Predictive Ability of a Clinical-Genetic Risk Score for Venous Thromboembolism in Northern and Southern European Populations.

Eduardo Salas,Sara Pich,Jovan P Antovic,Israel Ortega,Kevin Guillen,Jose Manuel Soria,Maria Farm,Liselotte Onelöv

doi:10.1055/s-0041-1729626

Abstract

Venous thromboembolism (VTE) is a complex, multifactorial problem, the development of which depends on a combination of genetic and acqfiguired risk factors. In a Spanish population, the Thrombo inCode score (or TiC score), which combines clinical and genetic risk components, was recently proven better at determining the risk of VTE than the commonly used model involving the analysis of two genetic variants associated with thrombophilia: the Factor V Leiden (F5 rs6025) and the G20210A prothrombin (F2 rs1799963).The aim of the present case–control study was to validate the VTE risk predictive capacity of the TiC score in a Northern European population (from Sweden).The study included 173 subjects with VTE and 196 controls. All were analyzed for the genetic risk variants included in the TiC gene panel. Standard measures —receiver operating characteristic (ROC) area under the curve (AUC), sensitivity, specificity, and odds ratio (OR)—were calculated.The TiC score returned an AUC value of 0.673, a sensitivity of 72.25%, a specificity of 60.62%, and an OR of 4.11. These AUC, sensitivity, and OR values are all greater than those associated with the currently used combination of genetic variants. A TiC version adjusted for the allelic frequencies of the Swedish population significantly improved its AUC value (0.783).In summary, the TiC score returned more reliable risk estimates for the studied Northern European population than did the analysis of the Factor V Leiden and the G20210A genetic variations in combination. Thus, the TiC score can be reliably used with European populations, despite differences in allelic frequencies.

Highlights

Venous thromboembolism (VTE)—primarily deep vein thrombosis (DVT) and pulmonary embolism (PE)—is a common disorder that affects some 0.2% of the population annually
Study Population This case–control study was performed at the Department of Molecular Medicine and Surgery at the Karolinska Institute (Stockholm, Sweden), in a Swedish population whose members had experienced a VTE, and who had been tested for thrombophilia
For the purpose of comparison and considering that of those genetic variants included in Thrombo inCode (TiC), ABO variant was the most significantly present in VTE cases, we studied the performance of a new score

Summary

Introduction

Venous thromboembolism (VTE)—primarily deep vein thrombosis (DVT) and pulmonary embolism (PE)—is a common disorder that affects some 0.2% of the population annually. Survivors of VTE are at risk of long-term complications, such as recurrence, postthrombotic syndrome, and pulmonary hypertension.[1,4,5] VTE recurs in 20 to 30% of patients within 5 years.[6,7] It is, a considerable public health problem with a large economic burden.[8,9,10]

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