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D-Dimer pathology test

the D-Dimer test

  • the D-Dimer test was originally designed to detect DIC as D-Dimers are plasmin fibrinolytic breakdown products òf the fibrin mesh that has been stabilised by Factor XIII.
  • the test was found to be of use in detecting thromboembolism.

upper limit of normal for D-Dimer

  • age < 50yrs: 0.5µg/mL
  • age > 50yrs: age in yrs/100 µg/mL

utility in pregnant patients

  • although there are D-Dimer cutoffs adjusted for trimesters, these have not been adequately validated and thus obstetricians generally DO NOT USE D-Dimer in pregnancy
  • consider discussing all suspected cases of PE with an obstetric service
  • 1st trimester pregnancy: 0.95µg/mL
  • 2nd trimester pregnancy: 1.29µg/mL
  • 3rd trimester pregnancy: 1.7µg/mL1)
  • Kline's approach
    • 1st trimester pregnancy: modified PERC with HR > 105 and D-Dimer > 50% higher than normal cutoff
    • 2nd trimester pregnancy: modified PERC with HR > 105 and D-Dimer > 100% higher than normal cutoff
    • 3rd trimester pregnancy: modified PERC with HR > 105 and D-Dimer > 125% higher than normal cutoff
  • BUT The DiPEP study2) looked at biomarkers and VTE in pregnant women and concluded that D-dimer among other biomarkers were not reliable to rule VTE in or out in pregnancy
  • THUS some suggest the following approach3):
    • IF your gestalt for PE is high risk then do CXR and if normal, a V/Q scan
    • IF gestalt for PE is moderate risk then:
      • if 1st trimester can do D-Dimer and if negative then no imaging
      • otherwise, do CXR to exclude other causes and bilateral leg doppler USS
        • if DVT found then treat as per PE
        • if no DVT then PE is unlikely

causes of raised D-Dimer levels:

  • clots
  • increasing age
    • this can be addressed by using age-related cut off values (in μg/L) of 10 x age once age > 50 yrs 4)
  • pregnancy
  • ? racial variation
  • DIC ⇒ markedly high levels
  • post-op.
  • sepsis
  • trauma
  • cancer - may have very high levels
  • functionally impaired
  • major haemorrhage
  • venous thrombo-embolism ⇒ subtle increased levels
  • post-vaccination thrombosis with thrombocytopenia syndrome (TTS / VITT) usually have 5x upper limit of normal values
  • aortic dissection - sensitivity seems to be > 82% at cutoff values of 400mcg/L
    • average yearly increase in AAA diameter was positively correlated with plasma D-dimer (r=0.39, p<0.001). Plasma D-dimer was independently associated with AAA progression after adjusting for other risk factors, including initial AAA diameter5)6)

false negative D-Dimer results

  • anticoagulant Rx
  • early testing
  • delayed testing

Simply-RED D-Dimer test:

  • whole blood agglutination method
  • sensitivity 66%, NPV 89%
  • if low pre-test probability of PE then NPV almost 100%

Mx of the patient with a raised D-Dimer

1. Is there a reasonable explanation for it?

  • for example: pregnancy, recent surgery, recent trauma / bruise / fractures, severe sepsis, or known chronic raised DDimer due to malignancy
  • in general, D-Dimer should not be performed on these patients unless looking for very high levels for another cause such as snakebite or AZ vaccine thrombosis with thrombocytopenia syndrome (TTS / VITT) and if not doing this, the dDimer should probably be ignored and the patient treated on their merits as to their underlying presentation thus EXIT this algorithm.

2. Is the level greater than 5x upper limit of normal?

3. Abnormally high levels adjusted for age but less than 5x the upper limit of normal

  • if there is associated thrombocytopenia in the 4-30 days post-AZ vaccine, consider thrombosis with thrombocytopenia syndrome (TTS / VITT) as a possibility
  • If there are symptoms or signs of PE (eg. SOB, chest pain, unexplained persistent tachycardia, near-syncope) then consider CTPA or VQ scan
  • If there are no features of PE but possible symptoms/signs of DVT then consider a Doppler USS legs
  • If there are features of aortic dissection consider a CT aortogram
  • If the presentation is consistent with ruptured abdominal aortic aneurysm (AAA) then investigate urgently with CT aortogram
  • If the patient is on anticoagulants consider the possibility of occult bleeding such as retroperitoneal haemorrhage if there are other features such as pain to suggest this.
  • If none of the above are present:
    • if there are risk factors for aortic aneurysm such as age > 60, male, smoker, raised lipids or FH of AAA, then consider an outpatient screening abdominal USS assuming patient's presentation is stable and not of a ruptured AAA in which case an emergent CT aortogram should be considered

clinical utility in possible VTE:

  • as a method of excluding venous thromboembolism with a normal result (ie. no need to perform V/Q scan or CTPA if normal):
    • ONLY perform if:
      • low pre-test probability of venous thromboembolism:
        • patient < 50yrs age (unless you are happy to use the age-related cutoffs - see above)
        • heart rate : systolic BP ratio < 1
        • no unexplained hypoxia (ie. SaO2 > 95% on room air)
        • no haemoptysis
        • no calf swelling
        • no recent general aneasthetic past 4wks
      • AND other causes of raised levels unlikely:
        • ie. not for most inpatients & pts with substantial comorbidities
      • THUS only for previously well pts presenting to ED with new possible venous thromboembolism but low pretest probability of it

newer ELISA & whole blood agglutination:

  • not available in all hospitals
  • positive if > 500ng/ml
  • high negative predictive values (90%)
  • positive predictive value 30%

immunochromatographic bedside D-Dimer tests:

  • eg. Simplify by Agen Biochemical.
  • similar design to urine pregnancy test strips, results available in 10min
  • in the population whose Hamilton Score for DVT is “unlikely”, then the negative predictive value for an acute lower limb DVT is 98.8%.
  • unfortunately, in the group whose Hamilton Score is “likely DVT” the negative predictive value is only 82% and cannot be used to rule it out and thus USS is indicated.
ddimer.txt · Last modified: 2021/07/17 08:59 by gary1