Antithrombotic drug removal from whole blood using Haemoadsorption with a porous polymer bead sorbent

Author:

Tripathi Ritu1ORCID,Morales Jesus1,Lee Victoria1,Gibson C Michael2,Mack Michael J3,Schneider David J4,Douketis James5,Sellke Frank W6,Ohman Magnus E7,Thourani Vinod H8,Storey Robert F9,Deliargyris Efthymios N1

Affiliation:

1. CytoSorbents Medical Inc. 305 College Road E, Princeton, NJ-08540 , USA

2. Department of Medicine at Beth Israel Deaconess Medical Center, The Baim Institute and Harvard Medical School , Boston, MA-02215 , USA

3. Baylor Scott & White Health, Baylor Scott & White Research Institute , Dallas, TX-75093 , USA

4. Department of Medicine, Cardiovascular Research Institute, University of Vermont , Burlington VT-05401 , USA

5. Vascular Medicine and General Internal Medicine, St. Joseph's Healthcare Hamilton, McMaster University , ON-L9C 0E3 , Canada

6. Division of Cardiothoracic Surgery, Alpert Medical School of Brown University , Providence RI-02903 , USA

7. Duke Clinical Research Institute, Duke Heart Center, Duke Program for Advanced Coronary Disease, Duke University Medical Center , Durham, NC-27701 , USA

8. Department of Cardiovascular Surgery, Marcus Valve Center, Piedmont Heart Institute , Atlanta, GA-30309 , USA

9. Cardiovascular Research Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield , Sheffield S10 2RX , UK

Abstract

Abstract Aim To evaluate the ability of the DrugSorb™-AntiThrombotic Removal (ATR) haemoadsorption device utilizing porous polymer bead sorbent technology to remove three commonly used antithrombotic drugs from whole blood. Methods and results We evaluated the removal of apixaban, rivaroxaban, and ticagrelor by the DrugSorb-ATR haemoadsorption device in a benchtop clinical scale model using bovine whole blood. Blood spiked at clinically relevant concentrations of an antithrombotic agent was continuously circulated through a 300-mL DrugSorb-ATR haemoadsorption device at a flow rate of 300 mL/min. Drug concentration was monitored over 6 h to evaluate drug removal. Results were compared with a control circuit without the haemoadsorption device. Removal rates at 30, 60, 120, and 360 minutes were: apixaban: 81.5%, 96.3%, 99.3% >99.8%; rivaroxaban: 80.7%, 95.1%, 98.9%, >99.5%; ticagrelor: 62.5%; 75%, 86.6%, >95% (all P <0.0001 vs. control). Blood pH and haematological parameters were not significantly affected by the DrugSorb-ATR haemoadsorption device when compared with the control circuit. Conclusion DrugSorb-ATR efficiently removes apixaban, rivaroxaban, and ticagrelor in a clinical-scale benchtop recirculation circuit with the bulk of removal occurring in the first 60 minutes. The clinical implications of these findings are currently investigated in patients undergoing on-pump cardiothoracic surgery in two US pivotal trials (ClinicalTrials.gov Identifiers: NCT04976530 and NCT05093504).

Funder

CIHR

HSFC

Boehringer Ingelheim

AGEN

AstraZeneca

Bayer

Biotie

BMS

Daiichi Sankyo Company

Portola Pharmaceuticals

Cytori

Janssen Pharmaceuticals

Leo Pharma

Pfizer

Medicines Company

Servier

Bristol Meyers Squibb

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Cardiology and Cardiovascular Medicine

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