title: Longitudinal analysis of hemostasis biomarkers in cancer patients during antitumor treatment.
abstract: ESSENTIALS: Hemostasis biomarkers impact thrombosis occurrence and survival in cancer patients. We performed a longitudinal analysis of hemostatic parameters in 112 cancer patients. Hemostatic parameters are associated with disease state, patients' prognosis, and the risk of VTE. The procoagulant state exists not only at diagnosis, but also during the course of disease.
  
  
  BACKGROUND
  Hemostasis biomarkers are known to have an impact on venous thromboembolism (VTE) occurrence and survival in cancer patients.
  
  
  OBJECTIVE
  As there are almost no data on longitudinal changes, we aimed to evaluate those in the present prospective observational study during chemotherapy and the course of disease.
  
  
  METHODS
  Patients with cancer of the brain (n = 39), lung (n = 41), colon (n = 15) or pancreas (n = 17) were included before initiation of antitumor therapy. Blood samples for determination of factor VIII, thrombin peak height, D-dimer, F1 + 2 , fibrinogen and soluble P-selectin (sP-selectin) were drawn on a monthly basis. The study endpoints were death, VTE occurrence, or completion of the study period.
  
  
  RESULTS
  Overall, 546 blood samples of 112 patients were analyzed. D-dimer and sP-selectin levels were significantly higher in patients with distant metastasis than in those without. Patients with complete remission had significantly lower levels of F1 + 2 , D-dimer and fibrinogen. Peak height thrombin levels showed a decrease over time in all tumor types. Levels of biomarkers behaved differently in the various tumor types. Patients who developed VTE (n = 14) showed increasing levels of FVIII, sP-selectin, and D-dimer. At the last blood sampling time-point before VTE occurrence, in 13 patients the D-dimer level was above the median, and in seven of these patients it was even above the 75th percentile; however, the individual course was highly variable. Regarding survival, steadily increased FVIII, sP-selectin and D-dimer levels were associated with higher mortality.
  
  
  CONCLUSIONS
  Hemostatic parameters show an association with disease state, prognosis, and the risk of VTE, not only at diagnosis, but also during the course of antineoplastic treatment.
authors.affiliation: Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: E-M
authors.initials: EM
authors.lastname: Reitter
authors.affiliation: Section for Clinical Biometrics, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Kaider
authors.affiliation: Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.identifier: http://orcid.org/0000-0003-2607-9717
authors.initials: C
authors.lastname: Ay
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Quehenberger
authors.affiliation: Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Marosi
authors.affiliation: Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Zielinski
authors.affiliation: Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006487:Hemostasis; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011516:Prothrombin; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000209:etiology* / Q000401:mortality; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D019007:P-Selectin; D010446:Peptide Fragments; C546937:SELP protein, human; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; C078147:F8 protein, human; D011516:Prothrombin; D005169:Factor VIII; D005340:Fibrinogen; D013917:Thrombin
keywords: D-dimer; biomarkers; cancer; hemostasis; survival; venous thromboembolism