Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in CRSwNP. More information is needed concerning mechanisms of coagulation in CRSwNP.To investigate mechanisms, initiation and regulation of coagulation cascade activation in CRS.Samples were collected from 135 subjects with CRSwNP, 80 subjects with CRSsNP, and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-anti-thrombin complex (TATc), tissue factor (TF) and pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, IHC or immunofluorescence. Heteromeric complexes of TF with FVIIa and TF with FVIIa and FXa were assessed by coimmunoprecipitation and Western blotting.Increased levels of FXa, F1+2 and TATc were detected in NP tissue compared to uncinate tissue (UT) 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.The coagulation cascade is associated with NP as compared to control and UT 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 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.Copyright © 2022. Published by Elsevier Inc.