Paul Smith writes, “I have a family member on Xarelto and his D-dimer reference range was 450 while taking Xarelto. What is the reference range?
Hello, Mr. Smith, and thank you for your question. There is some mild confusion about the D-dimer reference intervals (reference ranges) because several distributors use varient methods. These methods result in two distinct reference intervals that are reported in D-dimer units (DDUs) and in fibrinogen equivalent units (FEUs). About 70% of labs use the method that reports in FEUs. We only report the high limit of the interval because a low D-dimer has no clinical meaning. The DDU limit is typically 240 ng/mL and the FEU limit is 500 ng/mL. The actual numbers vary among laboratories because each laboratory director is required to carefully vaildate based on their local healthy population. Examine your family member’s lab report to confirm whether his/her lab is using DDUs or FEUs.
We had a thorough discussion about age-adjusted D-dimer in 2014, and many physicians use age times 10 for people over 50, thus at age 60 the limit would be 600 ng/mL FEUs and at 70, 700 ng/mL FEUs. We don’t have published age-adjusted levels for DDUs.
If your relative’s D-dimer result is normal, meaning below the limit, the result may be used to rule out deep vein thrombosis (a clot in a leg vein) or pulmonary embolism, (clot in the lung). D-dimer results above the reference limit are not diagnostic, as several non-specific forms of inflammation mey elevate the level. There is no evidence that suggests Xarelto or any of the anticoagulants (blood thinners) affect the D-dimer result.
I hope this answers your question, and watch here for comments from our various expert participants.
From Bob Gosselin: I concur
From Bob Gosselin: I concur with statements made by Geo and EF. One must also emphasize that “cut-offs” are strictly related to VTE exclusion, and do not apply to DIC or other indications. I agree that clinicians use age-adjusted D-dimer–they want it, and that was a hurdle we had to face based on publications. I think the Europeans are more apt to use age-adjusted D-dimer VTE exclusion cut-offs, but with US/FDA labelling, offering age adjusting cut-offs would constitute an LDT. At my former place, UC Davis Health System, we adopted an age-adjusted VTE exclusion platform after retrospectively evaluating our ED patients over 5 years. The age adjusting seem to work best in the 50–60 group, older, it had little effect. The overall estimated reduction in age-adjusted VTE exclusion was relatively modest at ~10-15%. As another aside, the VTE exclusion for our method was something odd, like 246, so we had to create a calculation tool within the EMR/LIS since it wasn’t a simple multiply by age factor.
So, my take on the case study would be: was there a change in D-dimer over time after treatment? If it doesn’t change or elevate, then perhaps there is another underlying cause for elevated D-dimer (e.g. occult CA). Just one number, in the scope of things, wouldn’t really mean a whole lot–serial testing may be indicated.
To follow on from George and
To follow on from George and as a follow up to our contribution to the 2014 discussion: I would generally concur. FEU values are around twice those of DDU. So, we would use a cut-off of 500 ng/mL FEU or 250 ng/mL DDU. However, there are also many other units in use (e.g., mg/L, ug/L, ug/mL, ng/mL), so it is difficult to know what ’450’ means without knowing what units are being reported. Xarelto would not be expected to raise D-dimer levels per se. However, raised D-dimer levels whilst on treatment with an anticoagulant such as Xarelto may suggest an increased risk of future events and is sometimes used to prolong anticoagulant therapy. If the 450 is ng/mL FEU, then this is below the standard cut-off, and often considered as ‘negative’ – we usually don’t report values below 500 ng/mL FEU, as this often confuses clinicians who then ask how can the result be ‘negative’ since a value has been reported? If the 450 is ng/mL DDU, then this is above the standard cut-off, and therefore would be considered as ‘positive’. However, you would need to consider timing of the test (after 3 months of anticoagulant treatment would be more significant than with 3 months of anticoagulant treatment) and also exclude other causes of elevated D-dimers (e.g., recent surgery, cancer). There is a handy D-dimer calculator available online: http://unitslab.com/node/83. Anyone more interested in the D-dimer story is referred to our recent publications on the topic: Lippi G, Favaloro EJ, Cervellin G. A review of the value of D-dimer testing for prediction of recurrent venous thromboembolism with increasing age. Semin Thromb Hemost. 2014;40:634–9. // Lippi G, Tripodi A, Simundic AM, Favaloro EJ. International survey on d-dimer test reporting: a call for standardization. Semin Thromb Hemost. 2015;41:287–93.//Longstaff C, Adcock D, Olson JD, Jennings I, Kitchen S, Mutch N, Meijer P, Favaloro EJ, Lippi G, Thachil J. Harmonisation of D-dimer–a call for action. Thromb Res. 2016;137:219–20. // Thachil J, Lippi G, Favaloro EJ. D-dimer testing: laboratory aspects and current issues. Methods Mol Biol. 2017;1646:91–104.