title: Age- and sex-dependent reference intervals for D-dimer: evidence for a marked increase by age.
abstract: BACKGROUND
  A low D-dimer is commonly used to exclude venous thromboembolism in low risk patients. However, the reference intervals are poorly defined and D-dimer has been shown to increase by patient age. We aimed to establish age- and sex-dependent D-dimer reference intervals and to test the consequence of different cut-off limits.
  
  
  METHODS
  By means of the STA-Lia test D-dimer was measured in 1,352 subjects aged between 23 and 93years from the general population. A further 94 subjects were measured with the HemosIL test.
  
  
  RESULTS
  The reference intervals were age-dependent with the upper 95% limit increasing from 0.92 FEU mg/L in the age group <50years to 2.39 FEU mg/L in the group ≥70years. Minor differences in the reference intervals between sexes were found. The commonly used cut-off at 0.5 FEU mg/L resulted in a decrease of negatives from 91% in <50years to 56 % in ≥70years. The age-dependent cut-off value (patient's age*0.01 FEU mg/L in 50+ years) resulted in an increase of negatives by age. The linear increase in D-dimer has a slope at approximately 0.0077*age, meaning that a cut-off at (patient's age*0.0077) FEU mg/L, gives an almost constant number of positives across age groups. The two assays showed a poor correlation and a higher percentage of positives using the STA Lia test.
  
  
  CONCLUSIONS
  The age-dependent increase in D-dimer seen in patients was confirmed, which questions the clinical value of the present cut-off for venous thromboembolism.
authors.affiliation: Department of Clinical Biochemistry, Slagelse-Naestved Hospital; Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital.
authors.forename: Christine
authors.initials: C
authors.lastname: Haase
authors.forename: Maja
authors.initials: M
authors.lastname: Joergensen
authors.forename: Christina
authors.initials: C
authors.lastname: Ellervik
authors.forename: Mikala Klok
authors.initials: MK
authors.lastname: Joergensen
authors.forename: Lise
authors.initials: L
authors.lastname: Bathum
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005338:Fibrin Fibrinogen Degradation Products / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D012737:Sex Factors; D055815:Young Adult
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
keywords: CT; Computer Tomography; D-dimer; DIC; DVT; Deep Vein Thrombosis; Disseminated Intravascular Coagulation; FEU; Fibrinogen Equivalent Unit; GESUS; IFCC; INR; International Federation of Clinical Chemistry and Laboratory Medicine; International Normalised Ratio; PE; Pulmonary Embolism; Reference intervals; The Danish General Suburban Population Study; VTE; Venous Thromboembolism; Venous thromboembolism