ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer

J Thromb Haemost. 2016 Feb;14(2):306-15. doi: 10.1111/jth.13205. Epub 2016 Jan 25.

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.

Objectives: 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.

Patients/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.

Keywords: ADAMTS-13 protein, human; D-dimer; P-selectin; cancer; thrombosis; von Willebrand factor.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS13 Protein / blood*
  • Aged
  • Area Under Curve
  • Biomarkers / blood
  • Case-Control Studies
  • Europe
  • Female
  • Humans
  • Male
  • Mexico
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / blood*
  • Neoplasms / complications
  • Neoplasms / diagnosis
  • Peptide Fragments / analysis
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Prothrombin / analysis
  • ROC Curve
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / etiology*
  • von Willebrand Factor / analysis*

Substances

  • Biomarkers
  • Peptide Fragments
  • prothrombin fragment 1.2
  • von Willebrand Factor
  • Prothrombin
  • ADAMTS13 Protein
  • ADAMTS13 protein, human