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Three Part Question

In [pregnant patients presenting to the emergency department with suspected pulmonary embolism] is there a [clinical decision rule] that can effectively rule out [pulmonary embolism]?

Clinical Scenario

A 27 year old primigravida at 19 weeks gestation presents to the Emergency Department with shortness of breath and pleuritic chest pain. She is afebrile, has a respiratory rate of 28, a heart rate of 120 and oxygen saturation of 96% on room air. There is no evidence of leg pain or swelling. Her ECG is normal. Since imaging tests expose both mother and fetus to ionizing radiation, you wonder whether a clinical decision rule will allow you to safely rule out a pulmonary embolism.

Search Strategy

Medline 1966-07/19 using PubMed, Cochrane Library (2019), and Embase
[(pulmonary embolism/diagnosis OR pulmonary embolism/diagnostic imaging) AND (exp pregnancy) AND (decision rule OR decision support techniques OR risk assessment OR algorithms OR predictive value of tests)]. Limit to English language

Search Outcome

83 studies were identified; 5 papers addressed the clinical question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
OConnor C, et al. Dec. 2011 Ireland	125 pregnant or early postpartum patients referred for CT pulmonary angiogram.	Retrospective	Diagnostic test accuracy of modified Wells score (MWS) for detecting PE as compared to CTPA.	An MWS less than 6 had a sensitivity of 100% and specificity of 90%.	Retrospective; particularly open to observer bias since a large part of the MWS is subjective; small sample size; and 18% of patients lost to follow up.
Cutts BA et al. June 2014 UK	183 pregnant women with suspected PE that underwent a V/Q scan at 2 tertiary institutions	Retrospective	Diagnostic test accuracy of modified Wells score (MWS )for detecting PE as compared to V/Q scan	An MWS greater or equal to 5 had a sensitivity of 100% and specificity of 60%.	Retrospective, non-blinded study; prone to observer bias since large part of MWS score is subjective; small sample size Follow-up to determine whether subsequent PE developed during pregnancy and post-partum was done by checking medical record and not verified by medical imaging or patient contact
Parilla BV et al. April 2016 USA	45 pregnant women with signs and symptoms suspicious for PE were prospectively enrolled; 14 pregnant patients with confirmed PE were retrospectively included.	Prospective and retrospective observational	Diagnostic test accuracy of Modified Wells Score (MWS)	Sensitivity 23.5%, specificity 100%, NPV 76.4%, PPV 100%	Partially retrospective, non-blinded observational study; particularly open to observer bias as large part of MWS score is subjective; small sample size
			Diagnostic test accuracy of trimester-specific D-dimer	Sensitivity 94.1%, specificity 73.8%, NPV 97%, PPV 59.3%
			Diagnostic test accuracy of combined MWS and trimester-specific D-dimer	Sensitivity 100%, specificity 73.8%, NPV 100%, PPV 60.7%
Goodacre S et al 2018 UK	324 pregnant/postpartum women with suspected PE and 198 pregnant/postpartum women with diagnosed PE	Prospective and retrospective observational	Diagnostic test accuracy of three clinical decision rules	Clinical decision rules had areas under reciever-operator characteristic curve ranging from 0.577-0.732 and no clinical useful threshold for decision making	Clinical decision tool scores were calculated retrospectively; D-dimer was only recorded in 38% of patients which makes the calculation of sensitivity and specificity unreliable; 47/324 in the suspected PE group did not have definitive imaging in the form of CTPA or V/Q scan; 35/198 in the diagnosed PE group were diagnosed and treated clinically without definitive imaging.
			Diagnostic test accuracy of d-dimer	Sensitivities and specificities were 88.4% and 8.8% using a standard threshold and 69.8% and 32.8% using a pregnancy-specific threshold
van de Pol LM et al. March 2019 Netherlands	498 pregnant patients with suspected pulmonary embolism from who underwent work up with the YEARS algorithm.	Prospective	The primary outcome was Incidence of VTE at 3 months.	During followup popliteal DVT was diagnosed in 1 patient; no patient had a PE.	Study design was not randomized. There were a number of protocol violations. 12 patients underwent CTPA when it was not indicated by the algorith. 2 patients underwent V/Q scanning instead of CTPA and 24 patients did not receive imaging when CTPA was indicated by the algorithm. However none of these instances led to an unwanted outcome.
			The secondary outcome was proportion of patients in whom CTPA was not indicated to safely rule out PE	CTPA was not indicated and therefore avoided in 195 patients. The proportion of patients that avoided CTPA was highest in the 1st trimester (65%) and lowest in the third trimester (32%)

Comment(s)

Two studies looked at modified Wells score (MWS) for PE. They both documented a sensitivity of 100% and a negative predictive value of 100% for low risk patients. A third study also showed a sensitivity of 100% when an unlikely clinical probability by MWS was combined with a normal trimester-specific D-dimer level. These studies support the use of MWS to help rule out PE however they are limited by their retrospective nature and small ample size. Goodacre and colleagues tested a number of clinical decision rules, both established rules such as MWS and novel rules. They did not find any rule to be sufficiently discriminatory to be clinically useful. All of these scores were calculated retrospectively and patients were a mix of prospective and retrospective cases. The only prospective trial used a clinical decision rule employing three items of the MWS: hemoptysis, signs of DVT and PE as most likely diagnosis. These were combined in an algorithm with two different D-dimer cut offs. This study was well designed, adequately powered and shows PE can be safely ruled out with a clinical decision rule incorporated with a d-dimer measurement.

Editor Comment

CR

Clinical Bottom Line

The adapted YEARS algorithm can be safely used to rule out PE in pregnancy without imaging for those patients deemed to be low risk.

References

1. OConnor C, Moriarty J, Walsh J, Murray J, Coulter-Smith S, Boyd W. The application of a clinical risk stratification score may reduce unnecessary investigations for pulmonary embolism in pregnancy J Matern Fetal Neonatal Med 2011 Dec;24(12):1461-1464.
2. Cutts BA, Tran HA, Merriman E, Nandurkar D, Soo G, DasGupta D, Prassannan N, Hunt BJ. The utility of the Wells clinical prediction model and ventilation-perfusion scanning for pulmonary embolism diagnosis in pregnancy. Blood Coagul Fibrinolysis 2014 Jun;25(4):375-8.
3. Parilla BV, Fournogerakis R, Archer A, Sulo S, Laurent L, Lee P, Chhotani B, Hesse K, Kulstad E. Diagnosing Pulmonary Embolism in Pregnancy: Are Biomarkers and Clinical Predictive Models Useful? AJP Rep 2016 Apr;6(2):e160-164
4. Goodacre S, Horspool K, Nelson-Piercy C, Knight M, Shephard N, Lecky F, Thomas S, Hunt BJ, Fuller G; DiPEP research group. The DiPEP study: an observational study of the diagnostic accuracy of clinical assessment, D-dimer and chest x-ray for suspected pulmonary embolism in pregnancy and postpartum. BJOG BJOG. 2019 Feb;126(3):383-392
5. van der Pol LM, Tromeur C, Bistervels IM, Ni Ainle F, van Bemmel T, Bertoletti L, Couturaud F, van Dooren YPA, Elias A, Faber LM, Hofstee HMA, van der Hulle T, Kruip MJHA, Maignan M, Mairuhu ATA, Midd Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. N Engl J Med 2019 Mar 21;380(12):1139-1149