Abstract Number: PB0127
Meeting: ISTH 2021 Congress
Background: Predictable pharmacokinetics allows for subcutaneous injection of enoxaparin once daily. Uncontrolled bleeding after enoxaparin is rare but may occur. The only registered antidote – protamine sulfate has only 60% efficacy and can cause severe complications. We developed heparin-binding copolymer (HBC), a diblock copolymer that reverses intravenously administered heparins and fondaparinux (Kalaska et al., Trans Res, 2016, Kalaska et al., J Pharmacol Exp Ther, 2020).
Aims: We focused on the optimal dosage regimen of HBC for reversing the anticoagulant activity of subcutaneously-administered enoxaparin in healthy mice.
Methods: Male BALB/c mice were subcutaneously injected with enoxaparin (5 mg/kg). After 110 minutes, vehicle (PBS), HBC (6.25 mg/kg or 12.5 mg/kg) or protamine (5 mg/kg or 10 mg/kg) were administered into the tail vein. The blood was collected after 3, 10, 60, 180, 360, and 600 minutes after their administration. Then, the activity of anti-factor Xa and IIa, and blood parameters were measured. All procedures involving animals were approved (Permit Numbers 6/2021) and conducted according to Directive 2010/63/EU. The data were analyzed with GraphPad Prism 6 software using the Mann-Whitney test. P values less than 0.05 were considered significant.
Results: HBC at a lower dose reversed the effect of enoxaparin on anti-factor Xa activity after 3 and 10 minutes, whereas higher dose reversed anti-factor Xa activity, whenever it was increased by enoxaparin (Figure 1). Both doses of HBC completely reversed the effect of enoxaparin on anti-factor IIa activity. Protamine did not reverse anti-factor Xa activity, and only partially reversed anti-factor IIa activity increased by enoxaparin. Safety studies revealed decreased number of blood platelets, and elevated liver enzymes in group treated with HBC at higher dose.
Conclusions: HBC might be an efficient substitute for protamine sulfate to stop major bleeding that may occur in patients receiving subcutaneously enoxaparin.
Funding: National Science Centre, Poland (2016/21/B/ST5/00837).
To cite this abstract in AMA style:Swieton J, Kalaska B, Miklosz J, Yusa S-, Szczubialka K, Pawlak D, Mogielnicki A. Heparin-binding Copolymer Completely Reverses the Anticoagulant Effect of Subcutaneously Administered Enoxaparin in Mice [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/heparin-binding-copolymer-completely-reverses-the-anticoagulant-effect-of-subcutaneously-administered-enoxaparin-in-mice/. Accessed September 21, 2023.
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