Experiences with AHA in Two Czech Centers and Risk Factor Evaluation

Acquired Hemophilia A

Acquired hemophilia A is an autoimmune disease caused by the acquired presence of autoantibodies against coagulation factor VIII (FVIII), which is rare, often life-threatening, and associated with high morbidity and mortality. Half of AHA cases are idiopathic, and the others are commonly associated with malignancies or autoimmune diseases. Bleeding episodes are predominantly acute, occurring without a prior history of bleeding, and can range in severity from severe to mild. The most common type is subcutaneous bleeding; however, retroperitoneal bleeding, for example, can be risky.

Characteristics of Patients and Analysis Objectives

Patients in this cohort were treated at two specialized centers: the Institute of Hematology and Blood Transfusion in Prague and the University Hospital Hradec Králové. The first line of treatment was mainly hemostatic therapy with rFVIIa and immunosuppression with corticosteroids/cyclophosphamide.

The analysis included 66 patients with a median age of 72.1 years (range 22–88). A quarter of the patients were under 65 years of age, and women made up 52% of the cohort. Only 8% of the patients did not show signs of bleeding at the time of diagnosis, 20% had only mild symptoms, 12% had moderate, and 61% had severe bleeding manifestations. The difference in inhibitor titer between patients with mild or no bleeding and those with severe bleeding was not statistically significant (p = 0.07).

Possible associations between early death (within 8 weeks of diagnosis) and age, malignancy, FVIII levels, and bleeding severity were analyzed.

Results

Initial complete remission, defined as an FVIII level > 50% and no bleeding manifestations, was achieved in 79% of patients.

Early death occurred in 20% of patients (n = 13), with 6 cases directly associated with bleeding. Early death was associated with FVIII levels < 1% and severe bleeding manifestations (p = 0.01 and p = 0.046); a trend toward negative outcomes was observed in older patients or those with malignancy, but statistical significance was not reached. However, patients with malignancy or those requiring longer-term hemostatic treatment had significantly lower 2-year survival compared to those without these risk factors (p = 0.007 and p = 0.006).

A total of 44 relapses were recorded in 22 patients, ranging from 1 to 7 per individual. There was no significant association between relapse incidence and 2-year survival. Patients with another concurrent autoimmune disease (69% relapse rate in this AHA etiology) had more frequent relapses compared to other patients (31% relapse rate; p = 0.015).

Higher doses of corticosteroids were associated with a significantly higher incidence of early death (p < 0.001), but also with early remission (p < 0.001).

Conclusion

The Czech authors presented a relatively large cohort of patients with AHA in their study. The analysis of their data showed that a significant FVIII deficit (< 1%), older age, and malignancy are negatively associated with patient survival. Additionally, it was demonstrated that the association of AHA with another autoimmune disease is a significant risk factor for disease relapse.

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Source: Salaj P., Geierová V., Ivanová E. et al. Identifying risk factors and optimizing standard of care for patients with acquired haemophilia A: results from a Czech patient cohort. Haemophilia 2020 Jul; 26 (4): 643–651, doi: 10.1111/hae.14084.