title: Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors: Deborah A
authors: DA
authors: Lewis
authors: Gregg J
authors: GJ
authors: Stashenko
authors: Olga M
authors: OM
authors: Akay
authors: Lulit I
authors: LI
authors: Price
authors: Kouros
authors: K
authors: Owzar
authors: Geoffrey S
authors: GS
authors: Ginsburg
authors: Jen-Tsan
authors: JT
authors: Chi
authors: Thomas L
authors: TL
authors: Ortel
mesh_terms: D000990:Antithrombin III; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D012008:Recurrence; D012307:Risk Factors; D015854:Up-Regulation; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D019007:P-Selectin; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D010447:Peptide Hydrolases