title: Can causes of false-normal D-dimer test [SimpliRED] results be identified?
abstract: BACKGROUND
  To simplify the diagnostic strategy of patients suspected for venous thromboembolism, the use of D-dimer tests has been advocated. Very important for the safety of such diagnostic strategies would be the capacity to recognise false-normal D-dimer results, in order to prevent inadequately withholding anticoagulant treatment in patients who actually have the disease. Insight in the causes of false-normal D-dimer results would therefore be necessary. We hypothesised that certain patient characteristics are associated with relatively low plasma D-dimer levels and, therefore, could increase the risk of false-normal results.
  
  
  METHODS
  Consecutive patients with an objectively confirmed venous thromboembolic event and an independently obtained false-normal SimpliRED D-dimer test result were included in the study. For each patient, two controls with objectively confirmed venous thromboembolism and an adequate abnormal D-dimer result were selected. Baseline patient characteristics, obtained by standardised questionnaires, were compared between the two groups of patients.
  
  
  RESULTS
  In total, 686 patients had a venous thromboembolic event and 47 of these patients had a false-normal SimpliRED result. Therefore, the overall sensitivity of the SimpliRED test for venous thromboembolism was 94% (95% CI: 92-95%). Although the prevalence of certain clinical characteristics was significantly higher in patients with a false-normal D-dimer result than in the controls [odds ratios for (LMW)heparin treatment and symptoms lasting more than 10 days: 5.1 (95% CI: 1.5-18.7) and 3.2 (95% CI:1.4-7.4), respectively], the prevalence of these characteristics was also high in the control group with an adequate abnormal D-dimer. Combining two or more of these characteristics had a low prevalence and did not further improve the ability to identify those patients with a false-normal D-dimer test at presentation.
  
  
  CONCLUSIONS
  Although these findings clearly indicate an association between certain baseline clinical characteristics and the occurrence of a false-normal SimpliRED test, the clinical utility for these characteristics is limited.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands. r.a.kraaijenhagen@amc.uva.nl
authors.forename: R A
authors.initials: RA
authors.lastname: Kraaijenhagen
authors.forename: J
authors.initials: J
authors.lastname: Wallis
authors.forename: M M W
authors.initials: MM
authors.lastname: Koopman
authors.forename: M R
authors.initials: MR
authors.lastname: de Groot
authors.forename: F
authors.initials: F
authors.lastname: Piovella
authors.forename: P
authors.initials: P
authors.lastname: Prandoni
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005188:False Negative Reactions; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013923:Thromboembolism / Q000097:blood / Q000175:diagnosis*; D020246:Venous Thrombosis / Q000175:diagnosis*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D