RESUMEN
OBJECTIVES: In Acquired Haemophilia (AH) autoantibodies against blood coagulation factors, mainly FVIII, inhibit the blood coagulation cascade. The clinical symptoms can vary from minor to severe life threatening bleedings. At present it is unclear if the intensity of the treatment needs to be adapted to the severity of the disease. METHODS: The clinical data and long term outcome from 20 patients suffering from minor severe AH were summarized. Bleedings requiring no blood transfusions were defined as less severe. In case of FVIII concentration <5% an immunosuppressive treatment (IT) consisting of cyclophosphamide 1-2 mg/kg BW/d and/or prednisolone 1-2 mg/kg BW/d was initiated. RESULTS: IT induced complete remission (CR) in only 40% of patients (8/20) after a mean time of 133.4 d (±90.7 d). Treatment associated severe side effects occurred in all patients. 15 patients required a factor substitution therapy due to proceeding bleedings. In 7 patients a partial remission (PR) of AH could be achieved; bleedings progressed in 5 of them and they underwent successfully second line immunoadsorption-based protocol. The inhibitor titer differed statistically significant between CR and PR with a mean of 3.7 BU vs. 16 BU. 5 patients had a fatal outcome mainly due to severe disease associated co morbidities. CONCLUSION: Immunosuppressive treatment failed in nearly a half of AH patients. Mortality was with 25% still high. The majority of patients required an intense long-term IT and developed severe treatment related side effect. Immediate start of IT did not control bleeding. In consequence, less severe AH also should be treated with a more rigorous regime because the occurrence of minors bleedings at initial presentation is not a predictive of clinical outcome. An Immunoadsorption-based protocol should be considered first line or even as a salvage strategy.
Asunto(s)
Autoanticuerpos/sangre , Eliminación de Componentes Sanguíneos/métodos , Factor VIII/inmunología , Hemofilia A/terapia , Hemorragia/prevención & control , Técnicas de Inmunoadsorción , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Eliminación de Componentes Sanguíneos/efectos adversos , Eliminación de Componentes Sanguíneos/mortalidad , Transfusión Sanguínea , Comorbilidad , Femenino , Hemofilia A/sangre , Hemofilia A/diagnóstico , Hemofilia A/inmunología , Hemofilia A/mortalidad , Hemorragia/inmunología , Hemorragia/mortalidad , Humanos , Técnicas de Inmunoadsorción/efectos adversos , Técnicas de Inmunoadsorción/mortalidad , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Inducción de Remisión , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Diabetes mellitus (DM) is a risk factor for death from heart failure (HF) in patients with dilated cardiomyopathy (DCM) but DM patients are less eligible for heart transplantation (HTx) and DM is a risk factor for death also after HTx. New therapies are therefore necessary to improve survival of diabetic DCM patients. Immunoadsorption (IA) can improve heart function in DCM but its usefulness for therapy of DM-associated DCM is unknown. We assessed this aspect. METHODS: Cardiac function and HTx-free survival were evaluated in diabetic HTx-candidates with DCM who underwent IA (Globaffin(®), a broadband-immunoadsorber containing synthetic peptide-GAM(®)) in 6/2003-6/2012 (follow-up 1-10 yrs). Non-diabetic HTx-candidates with DCM who received IA in the same time-period served as controls. Before and after IA patients were tested for serum ß1-autoantibodies (ß1-AABs). RESULTS: We evaluated 31 patients with and 31 without DM. Before IA there were no differences between the 2 groups in LV size, LVEF and ß1-AAB levels. However, DM patients were older, their HF duration was longer and their peak oxygen-uptake was lower (p < 0.005). During the 1st post-IA year in both groups there was a decrease in LV size and improvement in both LVEF and NYHA-class (p < 0.05). Post-IA 3-year HTx-free survival and prevalence of responders to IA in patients with and without DM was 81.3 ± 8% and 78.4 ± 8%, respectively and 73.3% and 67.7%, respectively. Post-IA 3-year freedom from ß1-AAB reappearance in patients with and without DM reached 72.1 ± 9.0% and 71.1 ± 8.6%, respectively. CONCLUSIONS: IA improves heart function, exercise tolerance and Tx-free survival in patients with DM-associated end-stage DCM. Our results also suggest that IA can delay HTx-listing, improve survival on HTx lists and even spare some diabetic patients from HTx, benefits of particular importance for these patients who are at high risk for pre-HTx and post-HTx mortality.