Comparison of thrombin biomarkers and activated protein C in patients with cerebral venous sinus thrombosis and splanchnic vein thrombosis

Introduction: Compared with VTE in typical sites, the pathomechanism of atypical thromboses are less understood. A recent retrospective analysis revealed that, compared with typical site VTE, splanchnic vein thrombosis (SVT) and cerebral venous sinus thrombosis (CVST) both share an increased rate of the F2 20210G>A mutation [1]. In order to comparatively characterize the prothrombotic state in SVT, CVST, and typical site VTE on a molecular level, biomarkers of thrombin formation and activated protein C (APC) were studied.

Method: The study population included patients with SVT (n=30), CVST (n=31), and typical site VTE (deep vein thrombosis of the lower extremity and/or pulmonary embolism, n=31) who were not on therapeutic anticoagulation at the time of analysis. Thrombin formation was assessed by measurement of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) levels. Plasma levels of APC were measured using an oligonucleotide-based enzyme capture assay. Additionally, D-dimer levels were measured.

Results: With median (interquartile range) levels of 302 (193-489) versus 173 (125-243) pmol/L, F1+2 in the SVT cohort was higher than in the typical site VTE cohort (p=4x10^-4), whereas the differences between both groups and the CVST cohort (208; 177-295 pmol/L) did not reach statistical significance (p=0.052 respectively p=0.109). Median plasma levels of TAT remained below the lower limit of quantification of 21.3 pmol/L in all three cohorts. D-dimer levels also were higher in the SVT cohort than in the CVST and typical site VTE cohorts, with 0.53 (0.29-0.78) versus 0.29 (0.20-0.33) µg/ml (p=0.001) respectively 0.33 (0.22-0.50) µg/mL (p=0.013), but did not differ between patients with CVST and typical VTE (p=0.362). APC did not differ between the three cohorts (Kruskal-Wallis test p=0.296) with median levels of 1.04 pmol/L in the SVT cohort, 0.79 pmol/L in the CVST cohort, and 0.80 pmol/L in the typical site VTE cohort.

Conclusion: Of the disease entities studied, SVT is distinguished by increased thrombin formation, resulting in increased activation of coagulation and fibrinolysis. These features of SVT can most probably be explained by hepatopathy, which is frequently associated with thrombosis at this site. As the biomarkers studied were not able to distinguish between CVST and typical site VTE, further research in this direction is warranted.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025

• References

• 1 Khaddam D, McRae HL, Schwarz N, Oldenburg J, Pötzsch B, Rühl H, Reda S.. High Prevalence of F2 20210G>A in Splanchnic Vein Thrombosis and Cerebral Venous Sinus Thrombosis: A Retrospective Cohort Study of Patients with Thrombosis in Atypical Sites. Hamostaseologie 2024;