Collins P, Baudo F, Knoebl P, et al


Collins P, Baudo F, Knoebl P, et al. between patient characteristics and clinical outcomes. A total of 143 patients (median age 73?years; 52.4% male) were included with a median follow\up of 16.8 months (IQR 3.6\41.5 months). First\line immunosuppressive treatment was mostly Cephapirin Sodium steroid monotherapy (67.6%), steroids/cyclophosphamide (11.9%) and steroids/rituximab (11.9%), with success rates of 35.2%, 80.0% and 66.7% respectively, ?.05. Eventually 75% of patients achieved complete remission (CR). A high anti\FVIII antibody titer, severe bleeding and steroid monotherapy were associated with lower CR rates. Infections, the most important adverse event, occurred significantly more often with steroid combination therapy compared to steroids alone (38.7% vs 10.6%; =?.001). Overall mortality was 38.2%, mostly due to infections (19.2%) compared to 7.7% fatal bleeds. Advanced age, underlying malignancy and ICU admission were predictors for mortality. This study showed that AHA is characterized by significant disease\related and treatment\related morbidity and mortality. A high anti\FVIII titer, severe bleeding and steroid monotherapy were associated with a lower CR rate. The efficacy of steroid combination therapies however, was overshadowed by higher infection rates and infections represented the most important cause of death. The challenging and delicate balance between treatment effectivity Cephapirin Sodium and safety requires ongoing monitoring of AHA and further identification of prognostic markers. 1.?INTRODUCTION Acquired hemophilia A (AHA) is a clinically challenging bleeding disorder, which is caused by Cephapirin Sodium the presence of antibodies against factor VIII (FVIII). These antibodies to FVIII partially or completely neutralize its coagulant function or cause an accelerated clearance. 1 The resulting lack of FVIII activity causes spontaneous and sometimes life\threatening bleeding. AHA affects mainly elderly patients and in about 50% an underlying cause can be identified, predominantly including malignancies or auto\immune disorders. 2 , 3 , 4 , 5 , 6 The estimated incidence of AHA is approximately 1.5 cases per million persons/y. 4 The rarity of the disease often results in a significant delay in diagnosis and start of appropriate treatment, further increasing morbidity and mortality. Treatment of AHA requires a dual approach, which includes both the control of bleeding with hemostatic agents as well as inhibitor eradication Cephapirin Sodium with immunosuppressive drugs. During the past decades, mortality due to bleeding dramatically decreased from about 22% in the early 1980s to 3%\4% reported in more recent studies, which is attributed to earlier diagnosis, the introduction of bypassing agents, and prompt inhibitor eradication. 2 , 3 , 5 , 7 However, this apparent success is overshadowed by the high rate of treatment\related side effects, including infections and sepsis, which nowadays seem to be a major contributor to the morbidity and mortality in AHA patients. The challenge is to balance the minimization of bleeding risk by rapid inhibitor eradication with the risk of treatment\related side effects, especially in an elderly and frail population. This delicate balance urges the need for identification of prognostic patient characteristics to help tailor the intensity of immunosuppressive therapy. In the GTH\AH 01/2010 study of Tiede et al a FVIII concentration 1 IU/dL, a poor performance status and the presence of anti\FVIII IgA antibodies were associated with lower complete remission (CR) rates and overall survival. 5 , 8 However, to our knowledge, no protocols use these potential predictors as criteria to guide therapy. Due to the challenge of performing randomized controlled trials in rare diseases like AHA, observational studies provide the main source of clinical data. A retrospective analysis of Dutch patients diagnosed with AHA from 1992 to 2018, predicated on the Dutch nationwide BAIAP2 hemophilia problem registry, was performed to judge clinical display as.