PB1336 - Clustering of coagulation factors in acute venous thromboembolism identifies clusters of thromboinflammatory and endothelial activation markers as independent predictors of recurrence and mortality.

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Alejandro Pallares Robles

PhD student
Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz (UMCM), Mainz, Germany
Mainz, Rheinland-Pfalz, Germany

Co-Author(s)

Vt

Vincent ten Cate

Postdoc
Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz (UMCM), Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
AS

Andreas Schulz

Head of Statistics and Data Management
Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, 55131, Germany
Mainz, Rheinland-Pfalz, Germany
JP

Jürgen Prochaska

Head Junior Research Group Clinical Epidemiology and Systems Medicine
Center 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
TK

Thomas Koeck

Head of laboratory
Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
SH

Stefan Heitmeier

Principal Scientist
Bayer AG, Wuppertal, Germany
Wuppertal, Nordrhein-Westfalen, Germany
RE

Ralf Ewert

Professor Dr.
Department of Internal Medicine, Pulmonary Diseases, University Medicine Greifswald, Greifswald, Germany
Greifswald, Mecklenburg-Vorpommern, Germany
MH

Michael Halank

Senior Physician
Department of Internal Medicine I and Pulmonology, Carl Gustav Carus Hospital, University of Dresden, Germany
Dresden, Sachsen, Germany
CE

Christine Espinola-Klein

Professor
Department of Cardiology, University Medical Center Mainz, Mainz, Germany
Mainz, Rheinland-Pfalz, Germany
KL

Karl Lackner

Professor, Head of the Institute for Clinical Chemistry and Laboratory Medicine
Institute 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
TM

Thomas Münzel

Professor, Head of Cardiology I Department
Center 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
Hugo ten Cate, MD, PhD, FAHA

Professor, MD, PhD
Thrombosis Expertise Center, Heart & Vascular Center, Maastricht University Medical Center, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
At

Arina J. ten Cate-Hoek

Associate Professor, MD
Thrombosis Expertise Center, Heart & Vascular Center, Maastricht University Medical Center, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
SK

Stavros Konstantinides

MD, PhD
Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University
Mainz, Rheinland-Pfalz, Germany
PS

Philipp S. S. Wild

Professor
Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University Mainz (UMCM), Mainz, Germany
Mainz, Rheinland-Pfalz, Germany

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.