OKL-1111, A modified cyclodextrin as a potential universal reversal agent for anticoagulants
Joost C M Meijers1, Kamran Bakhtiari2, Alex Zwiers3
1Department of Molecular Hematology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Thrombosis Research
|May 19, 2023
Summary
A novel cyclodextrin compound, OKL-1111, effectively reverses the anticoagulant effects of direct oral anticoagulants (DOACs) and other antithrombotic agents. This procoagulant agent shows potential as a universal reversal agent for bleeding complications.
Area of Science:
- Pharmacology
- Biochemistry
- Hematology
Background:
- Antithrombotic therapy carries a significant bleeding risk, necessitating effective reversal agents.
- Current specific reversal agents for direct oral anticoagulants (DOACs) are expensive and limit practical application.
- A novel class of cyclodextrins with procoagulant properties has been identified.
Purpose of the Study:
- To characterize the lead compound OKL-1111, a cyclodextrin with procoagulant properties.
- To evaluate OKL-1111's potential as a universal reversal agent for anticoagulants and antiplatelet drugs.
Main Methods:
- In vitro thrombin generation assay to assess OKL-1111's effect on coagulation with and without DOACs.
- Rat tail cut bleeding model to evaluate in vivo reversal of various anticoagulants.
- Wessler model in rabbits to assess potential prothrombotic activity.
Main Results:
- OKL-1111 concentration-dependently reversed the anticoagulant effects of DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) in vitro.
- In vivo, OKL-1111 reversed anticoagulation from all tested DOACs, warfarin, enoxaparin, fondaparinux, and clopidogrel.
- OKL-1111 demonstrated no prothrombotic effects in the Wessler model.
Conclusions:
- OKL-1111 is a procoagulant cyclodextrin with potential as a universal reversal agent.
- The precise mechanism of action for OKL-1111 remains to be elucidated.
- OKL-1111 offers a promising solution for managing bleeding complications associated with antithrombotic therapies.
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