Total and extracellular vesicle-bound plasma P-selectin as diagnostic biomarkers for acute deep vein thrombosis

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.

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.

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.

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).

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.