Patient-specific half maximal factor VIII effective concentrations measured using thromboelastography may be an accurate biomarker to predict efficacy of prophylaxis in severe hemophilia A.
Ihosvany Fernández-Bello, PhD, of La Paz University Hospital in Spain, along with his colleagues, used thromboelastography to investigate the pharmacodynamics of FVIII in young patients with severe hemophilia A who were under a long-term-prophylactic regimen. The findings of the observational, cross-sectional study were published in the European Journal of Pharmaceutical Sciences.
The researchers followed 19 patients under 18 years of age with severe hemophilia A receiving prophylactic treatment. They analyzed their joint condition, bleeding phenotype, and physical activity, compared with their individual pharmacodynamic/pharmacokinetic parameters of FVIII.
They analyzed whole blood withdrawn before FVIII administration and at five time points after treatment. Treated spontaneous bleeding events in the previous 2 years were retrospectively assessed.
Dr. Fernández-Bello and his colleagues measured half maximal factor VIII effective concentrations using thromboelastography, which was correlated with variables related to individual bleeding phenotype.
After analysis, only half maximal FVIII effective concentration of FVIII for thromboelastography parameters R-time, K-time, and alpha-angle were correlated with the bleeding phenotype. Other parameters, including joint condition, type of prophylaxis regimen, and FVIII trough concentrations were not predictive of bleeding phenotype.
“Our results are encouraging and offer the added value of having been obtained in a particularly fragile population considered particularly difficult to study,” they wrote.
The authors noted two key limitations were the small sample size and retrospective nature of the study. Despite the low number of participants, statistical significance of key bleeding outcomes were still achieved.
“This study reveals [half maximal effective concentration of FVIII] for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in [severe hemophilia A],” they concluded.
The study was supported by grant funding from Novo Nordisk, the World Federation of Hemophilia, and the Spanish Society of Thrombosis and Hemostasis. The authors’ financial affiliations were not reported.
SOURCE: Fernández-Bello I et al. Eur J Pharm Sci. 2019 Feb 1;128:215-21.