10-year study: High incidence and mortality of acquired haemophilia A in HK

A retrospective, territory-wide, 10-year study has shown high incidence and mortality of acquired haemophilia A (AHA) in Hong Kong. Immunosuppression-related sepsis was the major cause of mortality, indicating the need for individualized immunosuppressive therapy (IST).

AHA, a rare bleeding disorder caused by anti–factor VIII (FVIII) autoantibodies, typically affects older individuals and young women during pregnancy or within 1 year of delivery, requiring haemostatic agents for bleeding control and/or IST for FVIII inhibitor eradication. [Haematologica 2020;105:1791-1801] “Previous AHA research primarily focused on Caucasians; therefore, a large-scale study in the Chinese population is essential,” wrote the researchers.

Using electronic public hospital patient records, the researchers analyzed data of Chinese patients diagnosed with AHA in Hong Kong between 2012 and 2021. Diagnostic criteria included isolated prolonged activated partial thromboplastin time, FVIII level <50 IU/dL or <50 percent of normal, and the presence of FVIII inhibitor confirmed by Bethesda assay. [Thromb Res 2024;233:138-144]

Of the 165 patients (median age, 80 years; female, 53.3 percent; ≥1 comorbidity, 81.8 percent) included in the study, 91 died during the study period. The estimated annual incidence of AHA was 2.4/100,000, and the morality rate was 55.2 percent. These figures were higher than those reported in Caucasians (estimated annual incidence, 1.5/100,000; mortality rate, 23.8–27.9 percent). [Thromb Res 2024;233:138-144; Blood 2007;109:1870-1877; Blood Adv 2021;5:3821-3829; J Thromb Haemost 2012;10:622-631]

Idiopathic AHA was present in 69.7 percent of all patients in the cohort. None of the female patients were diagnosed during pregnancy or postpartum. “Some pregnant women may seek consultation in the private sector, so the possibility of pregnancy-related and postpartum AHA cannot be excluded,” the researchers noted. [Thromb Res 2024;233:138-144]

Upon diagnosis, 93.9 percent of patients received ≥1 line of IST. The most common first-line option was steroid monotherapy (52.7 percent), followed by combined therapy with steroids and cyclophosphamide (28.5 percent). Additionally, 80.6 percent of patients received ≥1 line of haemostatic agents, including recombinant activated factor VIIa (37.0 percent) and anti-inhibitor coagulant complex (22.4 percent).

During the study period, 53.9 percent of patients achieved complete remission (CR; defined as no clinical bleeding and FVIII level >50 IU/dL or >50 percent normal, or undetectable FVIII inhibitors after IST cessation or resumption at patients’ usual dose). The median time to CR was 244 days.

Among patients who died, 65.9 percent failed to achieve CR. Immunosuppression-related sepsis (49.5 percent) was the major cause of death, while bleeding complications contributed to 13.2 percent of mortality. Median survival was 2.3 years.

In multivariate analysis, independent predictors of worsened overall survival (OS) were advanced age (>75 years; hazard ratio [HR], 1.065; 95 percent confidence interval [CI], 1.037–1.093), failure to achieve CR (HR, 22.005; 95 percent CI, 9.641–50.227), and longer time to CR (HR, 1.004; 95 percent CI, 1.002–1.005) (p<0.001 for each). However, the choice of first-line IST was not associated with OS.

Furthermore, age was an independent predictor of CR and time to CR (p=0.004 for both). The choice of first-line IST did not impact CR rate.