title: Determinants of hypofibrinolysis in patients with digestive tract cancer.
abstract: BACKGROUND
  Recently, we demonstrated that digestive tract cancer (DTC) is associated with reduced fibrin clot permeability and impaired fibrinolysis.
  
  
  OBJECTIVE
  We investigated determinants of fibrinolysis in DTC patients.
  
  
  METHODS
  In 44 consecutive patients with DTC and 47 controls matched for age, sex, and cardiovascular risk, we evaluated fibrinolysis proteins, platelet activation markers, thrombin formation, together with plasma clot lysis time assays in the absence (CLT) and presence of carboxypeptidase potato inhibitor (CLT CPI) that blocks thrombin activatable fibrinolysis inhibitor (TAFI).
  
  
  RESULTS
  In the DTC group CLT (by 22.3%) and CLT CPI (by 27.4%) were longer compared with controls. The DTC patients had higher plasma fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI-1) (by 18.2%), TAFI activity (by 17.3%), and antigen (by 11.2%). The patients had markedly increased platelet markers - soluble CD40 ligand (by 338%) and P-selectin (by 97%), together with von Willebrand factor (vWF) antigen (by 61%). Thrombin-antithrombin complexes (TAT) (by 48.7%) and soluble thrombomodulin (sTM) (by 17.2%) were also increased in the DTC group (all p < 0.05). Patients with high-grade tumours (n = 26) compared with remainders (n = 18) had longer CLT, higher tissue-type plasminogen activator antigen, both TAFI antigen and activity levels, vWF, and sTM. Multiple regression analysis after adjustment for potential confounders showed that independent predictors of CLT in DTC patients were TAT, TAFI activity, and vWF. The only independent predictor of CLT CPI was TAT.
  
  
  CONCLUSIONS
  Hypofibrinolysis in DTC patients is largely driven by enhanced thrombin generation, TAFI, and endothelial injury.
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gronostaj
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Richter
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Nowak
authors.affiliation: Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
keywords: digestive tract cancer; fibrinolysis; platelet activation; thrombin activatable fibrinolysis inhibitor; thrombin generation