PB1018 - Inter-relationship of Adhesion Molecules with Thrombo-Inflammatory Processes in Pulmonary Embolism.

Background: The pathogenesis of pulmonary embolism (PE) is complex, involving endothelial dysregulation, hemostatic activation, fibrinolytic deficit, inflammation and hemodynamic complications. Biomarker profiling of patient’s plasma in PE provides a useful approach to understand the molecular pathogenesis of this syndrome and may be useful for risk stratification and outcome prediction.

Aims: This study sought to investigate the relationship of adhesion molecules, such as E and P selectins with thrombo-inflammatory biomarkers.

Methods: Citrated blood samples from 300 patients with acute PE were collected under an IRB approved protocol from Loyola University Medical Center. Normal human plasma (NHP) was used for reference purpose. Adhesion molecules (E and P selectins), and thrombo-inflammatory biomarker (D-Dimer, PAI-1, tPA, TAFIa, vWF, CRP, IL-6, and TNF) were analyzed by using commercially available Sandwich ELISA kits (HYPHEN Biomed and R&D Systems). Applicable statistical analysis was performed by using GraphPad Prism Software.

Results: Both the thrombo-inflammatory markers and adhesion molecules were upregulated in PE Patients compared to NHP. E-selectin (1.63-fold), P-selectin (3.63-fold), D-Dimer (35.55-fold), PAI-1 (3.95-fold), tPA (4.77-fold), TAFIa (1.25-fold), vWF (1.88-fold), CRP (20.31-fold), IL-6 (23.49-fold) and TNF (0.77-fold) increased compared to NHP. Varying levels of correlations were noted between the selectins and thrombo-inflammatory biomarkers (figure 1). E-selectin levels were interrelated with PAI-1 antigen (r=0.20), and TNF (r=0.32), while P-selectins were interrelated with D-Dimer (r=0.38), PAI-1 (r=0.40), and CRP (r=0.22). Upon stratification on the severity of PE, there was no significant relationship demonstrated.

Conclusion(s): These results suggest that thrombo-inflammatory processes result in the upregulation of adhesion molecules, such as E and P selectins in PE. Adhesion molecules and thrombo-inflammatory biomarkers profiling provides an integrated platform for the risk stratification and prognosis of adverse outcomes in PE. This profile may be useful in the pharmacologic management of PE, where targeted drugs can be used. Furthermore, the therapeutic effects of drugs can be monitored utilizing these biomarkers.