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Blood Discovery Could Benefit Preemies, Help End Platelet Shortages

The emergency call issued by the American Red Cross earlier this year was of a sort all too common: Donations of platelets were needed, and desperately. But a new discovery from the University of Virginia School of Medicine may be the key to stopping shortages of these vital blood-clotting cells, cells that can represent the difference between life and death.

The finding also could offer big benefits for premature babies, opening the door to new treatments for a serious condition called neonatal thrombocytopenia that affects up to 30 percent of babies in neonatal intensive care units.

A ‘Master Switch’

The UVA researchers have identified a “master switch” that they may be able to manipulate to overcome the obstacles that have prevented doctors from producing platelets in large quantities outside the body. “The platelet supply is limited and the demand is growing,” said researcher Adam Goldfarb, MD, of UVA’s Department of Pathology. “The quantities we can produce outside the body are very, very small, and the inability to scale up right now is a major roadblock. We think that our understanding of this pathway is actually a critical step toward fixing that problem.”

Scientists also may be able to use this master switch to battle neonatal thrombocytopenia, a condition that complicates the care of babies who are already at great risk. “It turns out in premature infants and newborns that [the platelet] reserve is compromised. They are less capable of responding to distress and the demand for increased platelet production,” Goldfarb said. “A goodly percentage of those babies, these tiny little babies, require platelet transfusions to keep their platelets up.”

Bossing Bone Marrow

The switch discovered by Goldfarb’s team controls whether the bone marrow produces cells called megakaryocytes of the type seen in adults or of the sort found in infants. This is important because the adult and infantile versions have very different specialties: Adult megakaryocytes are great at making platelets. Lots and lots of them. Infantile megakaryocytes, on the other hand, are much smaller cells, and they concentrate on dividing to produce more megakaryocytes.

The ability to toggle between the two could be a huge asset for doctors. Now, doctors cannot produce large quantities of platelets in the lab and instead must rely on platelet donations for patients. The new finding, however, may help change that. “It's thought that in our bodies every single megakaryocyte produces like a thousand platelets, and when you do it in culture [outside the body] it's like 10,” he said. “We think the pathway we're studying enhances the efficiency of platelet release, and this pathway, we think, could be manipulated in both directions: to suppress the pathway to promote the growth [of megakaryocytes] and then to activate the pathway at some point to enhance the efficiency of platelet release.”

Helping Babies

For example, babies might be given a drug that would prompt their bodies to make more platelets. Researcher Kamal Elagib, MBBS, PhD, noted that the research team already has identified compounds that can flip the switch in the lab, but that those compounds likely aren’t the best option for treatment: “Those inhibitors have multiple effects, so there would be side effects,” he said.

The researchers, however, have already identified other drugs that look much more promising. “Our future efforts that Kamal is working on now are to identify better, cleaner, more effective approaches at flipping this switch,” Goldfarb said. “Understanding this process could really enhance the future approaches towards treating patients with low platelet counts.”

Findings Published

The researchers have published their findings in the Journal of Clinical Investigation. The research team consisted of Elagib, Chih-Huan Lu, Goar Mosoyan, Shadi Khalil, Ewelina Zasadzińska, Daniel R. Foltz, Peter Balogh, Alejandro A. Gru, Deborah A. Fuchs, Lisa M. Rimsza, Els Verhoeyen, Miriam Sansó, Robert P. Fisher, Camelia Iancu-Rubin and Goldfarb. Their article can be read for free at

The work was supported by the National Institutes of Health, grants DK090926 and HL130550.


UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

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  • New Plan Aims to Slash Unnecessary Medical Testing

    Researchers seek to improve patient outcomes while cutting medical costs.

    Researchers at top hospitals in the U.S. and Canada have developed an ambitious plan to eliminate unnecessary medical testing, with the goal of reducing medical bills while improving patient outcomes, safety and satisfaction.

    The researchers are urging physicians and other care providers to reconsider the use of routine daily lab tests performed on hospitalized patients. Automatically performing such tests without determining they are important to the patient’s treatment is a “wasteful clinical practice that threatens the value of healthcare,” the researchers warn in a new paper published in JAMA Internal Medicine, a journal of the American Medical Association.

    The researchers note, for example, that excessive blood testing can lead to hospital-acquired anemia, increase medical costs and generate additional unnecessary testing. It’s also painful for the patients who find themselves frequently being stuck with a needle. “Despite strong evidence for the negative effects of routine daily laboratory testing on patients, there remains a need for improved implementation of this high-value measure,” said the paper’s senior author, Andrew Parsons, MD, MPH, of the University of Virginia School of Medicine. “Our aim is to assist other institutions that would like to promote this high-value practice as a quality-improvement effort.”

    A Strategy for Better Healthcare

    The researchers note that there are many reasons for excessive testing, from fear of litigation to lack of knowledge of the costs involved. However, their paper suggests that there are simple ways for healthcare facilities to reduce unnecessary testing safely and without compromising the quality of patient care. Several previous studies have borne this out, they state. “Although reducing repetitive laboratory testing may bend the cost curve, patient safety should remain at the forefront of these efforts,” the researchers wrote.

    Their plan encourages healthcare facilities to:

    • Design and implement educational efforts to train care providers in better practices. Evidence should be provided that demonstrates the safety and effectiveness of those practices. This educational effort should range from bedside nurses all the way up through senior hospital leadership.
    • Audit testing and provide feedback to those ordering the tests. By giving healthcare providers real-time feedback on their ordering patterns, they can adjust those patterns to optimize care. Anonymized comparative data should be provided as well, the researchers urge.
    • Harness the power of electronic medical records to limit unnecessary testing. For example, hospitals might limit the ability to order repetitive daily labs on a perpetual basis.

    Be Safe

    The researchers’ efforts align with the UVA Health System’s Be Safe initiative, a groundbreaking program initiated by Richard M. Shannon, MD, UVA’s executive vice president for health affairs. Be Safe aims to make UVA the safest hospital in America, and it does so, in part, by calling on all employees to develop and consistently adhere to best practices that put the patient first.

    Parsons and George Hoke, MD, associate director of hospital medicine and faculty development, represent UVA on the High Value Practice Academic Alliance, a coalition of more than 80 academic medical centers working to improve healthcare by eliminating waste. The new paper represents the group’s third such initiative. “Unlike traditional clinical practice guidelines that describe best-practice objectives, these papers are designed to guide medical centers through the process,” Parsons said. “Each paper is being co-authored by experienced quality-improvement faculty from multiple academic medical centers that have safely reduced unnecessary practice.”

    The new guidelines were developed by experts at UVA, the University of Michigan, the University of Toronto, the University of Pennsylvania and Johns Hopkins University, as well as by residents in training.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

  • Susan G. Komen Awards UVA $450,000 for Innovative Breast Cancer Research

    Scientist Seeks to Harness Gut Bacteria to Battle Tumors and Stop Their Spread.

    Researcher Melanie Rutkowski, PhD, can envision a day when doctors prescribe a specific diet to prevent the spread of breast cancer. A day when doctors could identify women at high risk for breast tumors just by examining the bacteria in their guts.

    And now Susan G. Komen has awarded her $450,000 to fund pioneering research that could make that happen.

    Over the next three years, the grant will let Rutkowski, of the University of Virginia School of Medicine, expand our understanding of the relationship between the microbiome – the microorganisms that naturally live in our bodies – and the immune system’s response to breast cancer. She will seek to determine if chronic disruption of the microbiome, possibly caused by diets heavy in processed foods, fats and sugar, is hurting the immune system’s ability to battle breast tumors – and perhaps even facilitating the cancer’s spread through the body.

    “One of the underlying questions about breast cancer is why do some individuals with breast cancer develop more aggressive or metastatic disease? And why is there so much variability in the context of how their immune systems respond to these cancers?” said Rutkowski, of the UVA Cancer Center and UVA’s Carter Immunology Center. “What our research is suggesting is that these microbes that live within us, when they are unbalanced, they can dramatically influence disease progression, making the tumors more aggressive and ultimately result in the inability of the immune system to eliminate the tumor.”

    Breast Cancer’s Link to the Gut

    Doctors are increasingly realizing the importance of the microbiome in human health and disease, Rutkowski noted. “It’s becoming more and more appreciated now that these microbes are involved in a whole variety of different pathologies,” she said. “There have been links with neurological disorders, with certain metabolic disorders, and now there’s a lot of appreciation of how these microbes, especially within the gastrointestinal tract, influence the immune response against certain types of cancer.”

    Once breast cancer has spread, it is untreatable, so preventing its spread – known as metastasis – is vital. Rutkowski’s research suggests that manipulating the microbiome may lead to better outcomes. It could be as simple as a doctor instructing a patient to eat a diet high in fiber to complement her treatment regimen, Rutkowski said.

    “These microorganisms have many functions. They provide a first line of defense against invading pathogens, they are involved in aiding in digestion, they have a lot of metabolic products that they secrete that help to break down the food we ingest,” she said. “Those metabolic products actually have immune regulatory activity. They help to maintain the balance of good inflammation and bad inflammation, and what is becoming really appreciated about these microorganisms is that they are able to influence our immune system. Our interest, then, is to understand how they influence cancer.”

    That understanding could then be put to use in the war against breast cancer – leading to better treatments and better ways to identify women at risk, Rutkowski hopes. “Ultimately,” she said, “I’d like to see this work benefit patients.”

    About Susan G. Komen

    Susan G. Komen has invested more than $920 million to support pioneering research around the world since its founding in 1982. The group is committed to supporting research, people and resources that will reduce breast cancer deaths in the United States by 50 percent by 2026.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

    About UVA Cancer Center
    UVA Cancer Center is accredited by the Commission on Cancer and is one of 69 National Cancer Institute (NCI) designated cancer centers in the U.S. for its work in cancer research, prevention, detection and treatment. UVA Cancer Center provides comprehensive, world-class cancer treatment in an environment of caring for patients across Virginia, led by doctors who have been honored by publications such as Best Doctors in America® and America’s Top Doctors®.

  • Fast, Quality Heart Attack Care Earns UVA Two National Awards

    For providing prompt, high-quality care for patients suffering heart attacks, University of Virginia Health System has received two national awards from the American Heart Association (AHA).

    UVA received the Mission: Lifeline STEMI Receiving Center – Bronze Plus achievement award and the Mission: Lifeline NSTEMI – Silver achievement award from the AHA for meeting national standards to improve care and outcomes for heart attack patients.

    AHA guidelines include quickly restoring blood flow to blocked arteries during a heart attack; providing counseling on how to quit smoking; providing recommended medications; evaluating how well patients’ hearts are functioning following a heart attack; and referring patients to a cardiac rehabilitation program.

    “These two awards highlight the excellent teamwork both at UVA and across the region to provide excellent care for our patients,” said David R. Burt, MD, director of the UVA Chest Pain Center.

    When caring for heart attack patients, the UVA Heart and Vascular Center, Emergency Department and Pharmacy work closely with emergency medical service providers from across Central Virginia to provide fast, coordinated care.

    Arriving patients are seen at the Chest Pain Center inside the Emergency Department for assessment. If treatment is needed, UVA has five specialized procedure rooms for heart attack patients. When patients are ready for discharge, UVA provides cardiac rehabilitation as well as a Heart Attack Recovery Clinic, where patients are scheduled for a follow-up visit one week after leaving the hospital.

    Outcomes from January-December 2016, the most recent timeframe with available data, show the benefits of this teamwork for patients with a serious type of heart attack called an ST-elevation myocardial infarction (STEMI). During this period, the median time for STEMI patients to have their blocked heart arteries reopened after arriving at the UVA Emergency Department was 48 minutes – placing UVA in the top 10 percent nationally.

    “Our physicians and a multidisciplinary team across UVA are always seeking ways to enhance the care we provide our heart attack patients,” said Pamela M. Sutton-Wallace, chief executive officer of UVA Medical Center. “These awards showcase their commitment to our patients.”


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in Americaand America's Top Doctors.

  • A Clock Mystery From 350 Years Ago Is Shedding Light on Human Health

    In 1665, the inventor of the pendulum clock, Christiaan Huygens, noticed that two of his clocks hung on the same wall would eventually sync up, so that their pendulums swung in opposite directions in perfect time. This “insensible motion,” he thought, might be put to use so that clocks would regulate each other.

    Turns out important cells in our guts already had that figured out.

    Researchers have determined how the body controls the replacement of the barrier cells lining our guts, cells which protect us from disease. The cells’ internal clocks, the researchers found, are regulated by the same sort of interaction responsible for the strange effect in pendulum clocks.

    If that sounds freaky, it gets weirder: The researchers made their discovery while working with miniature guts they made in a laboratory — using intestinal stem cells from mice whose cellular clocks were labeled with enzymes from fireflies.

    The Gut Lining’s Critical Importance

    The cells lining our guts are vast in number and turn over at a remarkable rate. “If you add up all the surface area of all the cells and villi and micro-villi that line our guts, it’s roughly the equivalent of a double tennis court, and the double tennis court’s renewed by our stem cells every 3 to 5 days,” explained researcher Sean Moore, MD, a physician at the University of Virginia Children’s Hospital. “That surface area helps us to process tons of food and tons of liquid over our lifetime, and it also separates the contents of the bowel from our bloodstream and keeps away a lot of potentially dangerous things like bacteria or viruses [that] could be life-threatening.”

    As such, doctors are eager to understand how the body builds that wall. It’s particularly of interest as researchers come to better appreciate the role of the body’s circadian rhythms, the natural cycle of biological processes. Rather than looking at the body in terms of single points in time, doctors are increasingly thinking in more holistic terms, considering the many variations that occur over time. “During the day, our gut is absorbing nutrition and fluids from our diet, and during night it’s going through a repair phase and getting ready for the next day’s responsibilities of digestion and defense,” Moore said. “What is remarkable is that these clocks are not just governed by our brain but they’re actually built inside each of our cells.”

    Moore and collaborator Christian Hong, PhD, at the University of Cincinnati, have shed light on how those cellular clocks work. “What we were able to show was that in these miniature guts, the stem cells themselves do not have a robust clock. They rely on a specialized cell type produced by the stem cells called Paneth cells, and the Paneth cells were acting somewhat like a drill sergeant in providing the temporal cue to the intestinal stem cells that were governing overall rates of proliferation,” Moore said. “So now we have two oscillators: One oscillator will be circadian rhythm, so it’s going up and down over the 24-hour cycle, and then we have another oscillator, which is the cell cycle. And this idea of coupled oscillators has just celebrated its 350th birthday, so it’s very cool to see it at work here.”

    Treating Disease

    By understanding the cellular clocks, doctors can use that knowledge to battle disease and improve human health. There may be times when it’s more effective to give a cancer therapy or administer an oral vaccine for typhoid, for example. “Probably where the rubber meets the road is going to be colorectal cancer, chronotherapy, understanding that precision medicine is not just about the right drug for the right patient but at the right time,” Moore said. “This is going to help us develop precision therapies that take into account the time of day.”

    Findings Published

    The discovery has been outlined in the scientific journal Molecular Cell. The article was written by Toru Matsu-ura, Andrey Dovzhenok, Eitaro Aihara, Jill Rood, Hung Le, Yan Ren, Andrew E. Rosselot, Tongli Zhang, Choogon Lee, Karl Obrietan, Marshall H. Montrose, Sookkyung Lim, Moore and Hong.

    The work was supported by the U.S. Department of the Interior, grant D12AP00005.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

  • Discovery About How Heart Forms Sheds Light on Deadly Disease

    Kidney research at the University of Virginia School of Medicine has unexpectedly led to a discovery about the formation of the heart, including the identification of a gene responsible for a deadly cardiac condition.

    UVA scientists were surprised to discover that the heart’s inner lining forms from the same stem cells, known as “precursor cells,” that turn into blood. That means a single type of stem cell turns into both our blood and a portion of the organ that will pump it.

    The researchers determined that a particular gene, S1P1, is vital for the proper formation of the heart. Without it, the heart tissue produced by the precursor cells develops a sponginess that compromises the heart’s ability to contract tightly and pump blood efficiently. In people, that is known as ventricular non-compaction cardiomyopathy, a dangerous condition that often leads to early death.

    “Many patients who suffer from untreatable chronic diseases, including heart and kidney diseases, are in waiting lists for limited organ transplantation. Therefore, there is an urgent need to understand what happens to the cells during disease and how can they be repaired,” said researcher Yan Hu, PhD. “Every organ is a complex machine built by many different cell types. Knowing the origin of each cell and which genes control their normal function are the foundations for scientists to decipher the disease process and eventually to find out how to guide the cells to self-repair or even to build up a brand new organ using amended cells from the patients.”​

    Far-Reaching Consequences

    The researchers, led by Maria Luisa S. Sequeira-Lopez, MD, of UVA’s Child Health Research Center, were investigating how the kidney forms when they noted that the deletion of the S1P1 gene in research mice had deadly consequences elsewhere in the body. “We were studying the role of these genes in the development of the vasculature of the kidney,” she recalled. “The heart is the first organ that develops, and so when we deleted this gene in these precursor cells, we found that it resulted in abnormalities of the heart, severe edema, hemorrhage and low heart rate.”

    That led them to look more closely at the heart. It was then that they discovered the gene deletion had caused thin heart walls and other cardiac problems in developing mice embryos. “So then we had to study the heart when the kidneys were still not even formed,” she said. “We had to go far outside our comfort zone.”

    Their findings would prove unexpected even for scientists who specialize in the development of the heart. “For a long time, scientists believed that each organ developed independently of other organs, and the heart developed from certain stem cells and blood developed from blood stem cells,” explained researcher Brian C. Belyea, MD, of the UVA Children’s Hospital. “A number of studies done in this lab and others, including this work, shows that there’s much more plasticity in these precursor cells. What we found is that cardiac precursor cells that are present in the embryonic heart do indeed give rise to components of the heart in adults but also give rise to the blood cells.”

    The researchers were so surprised by their discovery that they went back and validated their findings repeatedly, using multiple techniques, including new techniques that they developed.

    Belyea said that the discovery about the important role of the S1P1 gene may one day lead to better treatments for that condition. “We hope,” he said, “that this is a stepping stone for our clinical colleagues.”

    Findings Published

    The researchers have described their discovery in an article published in the journal Scientific Reports. The research team consisted of Yan Hu, Belyea, Minghong Li, Joachim R. Göthert, R. Ariel Gomez and Sequeira-Lopez.

    The work was supported by the National Institutes of Health, grants DK-091330, DK-096373, DK-096373 and HL-096735.


    UVA Health System is an academic health system that includes a 612-bed hospital, the UVA School of Medicine, a level I trauma center, nationally recognized cancer and heart centers and primary and specialty clinics throughout Central Virginia. UVA is recognized for excellence by U.S. News & World Report, Best Doctors in America and America's Top Doctors.

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