Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis

Abstract

Objective Although duplex ultrasound is the standard for the diagnosis of lower extremity deep venous thrombosis (LE-DVT), imaging is not always available. The use of D-dimer can exclude (high-sensitivity), but not rule in (low-specificity) LE-DVT. Previously, we demonstrated that soluble P-selectin (sP-sel) in combination with the Wells score, establishes the diagnosis of LE-DVT with a specificity of 96% and a positive predictive value of 100%. In order to validate our previous results, we applied the model to a separate but similar patient cohort. Additionally, we analyzed the role of biomarkers for diagnosing upper extremity DVT (UE-DVT). Methods Between April 2009 and March 2012, all patients presenting for a duplex ultrasound exam with concern of DVT were screened. Demographics, clinical data, D-dimer, sP-sel, C-reactive protein, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, and von Willebrand factor levels were prospectively collected in 279 patients (234 LE-DVT, 45 UE-DVT). Continuous and categorical variables among patients with DVT were compared with patients without DVT. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value were then calculated using our previously derived cut points to rule in or exclude DVT. Results Among 234 patients evaluated for LE-DVT, 112 (48%) patients had a confirmed LE-DVT with significant differences in all biomarkers. When Wells score ≥2, sP-sel could rule in LE-DVT with a specificity of 97.5% and a positive predictive value of 91%, which was more accurate than Wells score ≥2 and D-dimer (specificity, 65%; positive predictive value, 69%). When Wells score was <2, D-dimer was superior to sP-sel for excluding the diagnosis of LE-DVT (sensitivity, 98%; negative predictive value, 95% vs sensitivity, 91%; negative predictive value, 79%). The use of additional biomarkers did not increase accuracy. Had imaging not been available, we could have correctly ruled in or ruled out LE-DVT in 29% (67/234) of patients. The use of sP-sel in UE-DVT was nondiagnostic. Conclusions We demonstrate that when Wells score ≥2, sP-sel is an excellent biomarker to rule in LE-DVT. Different from our previous study, D-dimer and a Wells score <2 was most sensitive at excluding a diagnosis of LE-DVT. Combined, Wells score, sP-sel, and D-dimer can both rule in and exclude LE-DVT in approximately one-third of patients.

Inflammation in deep vein thrombosis: a therapeutic target?

“…In the same cohort of patients, sP-selectin levels were significantly higher at DVT onset than in controls and then decreased rapidly within the first month. Elevated plasma sP-selectin and CRP levels upon diagnosis of DVT were also observed by Mosevoll et al [51] and for sP-selectin by Vandy et al [52]. A similar pattern (with elevated CRP, IL6 and sICAM1 upon diagnosis) was reported in a prospective study of over 600 patients [53].…”

Soluble P-Selectin Level in Patients with Deep Venous Thrombosis

“…In follow-up study done by Vandy et al (24) , they established that a combination of Wells score ≥2 and a sP-sel >90 ng/mL could rule in the diagnosis of lower extremity DVT (LE-DVT) with a specificity of 95% and a positive predictive value of 100%. Conversely, a Wells score <2 and a sPsel <60 ng/mL could rule out the diagnosis with a sensitivity of 99% and a negative predictive value of 96%.22.…”

Risk Assessment Scores for Cancer-Associated Venous Thromboembolic Disease

“…Elevated soluble P-selectin has been shown to be highly predictive of VTE when combined with a high clinical probability score. 11 The cumulative VTE rate using the original Khorana score after 6 months was 17.7% in patients with score !3, 9.6% in those with score 2, 3.8% in those with score 1, and 1.5% in those with score 0. The higher rates of VTE across all risk categories can be explained by the longer median follow-up period in the Vienna CATS study versus the original study (656 vs. 73 days, respectively).…”

“…Soluble P-selectin has been shown to be highly predictive of the presence of VTE in the general population, especially when combined with clinical prediction scores. 11 To determine the predictive power of these and other biomarkers in cancer-associated VTE, plasma specimens from participants of the previously discussed CATCH trial were collected at enrollment. The association of biomarkers with recurrent VTE was presented at the ISTH 2015 meeting.…”