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Prediction of individual factor VIII or IX level for the correction of thrombin generation in haemophilic patients.

  • Chelle, P1, 2
  • Montmartin, A2
  • Piot, M2
  • Ardillon, L3
  • Wibaut, B4
  • Frotscher, B5
  • Cournil, M1, 2
  • Morin, C1, 2
  • Tardy-Poncet, B2, 6, 7
  • 1 Mines saint-Etienne, Univ Lyon, Univ Jean Monnet, INSERM, Centre CIS, Saint Etienne, France. , (France)
  • 2 INSERM, U1059, SAINBIOSE, Univ Lyon, Saint Etienne, France. , (France)
  • 3 Service d'Hématologie-Hémostase, CHU Trousseau, Tours Cedex, France. , (France)
  • 4 Unité d'Hémostase Clinique, Institut Cœur Poumon, Haemophilia Treatment Centre, CHRU Lille, Lille, France. , (France)
  • 5 Haemophilia Treatment Centre, CHU Nancy, Vandoeuvre-lès-Nancy, France. , (France)
  • 6 INSERM, CIC 1408, FCRIN-INNOVTE, Saint-Etienne, France. , (France)
  • 7 CHU Saint-Etienne, Haemophilia Treatment Centre, UMI, Hôpital Nord, Saint-Etienne, France. , (France)
Published Article
Haemophilia : the official journal of the World Federation of Hemophilia
Publication Date
Nov 01, 2018
DOI: 10.1111/hae.13539
PMID: 29957846


The thrombin generation (TG) assay can assess individual clotting potential. The thrombin generation potential is correlated with the patient's bleeding phenotype and varies from one patient to the other for the same degree of factor VIII or IX deficiency. To define in vitro for individual haemophilic patients the target factor VIII or IX level required to normalize their TG. Plasmas from 20 haemophilic patients were spiked with increasing levels of the deficient coagulation factor and TG parameters were measured. The relationships between factor levels and TG parameters were determined by linear regression. The normal range of thrombin generation was defined in 39 healthy male volunteers. Despite inter-individual heterogeneity in basal TG and responses to spiking, a linear relationship was found between factor VIII or IX levels and TG parameters for individual patients. Based on the individual responses of patient plasmas to spiking, it is possible to define in vitro the target factor VIII or IX levels needed to normalize the TG parameters. For both haemophilic A and haemophilic B patients, significant correlations were found between basal peak values and their correction slopes. The correction slope was steeper in haemophilic B patients, so the factor IX level needed to normalize the TG parameters was lower than for haemophilic A patients. The TG assay could be used to determine in vitro the patient-specific factor VIII or IX level to be reached to effectively normalize their TG. These in vitro results should be confirmed by ex-vivo studies. © 2018 John Wiley & Sons Ltd.

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