Minimum factor VIII levels to prevent joint bleeding in mild hemophilia A

Abstract

The severity of the bleeding phenotype in patients with hemophilia A (HA) broadly correlates with the degree of coagulation factor VIII (FVIII) deficiency in plasma. However, the FVIII level necessary to achieve the goal of zero joint bleeds remains unclear. This study aimed to identify the minimum FVIII level necessary to prevent joint bleeds in patients with HA. In this retrospective study, patients with congenital mild HA treated on demand, aged ≥16 years, with no history of FVIII inhibitors, followed at the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, were enrolled. We investigated 270 male patients with a median age of 45 years (16-88) and median lifelong FVIII of 21 IU/dL. One hundred patients (37%) had a lifelong history of at least 1 joint bleed. The mean annualized joint bleeding rate (AJBR) and spontaneous AJBR were 0.016 (standard deviation [SD], 0.032) and 0.001 (SD, 0.010), respectively. After adjusting for age, for each IU/dL increase in FVIII, there was a 6% reduction in AJBR and an 11% reduction in spontaneous AJBR. The minimum FVIII levels needed to prevent lifelong any joint bleeds and spontaneous joint bleeds resulted to be 19.2 IU/dL and 17.7 IU/dL, respectively. In this large cohort of persons with mild HA, we identified the minimum FVIII levels needed to prevent total and spontaneous joint bleeds (19.2 IU/dL and 17.7 IU/dL, respectively). These findings could suggest important implications for the accurate design of prophylactic therapies for persons with moderate and severe HA, including gene therapy.