Diagnostic Accuracy in Acute Venous Thromboembolism: Comparing D-Dimer, Thrombin Generation, Overall Hemostatic Potential, and Fibrin Monomers.

Aleksandra Antovic,Anwar J Siddiqui,David E Schmidt,Iva Pruner,Jovan P Antovic,Margareta Holmström,Maria Farm,Nida Soutari,Niklas Bark

doi:10.1055/s-0040-1714210

Aleksandra Antovic, Anwar J Siddiqui + Show 7 more

Open Access

https://doi.org/10.1055/s-0040-1714210

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Abstract

Introduction For acute venous thromboembolism (VTE), a biomarker with higher specificity than D-dimer would be of great clinical use. Thrombin generation and overall hemostatic potential (OHP) reflect the hemostatic balance by globally assessing multiple coagulation factors and inhibitors. These tests discriminate between healthy controls and patients with a prothrombotic tendency but have yet to be established as clinical biomarkers of VTE. Objective This study compares endogenous thrombin potential (ETP) and OHP to D-dimer and fibrin monomers (FM) in outpatients with suspected VTE. Methods A cross-sectional diagnostic study where 954 patients with suspected pulmonary embolism or deep venous thrombosis were recruited consecutively from the medical emergency department at Karolinska University Hospital. D-dimer, FM, OHP, and ETP were analyzed in a subpopulation of 60 patients with VTE and 98 matched controls without VTE. VTE was verified either by ultrasonography or computed tomography and clinical data were collected from medical records. Results Compared with healthy controls, both VTE and non-VTE patients displayed prothrombotic profiles in OHP and ETP. D-dimer, FM, ETP area under the curve (AUC), and ETP T lag were significantly different between patients with VTE and non-VTE. The largest receiver-operating characteristic AUCs for discrimination between VTE and non-VTE, were found in D-dimer with 0.94, FM 0.77, and ETP AUC 0.65. No useful cutoff could be identified for the ETP or the OHP assay. Conclusion Compared with D-dimer, neither ETP nor OHP were clinically viable biomarkers of acute venous thrombosis. The data indicated that a large portion of the emergency patients with suspected VTE were in a prothrombotic state.

Highlights

For acute venous thromboembolism (VTE), a biomarker with higher specificity than D-dimer would be of great clinical use
The data indicated that a large portion of the emergency patients with suspected VTE were in a prothrombotic state
Our results indicate that neither the endogenous thrombin potential (ETP) nor the overall hemostatic potential (OHP) assay would be clinically useful additions as biomarkers for the diagnosis of acute VTE in the emergency department

Summary

Introduction

For acute venous thromboembolism (VTE), a biomarker with higher specificity than D-dimer would be of great clinical use. Thrombin generation and overall hemostatic potential (OHP) reflect the hemostatic balance by globally assessing multiple coagulation factors and inhibitors. These tests discriminate between healthy controls and patients with a prothrombotic tendency but have yet to be established as clinical biomarkers of VTE. The only biomarker in common clinical use for diagnosis of VTE is D-dimer, the degradation product of polymerized and cross-linked fibrin. The specificity of D-dimer is low at the chosen cutoff, with false positive results in up to 30% of tested patients with suspected VTE.. Fibrin monomers (FM) can possibly improve diagnosis if used together with D-dimer for the exclusion of VTE. The specificity of D-dimer is low at the chosen cutoff, with false positive results in up to 30% of tested patients with suspected VTE. The low specificity is partially due to increased levels in patients with comorbidities. Increasing the effectiveness of the diagnostic process could potentially have major clinical and economical beneficial effects on the management of VTE

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