Background: Increased levels of inflammatory cytokines have been shown in venous thrombosis. Endothelial damage and shedding of endothelial glycocalyx have also been shown in certain thrombotic disease states, conferring that they have important functions in circulatory homeostasis.
Aims: We sought to quantify the levels of anti-PF4 antibody isotypes together with endogenous glycosaminoglycans (GAGs) in a patient cohort, comprised of PE, to determine their impact on pathophysiology of VTE and HIT and observe whether there is a relationship in between and inflammatory marker subtypes.
Methods: Whole blood samples were drawn from patients within 24 hours of confirmed diagnosis of acute PE under an Institutional Review Board approved protocol. The samples were tested for anti-PF4 isotypes of IgA, IgG, and IgM ELISA assay, endogenous GAGs with heparin red assay and inflammatory biomarkers with biochip assay. Circulating levels of each biomarker were compared to control plasma. P < 0.05 was considered statistically significant.
Results: The levels of anti-PF4 Ig A, Ig G and endogenous GAGs were elevated in acute PE patients compared to normal controls (P < 0.05). The increase in anti-PF4 Ig M was not significant (p: 0.78). Anti PF4 Ig A were correlated with IL-2, IL-6 and TNFA. Anti PF4 Ig G were correlated with IL-6 and d-dimer. Anti PF4 Ig M were correlated with IL-2 and MCP-1. The levels of endogenous GAGs were correlated with TNF-α, IL-10, IL-8, IL-1β, IL-1α and VEGF. We observed significant correlations in between anti-PF4 antibody isotypes. The correlation between the levels of anti-PF4 isotypes and endogenous GAGs were insignificant.
Conclusion(s): Our findings supports that the development of thrombosis is likely due to releasing of PF4 antigen from platelets and shedding of endogenous GAGS from the endothelial cells causing activation of endothelial cells, platelets, and leukocytes, resulting in inflammatory cytokine release and triggering of the coagulation system.
To cite this abstract in AMA style:Kantarcioglu B, Darki A, Siddiqui F, Hoppensteadt D, Lewis J, Krämer R, Fareed J. Levels Of Heparin Induced Anti-PF4 Antibodies and Endogenous Glycosaminoglycans and Their Relationship with Inflammatory Biomarkers in Pulmonary Embolism Patients. [abstract]. https://abstracts.isth.org/abstract/levels-of-heparin-induced-anti-pf4-antibodies-and-endogenous-glycosaminoglycans-and-their-relationship-with-inflammatory-biomarkers-in-pulmonary-embolism-patients/. Accessed September 29, 2023.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/levels-of-heparin-induced-anti-pf4-antibodies-and-endogenous-glycosaminoglycans-and-their-relationship-with-inflammatory-biomarkers-in-pulmonary-embolism-patients/