Contact system and intrinsic pathway activation in patients with advanced pancreatic cancer: a prospective cohort study.
factor XI
factor XII
pancreatic neoplasm
plasma kallikrein
venous thromboembolism
Journal
Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
05
03
2023
revised:
10
05
2023
accepted:
05
06
2023
medline:
25
9
2023
pubmed:
19
6
2023
entrez:
18
6
2023
Statut:
ppublish
Résumé
Despite high risk of venous thromboembolism (VTE) in patients with pancreatic cancer, there are little data on contact system activation in these patients. To quantify contact system and intrinsic pathway activation and subsequent VTE risk in patients with pancreatic cancer. Patients with advanced pancreatic cancer were compared with controls. Blood was drawn at baseline and patients were followed for 6 months. Complexes of proteases with their natural inhibitors, C1-esterase inhibitor (C1-INH), antithrombin (AT), or alpha-1 antitrypsin (α1at), were measured for complexes containing kallikrein (PKa:C1-INH), factor (F)XIIa (FXIIa:C1-INH), and FXIa (FXIa:C1-INH, FXIa:AT, FXIa:α1at). The association of cancer with complex levels was assessed in a linear regression model, adjusted for age, sex, and body mass index. In a competing risk regression model, we assessed associations between complex levels and VTE. One hundred nine patients with pancreatic cancer and 22 controls were included. The mean age was 66 years (SD, 8.4) in the cancer cohort and 52 years (SD, 10.1) in controls. In the cancer cohort, 18 (16.7%) patients developed VTE during follow-up. In the multivariable regression model, pancreatic cancer was associated with increased complexes of PKa:C1-INH (P < .001), FXIa:C1-INH (P < .001), and FXIa:AT (P < .001). High FXIa:α1at (subdistribution hazard ratio, 1.48 per log increase; 95% CI, 1.02-2.16) and FXIa:AT (subdistribution hazard ratio, 2.78 highest vs lower quartiles; 95% CI, 1.10-7.00) were associated with VTE. Complexes of proteases with their natural inhibitors were elevated in patients with cancer. These data suggest that the contact system and intrinsic pathway activation are increased in patients with pancreatic cancer.
Sections du résumé
BACKGROUND
Despite high risk of venous thromboembolism (VTE) in patients with pancreatic cancer, there are little data on contact system activation in these patients.
OBJECTIVES
To quantify contact system and intrinsic pathway activation and subsequent VTE risk in patients with pancreatic cancer.
METHODS
Patients with advanced pancreatic cancer were compared with controls. Blood was drawn at baseline and patients were followed for 6 months. Complexes of proteases with their natural inhibitors, C1-esterase inhibitor (C1-INH), antithrombin (AT), or alpha-1 antitrypsin (α1at), were measured for complexes containing kallikrein (PKa:C1-INH), factor (F)XIIa (FXIIa:C1-INH), and FXIa (FXIa:C1-INH, FXIa:AT, FXIa:α1at). The association of cancer with complex levels was assessed in a linear regression model, adjusted for age, sex, and body mass index. In a competing risk regression model, we assessed associations between complex levels and VTE.
RESULTS
One hundred nine patients with pancreatic cancer and 22 controls were included. The mean age was 66 years (SD, 8.4) in the cancer cohort and 52 years (SD, 10.1) in controls. In the cancer cohort, 18 (16.7%) patients developed VTE during follow-up. In the multivariable regression model, pancreatic cancer was associated with increased complexes of PKa:C1-INH (P < .001), FXIa:C1-INH (P < .001), and FXIa:AT (P < .001). High FXIa:α1at (subdistribution hazard ratio, 1.48 per log increase; 95% CI, 1.02-2.16) and FXIa:AT (subdistribution hazard ratio, 2.78 highest vs lower quartiles; 95% CI, 1.10-7.00) were associated with VTE.
CONCLUSION
Complexes of proteases with their natural inhibitors were elevated in patients with cancer. These data suggest that the contact system and intrinsic pathway activation are increased in patients with pancreatic cancer.
Identifiants
pubmed: 37331518
pii: S1538-7836(23)00493-2
doi: 10.1016/j.jtha.2023.06.009
pii:
doi:
Substances chimiques
Anticoagulants
0
Antithrombin III
9000-94-6
Endopeptidases
EC 3.4.-
Kallikreins
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2863-2872Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of competing interests F.T.M.B., E.C., F.I.M., A.I., Y.P., M.W.H., S.G., A.P., R.S., H.M.O., N.S.K., H.R.B., and P.S. report no conflicts of interest. J.W.W. reports clinical trial support from Nordic, Servier, Novartis, Celgene, and BMS and advisory role/speaker’s fee from Astra Zeneca, Servier, MSD. N.v.E. reports receiving advisory board honoraria from Daiichi-Sankyo, LEO Pharma, and Bayer, which were transferred to his institution.