Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study

Am J Clin Pathol. 2024 May 2;161(5):501-511. doi: 10.1093/ajcp/aqad178.

Abstract

Objectives: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies.

Methods: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants.

Results: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%).

Conclusions: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

Keywords: D-dimer; P-selectin; cancer biomarkers; cell-derived microparticles; extracellular vesicles; occult cancer.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Case-Control Studies
  • Female
  • Fibrin Fibrinogen Degradation Products* / analysis
  • Fibrin Fibrinogen Degradation Products* / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms, Unknown Primary / complications
  • Neoplasms, Unknown Primary / diagnosis
  • P-Selectin* / blood
  • Prospective Studies
  • Venous Thromboembolism* / blood
  • Venous Thromboembolism* / diagnosis

Substances

  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • P-Selectin
  • Biomarkers, Tumor