Moroctocog alfa

In hemophilia, deficiency of factor VIII or IX prevents the activation of the common coagulation pathway, and inhibits the conversion of FX to activated FXa, which is required for thrombin generation. We hypothesized that the direct expressed FXa has the potential to activate the common pathway and restore coagulation in hemophilia patients. In this study, the cassettes that expressed FXa, FXaop and FXa-FVII were packaged into an engineered AAV capsid, AAV843, and were delivered into hemophilia A and B mice by intravenous injection. AAV-FXaop could be stably expressed in vivo and showed the best immediate and prolonged hemostatic effects, similar to those of commercial drugs (Xyntha and Benefix). AAV-FXaop also significantly inhibited bleeding in hemophilia A mice with inhibitors. In addition, FXa expression in joints significantly alleviated the occurrence of hemophilic synovitis. AAV-delivered FXa may be a novel target for treating hemophilic and hemophilic synovitis.

Objective: To investigate long-term health-related quality of life (HRQoL) and related factors in children with severe hemophilia A (HA) who received regular low-dose prophylaxis. Methods: Clinical data of severe HA children who began to receive regular low-dose coagulation factor Ⅷ (FⅧ) prophylaxis in Peking Union Medical College Hospital from January 1, 2008 to December 31, 2011 were retrospectively enrolled. The longest last follow-up period was May 31, 2023. The attendance of school or work and daily physical activity during the last follow-up were investigated. The patients were divided into full attendance group and incomplete attendence group according to attendance. The patients were divided into into exercise attainment group (reached Chinese sports recommendation) and exercise nonattainment group according to the exercise status. Barthel score was used to assess activities of daily living and Haemo-QoL was used to assess quality of life. Long-term HRQoL for children aged 8-16 years and patients aged 17 years and above were assessed using Haemo-QoL SF and Haem-A-QoL versions, respectively. Spearman correlation analysis was used to examine the correlation between treatment conditions and Haemo-QoL scores. Results: A total of 22 cases were enrolled, the prophylaxis initiation age ranged from 1.8-17.9 (10.4±3.8) years old. The average prophylactic FⅧ dose during low-dose prophylaxis was 24.2 U/kg per week and the follow-up time was 6.3-15.1 (9.6±2.8) years. At the last follow-up, the age of the patients was (20.2±5.4) years, of which 14 (63.6%) were adults over 18 years old. There were 15 patients in the full attendance group and 7 patients in the incomplete attendence group. Compared with the full attendance group, the incomplete attendence group had a smaller preventive treatment dose [M(Q_1, Q₃), (28.4±11.1) vs (15.3±3.7) U/kg, P=0.012], shorter preventive treatment time [148. 1 (18.6, 346.5) vs 48.0 (32.0, 156.9) weeks, P=0.017], and higher annual joint bleeding rate (AJBR) [12.5 (6.0, 22.3) vs 14.2 (13.2, 17.8) times, P=0.017]. There were 7 cases in the exercise attainment group and 15 cases in the exercise nonattainment group. Compared to the exercise attainment group, the exercise nonattainment group had shorter preventive treatment time[313. 7 (156.9, 366.0) vs 48.0 (16.5, 108.9) weeks, P=0.006], a higher AJBR [7.0 (5.1, 10.0) vs 23.3 (12.5, 29.8), P=0.003] and a higher hemophilia joint health score (HJHS) [9.0 (2.0, 15.5) vs 23.0 (12.0, 27.8), P=0.014]. Barthel score showed 81.8% (18 cases) of the patients' living ability was not influenced by the illness. In Haemo-QoL score, the total score of Haemo-QoL SF in 7 cases was (47.6±17.0) scores, the total score of Haem-A-QoL in 15 cases was (45.2±22.6) scores. The daily activity dimension of the Haem-A-QoL score was the lowest [38.2 (10.9, 45.5) scores], which was positively correlated with the starting age of prophylactic initiation (r=0.501, P=0.057), and negatively correlated with the duration of prophylaxis (r=-0.545, P=0.036). Conclusions: Regular low-dose prophylaxis could improve the long-term HRQoL of some children with severe HA, and children with higher prophylactic doses and longer prophylactic treatment time have higher quality of life.