Exposing the 'Great Masquerader' in Maternal Mortality

Laura Arenschield

July 16, 2019

Pulmonary embolism (PE) is a leading cause of maternal mortality, accounting for more than 10% of deaths in pregnancy and childbirth in regions of the world with access to high-quality healthcare.

A woman's risk for venous thromboembolism (VTE) can quadruple during pregnancy, but diagnosing the condition can be difficult because the symptoms — chest pain, shortness of breath, swelling in the legs — are symptoms that, for many women, go hand in hand with pregnancy. The signs of an embolism can go unseen, leaving both mother and child in danger.

VTE "is a very difficult subject to study, for the same reasons that studies in pregnant women are always challenging — everyone is worried, rightly so, about the baby," said Gregoire Le Gal, MD, PhD, from the University of Ottawa in Ontario, Canada.

"For that reason, we have very few studies about VTE in pregnant women and how we can better recognize the signs," he told Medscape Medical News.

Two recent studies show that existing tests and algorithms used to diagnose the "great masquerader" in the general population can be adapted to better diagnose the condition in pregnant women.

These studies could offer new solutions to a medical problem that is understudied and that leads to missed diagnoses, said Le Gal.

Without those tools, a CT scan is a physician's best tool to determine whether a woman has a clot that could lead to a PE, he explained. But many physicians are hesitant to employ that test because it exposes the mother and her fetus to radiation.

"Everyone is worried about that radiation and the fetus, and that means they are not always catching PE in these women," he added.

New Screening Methods

Better diagnostic techniques are critical to improving maternal mortality rates, especially in the developed world, said Le Gal, who discussed the results of the two studies at the International Society on Thrombosis and Haemostasis 2019 Congress, in Melbourne, Australia.

The first study, conducted by researchers from 11 universities in Switzerland, France, and Canada, including Le Gal, found that the best approach to evaluating a pregnant woman's risk for PE is multifaceted.

That study evaluated 395 pregnant women who presented to the emergency department for suspected PE. The women underwent a pretest clinical probability assessment followed by a D-dimer test.

For women with low or intermediate clinical probability of PE whose D-dimer test results were negative, PE was ruled out.

The other women underwent bilateral lower limb compression ultrasonography. If the results were negative, CT pulmonary angiography was performed. If pulmonary angiography was inconclusive, the researchers performed a ventilation–perfusion scan.

"The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up," the study authors report.

"We would recommend physicians estimate the risk, and then, if the woman is at high risk, start with the D-dimer test before moving on to CT scan," said Le Gal.

High-risk patients might, for example, have a history of deep-vein thrombosis prior to becoming pregnant, or have significant shortness of breath, he explained.

D-Dimer Testing

The second study that Le Gal discussed showed that an adaptation of clinical decision rules, called the YEARS algorithm, can be used to successfully diagnose PE in pregnant women.

The researchers assessed three criteria from the algorithm — clinical signs of deep-vein thrombosis, hemoptysis, and PE as the most likely diagnosis. They then performed a D-dimer test. If none of the criteria was met and the D-dimer level was less than 1000 ng/mL or if one or more of the three criteria were met and the D-dimer level was less than 500 ng/mL, PE was ruled out.

Although levels of D dimer increase during pregnancy, both studies indicate that the test can still be useful in evaluating a woman's risk for PE when combined with other clinical tools, said Le Gal.

As with the previous study, the researchers found that adding a fourth criterion — an ultrasound to assess for deep-vein thrombosis — could help diagnose PE.

CT Scan Still Needed

Although these studies are promising, physicians who believe a pregnant woman might be at risk for PE should rely less on the blood test and more on a CT scan, said Andra James, MD, MPH, a maternal-fetal medicine specialist at Duke University in Durham, North Carolina.

"Both studies understood that the symptoms of pulmonary embolism so closely match symptoms that are common in pregnancy that the traditional screening criteria can't be used to distinguish PE from non-PE in pregnant women," James told Medscape Medical News.

"And both appreciated the fact that providers have to have a very low index of suspicion for PE and should not hesitate to use the proper diagnostic test — a CT scan — and start treatment as necessary," he added.

Le Gal receives support from Portola Pharmaceuticals. Andra reports no relevant financial relationships.

International Society on Thrombosis and Haemostasis (ISTH) 2019 Congress: Presented July 9, 2019.

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