| IntroductionAcquired Hemophilia A(AHA)is a rare acquired autoimmune hemorrhagic disorder.Epidemiological studies show that the annual incidence rate is approximately 1.5/1,000,000.Early reports indicated a mortality rate as high as 42%,and in recent years it has remained as high as 12%.Due to the rarity of the disease,clinicians have inadequate knowledge of AHA,and most patients are unable to receive effective diagnosis and treatment,resulting in prolonged periods of high-risk bleeding and a severe threat to their lives.Additionally,the treatment guidelines for this disease rely on the results of large-scale registration centers and clinical experience,rather than randomized controlled studies.Therefore,any clinical experience in treating and managing this disease has significant value.Currently,the main treatment methods for AHA are hemostatic therapy and immunosuppressive therapy(IST).Approximately 60%-90% of patients respond to IST,but there may be a delayed response,and patients may still face the risk of fatal bleeding during treatment.About 30% of patients may experience IST-related adverse events,such as life-threatening infections,bone marrow suppression,etc.Adverse events can result in a high mortality rate of up to 11%,posing significant challenges to treatment.Our treatment goal is to achieve a rapid response without increasing the risk of ISTrelated deaths.Thus,it is crucial to summarize and analyze the clinical characteristics of AHA,early diagnosis,and explore factors that affect treatment outcomes and prognosis.ObjectiveThis study aimed to retrospectively analyze clinical data from multiple centers in Henan Province to explore the clinical characteristics of acquired hemophilia A(AHA)and investigate the factors affecting prognosis.MethodsA total of 42 AHA patients who were admitted to the People’s Hospital of Henan Province,the First Affiliated Hospital of Zhengzhou University,and the Central Hospital of Nanyang City between January2015 and August 2021 were analysed.The complete clinical data of patients were collected by reviewing outpatient and inpatient medical records and telephone follow-up.The collected data included:(1)general clinical data,such as patient name,gender,WHO Performance status,underlying and accompanying diseases,medication histories,time from first bleeding to diagnosis(days),transfusion data,bleeding sites;(2)laboratory tests,including activated partial thromboplastin time(APTT)(s),factor Ⅷ activity(FⅧ: C)(%),FⅧ inhibitor levels(BU/ml),hemoglobin(g/L),antinuclear antibodies,anti-cardiolipin antibodies,lupus anticoagulants,tumor markers,and other results;and(3)other data,including diagnosis,treatment plans,efficacy evaluation,time to disease remission,time to disease recurrence or progression,adverse events,time to death,and last follow-up time.Measurement data were expressed as medians and ranges or interquartile ranges(IQRs)and compared using t-tests or Mann-Whitney U tests.Count data were expressed as rates or percentages and compared using Pearson’s chi-square test or Fisher’s exact test as appropriate.The Log-rank test was used to compare the survival rates of patients with different clinical characteristics,and the Kaplan-Meier method was used to draw survival curves.Univariate and multivariate Cox proportional hazards models were used to identify the independent prognostic factors affecting the time to achieve complete remission(CR)and overall survival(OS)of patients.Results1.Among 42 patients,there were 17 males and 25 females,with a male-to-female ratio of 1:1.5.The age of onset ranged from 9 to 92 years,with a median age of 52 years.The majority of elderly patients were male(11/18,61.1%),while the majority of reproductive-age patients were female(10/13,76.9%).30 patients(71.4%)were idiopathic,6 patients(14.3%)were related to malignancies,4 patients(9.5%)were related to autoimmune diseases,1 patient(2.4%)was related to pregnancy,and 1 patient(2.4%)was related to drugs.All patients had isolated prolonged activated partial thromboplastin time(APTT),with a median APTT value of 88.3s(range: 56.2-146.30s)at diagnosis.The median FⅧ:C was 0.6%(range: 0-13.10%),and the median level of factor Ⅷ inhibitor was 9.5 BU/ml(range: 1.4-320 BU/ml)at diagnosis.2.41/42(97.6%)patients had bleeding symptoms,and the time from the onset of bleeding symptoms to diagnosis ranged from 0 to 684 days,with a median of 31.5 days.39/41(95.1%)patients received hemostatic treatment,and the total success rate of hemostasis was 96.4%.3.42 patients received immune suppression therapy(IST),and 34 patients had complete treatment data.The overall complete remission(CR)rate was 85.3%.5/34(14.7%)patients received corticosteroids monotherapy as the first line IST,with a CR rate of 60%.24/34(70.6%)patients received corticosteroids combined with cyclophosphamide as the first line IST,with a CR rate of 70.8%,the patients with FⅧ inhibitor titers <20 BU/m L had a significantly higher complete response(CR)rate compared to those with titers ≥20 BU/m L(92.3% vs 45.5%,P = 0.023).5/34(14.7%)patients received corticosteroids combined with cyclophosphamide and rituximab as the first line IST,with a CR rate of 80%.Among them,4/34(13.8%)patients experienced relapse after a median time of 410(21-1279)days.14/34(41.2%)patients experienced treatment-related adverse events,including infections(13/34,38.2%)and pancytopenia(1/34,2.9%).There were 2 patients of death(5.9%),both of which were due to refractory bleeding.4.Sex,age,WHO performance status,underlying diseases(autoimmune diseases/other types,malignancies/other types),factor Ⅷ activity(<1% vs.1%-50%),and inhibitor titer(<20 BU/m L vs.≥20BU/m L)were included in the univariate and multivariate Cox regression analyses.The results showed that an inhibitor titer of ≥20 BU/m L was the only independent prognostic factor affecting the time to achieve CR.Conclusion1.The incidence of acquired hemophilia A is low and can occur in both men and women of all ages.The age distribution of onset has a bimodal pattern,with females in the reproductive age group and males in the elderly population.It is rare in children.2.More than half of the cases are idiopathic,while others are associated with malignancies,autoimmune diseases,pregnancy,or drugs.3.Almost all patients have spontaneous bleeding symptoms,and there is a significant delay in diagnosis and effective treatment.4.Bypassing agents are the first-line therapy for hemostasis,and first-line immunosuppressive therapy consists of corticosteroids alone or in combination with cyclophosphamide,rituximab.5.FⅧ inhibitor titer ≥20 BU/m L is the only significant prognostic factor affecting time to CR and complete remission rate. |
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