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Antithrombotic and prohemorrhagic actions of different concentrations of apixaban in patients exposed to single and double antiplatelet regimens

1Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain., Barcelona, Catalonia, Spain, 2Department of Cardiology, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain., Barcelona, Catalonia, Spain, 3Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Barcelona, Catalonia, Spain, 4Department of Cardiology, Hospital Clinic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain., Barcelona, Catalonia, Spain, 5Department of Medicine, AtheroThrombosis Research Unit (ATRU), Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA., New York, New York, United States, 6Department of Medicine, AtheroThrombosis Research Unit (ATRU), Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, USA,, New York, New York, United States, 7Hospital Clinic, IDIBAPS, University of Barcelona, Spain, Barcelona, Catalonia, Spain

Abstract Number: PB0787

Meeting: ISTH 2022 Congress

Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Antiplatelet Therapy

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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