PB1264 - Thrombin generation assay as a treatment tracking tool in hemophilia patients: a retrospective cohort study

Background: Among the progress made in severe hemophilia treatment, the predicted pharmacokinetics profile (PK) is now used to optimize prophylaxis with clotting factors. However, laboratory monitoring, bleeding treatment and inhibitor surveillance remain a challenge.

Aims: The aim of this study is to identify biological markers associated with higher bleeding risk in our cohort of severe hemophiliac patients.

Methods: This is a retrospective monocentric cohort study from January 1st 2017 to December 31st 2021. Clinical (annual number of bleedings, factor consumption and lifestyle), demographic and biological data (TGA, FVIII levels, presence of inhibitor) were reviewed. Factor VIII (FVIII) level’s measurement was performed in parallel with thrombin generation assay (TGA) in patients who underwent PK with multiple samples (baseline, half, one, two and 24 hours after FVIII injection). Incidence risk ratios (IRR) for bleeding and 95% confidence intervals were calculated in order to identify ETP thresholds associated with higher risk of bleeding.

Results: Twenty-nine severe hemophilia A patients were included (15 children and 14 adults). The median age was 17 years (3-65y). All of them were on prophylaxis (1 to 4 injections per week) with mainly Advate (41.4%) and Kovaltry (27.6%). The median annual bleeding rate was 0 (IQR 0-1). Twenty percent of patients developed inhibitors during the study period. Nearly 38% of the patients had moderate sports activity (1-2 times/week). Patients with ETP values < 300 nM*min at baseline and < 500 nM*min 24h post factor VIII injection, had significant higher risk of bleeding (respectively: IRR 3,64, IC95% 1,4-9,9; IRR 4,99 IC95% 1,8-17,2).

Conclusion(s): Based on our findings, baseline and 24 hours after FVIII infection low ETP are associated with bleedings. A prospective study on a larger cohort should be considered to validate the ETP threshold of 300 nM*min at baseline and 500nM*min at 24h.