BACKGROUND: 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. OBJECTIVES: Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling. PATIENTS AND METHODS: 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. RESULTS: 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 (p < 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, n = 142). FVIII: C response was reproducible in 6 out of 14 patients receiving two desmopressin administrations. CONCLUSION: 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. FVIII: 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. Schattauer Stuttgart.
BACKGROUND: 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. OBJECTIVES: Our aims were to describe FVIII:C response after desmopressin and its reproducibility by population pharmacokinetic (PK) modelling. PATIENTS AND METHODS: 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. RESULTS: 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 (p < 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, n = 142). FVIII: C response was reproducible in 6 out of 14 patients receiving two desmopressin administrations. CONCLUSION: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. FVIII: 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. Schattauer Stuttgart.
Authors: Lisette M Schütte; Marjon H Cnossen; Reinier M van Hest; Mariette H E Driessens; Karin Fijnvandraat; Suzanne Polinder; Erik A M Beckers; Michiel Coppens; Jeroen Eikenboom; Britta A P Laros-van Gorkom; Karina Meijer; Laurens Nieuwenhuizen; Evelien P Mauser-Bunschoten; Frank W G Leebeek; Ron A A Mathôt; Marieke J H A Kruip Journal: BMJ Open Date: 2019-04-23 Impact factor: 2.692
Authors: Tim Preijers; Lisette M Schütte; Marieke J H A Kruip; Marjon H Cnossen; Frank W G Leebeek; Reinier M van Hest; Ron A A Mathôt Journal: Clin Pharmacokinet Date: 2021-01 Impact factor: 6.447