PB0653 - Can thrombin generation assays be used to guide the use of anticoagulants in people with haemophilia? – an exploratory study

Background: people with haemophilia (PWH) have traditionally been thought to be ‘protected’ against thromboembolic disease. This is changing due to the ageing population and evolution in treatment paradigms targeting higher trough levels and use of non-factor replacement products (NFRT). Management of PWH who develop cardiovascular disease, venous thromboembolism or atrial fibrillation can be challenging as the safety and efficacy of anticoagulants (AC) remain uncertain in such patients. Tools such as thrombin generation (TG) assays, to guide clinical decision-making are required but have not yet been evaluated.

Aims: To assess TG parameters in PWH of varying severity +/- receiving AC, non-haemophilia patients receiving AC and healthy controls

Methods: We collected platelet poor plasma (PPP) from PWH (see table 1); patients receiving anticoagulants; and healthy controls. Samples were run on the calibrated automated thrombinoscope (CAT) (Stago, France) using PPP-Reagent (5pM tissue factor).

Results: 30 PWH, including 3 mild haemophilia receiving an anticoagulant, 10 non-haemophilia patients receiving an anticoagulant, and 3 healthy controls were included. Further details are in Table 1. Results are shown in Table 2. In the mild and mod/severe haemophilia groups, we found a correlation between factor level and endogenous thrombin potential (ETP) (p=0.01), peak height (p=0.01) and velocity index (VI) (p=0.01) but not lag time (p=0.84). PWH receiving emicizumab have ETP close to normal, but a slower time to peak, lower peak height and lower VI than healthy controls. Three mild PWH receiving an anticoagulant had TG parameters close to severe haemophilia. Non-haemophilia patients receiving an anticoagulant have similar ETP to healthy control, but slower time to peak, and lower peak height and VI.

Conclusion(s): TG assays may prove to be a useful as an adjunctive tool in guiding the use of anticoagulation in PWH particularly in the era of NFRT, but larger studies are needed with clinical outcome correlates.