J. M., Potard, V., Bricaire, F., Herson, S., Katlama, C., Simon, A., Desplanque, N., Girard, P. M., Meynard, J. L., Meyohas, M. C., Picard, O., Cadranel, J., Mayaud, C., Pialoux, G., Clauvel, J. P., Decazes, J. M., Gérard, L., Molina, J. M., Diemer, M., Sellier, P., Bentata, M., Honoré, P., Jeantils, V., Tassi, S., Mechali, D., Taverne, B., Bouvet, E., Crickx, B., Ecobichon, J. L., Matheron, S., Picard-Dahan, C., Yeni, P., Berthé, H., Dupont, C., Chandemerle, C., Mortier, E., De Truchis, P., Tisne-Dessus, D., Weiss, L., Salmon, D., Auperin, I., Gilquin, J., Roudière, L., Viard, J. P., Boue, F., Fior, R., Delfraissy, J. F., Goujard, C., Jung, C., Lesprit, Ph, Vittecoq, D., Fraisse, P., Lang, J. M., Rey, D., Beck-Wirth, G., Stahl, J. P., Lecercq, P., Gourdon, F., Laurichesse, H., Fresard, A., Lucht, F., Bazin, C., Verdon, R., Chavanet, P., Arvieux, C., Michelet, C., Choutet, P., Goudeau, A., Maître, M. F., Hoen, B., Eglinger, P., Faller, J. P., Borsa-Lebas, F., Caron, F., Reynes, J., Daures, J. P., May, T., Rabaud, C., Berger, J. L., Rémy, G., Arlet-Suau, E., Cuzin, L., Massip, P., Thiercelin Legrand, M. F., Pontonnier, G., Viget, N., Yasdanpanah, Y., Dellamonica, P., Pradier, C., Pugliese, P., Aleksandrowicz, K., Quinsat, D., Ravaux, I., Tissot-Dupont, H., Delmont, J. P., Moreau, J., Gastaut, J. A., Poizot Martin, I., Retornaz, F., Soubeyrand, J., Galinier, A., Ruiz, J. M., Allegre, T., Blanc, P. A., Bonnet-Montchardon, D., Lepeu, G., Granet-Brunello, P., Esterni, J. P., Pelissier, L., Cohen-Valensi, R., Nezri, M., Chadapaud, S., Laffeuillade, A., Billaud, E., Raffi, F., Boibieux, A., Peyramond, D., Livrozet, J. M., Touraine, J. L., Cotte, L., Trepo, C., Strobel, M., Bissuel, F., Pradinaud, R., Sobesky, M., Cabié, A., Gaud, C., Contant, M., Aubert, V., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Burton-Jeangros, C., Calmy, A., Cavassini, M., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Haerry, D., Fux, C. A., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, H. H., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez De Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Casabona, J., Gallois, A., Esteve, A., Podzamczer, D., Murillas, J., Gatell, J. M., Manzardo, C., Tural, C., Clotet, B., Ferrer, E., Riera, M., Segura, F., Navarro, G., Force, L., Vilaró, J., Masabeu, A., García, I., Guadarrama, M., Cifuentes, C., Dalmau, D., Jaen, Agustí, C., Montoliu, A., Pérez, I., Gargoulas, Freyra, Blanco, J. L., Garcia-Alcaide, F., Martínez, E., Mallolas, J., López-Dieguez, M., García-Goez, J. F., Sirera, G., Romeu, J., Jou, A., Negredo, E., Miranda, C., Capitan, M. C., Saumoy, M., Imaz, A., Tiraboschi, J. M., Murillo, O., Bolao, F., Peña, C., Cabellos, C., Masó, M., Vila, A., Sala, M., Cervantes, M., Jose Amengual, Ma, Navarro, M., Penelo, E., Barrufet, P., Bejarano, G., Molina, J., Alvaro, M., Mercadal, J., Fernandez, Juanse, Ospina, Jesus E., Muñoz, M. A., Caro-Murillo, A. M., Sobrino, P., Jarrín, I., Gomez Sirvent, J. L., Rodríguez, P., Aleman, M. R., Alonso, M. M., Lopez, A. M., Hernandez, M. I., Soriano, V., Labarga, P., Barreiro, P., Medrano, J., Rivas, P., Herrero, D., Blanco, F., Vispo, M. E., Martín, L., Ramírez, G., De Diego, M., Rubio, R., Pulido, F., Moreno, V., Cepeda, C., Hervás, Rl, Iribarren, J. A., Arrizabalaga, J., Aramburu, M. J., Camino, X., Rodrí-guez-Arrondo, F., Von Wichmann, M. A., Pascual, L., Goenaga, M. A., Gutierrez, F., Masia, M., Ramos, J. M., Padilla, S., Sanchez-Hellín, V., Bernal, E., Escolano, C., Montolio, F., Peral, Y., Berenguer, J., Lopez, J. C., Miralles, P., Cosín, J., Sanchez, M., Gutierrez, I., Ramírez, M., Padilla, B., Vidal, F., Sanjuan, M., Peraire, J., Veloso, S., Vilades, C., Lopez-Dupla, M., Olona, M., Vargas, M., Aldeguer, J. L., Blanes, M., Lacruz, J., Salavert, M., Montero, M., Cuéllar, S., De Los Santos, I., Sanz, J., Oteo, J. A., Blanco, J. R., Ibarra, V., Metola, L., Sanz, M., Pérez-Martínez, L., Sola, J., Uriz, J., Castiello, J., Reparaz, J., Arriaza, M. J., Irigoyen, C., Moreno, S., Antela, A., Casado, J. L., Dronda, F., Moreno, A., Pérez, M. J., López, D., Gutiérrez, C., Hernández, B., Pumares, M., Martí, P., García, L., Page, C., García, F., Hernández, J., Peña, A., Muñoz, L., Parra, J., Viciana, P., Leal, M., López-Cortés, L. F., Trastoy, M., Mata, R., Justice, A. C., Fiellin, D. A., Rimland, D., Jones-Taylor, C., Oursler, K. A., Titanji, R., Brown, S., Garrison, S., Rodriguez-Barradas, M., Masozera, N., Goetz, M., Leaf, D., Simberkoff, M., Blumenthal, D., Leung, J., Butt, A., Hoffman, E., Gibert, C., Peck, R., Mattocks, K., Braithwaite, S., Brandt, C., Bryant, K., Cook, R., Conigliaro, J., Crothers, K., Chang, J., Crystal, S., Day, N., Erdos, J., Freiberg, M., Kozal, M., Gandhi, N., Gaziano, M., Gerschenson, M., Good, B., Gordon, A., Goulet, J. L., Hernán, M. A., Kraemer, K., Lim, J., Maisto, S., Miller, P., Mole, L., O'Connor, P., Papas, R., Robins, J. M., Rinaldo, C., Roberts, M., Samet, J., Tierney, B., Whittle, J., Babiker, A., Brettle, R., Darbyshire, J., Goldberg, D., Hawkins, D., Jaffe, H., Johnson, A., McLean, K., Pillay, D., Cursley, Adam, Ewings, Fiona, Fairbrother, Keith, Louisa Gnatiuc, S. 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Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Opportunistic infection, AIDS-Related Opportunistic Infections, Immunology, Population, Retinitis, HIV Infections, Article, 17 Psychology And Cognitive Sciences, Young Adult, Immune reconstitution inflammatory syndrome, Antiretroviral Therapy, Highly Active, Neoplasms, Virology, Internal medicine, medicine, Humans, Immunology and Allergy, education, Inverse probability weighting, Aged, education.field_of_study, business.industry, Developed Countries, Incidence, Progressive multifocal leukoencephalopathy, Hazard ratio, HIV, virus diseases, 11 Medical And Health Sciences, Middle Aged, 06 Biological Sciences, medicine.disease, United States, Europe, Infectious Diseases, Anti-Retroviral Agents, Unmasking, Female, Cytomegalovirus retinitis, business
Abstract

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis.Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting.Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis.Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Published
2014
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7. Comparison of fructosamine with glycated hemoglobin as an index of glycemic control in diabetic patients

Author

Pj, Guillausseau, Marie Aline Charles, Godard V, Timsit J, Chanson P, Paolaggi F, Peynet J, Eschwege E, Rousselet F, and Lubetzki J

Subjects
Adult, Blood Glucose, Glycated Hemoglobin, Male, Hexosamines, Middle Aged, Eating, Diabetes Mellitus, Type 1, Glucose, Diabetes Mellitus, Type 2, Reference Values, Fructosamine, Humans, Hypoglycemic Agents, Female, Longitudinal Studies, Biomarkers
Abstract

Fasting and postprandial (or post-glucose load) plasma glucose, total HbA1 and fructosamine (F) were simultaneously assessed in 371 diabetic patients (125 insulin dependent and 246 non-insulin dependent) and in 122 nondiabetic subjects, (98 with normal glucose tolerance and 24 with impaired glucose tolerance). Fructosamine yielded nearly similar information as HbA1 about glycemic control, since similar relationships were observed between plasma glucose values and HbA1 or fructosamine levels in the different groups. A longitudinal study performed during a three-month follow-up in 74 diabetic patients and extended to six months in 19 of them, without any modification of treatment, indicated that reproducibility of HbA1 and fructosamine was nearly the same with a slight advantage for HbA1. The only clinically significant difference results from the longer half-life of hemoglobin when compared to serum proteins. Fructosamine assay should be proposed as a complement of HbA1 in the management of diabetic patients when detection of recent metabolic changes is needed.

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