Hemophilia Clinical Trial
Official title:
Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
Haemophilia is a rare and serious congenital defect of blood coagulation due to a genetic
mutation on a sexual chromosome. It affects quasi-essentially the men and it is responsible
for bleeding. There are two types of haemophilia: Haemophilia A, (85 % of cases), due to a
factor VIII (FVIII) deficiency and Haemophilia B (15 % of cases) due to factor IX (FIX)
deficiency. According to the intensity of the defect, there are three forms of haemophilia:
severe (FVIII or FIX lower than 1 %), moderate (factor level between 1 and 5 %), minor
(factor level between 5 and 40 %). For a same level of factor VIII or IX, hemorrhagic
manifestations are variable from one patient to the other. Moreover, several studies showed
that haemophilic B patients bleed less and consume fewer anti-hemophilic concentrate that
haemophilic A patients.
The main inhibitors of the coagulation are antithrombin, Protein C-Protein S-Thrombomodulin
system, and tissue factor pathway inhibitor (TFPI). TFPI is the specific and exclusive
inhibitor of tissue factor pathway that is the main way by which plasmatic coagulation
starts. TFPI is a potent direct inhibitor of factor Xa and Xa-dependent inhibitor of the
VIIa-Tissue Factor (TF) complex. In hemophilic patient, the production of Xa by the
amplification pathway being strongly altered because of factor VIII or IX deficiency,
thrombin generation (via Xa) comes exclusively from TFPI regulated tissue factor pathway. We
can thus say that if haemophilic patients bleed, it is also because of the presence of TFPI
that inhibits at the same time Xa and the complex TF-VIIa as soon as factor Xa is generated.
n/a
Observational Model: Cohort, Time Perspective: Prospective
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