Objective: To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods: Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results: The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion: In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.
Humans ; Hemophilia A/drug therapy* ; Factor VIII/therapeutic use* ; Quality of Life ; Retrospective Studies ; Hemarthrosis/prevention & control* ; Hemorrhage/drug therapy*

Factor IX/therapeutic use* ; Factor VIII ; Hemophilia A/drug therapy* ; Hemophilia B/drug therapy* ; Humans ; Recombinant Proteins/therapeutic use*

Traditional replacement therapy is the main treatment method of hemophilia, while inhibitor generation makes replacement therapy ineffective. The emergence of non-factor therapy brings new hope for the treatment of patients with inhibitor. Non-factor products mainly achieve therapeutic purpose by imitating the function of coagulation factor Ⅷ, inhibiting the function of anti-tissue factor pathway inhibitors, the expression of antithrombin mRNA, and the function of activated protein C. This paper reviews the latest research progress of non-factor products in the treatment of hemophilia.
Antibodies, Monoclonal, Humanized/adverse effects* ; Factor VIII/therapeutic use* ; Hemophilia A/therapy* ; Humans

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Child ; Factor VIII/therapeutic use* ; Hemarthrosis ; Hemophilia A/drug therapy* ; Hemorrhage ; Humans ; Retrospective Studies

Objective: To compare the differences in population pharmacokinetic (PK) parameters between two recombinant coagulation factor Ⅷ (FⅧ) preparations, Kogenate FS and Advate, in patients with hemophilia A, and to provide the theoretical basis of precise individualized treatment for those patients. Methods: Patients with moderate or severe hemophilia A who had at least one injection of Kogenate FS or Advate at 41 international hemophilia centers were enrolled as subjects from the WAPPS-Hemo project since January 2015 to December 2017. The half-lives of the two drugs and the time of FⅧ activity reaching 2% (TAT 2%) were calculated, and the differences of PK between the two drugs among different age and dose subgroups were further analyzed. Results: ①The mean age of patients in the Kogenate FS (n=117) and Advate groups (n=120) were (27.6±17.7) and (23.4±16.2) years old, respectively. All patients in the two groups were males. ②The administration doses in the Kogenate FS and Advate groups were (31.5±13.1) IU/kg and (38.17±14.83) IU/kg, respectively; the half-lives of the two drugs were (12.3±3.5) h and (10.8±2.9) h, respectively; and the TAT 2% were (65.2±21.7) h and (57.0±17.9) h, respectively. ③In the Kogenate FS group, the drug half-lives in patients aged ≥12 and <12 years old were (12.7±3.7) h and (11.1±2.5) h, respectively; the TAT 2% were (68.6±22.9) h and (55.8±14.6) h, respectively. In the Advate group, the drug half-lives in patients aged ≥12 and <12 years old were (11.4±3.1) h and (9.4±1.8) h, respectively; and the TAT 2% were (61.1±18.0) h and (45.2±11.3) h, respectively. ④In the Kogenate FS group, the drug half-lives in <20 IU/kg, (20-29) IU/kg, (30-39) IU/kg and ≥40 IU/kg groups were (13.3±4.0) h, (12.3±3.6) h, (12.2±3.5) h and (11.6±2.6) h, respectively; and the TAT 2% were (61.5±21.4) h, (63.9±22.4) h, (67.0±24.3) h and (68.0±19.5) h, respectively. In the Advate group, the drug half-lives in <20 IU/kg, (20-29) IU/kg, (30-39) IU/kg and <40 IU/kg groups were (11.5±3.8) h, (11.4±3.7) h, (11.0±2.9) h and (10.4±2.3) h, respectively; and the TAT 2% were (50.8±19.2) h, (56.7±21.0) h, (58.2±18.8) h and (58.1±15.8) h, respectively. Conclusion: The PK parameters of Kogenate FS are superior to those of Advate among different age and dose subgroups.
Adolescent ; Adult ; Blood Coagulation Tests ; Child ; Factor VIII/therapeutic use* ; Hemophilia A/drug therapy* ; Humans ; Male ; Recombinant Proteins ; Young Adult

Aneurysm, False ; surgery ; Factor VIII ; therapeutic use ; Hemophilia A ; drug therapy ; Humans ; Uremia

PURPOSE: Beroctocog alfa is a second generation recombinant factor VIII manufactured by removing the B-domain from factor VIII. This prospective clinical trial was conducted to evaluate the efficacy, safety, and pharmacokinetics of beroctocog alfa in patients of ages > or =12 years previously treated for severe hemophilia A. MATERIALS AND METHODS: Seventy subjects received beroctocog alfa as an on-demand treatment for acute hemorrhage. RESULTS: The final hemostatic effect was excellent in 35 subjects (50%) and good in 26 subjects (37.1%). The drug showed an overall efficacy rate of 87.1%. The majority of acute hemorrhages was treated by administering the study drug once (86.2%) or twice (10.0%), and the mean dose administered per single infusion was 28.55+/-6.53 IU/kg. Ten subjects underwent 12 surgical procedures, and hemostatic efficacy was excellent in seven cases (58.3%) and good in five cases (41.7%), showing a 100% efficacy rate. A total of 52 of 88 subjects (59.0%) experienced 168 adverse events. There were 18 serious adverse events (10.7%) in 11 subjects, and two (mild dyspnea and facial edema) in one subject were related to the study drug. Only one subject formed a de novo factor VIII inhibitor, for an occurrence rate of 1.4% (one-sided 95% upper confidence limit: 3.85%). The final elimination half-life was 13.3 h and 12.6 h at baseline and 6 months after administration, respectively. CONCLUSION: Our results suggest that beroctocog alfa is safe and efficacious as either an on-demand treatment for acute hemorrhage or a surgical prophylaxis in patients with hemophilia A.
Adult ; Consumer Product Safety ; Dyspnea ; Factor VIII/adverse effects/*pharmacokinetics/therapeutic use ; Female ; Hemophilia A/*drug therapy ; Hemorrhage/prevention & control ; Hemostasis ; Hemostasis, Surgical/methods ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recombinant Proteins/adverse effects/*pharmacokinetics/*therapeutic use ; Treatment Outcome

OBJECTIVE: To study the correlation between dosage and curative effect of blood coagulation factor VIII in the prevention and treatment of haemophilia A in children and to determine the suitable dose for prevention of hemophilia in developing countries. METHODS: For different body weights of child patient, every time we used the same dosage of blood coagulation factor VIII (250 U each time, 3 times a week) and observed and recorded the number of hemorrhages in child patients. Then we compared the number of hemorrhages with children without treatment to determine the curative effect. According to the different body weights, we calculated the dosage of VIII factor of blood coagulation per kilogram (hereinafter referred to as the dose), and used Spearman correlation coefficient to study the correlation between dose and curative effect. RESULTS: The number of hemorrhages in 58 child patients before the treatment was 4.36 ± 1.78, while after the treatment was 2.22 ± 1.04 (t=7.91, P<0.001). The Spearman correlation coefficient of child patients of 5-10 U/kg was -0.421 (P=0.005); the Spearman correlation coefficient of child patients of 10-15 U/kg was -0.331 (P=0.030); the Spearman correlation coefficient of child patients over 15 U/kg was -0.16 (P=0.325). CONCLUSION Prevention and treatment can significantly reduce the times of hemorrhage in hemophilia patients.
Blood Coagulation ; Child ; Factor VIII ; administration & dosage ; therapeutic use ; Hemophilia A ; therapy ; Hemorrhage ; prevention & control ; Humans

Blood Coagulation Factor Inhibitors ; antagonists & inhibitors ; blood ; Factor VIII ; administration & dosage ; antagonists & inhibitors ; immunology ; Hemophilia A ; drug therapy ; genetics ; immunology ; Humans ; Immune Tolerance ; Isoantibodies ; blood ; immunology ; Recombinant Proteins ; adverse effects ; immunology ; therapeutic use ; Risk Factors ; Time Factors

Adolescent ; Child ; Child, Preschool ; Factor IX ; administration & dosage ; therapeutic use ; Factor VIII ; administration & dosage ; therapeutic use ; Hemophilia A ; drug therapy ; prevention & control ; Hemophilia B ; drug therapy ; prevention & control ; Humans