TY - JOUR
T1 - Contact system and intrinsic pathway activation in patients with advanced pancreatic cancer
T2 - a prospective cohort study
AU - Bosch, Floris T. M.
AU - Campello, Elena
AU - Mulder, Frits I.
AU - Ilich, Anton
AU - Henderson, Michael W.
AU - Prokopenko, Yuriy
AU - Gavasso, Sabrina
AU - Pea, Antonio
AU - Salvia, Roberto
AU - Wilmink, Hanneke W.
AU - Otten, Hans-Martin
AU - van Es, Nick
AU - Key, Nigel S.
AU - Büller, Harry R.
AU - Simioni, Paolo
N1 - Publisher Copyright: © 2023
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - factor XI
KW - factor XII
KW - pancreatic neoplasm
KW - plasma kallikrein
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85164425790&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtha.2023.06.009
DO - https://doi.org/10.1016/j.jtha.2023.06.009
M3 - Article
C2 - 37331518
SN - 1538-7933
VL - 21
SP - 2863
EP - 2872
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 10
ER -