PB1154 - Impact of emicizumab on anticoagulant drugs at therapeutic concentrations using thrombin generation assay

Background: Emicizumab is a non-substitutive prophylactic treatment approved for patients with severe haemophilia A (HA). Emicizumab is a bispecific monoclonal antibody mimicking the activity of factor VIII (FVIII) that binds to factors IXa and factor X. Studies have shown that emicizumab can also bind to factor Xa. Under particular clinical situations, even in patients with HA, an anticoagulant therapy is needed.

Aims: The potential interference of emicizumab on the anticoagulant effect of therapeutic drugs is poorly evaluated.

Methods: FVIII-deficient plasma (Siemens®) and a pool of normal plasma (PNP) were used to assess the thrombin generation in the presence of anticoagulant drugs (UFH, LMWH, fondaparinux, rivaroxaban, apixaban, dabigatran) at therapeutic doses alone or in presence of emicizumab. Thrombin generation was evaluated on the ST-Genesia (Stago®) with the STG-BleedScreen reagent (Stago®). The anticoagulant effect of heparins or DOACs in the absence or presence of emicizumab (50 μg/mL) was assessed using the inhibition of ETP and the peak-thrombin and the increase of lag-time.

Results: Addition of emicizumab (50 μg/mL) to FVIII-deficient plasma significantly increased thrombin generation parameters (equivalent to a plasma containing 0.1 to 0.2 IU/mL of FVIII). Under our experimental conditions, the different anticoagulant-drug tested (UFH 0.3-0.6 IU/mL, LMWH 0.5-1.5 IU/mL, DOACs 20 to 500 ng/mL) significantly inhibited thrombin generation. The addition of emicizumab (50μg/mL) did not alter the anticoagulant action of tested drugs. The inhibition of ETP and peak-thrombin and the increase of lag-time were not significantly different in presence of emicizumab.

Conclusion(s): To our knowledge, this is the first study evaluating the interference of emicizumab on the action of different anticoagulant drugs including heparins and DOACs. These results suggest the absence of impact of emicizumab, at a therapeutic dose, on the anticoagulant effect of heparins and DOACs. These data need to be confirmed in samples from severe HA A patients treated with emicizumab.