Studies on activation and regulation of the coagulation cascade in chronic rhinosinusitis with nasal polyps

Ping Ping Cao, Bao Feng Wang, James E. Norton, Lydia A. Suh, Roderick G. Carter, Whitney W. Stevens, Anna G. Staudacher, Julia H. Huang, Kathryn E. Hulse, Anju T. Peters, Leslie C. Grammer, David B. Conley, Kevin C. Welch, Robert C. Kern, Zheng Liu, Jingying Ye, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP. Objective: We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS. Methods: Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin–antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting. Results: Increased levels of FXa, F1+2, and thrombin–antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue. Conclusion: The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology
DOIs
StateAccepted/In press - 2022

Keywords

  • CRSwNP
  • Chronic rhinosinusitis
  • FVII
  • FXa
  • coagulation
  • nasal polyps
  • prothrombin fragment 1+2
  • thrombin-anti-thrombin complex
  • tissue factor
  • tissue factor pathway inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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