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Clustering of coagulation factors in acute venous thromboembolism identifies clusters of thromboinflammatory and endothelial activation markers as independent predictors of recurrence and mortality.

1Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands, Mainz, Rheinland-Pfalz, Germany, 2Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 3Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55131, Germany, Mainz, Rheinland-Pfalz, Germany, 4Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 5Bayer AG, Wuppertal, Germany, Wuppertal, Nordrhein-Westfalen, Germany, 6Department of Internal Medicine, Pulmonary Diseases, University Medicine Greifswald, Greifswald, Germany, Greifswald, Mecklenburg-Vorpommern, Germany, 7Department of Internal Medicine I and Pulmonology, Carl Gustav Carus Hospital, University of Dresden, Germany, Dresden, Sachsen, Germany, 8Department of Cardiology, University Medical Center Mainz, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 9Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, mainz, Rheinland-Pfalz, Germany, 10Center for Cardiology - Cardiology I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany, Mainz, Rheinland-Pfalz, Germany, 11Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands;, Maastricht, Limburg, Netherlands, 12Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; Thrombosis Expertise Center, Heart+ Vascular Center, Maastricht University Medical Center, Maastricht, the Netherlands, Maastricht, Limburg, Netherlands, 13Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany, Mainz, Rheinland-Pfalz, Germany

Abstract Number: PB1336

Meeting: ISTH 2022 Congress

Theme: Venous Thromboembolism » VTE Epidemiology

Background: Blood coagulation is a complex and highly coordinated process, modulated by procoagulant and anticoagulant factors. Genetic or environmental defects in their hemostatic balance contribute to venous thromboembolism (VTE). We hypothesized that patterns in coagulation system activity observed in acute VTE may also predict recurrent events.

Aims: To identify patterns of coagulation factors and their relation with risk factors and clinical outcomes of VTE patients.

Methods: Acute-phase plasma samples from 612 subjects from the GMP-VTE project were analyzed. This study was approved by the local Ethics Committee. All patients signed the informed consent. FII, FVII, FVIII, FIX, FX, FXI, FXIII, activated Protein C (aPC), Protein S (PS), D-dimer, fibrinogen, tissue factor protein inhibitor (TFPI), thrombomodulin and plasminogen activator inhibitor-1 levels were quantified, and principal component (PC) analysis was used to derive coagulation system patterns. Cox regression and elastic net-regularized linear regression were used to identify associations of PC scores with clinical outcome and risk factors.

Results: Four PCs were retained, accounting for 51.3% of the total variance. PC1 was mainly driven by vitamin K dependent factors (FII, FVII, FX, and aPC); PC2 by FVIII, FIX, FXI, and fibrinogen; PC3 by D-dimer and FXIII, and TFPI and PS contributed to PC4. PC3 and PC4 significantly predicted recurrent VTE risk (HR: 1.27; 95 %CI: [1.05-1.53]; p=0.014, and 1.31 [1.06-1.62]; p=0.013, respectively), independently of age, sex, body mass, VTE risk factors, thrombus site, and medication intake. Additionally, PC2 and PC4 exhibited good prognostic ability for all-cause death (HR: 1.36 [1.04-1.77]; p=0.024, and 1.76 [1.42-2.20]; p < 0.001). PC4 scores were elevated in subjects with comorbidities reflecting endothelial dysfunction (diabetes, chronic kidney disease, coronary artery disease).

Conclusion(s): Principal component analysis of the coagulation system characterized clusters of thrombo-inflammation and endothelial activation markers related to recurrent VTE and mortality.

APR is supported by EU-TICARDIO No. 813409.

To cite this abstract in AMA style:

Pallares Robles A, ten Cate V, Schulz A, Prochaska J, Koeck T, Heitmeier S, Ewert R, Halank M, Espinola-Klein C, Lackner K, Münzel T, ten Cate H, ten Cate-Hoek A, Konstantinides S, Wild P. Clustering of coagulation factors in acute venous thromboembolism identifies clusters of thromboinflammatory and endothelial activation markers as independent predictors of recurrence and mortality. [abstract]. https://abstracts.isth.org/abstract/clustering-of-coagulation-factors-in-acute-venous-thromboembolism-identifies-clusters-of-thromboinflammatory-and-endothelial-activation-markers-as-independent-predictors-of-recurrence-and-mortality/. Accessed September 27, 2023.

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