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

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: = 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.