Contact system and intrinsic pathway activation in patients with advanced pancreatic cancer: a prospective cohort study

Floris T. M. Bosch, Elena Campello, Frits I. Mulder, Anton Ilich, Michael W. Henderson, Yuriy Prokopenko, Sabrina Gavasso, Antonio Pea, Roberto Salvia, Hanneke W. Wilmink, Hans-Martin Otten, Nick van Es, Nigel S. Key, Harry R. Büller, Paolo Simioni

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)2863-2872
Number of pages10
JournalJournal of thrombosis and haemostasis
Issue number10
Early online date2023
Publication statusPublished - Oct 2023


  • factor XI
  • factor XII
  • pancreatic neoplasm
  • plasma kallikrein
  • venous thromboembolism

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