Could a D-dimer/fibrinogen ratio have a role in ruling-out venous thromboembolism?

Abstract

Background: Diagnosis of venous thromboembolism (VTE) requires chest CT angiography for pulmonary embolism and venous ultrasound for deep vein thrombosis. To reduce imaging, guidelines recommend D-dimer levels to rule-out VTE in patients with a low pre-test probability. The most widely used D-dimer cut-off is 500 ng/mL. This cut-off has low specificity, meaning many patients without disease require imaging.

Methods: In this retrospective chart review, we evaluated the diagnostic performance of the D-dimer/fibrinogen ratio (DFR) for identifying thromboembolism and compared it to the performance of two different D-dimer cut-offs (500 ng/mL and 1000 ng/mL) in patients who underwent a chest CT angiography or a venous ultrasound in the ED of San Raffaele Hospital, Italy, in 2017. Patients had a retrospective Wells score calculated after chart review, identifying both high-risk and low-risk pre-test probability patients for this study and low probability patients were further stratified into low-risk of deep vein thrombosis or pulmonary embolism.

Results: Enrolled patients included 92 with suspected pulmonary embolism and 154 with suspected deep vein thrombosis; of whom 67 (27%) were diagnosed with VTE. The most accurate cut-off for DFR in terms of discriminative power was 2.65. In the whole sample and in low-risk patients, this cut-off had the same sensitivity values of the 500 ng/mL D-dimer cut-off (97% (95% CI: 89.8% to 99.2%)), while slightly lower sensitivity values were found for the 1000 ng/mL D-dimer cut-off (95.5% (95% CI: 87.6% to 98.5%)). Specificity was higher for the 2.65 DFR cut-off (55.3% (95% CI: 48.0% to 62.4%)) in the whole sample compared with both 500 ng/mL D-dimer cut-off (22.9% (95% CI: 17.4% to 29.6%)) and 1000 ng/mL D-dimer cut-off (45.8% (95% CI: 38.7% to 53.1%)). Similar results were found in all subgroups.

Conclusion: A DFR, with a cut-off of 2.65, may improve the specificity for VTE patients when compared with D-dimer alone in high-risk VTE emergency medicine populations. This is exploratory information only, needing evaluation in prospective, multicentre studies, prior to consideration for use in routine clinical work.

Keywords: diagnosis; emergency department; pulmonary embolism; thrombo-embolic disease.