title: Clinical Evidence that Coagulation Activation Drives Cancer Progression--a Report of 2 Cases.
abstract: BACKGROUND
  Tissue factor (TF), the principal initiator of the extrinsic coagulation pathway, is expressed by many tumors and can be released into the bloodstream on plasma microparticles (MPs). Experimental studies indicate that TF may facilitate hematogenous metastasis by promoting tumor cell-induced microvascular thrombosis, but clinical data supporting this hypothesis is sparse.
  
  
  METHODS
  Here, we report 2 unusual cases of rapidly progressive solid malignancies (gastric and urothelial carcinoma). In both patients, cancer cell dissemination with diffuse bone marrow involvement was either strongly suggested by leukoerythroblastic changes on peripheral blood smear or directly proven by positive findings on aspiration cytology. Furthermore, laboratory evidence of thrombotic microangiopathy (TMA) and disseminated intravascular coagulation was accompanied by new-onset severe pulmonary hypertension and a hemolytic uremic syndrome-like disorder in the gastric and the urothelial carcinoma patient, respectively. TF-specific procoagulant activity of isolated plasma MPs, as assessed by single-stage clotting assay, was dramatically increased in both patients compared to healthy controls (21- and 55-fold), and primary tumor samples stained strongly positive for TF by immunohistochemistry.
  
  
  CONCLUSIONS
  TMA was likely caused by TF-triggered tumor cell embolization in both patients. Further clinical evidence is thus provided that TF directly links coagulation activation to cancer cell dissemination.
authors.affiliation: II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum - Universitx00E4;res Cancer Center Hamburg, Universitx00E4;tsklinikum Eppendorf, Hamburg, Germany.
authors.forename: Minna
authors.initials: M
authors.lastname: Voigtlaender
authors.forename: Katharina
authors.initials: K
authors.lastname: Holstein
authors.forename: Sven
authors.initials: S
authors.lastname: Leuenroth
authors.forename: Jonas
authors.initials: J
authors.lastname: Mudter
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Florian
authors.initials: F
authors.lastname: Langer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D013925:Thromboplastin / Q000378:metabolism; D057049:Thrombotic Microangiopathies / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D013925:Thromboplastin