title: ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer.
abstract: ESSENTIALS: Cancer patients are at high risk of venous thromboembolism (VTE). In this study, cases and controls were cancer patients who did or did not develop VTE. von Willebrand factor (VWF) levels were higher if compared with controls and correlated with cancer stage. VWF and ADAMTS-13 are associated with the occurrence of VTE in cancer.
  
  
  BACKGROUND
  Patients with cancer are at high risk of venous thromboembolism (VTE). ADAMTS-13 regulates von Willebrand factor (VWF) activity, which plays a role in the development of cancer and in VTE.
  
  
  OBJECTIVE
  The aim of this study was to search for an association between the levels of VWF and ADAMTS-13 and VTE in patients with cancer and to compare current scoring systems for prediction of VTE before and after addition of these parameters.
  
  
  METHODS
  In a case-control study, in which patients with recently diagnosed cancer were followed-up for 6 months, we compared 20 patients who developed VTE (cases) and 140 patients with cancer without VTE (controls), matched for sex, age, and type and stage of cancer. We measured VWF, ADAMTS-13 (activity and antigen), P-selectin, D-dimer and F1 + 2 levels at baseline, and calculated both the Khorana score and the Khorana score expanded after addition of P-selectin and D-dimer levels.
  
  
  RESULTS
  VWF levels were significantly higher in cases when compared with controls (326 ± 185% vs. 242 ± 158%) and correlated with advanced stage of cancer: localized, 185 [142; 222]; locally advanced, 240 [146; 257]; metastatic, 267 [153; 324] (mean [interquartile range]). The addition of two biomarkers, ADAMTS-13 activity and F1 + 2 levels, to the Khorana score improved receiver operating curves.
  
  
  CONCLUSIONS
  von Willebrand factor and ADAMTS-13 are associated with the occurrence of VTE in patients with cancer. Moreover, addition of ADAMTS-13 and F1 + 2 levels to the Khorana score considerably increases the predictive value for VTE.
authors.affiliation: Service de Médecine Interne, Hôpital Louis Mourier (AP-HP), Colombes, France.|Unité 1176, INSERM, Le Kremlin-Bicêtre, France.
authors.forename: M
authors.initials: M
authors.lastname: Pépin
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Kleinjan
authors.affiliation: Département d'Epidémiologie et Recherche Clinique, URC Paris-Nord, Hôpital Bichat-Claude Bernard (AP-HP), Paris, France.|INSERM, CIC 1425-EC, UMR1123, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Hajage
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Department of Medical, Oral and Biotechnological Sciences, University G. D'Annunzio, Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Nisio
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Kamphuisen
authors.affiliation: Département de Recherche, Centre Ophtalmologique Rothschild, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Salomon
authors.affiliation: Service d'Hématologie biologique, Hôpital Lariboisière (AP-HP), Paris, France.|Universitaire Paris Diderot, EA 7334 REMES Sorbonne Paris Cité, Paris, France.|Université Paris Diderot, Institut Universitaire d'Hématologie, EA3518, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Veyradier
authors.affiliation: Service d'Hématologie biologique, Hôpital Lariboisière (AP-HP), Paris, France.|Université Paris Diderot, Institut Universitaire d'Hématologie, EA3518, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Stepanian
authors.affiliation: Service de Médecine Interne, Hôpital Louis Mourier (AP-HP), Colombes, France.|Universitaire Paris Diderot, EA 7334 REMES Sorbonne Paris Cité, Paris, France.|Université Paris Diderot, Institut Universitaire d'Hématologie, EA3518, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Mahé
mesh_terms: D000071120:ADAMTS13 Protein / Q000097:blood*; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D010446:Peptide Fragments / Q000032:analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011516:Prothrombin / Q000032:analysis; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D014841:von Willebrand Factor; D011516:Prothrombin; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS-13 protein, human; D-dimer; P-selectin; cancer; thrombosis; von Willebrand factor