The analysis of the treatment outcome of patients with acquired hemophilia in Croatia

Background: Acquired haemophilia A (AHA) is a rare autoimmune disease, caused by antibodies (inhibitors) against coagulation FVIII and characterized by spontaneous hemorrhage in patients with no previous history of bleeding. Risk factors for the occurrence of AHA include advanced age and underlying diseases (malignancy, autoimmune disorders, pregnancy, and the postpartum period). Aims: The aim is to analyze treatment outcomes of patients with acquired hemophilia A during the last ten years at the University Hospital Center Zagreb. Methods: We analyzed retrospectively treatment outcomes of patients with AHA in the Department of Hematology, University Hospital Center Zagreb from 2010-2020. Response to treatment was assessed as partial (PR) or complete remission (CR). Results: We analyzed the outcomes of twenty patients (11 (55%) male, 9 (45%) female), median age was 68 (33-81) years, and with median FVIII activity 5 (1 - 15) IU/dL and median inhibitor titer at the time of AHA diagnosis was 9 (2,3 - 2000) BU/ml. Severe bleeding had 75 % patients requiring erythrocyte transfusion. In 12 patients (60%) were identified underlying diseases: malignancies 2 (oligodendroglioma, B-CLL), autoimmune diseases 9 (autoimmune haemolytic anaemia - 2 rheumatoid arthritis - 2, polymyalgia rheumatica - 3, pemphigus -1 and myasthenia -1). One patient had postpartal AHA. The last female patient with myasthenia was diagnosed in December 2020. and she developed COVID19 bilateral pneumonia with ARDS. 90% of patients recieved hemostatic treatment (65 % - aPCC, 10% aPCC and rFVIIa, 25 % - rFVIIa). All patients were treated with immunosuppressive therapy, combination of cyclophosphamide and steroids in 18/20, steroids alone in 2/20 patients, while 3/20 patients (15%) were treated in the second line therapy. The response rate to the first line eradication therapy was 90%. Inhibitor eradication time was 18 (3-300) days, time to achieve CR was 32 (15- 300) days. At follow up of 31 (1-90) months 13 patients (65%) are alive, 7 (35%) dead. No death was due to bledding. Two patients died of pneumonia, two deaths were associated with sepsis, one with progressive malignant disease and one with cardiogenic shock. One female patient died of COVID19 at the age of 55 years, 25 days after AHA was diagnosed. Higher inhibitor activity, known underlying cause of AHA with advanced age, comorbidities were unfavourable factors of survival. Summary/Conclusion: Our treatment outcomes are very similar to the large European Registries, with the quite high response rate of eradication therapy in the first line treatment (90%). Infective complications and comorbidities were the leading causes of death. Patients with AHA and COVID19 could have a worse outcome due to immunosuppressive therapy.