Pregnant with a PE: What to do

A young woman presents to your ED with shortness of breath and pleuritic chest pain. She states she got off a long plane flight from the Philippines. She is mildly tachycardic. OK, you think, let’s just whip out the ol’ Well’s criteria and get to work. You pull up her chart to do some basic review and wham! A positive point-of-care pregnancy test! What to do?

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Pulmonary embolism (PE) is a relatively common disorder with a notoriously nonspecific presentation and is an already debated topic in patients who are not pregnant. The Wells score is controversial in pregnant patients, as it is not validated and has a poor predictive value in pregnancy.^{^[1]}^{,^[2]} Depending on the source, pregnant patients have 10 times the risk of developing a deep vein thrombosis (DVT) or PE compared to the rest of the population^{^[3]}^{,^[4]}. A recent meta-analysis by Meng et al found that the incidence of VTE in pregnancy was only 1.4%, but also that this was significantly higher than in a non-pregnant, age-matched population.^[5] Then, although really a discussion for another time, there’s the issue of whether anticoagulating a patient for PE is even beneficial at all or is, in fact, harmful. According to a Cochrane review via theNNT.com, there’s no clear benefit of anticoagulation for DVT/PE, and the number needed to harm is 1 in 50 – 111 for a major bleeding event.^[6] To focus and keep it brief, I’ll only cover the work-up for PE in pregnant patients for now.

Start with a workup for DVT

There’s no current expert consensus, but Simcox et al in a review of recent literature recommends anticoagulation for pregnant patients with DVT if the diagnosis of DVT can be made with clinical presentation combined with positive compression ultrasound (US). Those with clinical signs of DVT and negative US should have repeat US at 3 and 7 days, and anticoagulation should be started at time of positive result.^{^[7]}

Unfortunately, it gets more complicated from there.

Lets start with PERC and D-dimer for those deemed low-risk. According to a meta-analysis of 25,339 patients by PE guru Jeff Kline, only 4.1% of pregnant patients who were investigated for PE had positive findings compared to 12.6% of the general population.^{^[8]} This suggests that we are over-testing in pregnant patients, and that low-risk patients should be better stratified. With regards to D-dimer, Dr. Kline stated on both EMRAP (March 2016) and in a recent publication ^[11] that he thinks D-dimer is a reasonable rule-out test if modified cutoff levels are used (750ng/ml, 1,000ng/ml, and 1,250 ng/ml for 1st, 2nd and 3rd trimester, respectively). It’s worth noting that if these cutoffs aren’t used, the odds ratio of getting a false positive in pregnancy is 7.3 in the 2nd trimester, 51.3 in the 3rd, and 4.3 in the postpartum period.^[11] Those are some big numbers! He also thinks that in risk-stratifying these patients, it’s acceptable to use PERC and Wells, although the use of these decision instruments remains conjectural and has yet to be validated.^[9] His hunch does seem to be backed up by at least one small study, though: In a trial of 42 pregnant patients that combined a modified Wells score (table below) and D-dimer, 0/17 PEs confirmed with imaging were missed, while false positives (women with either findings on modified wells or elevated d-dimer) were found in 11/42 of those without PE on imaging.^[9] In this study, they set their D-dimer levels at 950 ng/ml, 1,290 ng/ml and 1,700 ng/ml for each respective trimester, all of which are slightly higher than Kline’s suggested cutoffs. Again, it’s a small study, but it suggests that negative D-dimers may be helpful in ruling out PE in pregnancy. Do keep in mind, however, any false positives of Wells or D-dimer may lead to unnecessary downstream imaging and radiation, and then potentially, an increased risk of bleeding in any patients then treated with anticoagulation.

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A “modified Wells score” for pregnant women

Lets irradiate some fetuses!

Given the low radiation dose of chest radiography compared to other imaging modalities, Ian Greer as well as Jeff Kline recommend chest radiography before further workup, as it can check for other causes of dyspnea.^[10],[11] If radiography is negative, and your suspicion for PE is high enough, then you may move on to the higher radiation test. But, what about fetal effects of all those rays? Luckily, the dose of radiation from any of the imaging modalities from which you might choose is below than the threshold for fetal malformation. See the chart below from Simcox et al.^[6],[12]

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Pick your poison

The debate here, once you get over the fact that you are shooting radiation directly through the chest of a young woman, is whether to move on to CT pulmonary angiogram (CTPA) or pulmonary scintigraphy (V/Q scan). Those in favor of CTPA argue that it is more sensitive and specific and will pick up other pathology that may be missed by V/Q scanning.^{^[13]} Indeed, one study that compared CTPA and V/Q head-to-head found that CTPA picked up pathology other than PE in 8/19 of CTPAs performed; in another study, CTPA picked up other pathology in 3/10.^[7]^,[14] CTPA also delivers a smaller radiation dose to the fetus than a V/Q scan,^{^[15]} although according to Simcox et al, neither test should not be much of a concern.

On the other hand, proponents of V/Q scans point out that although the associated radiation dose to the fetus is higher, it can avoid the 13% increased risk of breast cancer when maternal breast tissue is exposed to radiation from a CTPA.^{^[16]}

After all that, if you’re in need of a flow sheet, I’ve attached below one from Kline’s publication for those of us that are more visual.¹⁰

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TL;DR

Pregnant patients present a conundrum if you’re concerned about PE. PERC, Wells, and D-dimer are recommended by some experts, but the tools have not been validated in these patients to date. If it comes to imaging, many are afraid of irradiating a fetus, but it turns out that the radiation involved in a typical workup is more of a malignancy risk to the mother than a birth defect risk to the fetus! CTPA is better for evaluating for other possible, non-PE lung pathology, while V/Q minimizes the risk of maternal breast cancer down the line. Given these two facts together, a discussion of risks/benefits/alternatives with the patient would be prudent: Go with CTPA if you have any suspicion for alternative significant pathology and use V/Q scanning if you’re really just worried about PE. 9LOtja6csC-9

Thanks to Dr. deSouza and Dr. Shibata for editing this post.

^{^[1]} Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet 2010; 375: 500–512.

^{^[2]} Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model 135: 98–107.

^{^[3]} Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, Forcier A, Dalen JE.A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med. 1991 May;151(5):933-8.

^{^[4]} White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: 23 Suppl 1, I4–I8.

^[5] Meng, K et al. Incidence of venous thromboembolism during pregnancy and the puerperium: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2015 Feb; 28(3):245-53. PMID: 24716782

^[6] Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism. Cundiff DK, Manyemba J, Pezzullo JC. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003746.

^{^[7]} Simcox LE, Ormesher L, Tower C, Greer I. Pulmonary thrombo-embolism in pregnancy: diagnosis and management. Breathe (Sheff). 2015 Dec;11(4):282-9. doi: 10.1183/20734735.008815

^{^[8]} Kline JA, Richardson DM, Than MP, Penaloza A, Roy PM. Systematic review and meta-analysis of pregnant patients investigated for suspected pulmonary embolism in the emergency department. Acad Emerg Med. 2014 Sep;21(9):949-59. doi: 10.1111/acem.12471.

^[9] Barbara V. Parilla, MD1 Rachel Fournogerakis, DO1 Amy Archer, MD2 Suela Sulo, PhD. Diagnosing Pulmonary Embolism in Pregnancy: Are Biomarkers and Clinical Predictive Models Useful? Lisa Laurent, MD Patricia Lee, MD Benazir Chhotani, MD Kathleen Hesse, RN Erik Kulstad, MD. Am J Perinatol Rep 2016;6:e160–e164.

^{^[10]} Greer IA. Thrombosis in pregnancy: updates in diagnosis and management. Hematology (Am Soc Hematol EducProgram) 2012; 2012: 203–207.

^[11] Jeffrey A. Kline, MD and Christopher Kabrhel, MD, MPH. Emergency Evaluation for Pulmonary Embolism Part 2: Diagnostic Approach. The Journal of Emergency Medicine, Vol. 49, No. 1, pp. 104–117, 2015

^{^[12]} Eskandar OS, Eckford SD, Watkinson T. Safety of diagnostic imaging in pregnancy. Part 1: X-ray, nuclear medicine investigations, computed tomography and contrast media. Obstet Gynaecol 2010; 12: 71–78.

^{^[13]} Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015 Nov 3;163(9):701-11. doi: 10.7326/M14-1772. Epub 2015 Sep 29.

^{^[14]} Ridge CA, McDermott S, Freyne BJ, et al. Pulmonary embolism in pregnancy: comparison of pulmonary CT angiography and lung scintigraphy. AJR Am J Roentgenol 2009; 193: 1223–1227.

^{^[15]} Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues in the investigation of pulmonary embolism. Semin Nucl Med 2010; 40: 442–454.

^{^[16]} Remy-Jardin M, Remy J. Spiral CT angiography of the pulmonary circulation. Radiology 1999; 212: 615–636.