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Correlation between Thrombin Generation and Prothrombin Fragment F1+2 Plasma Levels

1Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy, 2Università degli Studi di Milano, Department of Biomedical Sciences for Health, Milan, Italy, 3Università degli Studi di Milano, Fondazione Luigi Villa, Milan, Italy, 4Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan, Italy

Abstract Number: PB0578

Meeting: ISTH 2020 Congress

Theme: Diagnostics and OMICs » Laboratory Diagnostics

Background: The thrombin generation assay (TGA) is a global coagulation procedure evaluating the balance between thrombin generation and decay. It has been developed to overcome the poor potential of the basic coagulation tests to represent the coagulation balance as it occurs in-vivo. However, TGA itself is an ex-vivo procedure, estimating the potential of the test plasma to produce thrombin, and not representing the real amount of thrombin in the test plasma. Markers of coagulation activation in-vivo do exist and one of these is the prothrombin fragment F1+2, which is a degradation peptide produced when prothrombin is converted to thrombin.

Aims: The study aimed to correlate TGA parameters versus F1+2 plasma levels in a population of healthy volunteers and patients on vitamin K antagonists (VKA), known to be at normal or reduced levels of TGA/F1+2, respectively.

Methods: We used a homemade TGA according to Hemker et al. and performed the test in platelet-poor plasma with or without triggers [tissue factor (1pM) and synthetic phospholipids (1µM)], without or with thrombomodulin (2nM). F1+2 was measured with an immunoenzymatic assay (Siemens).

Results: Fifty-seven healthy subjects and 28 patients on VKAs were enrolled. As expected, F1+2 and TGA parameters were significantly different (p< 0.001) between patients on VKA and healthy subjects. The comparison of results showed a significant linear correlation (Spearman's Rho=0.5, p < 0.01) between F1+2 levels and four of the TGA parameters [LagTime, Peak, Time to Peak and Endogenous Thrombin Potential (ETP)], when analyzed with triggers with or without thrombomodulin.

Conclusions: The study showed a linear correlation between F1+2 plasma levels and TGA parameters, indicating that subjects with high potential to generate thrombin in-vitro, have also an ongoing thrombin generation in-vivo.


[Figure 1. Correlation between F1+2 plasma levels and TGA parameters without (upper panel) and with (bottom panel) thrombomodulin.]

To cite this abstract in AMA style:

Capecchi M, Scalambrino E, Griffini S, Grovetti E, Clerici M, Merati G, Chantarangkul V, Cugno M, Peyvandi F, Tripodi A. Correlation between Thrombin Generation and Prothrombin Fragment F1+2 Plasma Levels [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/correlation-between-thrombin-generation-and-prothrombin-fragment-f12-plasma-levels/. Accessed September 27, 2023.

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