Demographic and Clinical Data in 118 Acquired Hemophilia a: Results from a Single Center Study

Introduction:

Acquired hemophilia A (AHA) is an autoimmune disorder marked by the development of autoantibodies targeting coagulation factor VIII. This rare condition has an incidence rate of 1.5 per million annually. Clinically, AHA manifests as severe bleeding at multiple sites, with about half of the affected individuals having underlying conditions. The primary treatment approaches include hemostatic management and immunosuppression. This retrospective study aims to describe and analyze the clinical characteristics and outcomes associated with various treatment strategies for AHA, based on data from our center.

Methods:

We conducted a retrospective analysis of patients diagnosed with AHA at Southern Medical University Nanfang Hospital between January 2012 and June 2024. The collected data encompassed patient demographics, clinical characteristics, treatment modalities, and prognostic outcomes. Ethical approval and informed consent were obtained for the study. Bleeding severity was classified into minor and major categories based on Schulman's criteria[1]. Coagulation factor VIII (FVIII) activity was categorized as severely reduced (FVIII < 1 iu/dl) or non-severely reduced (FVIII ≥ 1iu/dl). Immunosuppressive therapy (IST) regimens included full-dose cyclophosphamide (CTX) and prednisone (Pred) (Pred 1 mg/kg/day, CTX 1.5-2 mg/kg/day), as well as reduced-dose regimens (Pred < 1 mg/kg/day or CTX < 1.5-2 mg/kg/day).

Results:

Between January 2012 and June 2024, a total of 122 patients were diagnosed with AHA, of whom 118 were included in the analysis (60 males and 58 females, with a median age of 50 years, ranging from 1 to 91 years). Among these patients, 41 (34.7%) had underlying conditions: 19 (16.1%) had autoimmune diseases, 3 (2.5%) had malignancies, 14 (11.9%) were postpartum, and 5 (4.2%) had infections. The remaining 77 patients (65.3%) had no identifiable secondary cause. All patients experienced at least one bleeding event: 71 (60.7%) had skin or subcutaneous bleeding, 35 (30.0%) had muscle bleeding, 4 (3.3%) had gastrointestinal bleeding, 3 (2.5%) had urinary tract bleeding, 5 (4.2%) had genital bleeding, 1 (0.8%) had spinal bleeding, 3 (2.5%) had joint bleeding, and 4 (3.3%) had gum bleeding. Hemostatic treatment with prothrombin complex concentrate (PCC) or activated recombinant factor VII (FVIIa) was administered to 88 patients, achieving a 92.0% success rate (81 patients).

Inhibitor titers showed no correlation with FVIII activity, activated partial thromboplastin time (APTT), or hemoglobin levels. Patients with inhibitor titers ≥ 20 Bu/ml experienced significantly more severe bleeding compared to those with titers < 20 Bu/ml (P < 0.001). Additionally, patients with severe FVIII reduction had a substantially higher risk of severe bleeding compared to those with non-severe reduction (P < 0.001).

All AHA patients received IST. Full-dose CTX and Pred were administered to 56 patients, with a response rate of 83.9%. Reduced-dose regimens were given to 40 patients, with a response rate of 67.5%. Other treatments were used for 22 patients, with a response rate of 27.3% (P < 0.001). Complete response rates were 77.8% for patients with inhibitor < 20 Bu/ml and 59.4% for those with ≥ 20 Bu/ml (P < 0.05). Patients with severe FVIII deficiency had a complete response rate of 47.7%, compared to 67.8% for those with non-severe deficiency (P < 0.01).

There were 15 deaths (12.7%): 8 due to uncontrollable bleeding, 4 from IST-related infections, 1 from lung cancer, 1 from heart failure, and 1 from unknown causes. Logistic regression analysis identified age and gender as significant factors affecting mortality, with patients ≥ 65 years and males having higher mortality rates (P < 0.001 and P < 0.05, respectively).

There were 15 deaths (12.7%) among the cohort: 8 from uncontrollable bleeding, 4 from IST-related infections, 1 from lung cancer, 1 from heart failure, and 1 from unknown causes. Logistic regression analysis identified age and gender as significant factors influencing mortality, with patients aged ≥ 65 years and males exhibiting higher mortality rates (P < 0.001 and P < 0.05, respectively).

Xuan Zhou is the corresponding author who is responsible for all correspondence.

1. Schulman, S. and C. Kearon, Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non‐surgical patients. Journal of Thrombosis and Haemostasis, 2005. 3(4).