Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study

Frits I Mulder, Noémie Kraaijpoel, Marc Carrier, Noori A Guman, Luis Jara-Palomares, Marcello Di Nisio, Walter Ageno, Jan Beyer-Westendorf, Frederikus A Klok, Thomas Vanassche, Hans-Martin B Otten, Benilde Cosmi, Marije Ten Wolde, Sjors G J G In 't Veld, Edward Post, Jip Ramaker, Kenn Zwaan, Mike Peters, Aurélien Delluc, Pieter W KamphuisenVeronica Sanchez-Lopez, Ettore Porreca, Patrick M M Bossuyt, Harry R Büller, Thomas Wurdinger, Myron G Best, Nick van Es

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies.

OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE).

METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity.

RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47).

CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.

Original languageEnglish
Pages (from-to)905-916
Number of pages12
JournalJournal of thrombosis and haemostasis : JTH
Issue number4
Early online date11 Jan 2023
Publication statusPublished - 1 Apr 2023


  • blood platelets
  • early detection of cancer
  • neoplasms
  • thrombosis
  • tumor biomarkers
  • venous thromboembolism

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