Document Detail

Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism.
MedLine Citation:
PMID:  20956709     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: In patients with a first unprovoked venous thromboembolism (VTE), an elevated d-dimer level after anticoagulation is stopped is a risk factor for recurrent VTE. However, questions remain about the utility of measuring d-dimer in clinical practice.
PURPOSE: To determine whether the timing of testing, patient age, and the cut point used to define a positive or negative result affect the ability of d-dimer testing to distinguish risk for recurrent disease.
DATA SOURCES: Comprehensive search of electronic databases (MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials) until July 2010, supplemented by reviewing conference abstracts and contacting content experts.
STUDY SELECTION: 7 prospective studies that investigated an association between d-dimer, measured after stopping anticoagulation, and disease recurrence in patients with a first unprovoked VTE (proximal deep venous thrombosis, pulmonary embolism, or both).
DATA EXTRACTION: Patient-level databases were obtained, transferred to a central database, checked, completed with further information provided by study investigators, and pooled into a single database.
DATA SYNTHESIS: 1818 patients with a first unprovoked VTE were followed for a mean of 26.9 months (SD, 19.1). A study-stratified multivariate Cox regression model, which included patient age, sex, hormone therapy use at the time of the index event, body mass index, timing of postanticoagulation d-dimer testing, and inherited thrombophilia as possible confounders, indicated that the hazard ratio for d-dimer status (positive vs. negative) was 2.59 (95% CI, 1.90 to 3.52). Only male sex had a significant effect on risk for recurrent VTE independent of d-dimer status. The Cox regression model and the log-rank test confirmed that the risk for recurrent VTE was higher in patients with a positive d-dimer result than in those with a negative result, regardless of the timing of postanticoagulation d-dimer testing or patient age. No study- or assay-specific d-dimer effect was found, and reassessing the analysis after recoding data according to specific quantitative d-dimer cut points (500 µg/L and 250 µg/L) did not change the results.
LIMITATIONS: Unmeasured variables could have affected the risk for recurrent VTE. The study population was predominantly white.
CONCLUSION: In patients with a first unprovoked VTE who have their d-dimer level measured after stopping anticoagulation, the timing of d-dimer testing, patient age, and the assay cut point used do not affect the ability of d-dimer to distinguish patients with a higher or lower risk for recurrent VTE.
James Douketis; Alberto Tosetto; Maura Marcucci; Trevor Baglin; Mary Cushman; Sabine Eichinger; Gualtiero Palareti; Daniela Poli; R Campbell Tait; Alfonso Iorio
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annals of internal medicine     Volume:  153     ISSN:  1539-3704     ISO Abbreviation:  Ann. Intern. Med.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-19     Completed Date:  2010-11-22     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  0372351     Medline TA:  Ann Intern Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  523-31     Citation Subset:  AIM; E; IM    
McMaster University, Hamilton, Ontario, Canada.
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MeSH Terms
Age Factors
Aged, 80 and over
Anticoagulants / therapeutic use*
Biological Markers / blood
Fibrin Fibrinogen Degradation Products / analysis*
Middle Aged
Proportional Hazards Models
Risk Factors
Sex Factors
Time Factors
Venous Thromboembolism / blood*,  drug therapy
Withholding Treatment
Young Adult
Grant Support
Reg. No./Substance:
0/Anticoagulants; 0/Biological Markers; 0/Fibrin Fibrinogen Degradation Products; 0/fibrin fragment D
Comment In:
Ann Intern Med. 2011 May 3;154(9):644; author reply 644   [PMID:  21536944 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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