Prediction of Coagulation Factor Ⅷ Level in Chinese Hemophilia A Patients by the Pharmacokinetic Management Tool myPKFiT / 中国医学科学院学报

Objective To evaluate the performance of myPKFiT,a tool guiding the dosing of antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM),in maintaining the coagulation factor Ⅷ (FⅧ) level above a target threshold at the steady state and estimating the pharmacokinetics (PK) parameters in hemophilia A patients in China. Methods The data of 9 patients with severe hemophilia A in a trial (CTR20140434) assessing the safety and efficacy of rAHF-PFM in the Chinese patients with hemophilia A were analyzed.The myPKFiT was used to predict the adequate dose to maintain a patient's FⅧ level above target threshold at the steady state.Furthermore,the performance of myPKFiT in estimating the pharmacokinetics parameters of individuals was evaluated. Results Twelve combinations of two dosing intervals and six sparse sampling schedules were investigated,and 57%-88% of the patients remained the FⅧ level above the target threshold of 1 U/dl (1%) for at least 80% of the dosing interval.The clearance and time to FⅧ level of 1% obtained from sparse sampling by myPKFiT were similar to those obtained from extensive sampling. Conclusions The myPKFiT can provide adequate dose estimates to maintain the FⅧ level above the target threshold at the steady state in Chinese patients with severe hemophilia A.Moreover,it demonstrates good performance for estimating key pharmacokinetics parameters,including clearance and time to FⅧ level of 1%.

Pharmacokinetics of Recombinant Human Coagulation Factor Ⅷ Preparations in Patients with Severe Hemophilia A / 中国实验血液学杂志

OBJECTIVE@#To calculate the pharmacokinetic parameters of recombinant human coagulation factor Ⅷ using myPKFiT in patients with severe hemophilia A, and provide an individualized treatment plan for patients.@*METHODS@#A total of 42 patients with severe hemophilia A who were treated with recombinant human coagulation factor Ⅷ were included from January 2021 to December 2021. myPKFiT was used to calculate the pharmacokinetic parameters of FⅧ, and the individualized treatment plan for hemophilia A patients was formulated.@*RESULTS@#The median age of 42 patients with severe hemophilia A was 31（16-50） years old, the average weight was 54.0±9.9 kg, the half-life of FⅧ was 12.05±1.6 h, the time to more than 1% of the baseline was 62.3±15.3 h, and the 0 bleeding rate after the guidance of myPKFiT was significantly increased from 39% to 49%, the Annual bleeding rate was reduced from 3.6±2.5 to 2.1±2.0, and the Annual joint bleeding rate was reduced from 3.2±2.2 to 1.9±0.9, all of which were statistically different (P<0.05).@*CONCLUSION@#Individualized therapy in patients with severe hemophilia A who were guided by myPKFiT assay of pharmacokinetics parameters can significantly reduce the annual bleeding rate and annual joint bleeding rate of patients.

Effect of plasma freezing temperature, anticoagulant and time of storage on factor VIII: C activity in cryoprecipitate

The influence of ACD and CPDA-1 anticoagulants, and storage time for 3 and 6 months on F VIII:C activity were compared in cryprecipitate obtained at -70ºC, and -30ºC plasma freezing temperature. To eliminate variations in F VIII:C activity between donor plasma, the cryoprecipitation at -70ºC and -30ºC was made in paired plasma volumes (approximately 100 ml) from each blood unit. Employing ACD plasmas (n= 50), there was no significant difference in F VIII:C activity between cryoprecipitate prepared at -70ºC (X=31.1 IU/bag) and -30ºC was made in paired plasma volumes (approximately 100 ml) from each blood unit. Employing ACD plasmas (n= 50), there was no significant difference in F VIII:C activity between cryprecipitate prepared at -70ºC (X= 31.1 IU/bag) and -30ºC (X = 30.5 IU/bag), and the storage did not modifify FVIII:C activity. In contrast, in cryprecipitate prepared from CPDA-1 plasma (n= 31), the F VIII:C levels obtained at-30ºC (X= 43.8IU/bag) were significantly higher than those at-70ºC (X=37.3 IU/bag), but a deterioration of F VIII:C activity (about 50 percent) was observed after 6 months of cryprecipitate storage. Therefore, if cryprecipitate is stored it stored it would be more convenient to use ACD instead of CPDA-1 and make cryoprecipitation either at-70ºC or-30ºC