Sometimes there’s just a question that rattles around in the back of my head. I feel like whether or not a normal D-dimer can help rule out pulmonary embolus in kids is one such question.

What is D-dimer?

D-dimer is a fibrin degradation product left over in the blood after a clot is broken down. There are two “D” monomers of fibrin that are cross linked by activated factor XIII, hence the name. D-dimers are usually only present in the blood when the clotting cascade has been activated. They are detected in serum using antigen tests such as ELISA. There are a few different tests out there, and you also need to be familiar with your lab’s reference range; <500 ng/mL for fibrin equivalent units (FEU) or <250 ng/mL for D-dimer units (DDU). D-dimer will be elevated in DVT, PE, DIC, hyperthrombotic states and also variably in liver disease, vasculitis/rheumatic conditions, malignancy, trauma, pregnancy and recent surgery.

How has it been traditionally used?

An elevated D-dimer alone is insufficient to diagnose a PE but a negative or low D-dimer can help you rule one out when there is low to intermediate probability of PE

There has been an incredible amount of work done in grown ups regarding making the diagnosis of PE relative to that in children. The PIOPED study from 1991 helped define the findings that were most often present in adults with PE. Many of you are likely familiar with the Wells score. PERC is a clinical decision rule that performs well in low prevalence settings but does require a modicum of experience in that you must assign a pretest probability. Fortunately, there is a ton of excellent FOAM content about PE, and also great evidence-focused tools available online. Per a Cochrane Review, the “estimates of sensitivity ranged from 80% to 100%, and estimates of specificity from 23% to 63%.” In general, the utility of D-dimer in grown-ups really depends on your pre-test probability.

How is PE different in children? And what’s the evidence, specifically regarding D-dimer?

As you have gathered, PE is rare in children. Many of the existing studies are case series. One large retrospective descriptive study of Pediatric Emergency Department patients in a single center between 2003-2001 saw only 105 with PE out of almost 1.2 million total patients. In the Pediatric Emergency Department, where I work, I will consider PE as a moderate to highly likely diagnostic possibility only a few times a year. Most of these kids have known risk factors, some more common than others, and which include;

  • cancer
  • congenital heart disease
  • acquired and inherited thrombophilias including rheumatologic diseases
  • indwelling central line placement
  • oral-contraceptive use
  • recent trauma or surgery with admission to the hospital
  • heavy smoker
  • obesity

The physiologic effects of PE in children can mirror those in adults. They include;

  • Infarction, where small emboli lodge in the lower lobes of the lung, leading to pain and hemoptysis.
  • Abnormal gas exchange, which can lead to dyspnea and hypoxia because larger clots obstruct pulmonary venins, leading to VQ mismatch and atelectasis
  • Shock, whereby a massive PE obstructs the vascular bed, leading to a profound increase in pulmonary vascular resistance, reflex arterial vasoconstriction due to hypoxia, which impedes right ventricular outflow, dilates the right ventricle, pushing the septum into the left ventricle and compromising cardiac output.

Fortunately, the majority of children have smaller, peripheral PE that are not as physiologically deleterious. So, with that in mind let’s take a look at a few studies. starting with the one I just alluded to, with the caveat that this is by no means an exhaustive list, since I’m focusing on D-dimer.

Agha et al. Pulmonary embolism in the pediatric emergency department. Pediatrics, 2013

This large cohort retrospectively identified PE patients based on the Wells and PERC Criteria. Only 25 of their 105 met inclusion criteria (previous diagnosis of PE at another facility being one exclusion criteria). Many of the patients had a predisposing condition.

Overall they also noted that 52% had chest pain, 44% shortness of breath, and 32% cough aligning with other reports on symptom frequency. Additionally, by Wells criteria none were in the high probability group. And the most common PERC criteria not met was tachycardia. Only 80% of the patients had a D-dimer obtained. There was no comparison with patients that didn’t have a PE and what their D-dimer was.