Despite high risk of venous thromboembolism (VTE) in patients with pancreatic cancer, there is 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 to controls. Blood was drawn at baseline and patients were followed for six months. Complexes of proteases with their natural inhibitors, C1-esterase inhibitor (C1-INH), anti-thrombin (AT) or alpha-1 antitrypsin (α1at), were measured for complexes containing kallikrein (PKa:C1-INH), factor XIIa (FXIIa:C1-INH) and factor XIa (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.
109 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<0.001), FXIa:C1-INH (p<0.001) and FXIa:AT (p<0.001). High FXIa:α1at (SHR 1.48 per log increase; 95% CI 1.02-2.16) and FXIa:AT (SHR 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.
Copyright © 2023. Published by Elsevier Inc.
