By Sarah Sanders, NUFSOM, M4/Edited by Michael Macias
Pulmonary Embolism in Pregnancy
While the common belief has been long held that pregnant woman are at higher risk of pulmonary embolism, a new systematic review and meta-analysis of over 25,000 symptomatic pregnant ED patients by Jeff Kline et al challenges this dogma. He found that symptomatic ED pregnant patients actually had a low outcome rate of venous thromboembolism (VTE) and a lower relative risk of VTE that non-pregnant ED patients.
That being said, the pregnant, dyspneic patient in the emergency departments frightens us and continues to remain a situation that requires clinicians to employ a high index of suspicion. According to the CDC, PEs in pregnancy account for 20% of maternal deaths in the United States(1). The presentation is complicated by the fact that symptoms commonly associated with pulmonary embolisms in the non-pregnant population can be caused by normal physiologic changes of pregnancy.
Gherman and colleagues retrospectively reviewed venous thromboembolisms diagnosed in pregnant and post-partum patients and found thirty-eight cases of confirmed PEs. The most common presenting symptoms were found to be dyspnea (62%), pleuritic chest pain (55%), cough (24%), and sweating (18%)(2). However, Cahill and colleagues analyzed the association of common clinical presentations (chest pain, shortness of breath, O2 <95%, tachycardia, increased A-a gradient, and PaO2 <65mmHg) and the clinical suspicion of pulmonary embolism, and found no statistically significant association of any clinical feature, or grouping of features, that was associated with the confirmed presence of PE(3). Thus, symptomatology is non-specific in the approach of working up a suspected pulmonary embolism in pregnancy. The clinicians’ clinical judgment is key to starting down the road of investigation.
To D-Dimer or Not to D-Dimer?
In non-pregnant patients, the D-dimer is an appropriate first step to rule-out pulmonary embolisms in low pre-test probability patients. However, with pregnancy causing a normal physiologic increase in the D-dimer, the utility of this test has become a topic of debate. According to the American Thoracic Society, the recommendation is to not use a D-dimer to rule-out a PE in pregnancy(4). The guidelines cite Damodaram and colleagues who performed a retrospective chart review of thirty-seven pregnant patients with suspected PE and found the D-dimer to have a sensitivity of 73% and a specificity of 15% with a negative likelihood ratio of 1.8(5). However, Jeff Kline proposes that D-dimers can be of use with some alteration of “normal value.” In a podcast at ERCast.org, Dr. Kline proposes the D-dimer threshold should increase 50% from its original normal threshold for each pregnancy trimester. In example, for a normal threshold of 500ng/dL, the pregnancy-adjusted cutoffs would be: first trimester 750ng/mL, second trimester 1000ng/mL, and third trimester 1250 ng/mL(6). Of note, these proposed adjustment in D-dimers levels are solely a proposed next step in investigation, as they have not been validated in the literature. Currently, the general consensus is still that D-dimer is not an adequate enough test to rule-out a pulmonary embolism in a pregnant patient.
Wait, can we PERC out pregnant patients?
Unfortunately, the PERC rule has not been validated in pregnancy. Kline et al performed a retrospective analysis of 1880 patients with confirmed diagnosis of acute pulmonary embolisms. Within this cohort, both pregnant and post-partum patients showed a statistically significant difference in their results of PERC positive and PERC negative, suggesting the PERC rule is inadequate to rule-out PEs in these specific populations(7). Dr. Kline is in the midst of validating a modified PERC rule for pregnant patients, however no evidence for this modified test is supported at this time.
The American Thoracic Society (ATS) clinical guidelines for evaluation of pulmonary embolism in pregnancy are the most up to date and encompassing of the current literature. The ATS solicited recommendations of panelists from numerous experts in the field, including the presidents of ACOG and the Society of Nuclear Medicine. Panel participants included physicians who specialized in pulmonary embolism diagnostics, management, and treatment, especially in pregnant patients. These included cardiothoracic radiologists, nuclear medicine physicians, pulmonologists, and obstetric gynecologists.
Below is a brief summary of the guidelines with highlights of the thought-process and supporting evidence.
- Recommendation 1: D-dimer should not be used to rule-out the presence of pulmonary embolism in a pregnant patient. ( See “To D-Dimer or To Not D-Dimer?” for explanation.)
- Recommendation 2: If a pregnant patient has signs/symptoms of a deep venous thromboembolism (DVT), it is recommended to investigate with bilaterally lower extremity venous compression ultrasound.
- This recommendation stems from the common sense that if a DVT is found, anticoagulation can begin without further investigation. This scenario can benefit the patient by avoiding radiation from further imaging of a ventilation-perfusion (VQ) or a computed-tomography pulmonary angiogram (CTPA). However, with the prevalence of DVTs in pregnancy unknown, it is recommended that ultrasound should not be performed in instances where there are no signs/symptoms of DVT.
- Recommendation 3: In a pregnant patient with no signs/symptoms of DVT but with clinical suspicion of a pulmonary embolism, perform a chest x-ray (CXR) as the first imaging step.
- As described by Worsley and colleagues in review of the PIOPED trial, no CXR findings have been associated with the presence or absence of a pulmonary embolism(8). However, the CXR is an important first imaging step as it can point the clinician to the next imaging modality, VQ vs CTPA.
- Recommendation 4/5: In a pregnant patient with a normal CXR, the next imaging recommendation is to perform a VQ scan. In a pregnant patient with an abnormal CXR, the next imaging recommendation is to perform a CTPA.
- Cahill and colleagues performed a retrospective cohort study of 304 pregnant and post-partum patients with clinical suspicion of a pulmonary embolism. This study showed that after a normal CXR, patients were statistically more likely to obtain a diagnostic result (normal or high probability) with a VQ versus a CTPA (94% versus 70%, p<0.01). However, if the CXR was found to be abnormal, patients were statistically significant more likely to obtain a non-diagnostic VQ versus a non-diagnostic CTPA (40% versus 16.4, p<0.05), and thus the recommendation of jumping to CTPA after an abnormal CXR (3).
- Recommendation 6: In a pregnant patient with a non-diagnostic VQ, perform a CTPA.
- This recommendation stems from the fact that due to high morbidity and mortality caused by pulmonary embolisms in pregnancy, the focus should be on diagnostic certainty. Numerous studies have cited variable ranges of sensitivity and specificity of CTPA for diagnosing pulmonary embolisms. Unfortunately, most studies exclude pregnant patients in the cohort. PIOPED II, the largest study to date, also excluded pregnant patients, however the study cited a sensitivity of 83% and specificity of 96% of the CTPA for PE diagnoses(9).
SUMMARY OF RECOMMENDED STEPS FROM AMERICAN THORACIC SOCIETY
Shared Decision Making
At the end of the day, the work-up and choice of imaging will come down to shared decision-making with the patient, taking into account her wishes and the wishes for her fetus. The large concern for the patient is the radiation from the VQ and CTPA. While the consensus is the radiation exposure is most deadly to the fetus earlier in the pregnancy, different sources cite differing values for radiation caused by VQ versus CTPA. According to a blog at ERCast.org, Dr. Kline quantifies the radiation exposure in regards to money. 0.1 Gray is analogous to $100. CTPA is worth 25-50cents. VQ is worth 50-75 cents. And the amount of radiation necessary to increase a person’s risk of cancer to 1/1000 is $10. Thus, with CTPA and VQ causing less than $1 of radiation, the mortality caused by a pulmonary embolism greatly outweighs the risk of malignancy and it is highly recommended to err on the side of further investigation(6).
- Centers for Disease Control and Prevention. Pregnancy-related mortality surveillance –United States, 1991-1999. MMWR Morbidity Mortality Weekly Report 2003; 52:1-8.
- Gherman RB, Goodwin TM, Leung B, Byrne J, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstetrics Gynecology 1999; 94: 730-734.
- Cahill AG, Stout MJ, Macones GA, Ghalla S. Diagnosing pulmonary embolism in pregnancy using computed-tomographic angiography or ventilation-perfusion. Obstetrics Gynecology 2009; 114: 124-129.
- Leung AN, Bull TM, Jaeschke R, Lockwood CJ, Boiselle PM. Evaluation of Suspected Pulmonary Embolism in Pregnancy. American Journal of Respiratory Critical Care Medicine 2011; 184: 1200-1208.
- Damodaram M, Kaladini M, Luckit J, Yoong W. D-dimers as a screening test for venous thromboembolism in pregnancy: is it of any use? Journal of Obstetrics Gynecology 2009; 29: 101-103.
- Orman, Rob. "Pulmonary Embolism in Pregnancy with Jeff Kline." ERCAST.ORG. 24 Apr. 2013. Web. <http://blog.ercast.org/pulmonary-embolism-in-pregnancy/>.
- 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.
- Worsley DF, Alavi A, Aronchick JM, Chen JT, Greenspan RH, Ravin CE. Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study. Radiology 1993; 189: 133-136.
- Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, Leeper KV Jr, Popovich J Jr, Quinn DA, Sos TA, Sostman HD, Tapson VF, Wakefield TW, Weg JG, Woodard PK. Multidetector computed tomography for acute pulmonary embolism. New England Journal of Medicine. 2006; 354 (22):2317.
- Jeffrey A. Kline et al. Systematic Review and Meta-analysis of Pregnant Patients Investigated for Suspected Pulmonary Embolism in the Emergency Department. Academic Emergency Medicine. Volume 21, Issue 9, pages 949–959, September 2014.