title: Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers.
abstract: BACKGROUND
  Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.
  
  
  METHODS
  Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.
  
  
  RESULTS
  The study population comprised 117 patients, including pancreatic (n=80), biliary (n=34) or unknown primary histologically consistent with PBC (n=3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n=15), deep venous thrombosis (n=21) and other arterial or venous events (n=32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity<2.5 pg/mL (p<0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).
  
  
  CONCLUSIONS
  Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.
authors.affiliation: Departments of Medicine and Biostatistics, Roswell Park Cancer Institute, Buffalo, N.Y. USA.
authors.forename: Anubha
authors.initials: A
authors.lastname: Bharthuar
authors.forename: Alok A
authors.initials: AA
authors.lastname: Khorana
authors.forename: Alan
authors.initials: A
authors.lastname: Hutson
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wang
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Key
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.forename: Renuka V
authors.initials: RV
authors.lastname: Iyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000097:blood*; D001653:Bile Ducts, Intrahepatic; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood*; D011379:Prognosis; D016019:Survival Analysis; D013923:Thromboembolism / Q000097:blood* / Q000473:pathology; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D013925:Thromboplastin
keywords: Microparticles; Pancreatic cancer; Survival; Thromboembolism; Tissue factor