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

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.Prospective, multi-centre, large-scale, pan-European registry.A total of 117 haemophilia centres in 13 European countries.Pregnancy-associated AHA.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.Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome.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.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

Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

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.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.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.Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA

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

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\%)

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

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

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

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.Prospective, multi-centre, large-scale, pan-European registry.A total of 117 haemophilia centres in 13 European countries.Pregnancy-associated AHA.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.Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome.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.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

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

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

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

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%)

Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

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 73.9years. 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