nEWS rELEASE
May 19, 2014

Neutropenia and Sepsis, a Deadly Combination

Penn Medicine Researchers Seek to Understand the Biology of Sepsis in Neutropenic Patients

PHILADELPHIA —Sepsis comes with serious consequences. The blood infection, most commonly caused by bacteria, can lead to septic shock, organ failure, loss of limbs, and even death. Patients whose immune systems are already compromised are at even greater risk.

Nuala J. Meyer, MD, an assistant professor of Pulmonary, Allergy and Critical Care in the Perelman School of Medicine at the University of Pennsylvania examined the effects of sepsis on neutropenic patients. She will present her findings in the poster discussion session at the American Thoracic Society meeting, Monday, May 19, in San Diego.
Neutropenia, a condition in which patients have a low number of infection-fighting white blood cells, can occur as a result of anemia, certain cancers or chemotherapy treatment, and other hereditary disorders.

Meyer looked at a single-center cohort of patients who presented to the emergency department or medical ICU with severe sepsis. Of the 1,269 patients studied, nine percent were neutropenic; 75 percent had hematalogic malignancy; 15 percent had metastatic solid organ malignancy, and 15 percent were organ transplant recipients. Neutropenic patients had a higher incidence of shock and were more likely to die within 60 days, a retrospective review of their electronic health record found. Meyer and her team set out to understand why this occurs.

“We hypothesized that the neutropenic patients would have higher levels of the growth factor angiopoietin 2, a vascular growth factor and marker of injured blood vessels, and that these would serve as biomarkers for the most severe cases of neutropenic sepsis,” says Meyer. Increased levels of angiopoietin is known to lead to an increase of permeability of the blood vessel, which allows the contaminated blood to travel more easily from the vessel to the rest of the body and vice versa.

Contrary to this, the study showed that the neutropenic patients not only had lower than expected levels of angiopoietin 2, but they also had high levels of inflammatory cytokines, specifically interleukin-8, a protein important to the body’s immune response. “The neutropenic patients, despite a low white blood cell count, surprised us with the increased number of cytokines compared to the immunocompetant patients,” Meyer said.

This led the team to believe that mortality risk for sepsis patients might be associated with high cytokine levels independent of severity of illness, and that anti-inflammatory medications targeting interleukin-8 specifically, might be helpful, even among neutropenic patients, as interleukin-8 is highly associated with mortality. “In the future, testing for interleukin-8 in septic patients could lead to early intervention with inflammatory medication, and possibly, better outcomes for patients,” says Meyer.

This study was funded in part by the NIH National Heart Lung and Blood Institute (HL102254).

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.

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