A USF Health study finds that a screening test for major blood clots in the lungs, originally validated in seriously ill non-COVID patients, works as well for COVID patients

Human lung tissue with pulmonary embolism under a microscope

TAMPA, Fla. (Oct. 26, 2021) — A screening blood test originally validated in seriously ill patients without COVID-19 is still clinically useful for ruling out pulmonary embolism in patients hospitalized with the coronavirus, a University of South Florida Health (USF Health) Morsani College of Medicine research team reports.

Principal investigator Asa Oxner, MD, and USF Health colleagues published a single-center, diagnostic study Oct. 8 in JAMA Network Open investigating how well D-dimer testing performed at excluding pulmonary embolism in patients hospitalized with COVID-19. Doctors who suspect pulmonary embolisms routinely rely on widely available D-dimer screening to rule out the potentially life-threatening blood clotting disorder – most commonly in surgical patients immobilized for long periods and patients admitted to intensive care units.

D-dimer is a simple blood test that measures protein fragments of blood clots floating in the bloodstream. D-dimer levels, normally undetectable or detectable at very low levels, rise sharply when the body is breaking down the clots.

“Our study found that clinicians can feel confident interpreting the D-dimer levels the same in COVID patients as they do in every other patient; we don’t need a special (different) value for COVID patients,” said Dr. Oxner, associate professor and vice chair of USF Health Internal Medicine. “So, in hospitalized COVID patients, we can appropriately rule out a pulmonary embolism if d-dimer levels are low.”

Pulmonary embolisms occur when blood clots that form in another part of the body (often the leg), travel through the bloodstream, and lodge in the blood vessels of the lung, decreasing blood flow and causing low oxygen levels.

Research indicates COVID-19 patients are three to 10 times more likely to develop pulmonary embolisms than other hospitalized patients, even when they are not as seriously ill or immobilized, Dr. Oxner said. Scientists are still investigating why, but it appears the COVID-19 virus may create a cellular environment that promotes clotting by making the inside of blood vessels uneven, irritated, and prone to microtears.

Asa Oxner, MD, is as associate professor and vice chair of USF Health Internal Medicine.

A negative D-dimer test (one that rules out pulmonary embolism) can help patients avoid more expensive, invasive diagnostic tests, like a computed tomography pulmonary angiogram, or CTPA. “CPTA can be dangerous because the patient, who potentially has a blood clot, must lay immobile in the CT scanner for quite a while to capture (pulmonary artery) images. The test also requires injection with IV contrast, which carries a greater risk of kidney damage when you’re very sick,” Dr. Oxner said.

The USF Health researchers wondered if the increased risk for blood clotting in COVID-19 patients, and uncertainty of diverse D-dimer values found in earlier smaller studies, reduced the existing screening tool’s ability to correctly rule out pulmonary embolism in COVID patients. The conventional thinking was that D-dimer levels would almost always be high in COVID-19 patients, therefore the test as originally validated (in non-COVID patients) would not be accurate at differentiating COVID patients without clots, Dr. Oxner noted.

The retrospective study looked at the records of 1,541 patients hospitalized with COVID-19 at Tampa General Hospital from Jan. 1, 2020, to Feb. 5, 2021. They compared plasma D-dimer concentrations with CTPA, the criterion for diagnosing pulmonary embolism, in 287 of those patients. All COVID-19 patients with CTPA evidence of pulmonary embolism had D-dimer levels of 0.05 μg/mL or greater, as did the majority (91.2%) of patients without CTPA evidence of pulmonary embolism. (Concentrations of 0.05 μg/mL and higher are considered positive for pulmonary embolism, while anything below that D-dimer level is negative.)

The researchers also analyzed whether changing the cutoff levels defining positive or negative D-dimer test results specifically for the COVID patient population might improve the test’s performance. “We did not find that to be statistically significant; however, we may have been able to identify a different cutoff level if the study had more COVID patients,” Dr. Oxner said.

Within the limitations of this single-center study, setting higher D-dimer thresholds was associated with improved specificity – but at “the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk,” the study authors wrote.  A false-negative result means that the test does not detect a pulmonary embolism when the serious blood clotting problem is very likely present.

Doctors who suspect pulmonary embolisms routinely rely on widely available D-dimer screening to rule out the potentially life-threatening blood clotting disorder.

While clinicians must maintain heightened suspicion for pulmonary embolisms when evaluating symptoms in COVID-19 patients, the overall USF Health study results indicate that the currently available D-dimer test adequately screens for the likelihood of pulmonary embolism in hospitalized COVID patients, Dr. Oxner said. “The mechanisms of developing pulmonary embolisms may differ for COVID patients, but the resulting physiology is the same for all patients. The little fragments of (undissolved) blood clots are still detectable with D-dimer.”

USF Health internal medicine resident Constantine Logothetis, MD, was lead author for the study.

Dr. Cindy Munro will be among the first researchers in the United States to study an audio-recording system to reduce delirium in ICU patients.

Tampa, FL (Dec. 19, 2016) – The National Institutes of Nursing Research (NINR) has awarded more than $1.9 million to the University of South Florida College of Nursing to study an audio-recording reorientation intervention to prevent delirium in the intensive care unit (ICU).

Cindy Munro, PhD, professor and associate dean of research and innovation at USF College of Nursing, will lead a team of USF Health researchers to study whether the intervention, called Family Automated Voice Reorientation (FAVoR), can help minimize delirium among patients receiving treatment in ICUs.

FAVoR uses scripted audio messages from the patient’s family, and is played to the patient in the ICU every hour during daytime. The audio recording helps inform the patient about the ICU environment in general terms –in a familiar voice. The recording calls the patients by name and explains what’s happening — telling them, “you’re not able to talk, because you are in a breathing tube,” “you’re in the hospital,” and “we will visit you soon.” 

Cindy Munro, PhD

Dr. Munro and her team will study 178 critically ill and mechanically ventilated adult patients hospitalized at Tampa General Hospital. The researchers will also follow the patients’ progress for six months after they leave the hospital.

“People with delirium have a lot more trouble with recovery,” Dr. Munro said. “Their memory and their long-term quality of life is affected even after they’re discharged from the hospital. So, by doing this alteration to the environment, we’re hoping to help reduce delirium in the ICU, and improve patients’ lives when they go home.”

According to the ICU Delirium and Cognitive Impairment Study Group, 50 percent of critically ill and 80 percent of mechanically ventilated adult patients suffer from delirium. Delirium is a serious disorder that affects one’s mental abilities, environment awareness and thinking, and causes behavioral changes and emotional disturbances.

During this four-year study, Dr. Munro will work with USF College of Nursing’s Ming Ji, PhD, professor, and Zhan Liang, MSN, assistant professor. She will also collaborate with two physicians from USF Health Morsani College of Medicine’s Division of Pulmonary, Critical Care and Sleep Medicine: Karel Calero, MD, assistant professor, and W. Mcdowell Anderson, MD, professor and director of Sleep Medicine.  

“We’re happy to be the one of the first institutions in the nation to study delirium in the ICU,” said Donna Petersen, ScD, CPH, interim dean of the USF College of Nursing, senior associate vice president of USF Health and dean of the USF College of Public Health. “This research will help tackle an untapped health care issue such as delirium as well as help advance our college research mission.”      

The study is supported by NINR, part of National Institute of Health (NIH). NINR helps promote and improve the health of individuals, families and communities. NINR is part of NIH’s 27 institutes and centers that support and conduct clinical and basic science research on health and illness. For more information about NIH and NINR visit www.ninr.nih.gov.

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. USF Health is an integral part of the University of South Florida, a high-impact, global research university dedicated to student success. For more information, visit www.health.usf.edu