Thrombin Generation Numerical Models Validation in Haemophilic Case
Condition: Haemophilia B; Haemophilia A
MeSH terms: Hemophilia A; Hemophilia B
Study type: Observational

Summary: 
      Personalized therapy in haemophilia has not been reached yet. Treatment is substitutive and
      its doses are only based on the levels of deficient factor VIII (for haemophilia A) or IX
      (for haemophilia B). The bleeding severity is not only related to the factor deficiency but
      also to levels of other coagulation factors (e.g. factor X, II, AT or TFPI). It's necessary
      to take them into account in order to individualize treatments; and Thrombin Generation Assay
      (TGA) with the CAT method (Calibrated Automated Thrombography) is a good way because it
      measures the result of the coagulation cascade. TGA on Platelet Rich Plasma (PRP) is even
      closer to physiological conditions than on Platelet Poor Plasma (PPP) because platelet
      influence is represented. It has already been shown (at least in PPP) that the bleeding
      tendency in haemophilic patients is usually well correlated to TG. Some TG parameters are
      used to characterize the individual coagulation phenotype, the most important being the
      Endogenous Thrombin Potential (ETP) and the Lag Time (LT). A hemorrhagic profile usually
      provides a longer lag time and / or a lower ETP. However, only few studies tried to determine
      the influence of each coagulation factor and inhibitor on TG. They were done on Platelet Poor
      Plasma (PPP) or on lyophilized plasma. So the relation between coagulation factors and the
      different TG parameters remains to be determined, especially in the haemophilic case. It is
      possible, experimentally, to find the optimal dose of the factor to be added by measuring TG
      in samples with different factor VIII or IX concentrations, but this method would be time
      consuming and expensive, especially because it should be done for each haemophilic patient. A
      better way consists in using TG numerical models. For a set of initial factor levels they
      simulate the TG and its associated parameters. It is now essential to validate the existing
      models, especially in haemophilic cases, in order to see whether they are reliable and can be
      used in clinical practice afterwards.The objective of this study is to validate thrombin
      generation numerical models which could predict the factor VIII or IX activity correction to
      reach a thrombin generation sufficient to avoid bleeding. A comparison between the TG
      observed in haemophilic patients and the TG predicted by the models is needed to validate the
      models. In order to define a 'safe' TG i.e. sufficient to avoid bleeding, normal ranges of TG
      parameters have to be measured.
    


Intervention name(s): blood sampling
Intervention type(s): Other
Intervention description(s): Samplings will be taken on 4 citrated S-monovette tubes, 3 citrated tubes and 1 EDTA tube, namely 36.5 ml for each volunteer
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        volunteers witch work in CHU Saint-Etienne
      
Biospecimen description: 
      blood
    
Keywords: Haemophilia; numerical models; thrombin generation; volunteers; endogenous thrombin potential