Relevance of Blood Cellular Indices with Inflammatory Cytokines in Patients with Pulmonary Embolism

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Relevance of blood cellular indices with inflammatory cytokines in patients with pulmonary embolism.

Fakiha Siddiqui, Amir Darki, Bulent Kantarcioglu, Debra Hoppensteadt, Jawed Fareed, Alfonso Tafur, Manuel Monreal.

Introduction Pulmonary embolism (PE) is a life-threatening condition and a leading cause of vascular disease and cardiovascular death worldwide, around 25% of the cases with PE encountered sudden death. Recently, blood cellular indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII, NLR*platelets) have emerged as reliable tool in assessing inflammation and immune response and can serve as a predictor of disease severity and prognosis for PE. Elevated NLR is related with an increase’s inflammatory response, PLR reflects platelet activation, a prothrombotic state and adverse outcomes, while SII is linked with pronounced inflammatory state together with platelet activation. We have previously demonstrated the prognostic value of cellular indices in a large cohort of PE patients in RIETE Registry (Siddiqui, F., Tafur, A., Hussain, M., et al. The prognostic value of blood cellular indices in pulmonary embolism. American journal of hematology, 10.1002/ajh.27379. Advance online publication. https://doi.org/10.1002/ajh.27379). This integrated study focused on the role of inflammation in patients with PE by profiling cellular indices and inflammatory cytokines and their relevance with outcome as all-cause mortality within the 30 days of diagnosis of PE.

Material and Method: In the cohort of 197 PE patients, blood cellular indices and levels of biomarker of inflammation were compared to controls. Furthermore, the relevance of cellular indices and biomarkers was determined. Patients with clinically confirmed diagnosis of PE were enrolled in the Loyola PERT program, and citrated blood samples were collected. Control samples (n= 50) from 25 male and 25 female were acquired from a George King Biomedical. Blood cellular indices, including NLR, PLR and SII were calculated by using the complete blood count. A panel of inflammatory cytokines and growth factors (including IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, IL-1β, MCP-1 and EGF) was measured using Sandwich Chemiluminescence Biochip Array from Randox Technology. Statistical analyses were performed using SPSS IBM and GraphPad Prism software.

Result: The cohort of 197 patients with PE, comprised of 46.1% female and 53.9% male, with a median age of 65-years. PE patients exhibited significantly higher levels of blood cellular indices NLR, PLR, and SII, as well as inflammatory cytokines including IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, IL-1β, MCP-1 and EGF except IL-2. Moderate correlations were observed among the cellular indices and cytokines. Notable and significant correlations include NLR vs. IL-6 (r= 0.44) and IL-10 (r= 0.41) and SII vs. IL-6 (r= 0.43) and IL-10 (r= 0.32). In the cohort of 197 patients, 14% died within the first 30-day of diagnosis. Remarkable increase in the levels of NLR, PLR, SII, IL-2, IL-6, IL-8, IL-10, TNF-α, IL-1β, and MCP-1 were observed with 30-day mortality.

Conclusion: These studies represent a novel approach by integrating cellular indices with inflammatory cytokines for the diagnosis of PE and predicting the outcome. The IL-6 and IL-10 showed positive correlations with NLR and SII, underscoring the role of neutrophils, lymphocytes and platelets white contribute to the relation of inflammatory cytokines. Most of the inflammatory cytokines are associated with severity and can be used along with current risk stratification scores. Moreover, the role of cell-mediated biomarker in conjunction with a panel of inflammatory cytokine utilizing biochip array technology provides additional understanding into the pathophysiology of PE and related syndromes.