Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients

NCT02540187 | Completed

• 1 other identifier: 1108164
• Study Type: observational
• Target: 164
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Hemophilia

Keywords

haemophilia; TFPI; thrombin generation; hemorrhagic score

Outcome Measures

Primary Outcomes (3)

• Comparison for TFPI level between Haemophilia A and Haemophilia B

  Comparison for TFPI level between Haemophilia A and Haemophilia B

  day 1

• Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B

  Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B

  Day 1

• Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B

  Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B

  Day 1

Secondary Outcomes (14)

• Correlation between free TFPI and hemorrhagic score

  day 1

• Correlation between TFPI activity and hemorrhagic score

  day 1

• Correlation between Endogenous Thrombin Potential (ETP) and free TFPI

  day 1

• Correlation between Lag Time and free TFPI

  day 1

• Correlation between Peak value and free TFPI

  day 1

Study Arms (2)

haemophilia A

1. Blood specimen for measuring : * Free TFPI and TFPI activity levels * Thrombin generation in platelet rich plasma (PRP) and platelet poor plasma (PPP) * Thrombin generation assay (TGA) in fresh PRP and frozen PPP 2. Hemorrhage score for each patient

Other: blood specimen

Haemophilia B

1. Blood specimen for measuring : * Free TFPI and TFPI activity levels * Thrombin generation in platelet rich plasma (PRP) and platelet poor plasma (PPP) * Thrombin generation assay (TGA) in fresh PRP and frozen PPP 2. Hemorrhage score for each patient

Other: blood specimen

Interventions

blood specimen OTHER

Haemophilia B; haemophilia A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease

You may qualify if:

• Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease, who have signed the informed consent form
• On-demand or on prophylactic therapy.
• Regular monitoring in investigator center.

You may not qualify if:

• \- Haemophilia patients under 18.
• Presence of an inhibitor at any time before or during the study period.
• Patients who received factor VIII concentrate less than 72 hours or factor IX concentrate less than 96 hours before blood collection
• Patients who refused to sign informed consent
• Patient data over the last 5 years at least not available.
• No regular monitoring in haemophilia center (required at least one visit every 18 months for severe or moderate hemophiliac patients).

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Pfizer: collaborator

Study Sites (7)

CHRU Lille

Lille, France

Location

HCL

Lyon, France

Location

AP-HM

Marseille, France

Location

Chu Nancy

Nancy, France

Location

Chu Reims

Reims, France

Location

CHU Saint-Etienne

Saint-Etienne, 42055, France

Location

Chu Tours

Tours, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood specimen

MeSH Terms

Conditions

Hemophilia A

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2015
• First Posted: September 3, 2015
• Study Start: February 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: March 10, 2016

Record last verified: 2016-03

Locations

FR (7)