Publikasjoner
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Xavier, Samantha; Wikan, Vårin Eiriksdatter; Ullsten-Wahlund, Casper Jan Elis; Latysheva, Nadezhda; Øverli, Øyvind & Antoun, Christopher
[Vis alle 12 forfattere av denne artikkelen]
(2025).
Total and extracellular vesicle–bound plasma P-selectin as diagnostic biomarkers for acute deep vein thrombosis.
Research and Practice in Thrombosis and Haemostasis (RPTH).
9(7).
doi:
10.1016/j.rpth.2025.103171.
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Background
Plasma P-selectin has shown moderate diagnostic potential for deep vein thrombosis (DVT). In plasma, P-selectin is found in soluble form and bound to extracellular vesicles (EVs). It is unknown whether specific detection of EV-bound P-selectin would improve the diagnostic performance of P-selectin. We aimed to investigate the diagnostic performance of EV-bound and total P-selectin for acute DVT, alone and in combination with D-dimer.
Objectives
We aimed to investigate the diagnostic potential of total extracellular vesicle-bound plasma P-selectin as diagnostic biomarkers for acute deep vein thrombosis in a cohort of patients admitted to hospital with suspected DVT.
Methods
A bead-based flow cytometric assay was developed for selective detection of EV-bound P-selectin. Total and EV-bound P-selectin was measured in 2 cohorts of patients (n = 168 and n = 200) referred to hospital with suspected DVT. DVT was confirmed or ruled out by compression ultrasound.
Results
DVT was confirmed in 53 patients and ruled out in 115 patients (first cohort) and in 54 and 146 patients (replication cohort), respectively. Only 2% of plasma P-selectin was bound to EVs, and EV-bound P-selectin showed poor diagnostic performance with an area under the receiver-operating characteristic curve (AUC) of 0.55 (95% CI, 0.45-0.65). Total plasma P-selectin had an AUC of 0.70 (95% CI, 0.62-0.78) in the first cohort and 0.77 (95% CI, 0.69-0.85) in the replication cohort. Combination of total P-selectin with D-dimer had diagnostic performance (AUC, 0.88; 95% CI, 0.84-0.91) inferior to D-dimer alone (AUC, 0.92; 95% CI, 0.89-0.95).
Conclusion
The proportion of P-selectin bound to EVs in plasma was low and could not discriminate between patients with and without acute DVT. The diagnostic performance of total P-selectin, alone or in combination with D-dimer, was inferior to the diagnostic performance of D-dimer alone.
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Xavier, Samantha & Snir, Omri
(2026).
P-selectin as a Biomarker for Venous Thromboembolism.
UiT Norges arktiske universitet.
ISSN 9788235000811.
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Venous thromboembolism (VTE), a severe multifactorial disease, is a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE). P-selectin is a single-chain glycoprotein that has been investigated for its role in inflammation, thrombosis, and hemostasis. It circulates in plasma in its soluble form as well as when it is bound to extracellular vesicles (EVs). Elevated P-selectin levels have been observed following incident VTE, are suggested to have moderate diagnostic performance for DVT, and have been proposed as a predictive biomarker for cancer-associated VTE. In this thesis, we investigated (i) the diagnostic performance of soluble and EV-bound P-selectin for acute DVT, (ii) the association between plasma P-selectin levels and the risk of future incident VTE, and (iii) the association between plasma P-selectin levels measured prior to incident VTE and the risk of VTE recurrence.
In paper I, the diagnostic performance of soluble P-selectin and P-selectin bound to EVs were studied. Individuals with suspected DVT consecutively admitted to the emergency department or VTE outpatient clinic at Akershus University Hospital in Oslo, Norway were included. DVT was confirmed or ruled out using compression ultrasound; plasma samples were collected and D-dimer was measured at inclusion. We developed a bead-based flow cytometric assay to assess EV-bound P-selectin levels and used an ELISA to measure soluble P-selectin levels in these plasma samples. We found that EV-bound P-selectin had no discriminatory power as a diagnostic biomarker for DVT. While soluble P-selectin demonstrated moderate diagnostic performance, it did not outperform or supplement the diagnostic performance of D-dimer.
In paper II, we performed a population-based nested case-control study of VTE cases and age- and sex-matched controls derived from the 4th survey of the Tromsø Study. P-selectin was measured by ELISA in plasma samples collected at inclusion, and odds ratios for association between plasma P-selectin levels and risk of future VTE were estimated across quartiles of P-selectin following sex stratification. We found that elevated levels of P-selectin were associated with an increased risk of VTE in women but not in men, suggesting a sex-specific association between P-selectin and risk of future VTE.
In paper III, we performed a prospective cohort study of patients with incident VTE recruited from the 4th survey of the Tromsø Study and the 3rd survey of the HUNT study (n=1,314). Plasma samples were collected at baseline, and P-selectin levels were measured using ELISA for the Tromsø 4 samples and by SomaScan® for the HUNT 3 samples. Following sex-stratification, we found no significant association between P-selectin levels and overall risk of VTE recurrence, nor did we find significant associations when stratifying by type of incident VTE.
The thesis summarizes the potential of P-selectin for use as a biomarker for incident and recurrent VTE, as well as DVT diagnosis. Our thorough evaluation of P-selectin in these studies exemplifies the challenges of discovering novel biomarkers for VTE and suggests strategies for interrogating new biomarker candidates.
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Publisert
14. aug. 2026 10:28
- Sist endret
14. aug. 2026 11:02
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