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Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin generation, procoagulant phospholipid and soluble P-selectin
  1. Nicoletta Riva1,
  2. Kevin Vella2,
  3. Kieron Hickey3,
  4. Lorenza Bertù4,
  5. Daniel Zammit2,
  6. Silvana Spiteri2,
  7. Steve Kitchen3,
  8. Michael Makris3,
  9. Walter Ageno4,
  10. Alex Gatt1,2
  1. 1 Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
  2. 2 Coagulation Medicine Laboratory, Department of Pathology, Mater Dei Hospital, Msida, Malta
  3. 3 Sheffield Haemophilia and Thrombosis Centre, University of Sheffield, Sheffield, UK
  4. 4 Department of Medicine and Surgery, University of Insubria, Varese, Italy
  1. Correspondence to Professor Alex Gatt, Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, MSD 2080, Malta; alexander.gatt{at}


Background The diagnostic algorithm for venous thromboembolism (VTE) currently involves a composite of pre-test probability, D-dimer and imaging. Other laboratory tests, however, may assist in the identification of patients with VTE.

Aim To assess the accuracy of different coagulation tests (D-dimer, thrombin generation, phospholipid-dependent (PPL) clotting time, soluble P-selectin (sP-selectin)) as biomarkers of acute VTE.

Methods Random samples arriving at the Coagulation Laboratory at Mater Dei Hospital (Msida, Malta) from the Accident and Emergency Department with a request for D-dimer measurement were collected between August 2015 and February 2016. The following tests were performed: Innovance D-dimer (Siemens Healthcare Diagnostics), HemosIL D-dimer HS (Instrumentation Laboratory), thrombin generation (using the calibrated automated thrombogram), STA Procoag PPL (Diagnostica Stago) and sP-selectin (Affymetrix; eBioscience). VTE was objectively confirmed by compression ultrasonography, CT pulmonary angiography or ventilation/perfusion lung scan.

Results 100 samples were collected (33 with VTE). A strong positive linear correlation was found between the two D-dimer tests (r=0.97, p<0.001). Patients with VTE showed significantly higher sP-selectin concentrations compared with patients without VTE (75.7 ng/mL vs 53.0 ng/mL, p<0.001). In the random forest plot, the two D-dimer assays showed the highest variable importance, followed by sP-selectin. A sP-selectin cut-off of 74.8 ng/mL was associated with 72.7% sensitivity and 78.2% specificity for acute VTE in our cohort.

Conclusion Our results confirmed D-dimer as the main biomarker of VTE and speculated a role for sP-selectin. The impact of thrombin generation was limited and no role emerged for the PPL clotting time. These observations need to be confirmed in large management studies.

  • biomarkers
  • diagnosis
  • venous thromboembolism

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  • Handling-editor Mary Frances McMullin.

  • Contributors NR and AG contributed to the conception and design of the study, analysis and interpretation of data and drafted the article. KV, KH, DZ, and SS contributed to acquisition and interpretation of data. LB contributed to analysis and interpretation of data. SK, MM and WA contributed to interpretation of data and critical revision of the manuscript. All authors provided final approval of the manuscript.

  • Funding This study was supported by a research grant from the University of Malta.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.