Abstract Number: PB0051
Meeting: ISTH 2021 Congress
Background: Unfractionated heparin (UFH) is the primary anticoagulant for highly procoagulant indications including cardiopulmonary bypass (CPB) and severe COVID-19. UFH is unable to fully inhibit thrombin generation increasing the risk for thrombo-inflammatory adverse events (AEs).
We attempt to address this limitation by evaluating the FX/Xa aptamer, 11F7t. We hypothesized that combinations of UFH and 11F7t would achieve enhanced anticoagulation while minimizing thrombin generation in models of CPB and COVID-19 associated coagulopathy (CoAC).
Aims: We determined optimal combinations of UFH and 11F7t that produced CPB-sufficient anticoagulation and minimized thrombin generation in whole blood in vitro and ex vivo models of CPB. Furthermore, we aimed to determine the utility of this anticoagulation strategy in addressing CoAC.
Methods: We employed whole blood coagulation assays to determine the optimal doses of UFH and 11F7t. Fresh human blood was treated with UFH+11F7t combinations and continuously circulated in an ex vivo oxygenator circuit for 2 hours to model CPB. Thereafter, thrombin generation was assessed using ELISAs. For CoAC studies, thrombin generation from severely ill COVID-19 patient plasma was determined using the Calibrated Automated Thrombogram (CAT) assay.
Results: In in vitro and ex vivo models of CPB, a combined dose of 2U/mL UFH with 2μM 11F7t was able to achieve anticoagulation similar to the therapeutic dose of UFH (5U/mL). Further investigation into thrombin generation with ex vivo experiments showed that the combinations of UFH and 11F7t are more effective than UFH alone at limiting thrombin generation (Figure 1). Similar anticoagulation and reduced thrombin generation was observed when blood from severely ill COVID-19 patients on heparin therapy was treated with 2μM 11F7t (Figure 2).
Conclusions: This study demonstrates that combining UFH with a FX/Xa aptamer produces potent anticoagulation with reduced thrombin generation and has the potential to address CPB-associated AEs and has potential utility in other procoagulant settings such as CoAC.
To cite this abstract in AMA style:Chabata CV, Frederiksen JW, Olson LB, Naqvi IA, Sullenger BA. Combining Heparin with a FX/FXa Aptamer to Reduce Thrombin Generation in Models of Cardiopulmonary Bypass and COVID-19 Associated Coagulopathy [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/combining-heparin-with-a-fx-fxa-aptamer-to-reduce-thrombin-generation-in-models-of-cardiopulmonary-bypass-and-covid-19-associated-coagulopathy/. Accessed November 29, 2023.
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