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.

Efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A.</p><p><b>METHODS</b>Thirteen adult Chinese patients with severe hemophilia A receiving on-demand or low-dose prophylaxis underwent ultrasound examination of the target joints and evaluation of Hemophilia Joint Health Score (HJHS). The data of annual bleeding episodes in the period of on-demand or low-dose prophylaxis were collected retrospectively from the patients, and the changes in bleeding and joint condition (ultrasound findings of the target joints and HJHS) were observed during short-term full-dose prophylaxis. The activity intensity of the patients was assessed using the IPAQ questionnaire, and the 72 h FⅧ trough activity was measured during full-dose prophylaxis.</p><p><b>RESULTS</b>The median age of the 13 patients was 26.0 (20.5-29.0) years. For full-dose prophylaxis, the patients received a median therapeutic dose of 31.0 (29.1-33.0) IU/kg, administered for 3 times per week; the median 72 h FⅧ trough activity of patients was 1.7% (1.3-3.4%). During the follow-up period for 3 months, the annual bleeding rates (ABR) and annual joint bleeding rates (AJBR) decreased significantly in all the patients (=0.001 and 0.001, respectively), but zero bleeding was achieved in only 4 patients (30.8%) and zero joint bleeding in 7 patients (53.8%); 9 patients (69.2%) still experienced breakthrough bleeding. The damage severity of target joints assessed by ultrasound and HJHS in 6 patients (46.2%)was worse than before and no obvious progression of target joints damage was found in 7 patients (53.8%). Compared with the patients without progression, the patients with worsened joint damage had poorer baseline joint condition, higher bleeding frequencies before and during the follow-up, a higher intensity of physical activity, and a lower baseline FⅧ activity.</p><p><b>CONCLUSIONS</b>At present, although short-term full-dose prophylaxis can significantly reduce the bleeding and partially prevent the progression of joint damage, it is not yet possible to achieve the goal of zero bleeding for all adult patients with severe hemophilia A in China, nor can it completely prevent further joint damage. For adult patients with different clinical bleeding phenotypes, joint conditions and physical activity intensity, individualized therapy involving additional evaluation methods should be implemented, and physiotherapy and surgical intervention can be considered when necessary.</p>

A Case of Secondary Pulmonary Hemosiderosis in a severe Hemophilia A with High Titer of FactorVIII Inhibitor / 대한소아혈액종양학회지

An 18-Year-old male hemophiliac with high titer of factorVIII inhibitor, stage V hemophilic arthropathy in right knee joint and a history of hematuria and retroperitoneal hemorrhage was admitted because of acute and massive bleeding of epistaxis, pulmonary hemorrhage and intestinal bleeding. The bleeing was not controolled by massive infusion of factorVIII concentrates but by prothrombin complex concentrates and high dose of factorVIII concentrates. He showned symptoms of sustained fever and diffuse pulmonary infiltration which was diagnosed as pulmonary hemosiderosis by MRI. We suppressed his immune reaction by prednisolne to prevent the formation of factorVIII inhibitor. He has been followed up for 3 years and shown no massive bleeding there-after.