Individually Tailored Prophylaxis in Patients With Severe Hemophilia A

Optimizing Prophylaxis in Patients With Severe Haemophilia A by Tailoring the Infusions to Individual Patients' Needs Using the Calibrated Automated Thrombin Generation Test

Patients with severe haemophilia A lack clotting factor FVIII and suffer from spontaneous and traumatic bleeds. In the absence of treatment, frequent bleeds in joints lead to severe joint destruction. In 1960s, prophylactic therapy was developed involving the infusion of clotting factor on a regular schedule in order to keep clotting levels sufficiently high to prevent spontaneous bleeding episodes. Prophylaxis is started at an early age before the age of 2 years or after the first joint bleed. The Malmö experience indicates that treatment is most effective when administered in large doses at least 3 times weekly. However, such an intensive treatment in young boys may be very difficult to carry out for home treatment. Currently, there is no international recommendation on prophylactic therapy regimens. Because of the high cost and limited availability of factor concentrates, dosing is an important issue in prophylaxis therapy. It was recently shown that 24 hours after FVIII concentrate administration, in patients presenting similar FVIIII levels, thrombin generation capacity may be significantly different. In addition, independently of the FVIII level, a correlation was found between severe clinical bleeding phenotype and thrombin generating capacity. The aim of the present clinical study is to assess the thrombin generation test as the main surrogate marker to evaluate the coagulating capacity of haemophiliacs on prophylaxis regimen. Optimizing prophylactic therapy to patient's phenotype with no loss of clinical effectiveness can significantly improve patients' quality of life, protect haemophilic children against arthropathy and possibly limit the cost of the prophylaxis therapy.

Inclusion Criteria:

• Severe haemophilia A (FVIII < 1 IU/dl)
• Currently on prophylactic therapy administered at least 3 times per week with a clinical efficiency
• Age: 6 - 45 years
• Adequate venous access in adults and children i.e. presence of 2 or more good quality peripheral veins, in order to avoid the need for a central venous device. One peripheral vein for FVIII infusions and one other for blood sampling are required.
• Competent in home treatment and infusion therapy (patient or parents)
• Ability of patient or family (for minors) to give informed consent
• Patient affiliated to French Social Insurance System.

Exclusion Criteria:

• Age < 6 years and > 45 years
• Hemophilia A with documented history of inhibitor
• Clinically symptomatic liver disease (supported by e.g. diagnosis of cirrhosis, portal hypertension, ascites, PT > 5 seconds above upper limit of normal)
• Platelet count < 100x109/l
• Planned elective surgery within 13 months
• Poor venous access according inclusion criteria
• Presence of a documented target joint