[Pharmacokinetic Study of Coagulation Factor Ⅷ in Adults with Severe Hemophilia A].

OBJECTIVE

To detect the pharmacokinetic (PK) parameters of coagulation factor Ⅷ (FⅧ) in adult patients with severe hemophilia A, identify the potential factors influencing FⅧ PK, and optimize the use of FⅧ in individual prophylaxis regimens.

METHODS

PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults. The correlation of patients' characteristics including age, von Willebrand factor antigen (vWF:Ag), blood group, weight, body mass index (BMI) and FⅧ genotype, with FⅧ PK were evaluated. Individual prophylaxis regimens were given based on FⅧ PK parameters.

RESULTS

The mean terminal half‑life (t1/2) of FⅧ was 20.6±9.3 h, ranged from 11.47 h to 30.12 h. The age (r =0.580) and vWF:Ag (r =0.814) were significantly positively correlated with t1/2 of FⅧ. The mean area under the plasma concentration curve (AUC) of FⅧ was 913±399 (328-1 878) IU·h/dl, and the AUC of FⅧ was positively correlated with age (r =0.557) and vWF:Ag (r =0.784). The mean residence time (MRT) of FⅧ was 24.7±12.4 (13.2-62.2) h, and the MRT of FⅧ was positively correlated with age (r =0.664) and vWF:Ag (r =0.868). The mean in vivo recovery (IVR) of FⅧ was 2.59±0.888 (1.5-4.29) IU/dl per IU/kg, the mean clearance (CL) of FⅧ was 3±1.58（0.97-7.18）ml/(kg·h)，and there was no significant correlation of IVR and CL with age and vWF:Ag. According to the individual PK parameters, ultra low-dose, low-dose and moderate-dose FⅧ were applied to 15, 6, 2 adults patients with severe hemophilia A for prophylaxis, respectively.

CONCLUSION

There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A. The older the patient, the higher the vWF:Ag level, and the longer the FⅧ half-life. Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.