Abstract Number: PB0787
Meeting: ISTH 2022 Congress
Background: Treatment with triple antithrombotic therapies may increase bleeding risks in patients.
Aims: We evaluated antithrombotic and prohemorrhagic actions of the combination of different concentrations of apixaban (APIX) in an exploratory study in patients exposed to current antiplatelet regimens.
Methods: A total of 25 healthy subjects and 53 patients treated with aspirin (ASA, n=21), ASA and clopidogrel (ASA+CLOPI, n=11), or ASA and ticagrelor (ASA+TICA, n=21) participated in the study. Studies were carried out ex vivo spiking blood samples from participants with 0 (APIX0), 40 (APIX40) and 160 ng/mL (APIX160). Specific tests were performed to detect high on-treatment platelet reactivity (HPR). We assessed the inhibitory effects of APIX on: 1) clot formation, by ROTEM thromboelastometry; 2) thrombin generation primed by platelets; and 3) platelet and fibrin interactions onto a thrombogenic surface, in an experimental microfluidic model with circulating blood.
Results: No evidence of HPR was detected in this study. Incubation with APIX caused a dose-related prolongation of the clotting time with minimal impact on other ROTEM parameters. Thrombin generation was significantly inhibited by APIX 160 ng/mL and moderately affected by the antiplatelet therapies being more intense in patients under ASA+TICA and decreasing slightly for ASA+CLOPI and ASA treated populations. Confocal analysis of microfluidic studies revealed a progressive antithrombotic activity for APIX and antiplatelet therapies. APIX 160 ng/mL was more potent to suppress platelet and fibrin interactions. APIX 40 ng/mL demonstrated a consistent antithrombotic action reducing platelet and fibrin interactions, but proved more respectful at preserving hemostatic parameters with all antiplatelet regimens.
Conclusion(s): APIX potentiated the antithrombotic effects of current antiplatelet regimens. At 40 ng/mL APIX shows an enhanced antithrombotic action in combination with the different antiplatelet regimens, but seems more conservative for hemostasis than the concentrations of 160 ng/mL that assimilates to the Cmax reached after the recommended dose for thromboprophylaxis.
To cite this abstract in AMA style:Martinez-Sanchez J, Castrillo L, Jerez D, Torramade-Moix S, Palomo M, Mendieta G, Zafar U, Badimon J, Roque M, Escolar G, Diaz-Ricart M. Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and double antiplatelet regimens [abstract]. https://abstracts.isth.org/abstract/antithrombotic-and-prohemorrhagic-actions-of-different-concentrations-of-apixaban-in-patients-exposed-to-single-and-double-antiplatelet-regimens/. Accessed September 27, 2023.
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