Abstract
D-Dimer has a high sensitivity but a low specificity for the diagnosis of deep vein thrombosis (DVT) which limits its implementation as a general screening parameter. There is a demand for additional biomarkers to improve its diagnostic accuracy. Soluble platelet endothelial cell adhesion molecule 1 (sPECAM-1) is generated at the site of venous thrombosis, thus, represents a promising biomarker. Patients with clinically suspected DVT (N = 159) were prospectively recruited and underwent manual compression ultrasonography (CCUS) to confirm or exclude DVT. The diagnostic value of D-Dimer, sPECAM-1 and the combination of both was assessed. sPECAM-1 levels were significantly higher in patients with DVT (N = 44) compared to patients without DVT (N = 115) (85.9 [76.1/98.0] ng/mL versus 68.0 [50.1/86.0] ng/mL; p < 0.001) with a diagnostic sensitivity of 100% and a specificity of 28.7% at the cut point > 50.2 ng/mL. sPECAM-1 improved the diagnostic accuracy of D-Dimer: the combination of both biomarkers yielded a ROC-AUC of 0.925 compared to 0.905 for D-Dimer alone and 0.721 for sPECAM-1 alone with a reduction of false-positive D-Dimer cases 72- > 43 (Δ = − 31.9%). The discrimination mainly occurred in a subgroup of patients characterized by an inflammatory background (defined by c-reactive protein level > 1 mg/mL). sPECAM-1 represents a novel diagnostic biomarker for venous thrombosis. It does not qualify as a diagnostic biomarker alone but improves the diagnostic accuracy of D-Dimer in patients with suspected DVT.
Highlights
Venous thromboembolism (VTE; i.e. deep vein thrombosis [DVT] and pulmonary embolism [PE]) is a common disorder with significant socioeconomic consequences due to high morbidity and treatment costs
We evaluated sPECAM-1 as a biomarker for DVT
Two major findings emerge from this study: Firstly, sPECAM-1 levels are significantly higher in patients with DVT as compared to those without DVT
Summary
Venous thromboembolism (VTE; i.e. deep vein thrombosis [DVT] and pulmonary embolism [PE]) is a common disorder with significant socioeconomic consequences due to high morbidity and treatment costs. In patients with clinically suspected DVT, clinical scoring tools such as the Wells Score [1] are frequently used to predict a priori DVT probability, and to determine if further diagnostic testing is warranted [2]. In patients with low-pretest probability plasma D-Dimer measurement is the first evaluating step as negative test results rule out venous thrombosis [3]. [7] and false positive results due to various co-morbidities (i.e. trauma, surgery [8], pregnancy [9], inflammation [10], malignancy) limit its implementation as a general screening test for suspected DVT. Additional biomarkers are needed in order to improve diagnostic specificity and avoid unnecessary further diagnostic testing
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