There is an urgent need for prospective studies on clinical prediction rules, D-dimer testing, and diagnostic imaging to better inform diagnosis of pulmonary embolism (PE) during pregnancy, according to a report published in Thrombosis Research. Researchers wrote that existing clinical guidelines provide only weak recommendations surrounding the selection of appropriate diagnostic methods for suspected PE in pregnant patients, primarily because of a lack of data from clinical trials.

Tony Wan, MD, of the University of Ottawa in Canada, and colleagues conducted a literature review to assess current clinical guideline recommendations on evaluating suspected PE in pregnant patients, as well as to examine the evidence underpinning these recommendations. Seven guidelines were identified. The researchers found a lack of high-quality research that may have led to significant differences in clinical practice across regions. “The reliance on retrospective studies and expert opinion likely contributes to discrepancies seen between guideline recommendations and practice variation among clinicians,” wrote Dr Wan and colleagues.

Despite low incidence, PE is one of the leading causes of maternal mortality, with several challenges impeding clinicians’ ability to make a proper diagnosis. For example, guidelines are highly varied and extrapolate almost entirely from results in nonpregnant patients because only a few observational studies in pregnant patients exist.

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“I would say that [this is a] topic that is certainly relevant, as pregnant patients are at a higher risk for thromboembolic events — deep vein thrombosis (DVT) or PE — [compared with] the general population,” said Eric Strand, MD, an associate professor in the department of obstetrics and gynecology at the Washington University School of Medicine in St Louis, Missouri.

Physiological changes in pregnancy that can overlap with clinical manifestations of venous thromboembolism (VTE) further complicate the diagnosis of PE. Dr Wan and colleagues noted that hyperdynamic circulation in pregnancy can influence the accuracy of diagnostic imaging. “We don’t have great data in a pregnant population. In particular, some of the scoring systems to determine pretest probability, like the Woods score, function poorly in pregnancy because pregnant [patients] are much more likely to have certain symptoms, such as elevated heart rate and leg swelling, that make the scoring less accurate,” Dr Strand told Hematology Advisor.

There was some controversy surrounding the use of D-dimer testing during pregnancy among the published guidelines. Guidelines from the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH) and the European Society of Cardiology (ESC) suggested that a normal D-dimer could be used to avoid unnecessary imaging in pregnant patients with suspected PE. However, the Royal College of Obstetricians and Gynaecologists (RCOG), the Society of Obstetricians and Gynecologists of Canada (SOGC), and the American Thoracic Society/Society of Thoracic Radiology (ATS/STR) recommended against using D-dimer to rule out PE in pregnancy.

“At this point, we believe that D-dimer testing should not be used to rule out PE in pregnancy for several reasons,” wrote the authors. “Data on the sensitivity and negative predictive value of D-dimer as a test for suspected PE in pregnancy is limited and inconsistent.” The authors also pointed to the lack of a clinical prediction rule in pregnancy and the high probability for a false-negative test result in patients with high pretest probability.

The use of lower limb ultrasound was recommended by 4 guidelines. However, there is significant debate on how to select the appropriate patients in order to optimize diagnostic yield. Both the GTH and the ESC recommended conducting a bilateral lower limb ultrasound in all pregnant patients with suspected PE regardless of presence of DVT symptoms, while the ATS/STR and RCOG guidelines called for lower limb ultrasound only if patients did not exhibit any clinical features of DVT.

In most cases, the diagnostic algorithm for PE in pregnant patients includes chest radiography as the initial mode of imaging investigation. Despite not having been validated in prospective outcome studies, chest radiography can be used to accurately interpret abnormal findings from ventilation perfusion (V/Q) scans. The review found that 5 guidelines recommended preferential use of V/Q scanning when chest radiography was normal. In cases of abnormal chest radiography, the use of computer tomography pulmonary angiography (CTPA) was recommended.

CTPA is commonly used to diagnose PE in nonpregnant patients, but its use as a first-line diagnostic tool in place of V/Q is unclear. Performing CTPA may be influenced by the physiological changes of pregnancy; 4 retrospective studies assessing nondiagnostic results demonstrated a favorable trend for V/Q scanning compared with CTPA. However, the difference between rates of nondiagnostic scans was statistically significant in only 1 study. “[Because] nondiagnostic results can come from use of either a V/Q scan or CTPA, I think it’s reasonable to do either depending on the resources available to the provider,” said Dr Strand.

Several trials are nearing completion that may help improve guidance on diagnosing PE in this patient population, including a prospective study (ClinicalTrials.gov Identifier: NCT00771303) underway in France to assess the role of D-dimer, leg ultrasound, and CTPA in a diagnostic algorithm for suspected PE in pregnant patients. Future research and improved pregnancy-specific diagnostic algorithms may lead to significant improvement in maternal mortality rates due to PE.

Reference

  1. Wan T, Skeitha L, Karovitch A, et al. Guidance for the diagnosis of pulmonary embolism during pregnancy: Consensus and controversies [published online June 23, 2017]. Thromb Res. doi: 10.1016/j.thromres.2017.06.025