The Battle for Age-Adjusted D-Dimer

Around these parts, we are fans of the age-adjusted D-dimer.  Jeff Kline proposes their use in his algorithm for the diagnosis of PE.  We embed decision-support in our EHR to encourage their use.  But, this new review from Annals of Emergency Medicine describes its test characteristics in the Kaiser Permanente population – and reports the age-adjusted D-dimer is not infallible.

These authors look retrospectively at 31,094 patients over 50, with a chest- or respiratory-related complaint, for whom a D-dimer was ordered.  14,434 of these patients had a D-dimer above the “customary” level of 500 ng/dL, and clinicians ordered 12,486 imaging studies to evaluate for PE.  Of these, 507 were diagnosed with PE.  This gives a 4.1% yield for CTPA – which, frankly, is disturbingly low – but another topic for another day.

The 500 ng/dL threshold was sensitive for 497 of the 507, while using an age-adjusted D-dimer would have reduced sensitivity to 471 of the 507.  Thus, using an age-adjusted D-dimer in this retrospective cohort may potentially have introduced an additional 26 missed PEs.  The savings, however, amount to 2,924 fewer CTPAs – or, roughly, 100 CTs per missed PE.

The contemporaneous Twitter response:

@EBMgoneWILD @ZackRepEM So age-adjusted D-dimer is dead? 26 misses to save $290K in costs = dead.

— Robert McNamara (@RobertMcNamar12) September 4, 2015

I don’t think so – but questions abound, many of which need be directly addressed by our specialty.  What is an acceptable miss rate for pulmonary embolism?  What is an acceptable miss rate of the pulmonary emboli in this age-adjusted range, just above our prior test threshold?  Does the net harm reduction from reduced testing outweigh the harms of missing those PEs?  Do those PEs convey the same level of morbidity or mortality if the diagnosis is missed or delayed?  How does the radiologic false-positive rate trend for PEs whose D-dimers are just over the test threshold?  And, finally – the age-adjusted D-dimer is not a static construct – would other age-adjustment formulas strike a better balance between sensitivity and specificity?

When all the questions are posed, I believe the summative value shows it reduces physiologic harms from testing, harms from healthcare costs, and harms from false-positives.  But, like everything we do, the age-adjusted D-dimer is still deserving of continued questioning and refinement.

“An Age-Adjusted D-dimer Threshold for Emergency Department Patients With Suspected Pulmonary Embolus: Accuracy and Clinical Implications.”
http://www.ncbi.nlm.nih.gov/pubmed/26320520