Evaluation of EC50 of factor VIII as predictor of prophylaxis efficacy in patients with severe haemophilia A.

Autor: Fernández-Bello I; La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain., Rode F; Novo Nordisk A/S, Global Research, Måløv, Denmark., Álvarez-Román MT; La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain., Butta NV; La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain., Rivas-Muñoz S; La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain., Hernández-Moreno AL; Hospital General La Raza, Department of Pediatric Hematology, Mexico DF, Mexico., de la Corte-Rodríguez H; La Paz University Hospital, Department of Physical Medicine and Rehabilitation, Madrid, Spain., Martín-Salces M; La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain., Larsen LF; Novo Nordisk A/S, Global Research, Måløv, Denmark., Jiménez-Yuste V; La Paz University Hospital, Haematology and Haemotherapy Department, Madrid, Spain. Electronic address: vjimenezy@salud.madrid.org.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2019 Feb 01; Vol. 128, pp. 215-221. Date of Electronic Publication: 2018 Dec 07.
DOI: 10.1016/j.ejps.2018.12.003
Abstrakt: Trough factor (F) VIII level is a not reliable bleeding risk indicator to predict prophylaxis efficacy in severe haemophilia A (SHA), therefore, accurate biomarkers are much needed. Thrombelastography (TEG) monitors both thrombin and clot formation addressing the global haemostatic status but its usefulness to tailor prophylaxis in haemophilia has been poorly evaluated. In this study, correspondence between individual pharmacodynamic/pharmacokinetic profile of FVIII and joint condition, physical activity and bleeding phenotype of SHA patients under prophylactic treatment was assessed. Nineteen SHA patients < 18 years old on long-term prophylaxis treatment with FVIII were studied in an observational cross-sectional study. Whole blood was withdrawn before FVIII administration and at five time-points after infusion for a TEG-based pharmacodynamic- and pharmacokinetic-study. Type of prophylaxis and joint condition at inclusion and physical activity as well as onset of treated spontaneous bleeding events in the previous two years were retrospectively assessed. Six patients had suffered at least one treated spontaneous bleeding event and were named as "bleeders". The rest were named as "non-bleeders". Only the half maximal effective concentration of FVIII (FVIII-EC50) for TEG parameters R-time, K-time and α-angle correlated with the bleeding phenotype being significantly higher in bleeders suggestive of a poorer response to FVIII. Poorer joint condition, trough FVIII levels or type of prophylaxis were not definitive predicting variables of bleeding phenotype. In conclusion, this study reveals FVIII-EC50 for the first time as a valuable biomarker to anticipate individual efficacy of prophylaxis in SHA.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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