Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism

Abstract

Introduction Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions concerning the duration of anticoagulant therapy. Objectives In this exploratory study, we investigated whether whole blood gene expression data could distinguish subjects with single venous thromboembolism from subjects with recurrent venous thromboembolism. Methods 40 adults with venous thromboembolism (23 with single event and 17 with recurrent events) on warfarin were recruited. Individuals with antiphospholipid syndrome or cancer were excluded. Plasma and serum samples were collected for biomarker testing, and PAXgene tubes were used to collect whole blood RNA samples. Results D-dimer levels were significantly higher in patients with recurrent venous thromboembolism, but P-selectin and thrombin-antithrombin complex levels were similar in the two groups. Comparison of gene expression data from the two groups provided us with a 50 gene probe model that distinguished these two groups with good receiver operating curve characteristics (AUC 0.75). This model includes genes involved in mRNA splicing and platelet aggregation. Pathway analysis between subjects with single and recurrent venous thromboembolism revealed that the Akt pathway was up-regulated in the recurrent venous thromboembolism group compared to the single venous thromboembolism group. Conclusions In this exploratory study, gene expression profiles of whole blood appear to be a useful strategy to distinguish subjects with single venous thromboembolism from those with recurrent venous thromboembolism. Prospective studies with additional patients are needed to validate these results.

Novel genetic predictors of venous thromboembolism risk in African Americans

“…The microarray data set, consisting of 70 adults with $1 prior VTE on warfarin and 63 healthy controls, was analyzed using an independent sample Student t test and the Benjamin-Hochberg false discovery rate correction for multiple testing (P , .05). 28 …”

Screening Feature Genes of Venous Thromboembolism with DNA Microarray

“…The incidence of VTE exceeds 1 per 1000, and there are over 200 000 new cases in the USA annually . Inherited and acquired risk factors are proved to be an individual person's risk for VTE , but these factors are frequently inadequate for the prediction of initial VTE or recurrent VTE . Moreover, drugs in anticoagulant therapy is commonly used for VTE treatment, such as aspirin and apixaban .…”

Whole blood gene expression profiles distinguish clinical phenotypes of venous thromboembolism

“…We previously used gene expression profiles to evaluate individuals with single versus recurrent VTE [16]. The two patient groups in that study included individuals with provoked as well as unprovoked events, resulting in a more heterogeneous mix of phenotypes.…”

“…We previously used whole blood gene expression profiles to distinguish patients with a single VTE from patients with recurrent VTE [16], but this study combined patients with provoked and unprovoked events. Here we extend this initial study by using clinically well-defined patient groups with the objectives of comparing individuals based on the type of VTE (provoked versus unprovoked) as well as by the number of events (single versus multiple).…”