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Sustained pro-haemostatic activity of rFVIIa in plasma and platelets in non-bleeding pigs may explain the efficacy of a once-daily prophylaxis in humans

Schut, A. M., Hyseni, A., Adelmeijer, J., Meijers, J. C. M., de Groot, P. G. & Lisman, T., Aug-2014, In : Thrombosis and Haemostasis. 112, 2, p. 304-310 7 p.

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  • Sustained pro-haemostatic activity of rFVIIa in plasma and platelets in non-bleeding

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DOI

  • A. M. Schut
  • A. Hyseni
  • J. Adelmeijer
  • J. C. M. Meijers
  • P. G. de Groot
  • T. Lisman

Recombinant factor Vila (rFVIIa) is registered for treatment of inhibitor-complicated haemophilia, and a once-daily prophylactic administration of rFVIIa is successful in reducing the number of bleeding events. This suggests that a single rFVIIa dose has a pro-haemostatic effect up to 24 hours (h), which is difficult to explain given its half-life of 2 h. In this study, six pigs received a 90 mu g/kg rFVIIa bolus. Plasma was collected and platelets were isolated at various time points up to 48 h, and analysed for FVIIa levels and associated haemostatic activity. Elevated plasma FVIIa levels were detected up to 24 h post-administration (36 (32-56) mU/ml [median (interquartile range [IQR]), 24 h] vs 2 (2-14) mU/ml [baseline]). Corresponding prothrombin time (PT) values remained shortened compared to baseline until 24 h post-ad-ministration (9.4 (9.3-9.9) secohds (s) 124 h] vs 10.5 (10.2-11.0) s [baseline], p

Original languageEnglish
Pages (from-to)304-310
Number of pages7
JournalThrombosis and Haemostasis
Volume112
Issue number2
Publication statusPublished - Aug-2014

    Keywords

  • Factor VIIa, haemophilia, prophylaxis, platelet, thrombin generation, RECOMBINANT FACTOR VIIA, ACTIVATED FACTOR-VII, HEMOPHILIA PATIENTS, INHIBITORS, REGISTRY, PHARMACOKINETICS, MANAGEMENT, ABILITY

ID: 13843773