Department of Haematology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Hospital Pharmacy, Academic Medical Centre, Amsterdam, The Netherlands.
Thromb Haemost. 2018 Apr;118(4):621-629. doi: 10.1160/TH17-06-0390. Epub 2018 Feb 19.
Nonsevere haemophilia A (HA) patients can be treated with desmopressin. Response of factor VIII activity (FVIII:C) differs between patients and is difficult to predict.
Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling.
Retrospective data of 128 nonsevere HA patients (age 7-75 years) receiving an intravenous or intranasal dose of desmopressin were used. PK modelling of FVIII:C was performed by nonlinear mixed effect modelling. Reproducibility of FVIII:C response was defined as less than 25% difference in peak FVIII:C between administrations.
A total of 623 FVIII:C measurements from 142 desmopressin administrations were available; 14 patients had received two administrations at different occasions. The FVIII:C time profile was best described by a two-compartment model with first-order absorption and elimination. Interindividual variability of the estimated baseline FVIII:C, central volume of distribution and clearance were 37, 43 and 50%, respectively. The most recently measured FVIII:C (FVIII-recent) was significantly associated with FVIII:C response to desmopressin ( < 0.001). Desmopressin administration resulted in an absolute FVIII:C increase of 0.47 IU/mL (median, interquartile range: 0.32-0.65 IU/mL, = 142).
C response was reproducible in 6 out of 14 patients receiving two desmopressin administrations.
FVIII:C response to desmopressin in nonsevere HA patients was adequately described by a population PK model. Large variability in FVIII:C response was observed, which could only partially be explained by FVIII-recent.
C response was not reproducible in a small subset of patients. Therefore, monitoring FVIII:C around surgeries or bleeding might be considered. Research is needed to study this further.
非重度血友病 A (HA) 患者可采用去氨加压素进行治疗。患者间因子 VIII 活性 (FVIII:C) 的反应存在差异，且难以预测。
本研究旨在描述去氨加压素治疗后的 FVIII:C 反应，并通过群体药代动力学 (PK) 模型进行其重现性研究。
回顾性分析 128 例接受静脉或鼻内给予去氨加压素的非重度 HA 患者 (7-75 岁) 的数据。采用非线性混合效应模型进行 FVIII:C 的 PK 建模。FVIII:C 反应的重现性定义为两次给药时的峰值 FVIII:C 差异小于 25%。
共纳入 142 次去氨加压素给药的 623 次 FVIII:C 测量值；14 例患者在不同时间接受了 2 次给药。FVIII:C 时间曲线最佳拟合模型为具有一级吸收和消除的两室模型。所估计的基础 FVIII:C、中央分布容积和清除率的个体间变异分别为 37%、43%和 50%。最近测量的 FVIII:C (FVIII-recent) 与去氨加压素的 FVIII:C 反应显著相关 ( < 0.001)。去氨加压素给药后 FVIII:C 的绝对增加值为 0.47 IU/mL (中位数，四分位间距：0.32-0.65 IU/mL， = 142)。在接受 2 次去氨加压素给药的 14 例患者中，有 6 例的 FVIII:C 反应具有重现性。
非重度 HA 患者去氨加压素治疗后的 FVIII:C 反应可通过群体 PK 模型充分描述。观察到 FVIII:C 反应存在较大的变异性，仅部分可由 FVIII-recent 解释。在一小部分患者中，FVIII:C 反应不可重现。因此，可能需要考虑在手术或出血前监测 FVIII:C。需要进一步研究来对此进行研究。
