Abstract Number: PB0420
Meeting: ISTH 2021 Congress
Background: Alpha2-plasmin inhibitor (A2PI) is the main inhibitor of plasmin. The secreted C-terminally intact form of A2PI (PB-A2PI) is proteolytically cleaved in the circulation. The C-terminally cleaved form lacks the plasminogen-binding site (NPB-A2PI), it remains an active plasmin inhibitor, but reacts more slowly with plasmin. It has not been studied in detail whether the truncated form is incorporated into the clot and affects clot lysis.
Aims: To investigate the effect of the incorporation of PB-A2PI and NPB-A2PI into fibrin clots on the lysis of the clot.
Methods: Citrated plasma samples from 86 healthy individuals were clotted by thrombin and calcium. Total-A2PI and PB-A2PI levels were measured by sandwich ELISAs from the original plasma and the extruded serum samples, and the concentration of NPB-A2PI was calculated from these values. An in vitro clot lysis assay was performed using platelet poor plasma samples. Clotting and subsequent lysis were induced by adding human tissue factor, rt-PA and CaCl2. Optical density was measured at 340 nm 37 °C for 300 min. Curves were analyzed using the Shiny app software.
Results: Total-A2PI, PB-A2PI and NPB-A2PI levels (mean±SD) in the plasma samples were 64.3±7.5 mg/L, 43.5±4.7 mg/L and 20.8±5.5 mg/L (32.0±6.1%), respectively. 43.6±5.9% of the plasma PB-A2PI and 62.2±12.4% of the plasma NPB-A2PI was found to be incorporated into the clot resulting in an elevated ratio of PB-A2PI to NPB-A2PI in the serum as compared to the ratio in the plasma. Plasma total-A2PI, NPB-A2-PI levels and the amount of incorporated NPB-A2PI showed significant correlation with 50% clot lysis time (CLT50) (r=0.313, p=0.003; r=0.387, p<0.001 and r=0.256, p=0.017, respectively), while PB-A2PI levels did not correlate (r=0.053, p=0.629) with lysis parameters.
Conclusions: Our results suggest that non-covalent incorporation of the C-terminally truncated NPB-A2PI may have an effect on clot lysis and it should be further investigated.
To cite this abstract in AMA style:Baráth B, Orbán-Kálmándi R, Bagoly Z, Katona É. Effect of Alpha2-plasmin Inhibitor C-terminal Forms on in vitro Clot Lysis [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/effect-of-alpha2-plasmin-inhibitor-c-terminal-forms-on-in-vitro-clot-lysis/. Accessed June 25, 2022.
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