Abstract Number: PB0753
Meeting: ISTH 2020 Congress
Background: Apha2-plasmin inhibitor (A2-PI) is the main inhibitor of plasmin. In the circulation A2-PI undergoes proteolytic cleavages. The C-terminally cleaved form of A2-PI lacks the plasminogen-binding site, which is located in the C-terminal 26 amino acids of the molecule. It remains an active plasmin inhibitor, but reacts more slowly with plasmin.
Aims: To investigate the incorporation of C-terminally intact and truncated A2-PI into the fibrin clot and the effect of FXIII on this process.
Methods: Citrated plasma samples from 42 healthy individuals were clotted by thrombin and calcium. Total A2-PI and C-terminally intact A2-PI and FXIII antigen levels were measured by sandwich ELISAs from the plasma and serum samples, and the concentration of the truncated form was calculated from these values. Washed and dissolved plasma clots were analyzed by western blotting using antibodies to total and C-terminally intact A2-PI.
Results: The ratio of intact:truncated A2-PI in the plasma samples was 66.3%:33.7%. 49.2±4.8% of the plasma total A2-PI incorporated into fibrin clot based on ELISA measurements. The amount of incorporated C-terminally intact A2-PI was significantly higher than the amount of the truncated form (32.2±5.1 mg/L vs. 18.7±3.4 mg/L, p< 0.0001) that was 43.3±5.7% and 60.9±8.5% of the original plasma values, respectively. Plasma FXIII significantly correlated with incorporation of the intact form (r=0.819, p< 0.001), however did not show correlation with incorporation of the truncated form (r=0.079, p=0.618). Western blotting results showed complete covalent cross-linking of the C-terminally intact form to α-chain monomer and α-chain polymers of fibrin, while the truncated form presented both in non-crosslinked and crosslinked bands.
Conclusions: Strong correlation of FXIII concentration with the incorporation of C-terminally intact A2-PI into fibrin clot suggests that C-terminally intact A2-PI is the primary substrate of FXIIIa for the cross-linking to fibrin.
Funding: GINOP-2.3.2-15-2016-00043, NKFI-K120633
To cite this abstract in AMA style:Baráth B, Katona É. Different Incorporation of Apha2-plasmin Inhibitor C-terminal Forms into the Fibrin Clot [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/different-incorporation-of-apha2-plasmin-inhibitor-c-terminal-forms-into-the-fibrin-clot/. Accessed September 24, 2023.
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