title: Tissue factor-bearing microparticles and CA19.9: two players in pancreatic cancer-associated thrombosis?
abstract: Cancer-related venous thromboembolism (VTE) heralds a poor prognosis, especially in pancreatic adenocarcinoma (PAC). Tissue factor (TF) is implicated as one of the main culprits in PAC-associated VTE and disease progression.
  
  
  
  In a prospective cohort study of 79 PAC patients, we measured plasma CA19-9 and microparticle-associated TF activity (MP-TF activity). In addition, we enumerated TF(+)MPs and MUC1(+)MPs in plasma (n=55), and studied the expression of TF, MUC1, CD31 and CD68 in tumour tissue (n=44).
  
  
  
  Plasma MP-TF activity was markedly elevated in PAC patients with VTE compared with those without (median: 1925 vs 113 fM Xa min(-1); P<0.001) and correlated with the extent of thromboembolic events, metastatic disease and short survival. Similar results were found for CA19-9. Patients with massively progressing thrombosis and cerebral embolisms despite anticoagulant therapy (n=3) had the highest MP-TF activities (12 118-40 188 fM Xa min(-1)) and CA19-9 (40 730-197 000 kU l(-1)). All tumours expressed MUC1 and TF. MP-TF activity did not correlate with intensity of TF expression in adenocarcinoma cells, but corresponded with numbers of TF(+) macrophages in the surrounding stroma.
  
  
  
  Circulating TF(+)MPs and mucins may concertedly aggravate coagulopathy in PAC. Understanding of underlying mechanisms may result in new treatment strategies for VTE prevention and improvement of survival.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.
authors.forename: F J Sherida H
authors.initials: FJ
authors.lastname: Woei-A-Jin
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 Amsterdam, The Netherlands.
authors.forename: Margot E T
authors.initials: ME
authors.lastname: Tesselaar
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.
authors.forename: Patrica
authors.initials: P
authors.lastname: Garcia Rodriguez
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.
authors.forename: Fred P H T M
authors.initials: FP
authors.lastname: Romijn
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Bertina
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.|Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 Leiden, The Netherlands.
authors.forename: Susanne
authors.initials: S
authors.lastname: Osanto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018395:CA-19-9 Antigen / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications*; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism
chemical_list: D018395:CA-19-9 Antigen; D013925:Thromboplastin