Tag Archives: d-dimer

PEM Playbook – Big Labs, Little People: Troponin, BNP, D-Dimer, and Lactate

Originally published at Pediatric Emergency Playbook on April 1,
2016 – Visit to listen to accompanying podcast. Reposted with permission.

Follow Dr. Tim Horeczko on twitter @EMTogether

It’s a busy shift.  Today no one seems to have a chief complaint.

Someone sends a troponin on a child.  Good, bad, or ugly, how are you going to interpret the result?

And while we’re at it – what labs do I need to be careful with in children – sometimes the normal ranges of common labs can have our heads spinning!

Read on for bread-and-butter pediatric blood work and further, to answer the question – what’s up with troponin, lactate, d-dimer, and BNP in kids?


A fundamental tenet of emergency medicine:

We balance our obligation to detect a dangerous condition with our suspicion of the disease in given patient.

Someone with a cough and fever may simply have a viral illness, or he may have pneumonia.  Our obligation is to evaluate for the pneumonia.  It’s ok if we “miss” the diagnosis of a cold. It could be bad if we don’t recognize the pneumonia.

How do we decide?  Another fundamental concept:

The threshold.

Depending on the disease and the particular patient, we have a threshold for testing, and a threshold for treating.  Every presentation – and every patient for that matter – has a complicated interplay between what we are expected to diagnose, how much we suspect that particular serious diagnosis, and where testing and treating come into play.

What’s wrong with “throwing on some labs”?

Easy to do right?  They are but a click away…

Often a good history and physical exam will help you to calibrate your investigational thresholds.  This is especially true in children – the majority of pediatric ambulatory visits do not require blood work to make a decision about acute care.  If your patient is ill, then by all means; otherwise, consider digging a bit deeper into the history, get collateral information, and make good use of your general observation skills.

First, a brief word about basic labs.

The punchline is, use a pediatric reference.

If you don’t have a trusted online reference available during your shift, make sure you have something like a Harriett Lane Handbook accessible to you. Don’t rely on your hospital’s lab slip or electronic medical record to save you, unless you are sure that they use age-specific pediatric reference ranges to flag abnormal values. Believe it or not, in this 21st century of ours, some shops still use adult reference ranges when reporting laboratory values on children.

Notable differences in basic chemistries

Potassium: tends to run a bit higher in infants, because for the first year of life, your kidneys are inefficient in excreting potassium.

BUN and creatinine: lower in children due to less muscle mass, and therefore less turnover (and usually lack of other chronic disease)

Glucose: tends to run lower, as children are hypermetabolic and need regular feeding (!)

Alkaline phosphatase: is always high in normal, growing children, due to bone turn over (also found in liver, placenta, kidneys)

Ammonia: high in infancy, due to immature liver, trends down to normal levels by toddlerhood

ESR and CRP: low in healthy children, as chronic inflammation from comorbidities is not present; both increase steadily with age

Thyroid function tests: all are markedly high in childhood, not as a sign of disease, but a marker of their increased metabolic activity

Big Labs


Reliably elevated in myocarditis, and may help to distinguish this from pericarditis (in addition to echocardiography)

Other causes of elevated troponin in children include: strenuous activity, status epilepticus, toxins, sepsis, myocardial infarction (in children with congenital anomalies).  Less common causes of troponemia are: Kawasaki disease, pediatric stroke, or neuromuscular disease.

Don’t go looking, if you won’t do anything with the test.

Brain natriuretic peptide (BNP)

In adults, we typically think of a BNP < 100 pg/mL as not consistent with symptoms caused by volume overload.

Luckily, we have data in children with congenital heart disease as well.  Although each company’s assay reports slightly different cut-offs, in general healthy pediatric values match healthy adult values.

One exception is in the first week of life, when it is high even in healthy newborns, due to the recent transition from fetal to newborn circulation.

Use of BNP in children has been studied in both clinic and ED settings. Cohen et al. in Pediatrics used BNP to differentiate acute heart failure from respiratory disease in infants admitted for respiratory distress. They compared infants with known CHF, lung disease, and matched them with controls.

Later, Maher et al. used BNP in the emergency department to differentiate heart failure from respiratory causes in infants and children with heart failure and those with no past medical history.

The bottom line is:

BNP reliably distinguishes cardiac from respiratory causes of shortness of breath in children with a known diagnosis of heart failure.


To cut to the chase: d-dimer for use as a rule-out for pulmonary embolism has not been studied in children.

The only data we have in using d-dimer in children is to prognosticate in established cases. It is only helpful to track therapy for children who have chronic clots.

This is where our adult approach can get us into trouble. Basically, think of the d-dimer in children like it doesn’t even exist. It’s not helpful in our setting for our indications.   An adult may have an idiopathic PE – in fact, up to a third of adults with PE have no known risk factor, which makes decision tools and risk stratification important in this population.

Children with PE almost always have a reason for it.


There is at least one identifiable risk factor in up to 98% of children with pulmonary embolism. The majority have at least two risk factors.

If you’re suspecting deep venous thrombosis, perform ultrasonography, and skip the d-dimer.

If you’re worried about PE, go directly to imaging. In stable patients, you may elect to use MR angiography or VQ scan, but most of us will go right to CT angiography. Radiation is always a concern, but if you need to know, get the test.

This is yet another reminder that your threshold is going to be different in children when you think about PE – they should have a reason for it. After you have excluded other causes of their symptoms, if they have risk factors, and you are still concerned, then do the test you feel you need to keep this child safe.

You are the test.

Risk factors only inform you, and you’ll have to just pull the trigger on testing in the symptomatic child with risk factors.


A sick child with sepsis syndrome?

The short answer – yes.

In the adult literature, we know that a lactate level above 4 mmol/L in patients with severe sepsis was associated with the need for critical care. This has been studied in children as well, and an elevated lactate in children – typically above 4 – was a predictor of prolonged ICU course and mortality in septic patients.

The acute recognition and treatment of sepsis is first and foremost, clinical.

Our goal is to promote perfusion and provide oxygen to the tissues. Laboratory testing is not a substitute for clinical assessment – it should be used as an extension of your assessment.  There are two main reasons for an elevated lactate: the stress state and the shock state.

The stress state is due to hypermetabolism and an increase in glycolysis, as an example, in early sepsis. The shock state is due to tissue hypoxia, seen in septic shock. The confusion and frustration with lactate is that we often test the wrong people for it.

We could use it to track treatment, and see if we can clear the lactate; decreased lactate levels are associated with a better outcome in adults. Serial clinical assessments are even more useful to gauge your success with treatment.

We should use lactate to detect occult shock. Children compensate so well for shock, that subtle tissue hypoxia may not be detected until later. It may inform your decision for level of care, intensive care versus some other lower level.

Have you every been in this situation:

“Why, oh why, did we send a lactate?”

There are times when a lactate is ordered – maybe by protocol or maybe accidentally – or maybe in retrospect, the patient didn’t need it. Here is a quick mnemonic to remember the reasons for an elevated lactate: LACTATES


Lliver – any liver disease affects how lactate is metabolized by the Cori cycle
Aalbuterol (or for our international friends, salbutamol), beta-agonists like albuterol, increase lactate production via cyclic amp
C“can’t breathe” – respiratory distress and increased work of breathing shifts the ratio of aerobic and anerobic repiration
Ttoxins – all kinds of wonder drugs and recreational drugs do it – look up your patient’s list if you’re suspicious
Aalcohol, not an infrequent offender
Tthiamine deficiency – think of this in your cachectic or malnourished patients
Eepinephrine – a by-product of the Cori cycle, how lactate is metabolized. Difficult to interpret lactates when a patient is on an epinephrine drip.
Sseizure or shock – most commonly septic, but can be any type: cardiogenic, bstructive, hypovolemic, distributive.

Bottom line: high serum lactate levels have been associated with morbidity and mortality in children with sepsis and trauma, the two best-studied populations.

A summary of how labs can help you – or hurt you – in pediatric emergency medicine:

  1. Have a good reference for normal values and always be skeptical of how your lab reports them.
  2. Troponin testing is great for the child with suspected cardiogenic shock, myocarditis, or in unwell children with congenital heart disease.
  3. BNP in children can be used just like you do in adults – to get a sense of whether the presenting symptoms are consistent with heart failure.
  4. D-dimer is mostly a waste of time in the PED.
  5. Lactate can be useful in the right patient – use it to risk-stratify the major trauma patient or the patient with sepsis that may be suffering from occult shock.
  6. And lastly, make sure that you are mindful of your threshold for testing, and our threshold for treatment. If will vary by disease and by the patient at hand.



Gupta SK, Naheed Z. Chest Pain in Two Athletic Male Adolescents Mimicking Myocardial Infarction. Pediatr Emer Care. 2014;30: 493-495.

Kelley WE, Januzzi JL, Christenson RH. Increases of Cardiac Troponin in Conditions other than Acute Coronary Syndrome and Heart Failure. Clinical

Chemistry. 2009; (55) 12:2098–2112.

Kobayashi D, Aggarwal S, Kheiwa A, Shah N. Myopericarditis in Children: Elevated Troponin I Level Does Not Predict Outcome. Pediatr Cardiol. 2012; 33:1040–1045.

Koerbin G, Potter JM, Abhayaratna WP et al. The distribution of cardiac troponin I in a population of healthy children: Lessons for adults. Clinica Chimica Acta. 2016; 417: 54–56.

Liesemer K, Casper TC, Korgenski K, Menon SC. Use and Misuse of Serum Troponin Assays in Pediatric Practice. Am J Cardiol. 2012;110:284 –289.

Newby KL et al. for the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. ACCF 2012 Expert Consensus Document on Practical Clinical Considerations in the Interpretation of Troponin Elevations. J Am Coll Cardiol. 2012; 60(23): 2427-2463.

Schwartz MC, Wellen S, Rome JJ et al. Chest pain with elevated troponin assay in adolescents. Cardiology in the Young; 2013. 23: 353–360.


Auerbach SR, Richmond ME, Lamour JM. BNP Levels Predict Outcome in Pediatric Heart Failure Patients Post Hoc Analysis of the Pediatric Carvedilol Trial. Circ Heart Fail. 2010;3:606-611.

Cohen S, Springer C, Avital A et al. Amino-Terminal Pro-Brain-Type Natriuretic Peptide: Heart or Lung Disease in Pediatric Respiratory Distress? Pediatrics. 2005;115:1347–1350.

Fried I, Bar-Oz B, Algur N et al. Comparison of N-terminal Pro-B-Type Natriuretic Peptide Levels in Critically Ill Children With Sepsis Versus Acute Left Ventricular Dysfunction. Pediatrics. 2006; 118(4): 1165-1168.

Koch A, Singer H. Normal values of B type natriuretic peptide in infants, children, and adolescents. Heart. 2003;89:875–878.

Maher KO, Reed H, Cuadrado A et al. , B-Type Natriuretic Peptide in the Emergency Diagnosis of Critical Heart Disease in Children. Pediatrics. 2008;121:e1484–e1488.

Mir TS, Marohn S, Laeer S, Eistelt M. Plasma Concentrations of N-Terminal Pro-Brain Natriuretic Peptide in Control Children From the Neonatal to Adolescent Period and in Children With Congestive Heart Failure. Pediatrics. 2002;110(6)1:6.

Mir TS, Laux R, Hellwege HH et al. Plasma Concentrations of Aminoterminal Pro Atrial Natriuretic Peptide and Aminoterminal Pro Brain Natriuretic Peptide in Healthy Neonates: Marked and Rapid Increase After Birth. Pediatrics. 2003;112:896–899.


Goldenberg NA, Knapp-Clevenger RA, Manco-Johnson MJ. Elevated Plasma Factor VIII and d-Dimer Levels as Predictors of Poor Outcomes of Thrombosis in Children for the Mountain States Regional Thrombophilia Group. Pediatrics. 2003;112:896–899.

Manco-Johnson MJ. How I treat venous thrombosis in children. Blood. 2006; 107(1)21-31.

Naqvi M, Miller P, Feldman L, Shore BJ. Pediatric orthopaedic lower extremity trauma and venous thromboembolism. J Child Orthop. 015;9:381–384.

Parasuraman S, Goldhaber SZ. Venous Thromboembolism in Children. Circulation. 2006;113:e12-e16.

Strouse JJ, Tamma P, Kickler TS et al. D-Dimer for the Diagnosis of Venous Thromboembolism in Children. N Engl J Med. 2004;351:1081-8.


Andersen LW, Mackenhauer J, Roberts JC et al. Etiology and therapeutic approach to elevated lactate. Mayo Clin Proc. 2013; 88(10): 1127–1140.

Bai et al. Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission. BMC Pediatrics. 2014; 14:83.

Scott HF, Donoghue AJ, Gaieski DF et al. The Utility of Early Lactate Testing in Undifferentiated Pediatric Systemic Inflammatory Response Syndrome. Acad Emerg Med. 2012; 19:1276–1280.

Shah A, Guyette F, Suffoletto B et al. Diagnostic Accuracy of a Single Point-of-Care Prehospital Serum Lactate for Predicting Outcomes in Pediatric Trauma Patients. Pediatr Emer Care. 2013; 29:715-719.

Topjian AA, Clark AE, Casper TC et al. for the Pediatric Emergency Care Applied Research Network. Early Lactate Elevations Following Resuscitation From Pediatric Cardiac Arrest Are Associated With Increased Mortality. Pediatr Crit Care Med. 2013; 14(8): e380–e387.

This post and podcast are dedicated to Daniel Cabrera, MD for his vision and his leadership in thinking ‘outside the box’.


Troponin     |     BNP     |     D-Dimer     |     Lactate

Powered by #FOAMed — Tim Horeczko, MD, MSCR, FACEP, FAAP

D-Dimer in Aortic Dissection Workup


  • Aortic Dissection is a cleavage of the aortic media layer created by a dissecting column of blood. This is different pathologically than an aortic aneurysm but the two terms are frequently interchanged incorrectly
  • Uncommon => 2-4 per 100,000 person-years (Acute Coronary Syndromes is about 100-200 times more common)
  • About 1 of every 2,000 ED patients presenting with any symptom associated with thoracic aortic dissection (TAD) will have TAD
  • Life-threatening – mortality rate of 1.2% per hour in the first 48hr

Recap / Basics

  • Three variants
    • Intimal Flap tear  – ~70-80% of cases
    • Intramural hematoma (believed to start from rupture of the vasa vasorum) – ~10-15%
    • Penetrating atherosclerotic ulcer – ~10-15%
  • Risk Factors
    • Hypertension – 72%
    • Collagen disorders – Marfan’s, Ehlers-Danlos
    • Inflammatory vasculitis disorders – Giant cell arteritis, Takayasu arteritis, rheumatoid arthritis
    • Instrumentation or structural abnormalities – cardiac cath / CABG, bicuspid valve, aortic coarctation, valve replacement
  • Classification
    • Stanford
      • Type AAscending and Arch
        • Higher Mortality
        • Surgical Management
      • Type  B – descending; Below the left subclavian
        • Lower Mortality
        • Often medical management
    • DeBakey
      • I – Ascending, arch and possible descending
      • II – Ascending only
      • III – Descending aorta
  • Pain is common >90%
    • Abrupt ~85%,  excruciating (“worst ever”) ~90% and most severe at onset
    • Chest or Back
    • Sharp, tearing, ripping but may be pressure or crushing
    • Migration suggests dissection but occurs only ~ 30% of cases
  • Physical exam, ECG, and chest x-ray are insufficiently sensitive to help with diagnosis
  • Other advanced imaging needed
    • Contrast CT Chest – sensitivity ~100%, specificity ~98%
    • MRI – sensitivity ~98%, specificity ~98%
    • Transesophageal Echocardiography (TEE) – sensitivity ~98%, specificity ~95%
  • Treatment
    • ED treatment is to reduce blood pressure to target systolic BP = 100-120
      • β-blockers – Esmolol or labetalol
      • Sodium nitroprusside
    • Surgery generally performed for Type A and complicated Type B dissections and possibly other Type Bs
    • Medication management for uncomplicated Type B

What’s New

  • Can the D-dimer help to include or exclude patients who might need advanced imaging?
  • The D-dimer is a fibrin degradation product indicating recent or ongoing coagulation
  • The D-dimer is very sensitive for picking up most dissections. Data from several different pooled studies show sensitivity 94-97%, specificity 34-100%
  • This has led several authors to suggest the D-dimer seems to have value as a screening tool for “ruling out” acute aortic dissection; i.e. if the D-dimer result is below a threshold level (generally below 400 – 500 ng/mL), then TAD is unlikely
  • However, false negatives (D-dimer levels below the threshold in patient with documented TAD) have been reported in several papers and one paper (Paparella) reported a surprising high false negative rate of 18% (11/61) with time of symptom onset to diagnosis ranging from 2 – 72 hours
  • Other authors have suggested the D-dimer should be part of the work-up if TAD is suspected. However using the D-dimer alone would lead to an unacceptably high number of false positives and follow-up advanced imaging
  • Higher d-dimer levels correlate with more segments of the aorta involved, with false lumen type dissections, and with higher mortality rates
  • D-dimers seem to be lower in patients with intramural hematomas

Bottom Line / Pearls & Pitfalls

  • A negative D-dimer (< 400 ng/mL) makes TAD unlikely but it is not 100% and false negatives occur
  • A positive D-dimer occurs in a very high percent of patients with TAD but also occurs in many other conditions
  • What is needed is a well-tested clinical decision rule to help select patients for further testing; that is when should we order, or not order, a D-dimer and/or when should we order, or not order, advanced imaging

Discussion Questions / Future Exploration

  • Can we develop decision rules similar to those developed for pulmonary embolus?
  • Are there time limits related to D-dimer testing: when is it too soon or too late after symptoms onset for the test to be useful?
  • Is there a better threshold level for D-dimer which might make it a more useful test?


  • Brown MD, Newman DH. Evidence-based emergency medicine. Can a negative D-dimer result rule out acute aortic dissection? Ann Emerg Med. 2011; 58(4): 375-6.
  • Fan Q, Wang W, Zhang Z, et al. Evaluation of D-dimer in the diagnosis of suspected aortic dissection. Clin Chem Lab Med. 2010;48(12):1733-1737.
  • Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): new insights into and old disease. JAMA 2000;283:897-903.
  • Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA. 2002;287:2262-72.
  • Manning WJ. Clinical manifestations and diagnosis of aortic dissection. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA 2014. Retrieved from http://www.uptodate.com/.
  • Marill KA. Serum D-dimer is a sensitive test for the detection of acute aortic dissection: a pooled meta-analysis. J Emerg Med. 2008; 34(4):367-76.
  • Ohlmann P, et al.  Diagnostic and prognostic value of circulating D-Dimers in patients with acute aortic dissection, Crit Care Med, 2006; 34(5):1358-64.
  • Paparella D, et al. D-dimers are not always elevated in patients with acute aortic dissection. J Cardiovasc Med (Hagerstown) 2009;10:212-4.
  • Sodeck G; et al.  D-dimer in ruling out acute aortic dissection: a systematic review and prospective cohort study. Eur Heart J; 2007; 28(24):3067-75.
  • Suzuki T, et al. Diagnosis of acute dissection by D-dimer: the International Registry of Acute Aortic Dissection Substudy on Biomarkers (IRAD-Bio) experience. Circulation 2009; 119(20);2702-7.
  • Shimony A, Filion KB, Mottillo S, et al. Meta-analysis of usefulness of d-dimer to diagnose acute aortic dissection, Am J Cardiol 2011; 107(8):1227-34.
  • Taylor RA, Iyer NS. A decision analysis to determine a testing threshold for computer tomography angiography and D-dimer in the evaluation of aortic dissection. Am J Emerg Med. 2013;31(7):1047-55.
  • http://www.ncbi.nlm.nih.gov/pubmed/24309566
  • http://www.ncbi.nlm.nih.gov/pubmed/22810964
  • http://www.ncbi.nlm.nih.gov/pubmed/24270306
  • http://www.ncbi.nlm.nih.gov/pubmed/22009630
Edited by Alex Koyfman

PERC Rule: Application and Limitations


Kline et al1 developed a clinical decision tool based on parameters that could be obtained from a brief initial assessment to reasonably exclude the diagnosis of pulmonary embolism (PE) without the use of D-dimer in order to prevent unnecessary cost and the use of medical resources.

The PERC rule includes:     

Age < 50
Heart rate < 100
Oxygen saturation on RA > 94%
No prior history of DVT or PE
No recent trauma or surgery
No hemoptysis
No exogenous estrogen
No clinical signs suggestive of DVT

If all criteria are met, then the patient can be called “PERC ruled out” or “PERC rule inclusive.”

A review and meta-analysis published in the Annals in 20122 found 12 qualifying studies evaluating the PERC rule and ultimately determined that the pooled sensitivity to rule out pulmonary embolism is 97.2%, which the authors concluded to be a low, but acceptable sensitivity to rule out PE without further testing. The pooled negative LR was 0.17. The overall proportion of missed PEs was 0.32% (44 of 13,855 total cases).

So who are the CT-PE or V/Q positive patients who could have been falsely “PERC ruled out?” In other words, when does the PERC rule fail?

Kline reworked the data from a previous paper showing the outcomes of patients who presented to the ED and were diagnosed with PE3, and used it as a dataset to determine the characteristics of patient who received an ED diagnosis of PE, but could have been included in the PERC clinical decision tool. The initial study was used to determine that the overall mortality attributed to PE was 1%, the mortality from hemorrhage was 0.2%, and the all-cause 30-day mortality was 5.4%. In the reworking of this dataset of 1,880 patients, Kline et al4 found that 114 would have been included in the PERC rule should it have been applied.

Of these patients, they found that only 3 variables that demonstrated a true difference in the proportions between those who would have been included within the PERC rule and those who would have not been able to be “PERC ruled out”: pleuritic chest pain, pregnancy, and postpartum status. Specifically, pleuritic chest pain, which is not included in any clinical decision rule to risk stratify potential PE patients, was found in 56% of the patients where the PERC rule would have failed. Although the N numbers were small for pregnancy and postpartum status, they concluded that the PERC rule should not be used in isolation to rule out PE in patients who are either pregnant or postpartum. Again, it should be noted that pleuritic chest pain is not a component of either the Wells PE or revised Geneva score for PE.

And the reason for its absence in these scores could be considered questionable. A large study including nearly 8,000 patients of whom 7.2% had PE by Courtney et al published in Annals in 20105 was designed to study the variables commonly believed to modify the pretest probability of PE and those already within the existing pretest probability scores. The odd ratio (OR) for pleuritic chest pain in patients diagnosed with PE was 1.53, which seems weak in comparison to the ORs for history of PE and unilateral leg swelling, which are 2.9 and 2.6, respectively. However, the ORs for hemoptysis and tachycardia (defined in this study as a pulse of > 94) are 0.78 and 1.52. Both of these factors are included in the Wells PE score and the revised Geneva score. Excluding hemoptysis and tachycardia, however, all variables used in the Wells PE score have higher ORs than pleuritic chest pain. The next closest OR of the variables included in the Wells PE score is immobilization with an OR of 1.72. The authors also found that the other two variables not included in clinical decision rules with useful ORs were a personal history of non-cancer related thrombophilia (OR 1.99) and a family history of PE (OR 1.51).

The original Kline manuscript1 excluded patients with beta blockers that might be masking tachycardia, yet not all of the follow-up studies included in the recent meta-analysis excluded patients on beta blockers, so the role that current treatment with beta blockers play in determining whether or not you can use the PERC rule on a beta-blocked patient is unclear.

It is important to note that the PERC rule was never intended to be applied to anything but a low-risk group of patients determined either by clinical gestalt or by the Wells PE score, and this point has been stressed in commentary.6 Only after knowing and applying the Wells PE score, an alternative method of risk stratification, or your clinical gestalt should you consider the PERC Rule in a patient you believe is at low risk for PE. As some of the leaders of our field have pointed out, if you believe that your patient population has a higher prevalence of both DVT and PE than the general population in which these rules were derived, then our use of these decision rules, however well-validated in the literature, should be employed with some hesitance.

In fact, the meta-analysis found some heterogeneity in the PERC rule sensitivity to exclude PE. Two studies from European populations with a prevalence of PE ranging from 21-30%7,8 found that a negative PERC rule combined with the low risk Revised Geneva Score only reduced the prevalence of PE in the studied patients to 6%. Only in one of these studies,7 did the PERC rule combined with clinical gestalt reduce the prevalence of PE down to nearly zero.

The prevalence of PE in your community will determine the NPV of the PERC rule where you are practicing, and it is suggested that the PERC rule only be utilized where the prevalence of PE is less than 7 percent.9 Most of the well-designed PE literature indicates that the PE prevalence in the US is around 6%.1

Teaching Points

  • The PERC rule cannot be a substitute for gestalt.
  • Gestalt or some form of risk stratification should be employed first before using the PERC rule.
  • The PERC rule should not be used in isolation to rule out PE in pregnant or postpartum patients.
  • It is unclear if patients on beta blockers can be included in the PERC rule, and this significance has yet to be borne out in the data.
  • The meta-analysis pooled negative LR is 0.17, which gives you a maximum pretest probability of about 15% to apply the PERC rule to risk stratify your patient down to the standard risk of 2%. However, your PE prevalence must be 7% or less (essentially a Wells < 2) before the PERC rule can be applied to patients presenting to ED with suspected PE in conjunction with clinical judgment to identify patients with a prevalence of PE that is below the 1.8% test threshold proposed by Kline.
  • In high PE prevalence populations (which based on the literature, seem to be in Europe) the PERC score inclusive patients will not be able to have a post-test probability at or below the accepted standard risk level.
  • The only evidence we have about PERC rule-inclusive CT-PE or V/Q positive patients suggests that 56% of those will have pleuritic chest pain, which is not in a validated clinical decision rule despite having a higher OR for PE than hemoptysis and recent immobilization, which are both included in the Wells score.

References / Further Reading

  1. Kline JA, Mitchell AM, Kabrhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2:1247-1255.
  2. Singh, et al. Diagnostic Accuracy of Pulmonary Embolism Rule-Out Criteria: A Systematic Review and Meta-analysis. Ann Emerg Med. 2012;59:517-520.3.
  3. Pollack CV, et al. Clinical Characteristics, Management, and Outcomes of Patients Diagnosed With Acute Pulmonary Embolism in the Emergency Department Initial Report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. 2011 Feb 8;57(6):700-6.
  4. Kline JA, et al. Clinical Features of Patients With Pulmonary Embolism and a Negative PERC Rule Result. Ann Emerg Med. 2013 January 60(1): 122-124.
  5. Courtney DM, et al. Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: results of a prospective, multi-center study. Ann Emerg Med. 2010 April 55(4): 307–315.
  6. Bossart PJ. Misuse of the Pulmonary Embolism Rule-Out Criteria. Ann Emerg Med. 2012 December 60(6): 820.
  7. Penazola A, et al. Performance of the Pulmonary Embolism Rule-out Criteria (the PERC rule) combined with low clinical probability in high prevalence population. Thrombosis Research. 2012: e189–e193.
  8. Hugli O, Righini M, Le Gal G, Roy P-M, Sanchez O, Verschuren F, Meyer G, Bounameaux H, Aujesky. The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism. J Thromb Haemost. 2011; 9: 300–4.
  9. Rhenberg JV, Vondy A. BET 3: Pulmonary embolism rule-out criteria (PERC) for excluding pulmonary embolism. Emerg Med J. 2014 Jan;31(1):81-2.
  10. http://www.ncbi.nlm.nih.gov/pubmed/23167851
  11. http://www.ncbi.nlm.nih.gov/pubmed/22720850
Edited by Alex Koyfman, MD