Abstract Number: PB0407
Meeting: ISTH 2020 Congress
Background: Coagulation activation in the thrombodynamics clot growth system follows two pathways:
(a) Tissue factor /factor VIIa to factor X and
(b) factor XIa/factor IX to factor X.
Both pathways have 2/3, 1/3 contribution to clot size and growth rate in normal plasma.
Aims: We tested inhibition by reversible factor Xa inhibitors (Xa-DOACs) on both pathways.
Methods: Normal and haemophilia plasma; spiking with purified factor VIII or emicizumab (emi). Rivaroxaban, apixaban, edoxaban, fondaparinux, heparin and emi from Pharmacy. Testing with and without 4 µM apixaban.
Results: Spiking factor VIII in Haemophilia A plasma increased stationary clot growth rate (Vst) about a factor of 1.5, reaching levels of normal plasma at 100% factor suppletion. Spiking of emi corrected clot growth similar to adding factor VIII with 80% correction at 20 µg/ml emi.
All Xa-DOACs had no effect on clot growth in haemophilia plasma. However, in normal and plasma corrected by spiking, all Xa-DOACs inhibited clot growth back to the level of the deficient plasma.
In contrast, fondaparinux and heparin inhibited also clot growth in haemophilia plasma, showing not the specificity of the Xa-DOACs.
In healthy control the tissue factor/ VIIa portion was the least variable. In 10 controls the portions were analysed using addition of 4 µM apixaban: the tissue factor /factor VIIa clot growth showed Vst of 21,3 (CV% 9) and the factor XIa/IX portion 14,0 with CV% 30.
Conclusions: Only the factor Xa generated by factor IXa can be inhibited by the Xa-DOACs, also when factor Xa is generated with emi as a cofactor. Addition of high apixaban enables detection of the tissue factor/ factor VIIa portion separately.
It shows that reversible Xa-inhibitors inhibit clot growth partially and specifically. It implies that in case of high factor VIII, IX or XI and with accidental high emi, Xa-DOACS are rational, specific inhibitors or antidotes.
To cite this abstract in AMA style:Kluft C, Klip N, Talens S, Karamzin S, Ataullakhanov F. Inhibition of Factor Xa by Specific Reversible Inhibitors Is Selective for Factor Xa Generated by Factor IXa [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/inhibition-of-factor-xa-by-specific-reversible-inhibitors-is-selective-for-factor-xa-generated-by-factor-ixa/. Accessed October 1, 2023.
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