PB0977 - Endogenous thrombin generation potential in patients with pulmonary embolism and its relevance to thrombo-inflammatory biomarkers.

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Fakiha Siddiqui, PhD Candidate

PhD Candidate
Department of Pathology and Laboratory Medicine, Cardiovascular Research Institute, Loyola University Chicago, Health Sciences Division, Maywood, IL, USA.
Maywood, Illinois, United States

Co-Author(s)

AD

Amir Darki

Associate Professor
Department of Internal Medicine, Division of Cardiology, Loyola University Medical Center, 2160 S. 1st Avenue, Maywood, IL 60153, USA.
Maywood, Illinois, United States
DH

Debra Hoppensteadt

Professor
Loyola University Chicago
Maywood, Illinois, United States
BK

Bulent Kantarcioglu

Senior Research Office
Department of Molecular Pharmacology & Neuroscience, Loyola University Medical Center, 2160 S. 1st Avenue, Maywood, IL 60153, USA.
Maywood, Illinois, United States
MM

Manuel Monreal

MD PhD
Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol. Badalona, Barcelona, Spain Chair for the Study of Thromboembolic Disease, Faculty of Health Sciences, UCAM - Universidad Católica San Antonio de Murcia, Spain
Barcelona, Andalucia, Spain
JF

Jawed Fareed, n/a

Professor
Loyola University Medical Center
MAYWOOD, Illinois, United States

Background: Pulmonary embolism (PE) is a catastrophic outcome in patients with venous thrombosis and third leading cardiovascular cause of death after myocardial infraction and stroke, estimates around 100,000 deaths annually. Inflammation, hemostatic dysregulation including fibrinolytic imbalance, endothelial compromise, and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement contribute to the pathogenesis of PE. Endogenous thrombin generation contributes to the overall pathology of PE.

Aims: The purpose of this study is to investigate endogenous thrombin potential (ETP) and the circulating levels of biomarkers of thrombo-inflammation in PE samples.

Methods: Citrated blood samples from 400 patients with confirmed PE were collected at Loyola University Medical Center and Gottlieb Memorial Hospital under an IRB approved protocol. Normal human plasma (NHP) comprised of 25 male and 25 female samples were obtained from a commercial source. Thrombin generation studies were carried out using a commercially available a kinetic system. Endogenous GAG’s contents were measured by fluorogenic quenching method. Thrombin generation parameters such as peak thrombin, lag time and area under the curve (AUC) were compiled. Plasma samples were retrospectively analyzed for biomarkers, including D-Dimer, PAI-1, tPA, TAFIa, vWF, CRP, IL6, TFPI and VEGF using commercially available sandwich ELISA methods. Results were compiled as mean ± SD and analyzed for significance and correlation by using GraphPad Prism software.

Results:

On a cumulative basis, PE patients showed a wide variation in thrombin generation parameters (Table 1). Biomarker analysis showed elevated levels of D-Dimer (37.05-fold), CRP (35.34-folds), IL6 (21.62-folds), tPA (4.69-folds), PAI-1a (3.95-folds), VEGF (2.38-folds), TFPI (2.17-folds), GAG’s (1.92-folds), vWF (1.89-folds), and TAFIa (1.21-folds). Peak thrombin levels exhibited varying degree of positive and negative correlations with various biomarkers (Figure 1).

Conclusion(s): PE patients exhibit a wide variation in endogenous thrombin generation parameters. However, biomarkers of hemostatic activation, vascular dysfunction and inflammation were increased.