East and West African sickle cell anaemia are genetically similar

African collaboration unpicks disease variations by combining local genomic research with large-scale genome-wide association techniques

 Sickle cell anaemia is most common in Africa and up to 11,000 children are born with the condition every year in Tanzania alone. Yet most of what is known about the genetic basis of this inherited disease comes from studies of US-based or UK-based African-Caribbean populations.

In African-American populations genetic variations can influence the ability to produce foetal haemoglobin by as much as 50 per cent, but knowledge of this effect in East African populations is scant. A collaboration between research teams in Tanzania and the UK applied the power of the genome-wide association techniques to the genomes of 1,213 individuals in Tanzania to confirm whether or not the same variations are at work in an East African population and to identify possible new ones.

Sickle cell anaemia is painful and disabling disease caused by variations in a gene involved in producing adult haemoglobin. But people who have greater levels of the foetal form of haemoglobin in their bloodstream are less affected. This first large-scale genomic study based in Tanzania has revealed a number of regions in the genome that appear to have an effect on foetal haemoglobin levels and will guide future research into African populations.

"By carrying out a large-scale genome-wide association study we have, for the first time, been able to identify powerfully the prevalence of genetic variants involved in sickle cell anaemia in the Tanzanian population and how that compares with other populations," says Siana Nkya Mtatiro, co-first author of the paper from Muhimbili University of Health and Allied Sciences. "We have also identified suggestive additional variants, which can now be studied further by the research community in the search for interventions for sickle cell anaemia in patients in Africa and worldwide."
 
The research confirmed the association of genetic variations near the genes BCL11A and HBS1L-MYB with sickle cell anaemia in the Tanzanian population but found that variations in HBB, which are associated with the disease in African-American populations, are not significant in East African populations. In addition, the study hinted at additional associations that require confirmation in other populations.









  The collaboration between research teams in Tanzania and the UK carried out a genome-wide association study of 1,213 individuals in Tanzania with sickle cell anaemia and confirmed that BCL11A and HBS1L-MYB are connected with the disease. [Muhimbili University of Health and Allied Sciences]

"We were unable to validate any of our new suggestive associations in a group of UK samples we used for comparison. This suggests we need bigger studies to more completely understand the genetics of this disorder," says Jeff Barrett, senior author from the Wellcome Trust Sanger Institute.
The work was a joint effort drawing on the skills and techniques developed by Tanzania- and UK-based teams and the free flow of information between them. The samples were gathered in Tanzania and genotyped at the Sanger Institute, the genome-wide scan was carried out by the UK-based team and subsequent data analysis was carried out the African-based researchers.

"This work demonstrates how scientists in Africa can collaborate both with one another and with colleagues in Europe to provide greater insight into the genomic landscape of health and disease in Africa, the cradle of humanity," says Julie Makani, senior author on the study from Muhimbili University of Health and Allied Sciences. "We hope that our approach could be used as a model for other researchers working to understand the genetic basis of health and disease in Africa."
The research was supported by the Wellcome Trust, which encourages collaborations between researchers on different continents to apply cutting-edge genomic techniques in low- to middle- income countries. Trust-funded research in this area aims to increase our understanding of diseases that might otherwise be neglected.

"This is an important contribution to sickle cell disease research, which clearly demonstrates how successful genomics research collaborations - in this case between researchers in Tanzania and the Wellcome Trust Sanger Institute - can be achieved," says Jimmy Whitworth, Head of Population Health at the Wellcome Trust. "The results of this study will form a firm foundation for further studies of the genetic basis for sickle cell disease and potential avenues for treatment in sub-Saharan Africa."

Acetate supplements speed up red blood cell production, anemia research shows

Researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

 UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

"Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy," said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.
Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.
"Our study shows that acetate functions as a biochemical 'flare,' linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway," Dr. Garcia said.

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.

Sickle cell trait tied to kidney disease among blacks

African Americans with sickle cell trait - generally thought to be benign, unlike sickle cell disease - may still be at increased risk of kidney disease, a new study suggests.

African Americans with sickle cell trait - generally thought to be benign, unlike sickle cell disease - may still be at increased risk of kidney disease, a new study suggests.

Based on data for more than 2,000 people, researchers found that about 19 percent of those with sickle cell trait had kidney disease, compared to about 14 percent of people without the trait.
The study team calculates that sickle-cell trait raises the risk of kidney disease by nearly 60 percent. They reported their results in JAMA and during a presentation at Kidney Week in Philadelphia.
“We set out to do this, because there has been some uncertainty and controversy around the health consequences of sickle cell trait, which is a genetic condition related to sickle cell disease,” said one of the study’s authors, Dr. Alexander Reiner from the Fred Hutchinson Cancer Research Center in Seattle.

Sickle-cell disease is an inherited disorder in which red blood cells contain an abnormal type of hemoglobin. The defective cells frequently take on a sickle- or crescent-shape and can block small blood vessels, which can lead to tissue damage or even stroke.

People with sickle cell disease have inherited two defective genes, one from each parent, whereas those with sickle cell trait inherit only one problematic gene and one healthy one - which helps to offset the effect of the malfunctioning gene.

Sickle cell disease affects about one of every 500 blacks, according to the U.S. Centers for Disease Control and Prevention. Sickle cell trait affects one in 12 blacks.

“Even though sickle cell trait has been considered to be relatively benign, it has been known that kidney complications, such as having blood in the urine, was more common in people with sickle cell trait versus people without sickle cell trait,” said the study’s lead author, Dr. Rakhi Naik from Johns Hopkins University in Baltimore.

Naik told Reuters Health that the red blood cells of people with sickle cell trait would look completely normal under a microscope.

“The theory is that under very highly stressful situations (such as a low oxygen levels) . . . there may be some localized sickling that happens in the kidney that is leading to functional impairment,” she said.

For the new study, the researchers combined data from five large U.S. studies that included 15,975 self-identified African Americans - 1,248 of them with sickle cell trait - who were followed for 12 to 26 years.

At the outset, people with sickle cell trait were 57 percent more likely overall to have chronic kidney disease than people without a defective gene. People who didn't have kidney disease at the start were 80 percent more likely to develop it if they had the sickle trait.
Kidney disease tended to appear later in life among those with sickle cell trait than it tends to do in sickle cell disease, Naik noted.

The findings were similar in each of the studies included in the analysis. Researchers accounted for other genetic factors that are tied to chronic kidney disease among African Americans and found that they did not explain the link.

The new study concludes, however, that together, other genetic factors, socioeconomic factors and sickle cell trait may explain the overall increased risk of kidney disease seen among African Americans, Reiner said.

“Exactly how much of the increased burden of kidney disease sickle cell trait explains or is explained by other factors is still an open question that will require additional study,” he said.
Testing for sickle cell disease is common in the U.S., Naik said. “As a byproduct, people with sickle cell trait are identified,” she added.

Without additional research, it’s difficult to say whether people with sickle cell trait should be screened for kidney disease, Naik said.

“They may want closer monitoring of kidney function if someone has been identified to be a sickle cell trait carrier,” Reiner said. He added that there is no specific treatment or intervention to prevent kidney failure or further decline in kidney function.

He said these findings may lead to greater awareness of the potential health impact of sickle cell trait.
“It’s a reasonably common condition in the Africa American community,” Reiner said. “It may be important in terms of greater community awareness and education, which may be important for general health.”

Additionally, he said, the findings may spur future research into how sickle cell trait might affect other systems in the body.
SOURCE: bit.ly/1EzO9tS JAMA, online November 13, 2014.

Anemia: One-minute point-of-care test shows promise in new study

A simple point-of-care testing device for anemia could provide more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

A simple point-of-care testing device for anemia could provide more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

 Erika Tyburski is shown with a prototype device for point-of-care testing of anemia. The device could enable more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

 The disposable self-testing device analyzes a single droplet of blood using a chemical reagent that produces visible color changes corresponding to different levels of anemia. The basic test produces results in about 60 seconds and requires no electrical power. A companion smartphone application can automatically correlate the visual results to specific blood hemoglobin levels.

By allowing rapid diagnosis and more convenient monitoring of patients with chronic anemia, the device could help patients receive treatment before the disease becomes severe, potentially heading off emergency room visits and hospitalizations. Anemia, which affects two billion people worldwide, is now diagnosed and monitored using blood tests done with costly test equipment maintained in hospitals, clinics or commercial laboratories.

Because of its simplicity and ability to deliver results without electricity, the device could also be used in resource-poor nations.
A paper describing the device and comparing its sensitivity to gold-standard anemia testing was published August 30 in The Journal of Clinical Investigation. Development of the test has been supported by the FDA-funded Atlantic Pediatric Device Consortium, the Georgia Research Alliance, Children's Healthcare of Atlanta, the Georgia Center of Innovation for Manufacturing and the Global Center for Medical Innovation.

"Our goal is to get this device into patients' hands so they can diagnose and monitor anemia themselves," said Dr. Wilbur Lam, senior author of the paper and a physician in the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta and the Department of Pediatrics at the Emory University School of Medicine. "Patients could use this device in a way that's very similar to how diabetics use glucose-monitoring devices, but this will be even simpler because this is a visual-based test that doesn't require an additional electrical device to analyze the results."
The test device was developed in a collaboration of Emory University, Children's Healthcare of Atlanta and the Georgia Institute of Technology -- all based in Atlanta. It grew out of a 2011 undergraduate senior design project in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. In 2013, it was among the winners of Georgia Tech's InVenture Prize, an innovation competition for undergraduate students, and won first place in the Ideas to SERVE Competition in Georgia Tech's Scheller College of Business.

Using a two-piece prototype device, the test works this way: A patient sticks a finger with a lance similar to those used by diabetics to produce a droplet of blood. The device's cap, a small vial, is then touched to the droplet, drawing in a precise amount of blood using capillary action. The cap containing the blood sample is then placed onto the body of the clear plastic test kit, which contains the chemical reagent. After the cap is closed, the device is briefly shaken to mix the blood and reagent.

"When the capillary is filled, we have a very precise volume of blood, about five microliters, which is less than a droplet -- much less than what is required by other anemia tests," explained Erika Tyburski, the paper's first author and leader of the undergraduate team that developed the device.
Blood hemoglobin then serves as a catalyst for a reduction-oxidation reaction that takes place in the device. After about 45 seconds, the reaction is complete and the patient sees a color ranging from green-blue to red, indicating the degree of anemia.

A label on the device helps with interpretation of the color, or the device could be photographed with a smartphone running an application written by Georgia Tech undergraduate student Alex Weiss and graduate student William Stoy. The app automatically correlates the color to a specific hemoglobin level, and could one day be used to report the data to a physician.

To evaluate sensitivity and specificity of the device, Tyburski studied blood taken from 238 patients, some of them children at Children's Healthcare of Atlanta and the others adults at Emory University's Winship Cancer Institute. Each blood sample was tested four times using the device, and the results were compared to reports provided by conventional hematology analyzers.

The work showed that the results of the one-minute test were consistent with those of the conventional analysis. The smartphone app produced the best results for measuring severe anemia.
"The test doesn't require a skilled technician or a draw of venous blood and you see the results immediately," said Lam, who is also an assistant professor in the Coulter Department of Biomedical Engineering. "We think this is an empowering system, both for the general public and for our patients."

Tyburski and Lam have teamed up with two other partners and worked with Emory's Office of Technology Transfer to launch a startup company, Sanguina, to commercialize the test, which will be known as AnemoCheck™. The test ultimately will require approval from the FDA. The team also plans to study how the test may be applied to specific diseases, such as sickle cell anemia -- which is common in Georgia.

The device could be on pharmacy shelves sometime in 2016, where it might help people like Tyburski, who has suffered mild anemia most of her life. "If I'd had this when I was kid, I could have avoided some trips to the emergency room when I passed out in gym class," she said.
About a third of the population is at risk for anemia, which can cause neurocognitive deficits in children, organ failure and less serious effects such as chronic fatigue. Women, children, the elderly and those with chronic conditions such as kidney disease are more likely to suffer from anemia.

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The above story is based on materials provided by Georgia Institute of Technology. The original article was written by John Toon. Note: Materials may be edited for content and length.

Developing first comprehensive guidelines for management of sickle cell disease

The National Heart, Lung, and Blood Institute has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life. Sickle cell anemia is the most common form of sickle cell disease, a serious disorder in which the body makes sickle-shaped red blood cells.

 

Shirley Miller with Dr. George Buchanan, Professor of Pediatrics and Internal Medicine, holder of the Children's Cancer Fund Distinguished Chair in Pediatric Oncology & Hematology.

 The National Heart, Lung, and Blood Institute (NHLBI) has released the first comprehensive, evidence-based guidelines for management of sickle cell disease from birth to end of life, based on recommendations developed by a nationwide team of experts co-chaired by a UT Southwestern Medical Center hematologist.

 Appearing today in JAMA, the guidelines are intended for general use by pediatricians, physicians treating adults, hematologists, emergency room personnel, hospitalists, and other health care providers. The new management guidelines consist of more than 500 specific directions for physicians who are caring for patients with sickle cell disease.

"The aim is to improve the care of all people with sickle cell disease, young and old, and to raise awareness among the entire medical profession regarding the need for better care and more research, so that someday everyone with sickle cell disease can receive the best possible care and lead a normal and productive life," said Dr. George Buchanan, Professor of Pediatrics and Internal Medicine.

Although currently most patients are diagnosed at birth and survive until adulthood, many sickle cell disease patients die in their 30s and 40s of acute complications or chronic organ damage. Dr. Buchanan and the team of expert panelists want to alter that statistic through improved and comprehensive treatment.

One survivor who beat those numbers is 58-year-old Shirley Miller, who worked at UT Southwestern with Dr. Buchanan from 2002 to 2010 as a program manager, patient advocate, and outreach coordinator.

"I lived my life in fear because I thought age 30 was it. I wasted a lot of time wondering how the end would happen. My parents never told me my life expectancy; I went to the library and looked it up," said Ms. Miller, who is now helping to launch a comprehensive sickle cell adult program in Charlotte, North Carolina.

Diagnosed at age three, and the only one of five siblings with the disease, she grew up without physical education classes and did not participate in sports. She made friends slowly and was embarrassed when others went through puberty before her. She credits her parents with helping her believe she could make it, and she credits the care she later received as an adult at UT Southwestern.

"Comprehensive care is the key to successful management of sickle cell disease, known as sickle cell disease. Currently, there are not enough physicians who specialize in the care of adults with sickle cell disease, which means that many are seen by primary care physicians or other specialists," said Ms. Miller. "These guidelines will provide physicians with a tool for basic understanding of the disease etiology and possible complications to look for when managing a patient. I attribute my survival to the comprehensive care that I received from this teaching and research university, which is on the cutting edge of so many developments. The knowledge and expertise available here have made all the difference."

The expert panel for the new guidelines is a 12-member team, all known for their experience in diagnosing and treating people with sickle cell disease. Panel members included two pediatric hematologists, four adult hematologists, an obstetrician, a psychiatrist, an emergency department nurse, two blood transfusion specialists, and one family physician. These experts were supported by a large staff of NHLBI leaders and other personnel, including experts in finding and analyzing the available scientific evidence that could help improve the lives of people with sickle cell disease.
Sickle cell disease is the world's most common serious condition due to a single gene mutation. An estimated 70,000 to 100,000 people in the U.S. have sickle cell disease. Of these, about 1,000 receive care annually at UT Southwestern. Dr. Buchanan has led the institutional pediatric and research sickle cell disease programs for 37 years.

More than 2 million Americans carry the sickle cell trait.
"African-Americans are far more likely than Caucasians to have the sickle cell trait, which is not a disease but a carrier state. One has to receive a copy of the abnormal gene from both parents to have the disease," said Dr. Buchanan, who holds the Children's Cancer Fund Distinguished Chair in Pediatric Oncology & Hematology.
"Every state now has mandatory newborn screening for the disease," said Dr. Buchanan, Director of the Barrett Family Center for Pediatric Oncology at UT Southwestern.
Dr. Buchanan was instrumental in ensuring that Texas became the third state to adopt newborn screening in 1983. Approximately 150 infants with sickle cell disease are diagnosed in Texas each year. Nearly one third of them receive their care at Children's Medical Center in Dallas.

When sickle cell disease progresses, it can delay puberty and cause acute and chronic complications, including debilitating pain, life-threatening infections, damage to vital organs, and stroke. Stem cell transplants offer a potential cure; however, the high cost, lack of suitable donors (ideally the donor is a sibling), and the risk of complications make these transplants relatively infrequent. The newly published comprehensive guidelines recommend better pain control; prevention and treatment of acute and chronic complications; general health maintenance; judicious use of blood transfusions; and teaching patients to manage their disease through behavioral changes.

The committee also strongly advocates for prescribing hydroxyurea, an oral medication taken once daily that has become the standard of care. Hydroxyurea reduces the impact of the disease by improving the anemia, and reducing the risk of pain events and acute chest syndrome. It can also decrease the need for transfusions and hospital admissions.
"These national guidelines are directed not just to hematologists but to all medical practitioners who might encounter sickle cell disease patients, to inform them about hydroxyurea and how to best offer general medical care to them," Dr. Buchanan said. "We have a lot of work to do to educate physicians."

September is National Sickle Cell Awareness Month, and the guidelines will be discussed and disseminated at professional conferences, as well as being available on the NHLBI website and in JAMA, the journal of the American Medical Association.
According to NHLBI, sickle cell anemia is the most common form of sickle cell disease, a serious disorder in which the body makes sickle-shaped red blood cells. "Sickle-shaped" means that the red blood cells are shaped like a crescent. Normal red blood cells are disc-shaped and look like doughnuts without holes in the center, moving easily through blood vessels. Red blood cells contain an iron-rich protein called hemoglobin, which carries oxygen from the lungs to the rest of the body. Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. They tend to block blood flow in the blood vessels of the limbs and organs, causing pain, organ damage, and increased risk for infection. In the U.S., the disease occurs in about one out of every 500 African-American births and in more than one out of every 36,000 Hispanic-American births.

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.

New Guidelines for Sickle Cell Disease

An expert panel has issued new guidelines for managing sickle cell disease, stressing the use of the drug hydroxyurea and transfusions for many with the genetic disorder.

By Kathleen Doheny
HealthDay Reporter

 “This is a major step forward to try to put together all of the evidence and try to highlight what is most important,” said Dr. Barbara Yawn, professor of family and community health at Olmsted Medical Center in Rochester, Minn. Yawn was also co-chair of the panel convened by the U.S. National Heart, Lung, and Blood Institute to develop the new guidelines.

As many as 100,000 Americans have sickle cell disease, according to background information with the guidelines. In sickle cell disease, the body makes sickle-shaped or crescent-shaped red blood cells. Normal red blood cells are disc-shaped, like a doughnut without holes, allowing the cells to move easily through blood vessels.

Sickle cells are stiff and sticky and tend to block blood flow, leading to organ damage, pain and increased risk of infection and strokes, among other problems. Black people are more commonly affected than other people.

The expert panel reviewed more than 12,000 scientific articles and sifted through the evidence to issue the new blueprint for care. The new guidelines are published Sept. 10 in the Journal of the American Medical Association.

One of the new recommendations is to give children oral penicillin daily until age 5. This is a preventive measure, aiming to reduce the risk of pneumonia and other infections.

“That has been the standard for a while now,” Yawn said. “Now we are saying ‘This is an absolute necessity.'”

In addition, everyone with sickle cell disease should be vaccinated against pneumonia, according to the guidelines. “The children need pneumococcal vaccine as early as they can possibly get it, around six weeks of age,” Yawn said.

Children from ages 2 to 16 should have an annual exam known as a transcranial Doppler, which measures blood flow in the brain, the guidelines explain. If it’s abnormal, long-term transfusion therapy to prevent stroke is recommended. 

When acute complications occur, opioids (also known as narcotics) are suggested to treat the pain linked with blood flow blockage. A method of encouraging deep breathing — incentive spirometry — is also advised for those hospitalized with a blood flow crisis.

If adults have three or more severe blood flow crises in a year, treatment with the drug hydroxyurea is recommended. The drug works in sickle cell by helping to prevent the formation of sickle-shaped red blood cells. Hydroxyurea can be used in infants, children and teens, whether or not they currently have symptoms, according to the guidelines.

One difficulty in developing the guidelines, Yawn said, is that there is “not enough research to answer all the questions.”

People with sickle cell disease are living longer, she said. A generation ago, many with sickle cell disease only survived until their 20s or 30s. “We know there are more living into their 40s, 50s and 60s,” she said.

Dr. Michael DeBaun, professor of pediatrics and medicine at the Vanderbilt University School of Medicine, said, “These are really strong recommendations.”

DeBaun wrote an editorial to accompany the guideline report. “This should now be a road map of how your child should be cared for,” he said.

The information also applies for adults with sickle cell disease, said DeBaun, who is also director of the Vanderbilt–Meharry Sickle Cell Disease Center of Excellence.

He advises patients and parents to use the new guidelines to have a dialogue with the doctors providing care. “We expect these recommendations to change over time as more evidence becomes available,” DeBaun said.

In his own recent study, published in August in the New England Journal of Medicine, DeBaun and his colleagues reported that monthly blood transfusions appear to reduce the risk of strokes in children with sickle cell anemia, the most common form of sickle cell disease.

More information

To learn more about sickle cell disease, visit the U.S. Centers for Disease Control and Prevention.

6 causes of anemia during pregnancy

Gestational anemia or anemia during pregnancy is one condition that can affect a woman at any time during her pregnancy.

While planning your pregnancy, you need to make sure that your health is at its optimum. This includes your blood count, fitness and management of various lifestyle related ailments. All this will ensure a smooth pregnancy and good health of both the mother and the child growing inside the womb. However, those nine months of pregnancy aren’t predictable, and health complications can arise at any time. Gestational anemia or anemia during pregnancy is one such condition that can affect a woman at any time during her pregnancy.

Here are a few causes that could lead to the same:

Deficiency of iron
Iron deficiency during pregnancy is a common cause of gestational anemia. This happens when the body is unable to produce enough iron to produce adequate hemoglobin. Hemoglobin is a protein that is present in the red blood cells. During pregnancy the blood supply in the body almost doubles up to meet the requirements of the mother and that of the growing baby. The hemoglobin in the blood is responsible for nutrient and oxygen exchange between a mother and the baby. It is also responsible for oxygen circulation in the mother to restore health during pregnancy. During pregnancy the iron requirement for a woman increases and one might need around 30 to 38 mg of iron either through dietary sources or by having iron supplements regularly. Here are reasons why you need to be regular with iron medications during pregnancy.

Deficiency of folic acid
Everyone knows the importance of folic acid during pregnancy. It is a type of B vitamin that helps produce new cells including healthy red blood cells. Therefore, during pregnancy a woman needs more folate. It is recommended that women take at least 400 mg of folate during pregnancy to avoid birth defects in babies. Folate or folic acid deficiency can lead to less production of red blood cells that could hamper oxygen and nutrient supply to the fetus and result in severe birth defects like neural tube abnormalities or spina bifida and lead to low birth weight of the baby. This kind of anemia can be easily corrected by taking folic acid pills or through proper diet management. Here are reasons why you need folic acid during pregnancy. 

Vitamin B 12 deficiency
Vitamin B 12 is an important vitamin for pregnant women that plays a major role in producing healthy red blood cells. Lack of Vitamin B 12 in the diet could give rise to the gestational anemia that could contribute to birth defects, such as neural tube abnormalities, and lead to preterm labor. Women who don’t eat meat, poultry, dairy products, and eggs have a greater risk of developing vitamin B12 deficiency. Here are other seven diet essentials you should take during pregnancy.  

Having twins
Mothers who are carrying twins or triplets need special care to meet the demands of their growing babies. Improper diet and ignorance of medications can lead to various health complications and gestational anemia could be one of them. Women with twins or triplets are always at risk of developing complications during pregnancy.

Improper diet
Gestational anemia as mentioned above could be easily avoided with proper diet management and being regular with medications. Irregularities in diet especially failing to get enough iron, folate and vitamin B 12 could lead to the gestational anemia in women. Know more about the causes, symptoms and treatment of anemia during pregnancy.

Being anemic before conception
If you were anemic or had lower hemoglobin count prior to conception you could be at a risk of developing gestational anemia. Even with adequate hemoglobin count during the start of pregnancy it is possible to suffer from gestational anemia. This happens due to altered body mechanism and the various hormonal changes. It is imperative to check with your doctor about medications and management of anemia during pregnancy, especially if you had suffered from the same before.

Educational Webcast on Beta-thalassemia

An online seminar lead by Prominent hematology expert, Ellis Neufeld, M.D., Ph.D.

Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel protein therapeutics for cancer and rare diseases,hosted an educational webcast seminar on beta-thalassemia with Ellis Neufeld, M.D., Ph.D on 17.10.2014. Acceleron and its collaboration partner, Celgene, are conducting phase 2 clinical trials of sotatercept and luspatercept in patients with beta-thalassemia, MDS, and end-stage renal disease with mineral and bone disorder.

Dr. Neufeld currently serves as Associate Chief of the Hematology/Oncology Division and Co-Chief of the Clinical Research Center at Boston Children’s Hospital, Director of the Boston Hemophilia Center, and is the Egan Family Foundation Professor of Pediatrics at Harvard Medical School.

Dr. Neufeld provided an overview of beta-thalassemia including the numerous clinical complications of the disease, current treatment and a review of the recently presented data from the sotatercept and luspatercept phase 2 studies in beta-thalassemia.

 To access the recorded webcast, please visit the "Events & Presentations" page in the Investors & Media section on the Company's website (http://investor.acceleronpharma.com/events.cfm).

First Patient with Sickle Cell Disease Transplanted with LentiGlobin Gene Therapy

bluebird bio Announces First Patient with Sickle Cell Disease Transplanted with LentiGlobin Gene Therapy

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 14, 2014-- bluebird bio, Inc. (Nasdaq: BLUE) a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases, today announced that the first subject with severe sickle cell disease has undergone infusion with bluebird bio’s LentiGlobin BB305 drug product in an autologous hematopoietic stem cell transplantation. This patient is enrolled in the HGB-205 Study being conducted in Paris, France. bluebird has also opened a separate US-based trial (HGB-206) in the United States for the treatment of up to 8 severe sickle cell disease patients with the company’s LentiGlobin BB305 drug product.

“We are treating a sickle cell patient for the first time with gene therapy,” stated Marina Cavazzana, MD, PhD, Professor of Medicine at Paris Descartes University and Research Director at the Centre for Clinical Research in Biotherapy, Necker Hospital, and at the Institute of Genetic Diseases, Imagine, Paris France. “Sickle cell disease is a devastating disease that affects hundreds of thousands of people in the US and Europe and millions around the world. The therapeutic options for patients with sickle cell disease are currently limited, so the opportunity to bring a one-time, potentially curative treatment to these patients by modification of autologous hematopoietic stem cells would represent a great advance for patients with sickle cell disease and for the field.”
“Sickle cell disease shortens life expectancy by decades even in developed countries, so it is exciting to contemplate that LentiGlobin may offer the curative potential of allogeneic stem cell transplantation by using a patient’s own cells,” stated David Davidson, MD, bluebird bio’s Chief Medical Officer. “In June 2014, we reported preliminary results from the HGB-205 Study demonstrating that treatment with LentiGlobin drug product led to high-level production of beta-T87Q-globin and rapid transfusion independence in two beta-thalassemia major patients. Given the anti-sickling property of the amino acid substitution engineered into beta-T87Q-globin, we are optimistic about the potential for LentiGlobin to mitigate the signs and symptoms of sickle cell disease. We anticipate providing initial clinical data on LentiGlobin in sickle cell disease patients in 2015.”

About the HGB-205 Study
The phase 1/2 study is designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with beta-thalassemia major and severe sickle cell disease. The study is designed to enroll up to seven subjects. Subjects will be followed to evaluate safety and transfusion requirements post-transplant. In sickle cell disease patients, efficacy will also be measured based on the frequency of vaso-occlusive crises or acute chest syndrome events.
For more information on the HGB-205 Study, please visit www.clinicaltrials.gov using identifier NCT02151526.

About the HGB-206 Study
The phase 1 study is designed to evaluate the safety and efficacy of LentiGlobin BB305 drug product in the treatment of subjects with severe sickle cell disease. The study is designed to enroll up to eight subjects. Subjects will be followed to evaluate safety and efficacy will be measured based on changes in red cell function tests, hemolysis markers and frequency of clinical events secondary to sickle cell disease (e.g. vaso-occlusive crises or acute chest syndrome events).
For more information on the HGB-206 Study, please visit www.clinicaltrials.gov using identifier NCT02140554.

About sickle cell disease
Sickle cell disease (SCD) is a hereditary blood disorder resulting from a mutation in the beta globin gene that causes polymerization of hemoglobin proteins and abnormal red blood cell function. The symptoms of SCD include anemia, vaso-occlusive crises and strokes. The global incidence of SCD is estimated to be 250,000 to 300,000 births annually, and the global prevalence of the disease is estimated to be about 20 to 25 million.

About bluebird bio, Inc.
bluebird bio is a clinical-stage company committed to developing potentially transformative gene therapies for severe genetic and orphan diseases. bluebird bio has two clinical-stage programs in development. The most advanced product candidate, Lenti-D, is in a recently-initiated phase 2/3 study, the Starbeam Study, for the treatment of childhood cerebral adrenoleukodystrophy (CCALD), a rare, hereditary neurological disorder affecting young boys. The next most advanced product candidate, LentiGlobin, is currently in two phase 1/2 studies, one in the US (the Northstar Study) and one in France (HGB-205), for the treatment of beta-thalassemia major. The phase 1/2 HGB-205 study also allows enrollment of patient(s) with sickle cell disease, and bluebird bio is conducting a separate U.S. sickle cell disease trial (HGB-206).

bluebird bio also has an early-stage chimeric antigen receptor-modified T cell (CAR-T) program for oncology in collaboration with Celgene Corporation.
bluebird bio has operations in Cambridge, Massachusetts, Seattle, Washington, and Paris, France. For more information, please visit www.bluebirdbio.com .

Iron supplements improve anemia, quality of life for women with heavy periods

A study by researchers from Finland found that diagnosis and treatment of anemia is important to improve quality of life among women with heavy periods. Findings published in Acta Obstetricia et Gynecologica Scandinavica, a journal of the Nordic Federation of Societies of Obstetrics and Gynecology, suggest clinicians screen for anemia and recommend iron supplementation to women with heavy menstrual bleeding (menorrhagia).

 One of the common causes of iron deficiency and anemia is heavy bleeding during menstration. Over time monthly mentrual iron loss without adequate dietary iron supplementation can reduce iron stores in the body. Previous studies have found that iron deficiency anemia may impact women's physical performance, cognitive function, mood, and overall quality of life.

Led by Dr. Pirkko Peuranpää from the Department of Obstetrics and Gynecology at Hyvinkää Hospital in Finland, this prospective study assessed the impact of anemia and iron deficiency on health-related quality of life in 236 women treated for heavy menstrual bleeding. The participants were randomized to either hysterectomy or treatment with a levonorgestrel-releasing intrauterine system such as Mirena®.

The team separated the participants into two groups. Women with hemoglobin -- the oxygen-carrying proteins in the red blood cells -- levels less than 120 g/L were defined as anemic and those with levels greater than 120 g/L were in the non-anemic group. Researchers also measured levels of ferritin in the blood to assess iron stores in both groups.

Results show that at the start of the study, 27% of women were anemic and 60% were severely iron deficient with ferritin levels less than 15 µg/L. In those women who were anemic only 8% took an iron supplement. One year following treatment hemoglobin levels had increased in both groups, but women who were initially anemic still had significantly lower levels compared to those in the non-anemic group.

One year after treatment women in the anemic group had a significant increase in energy, along with physical and social function, and a decrease in anxiety and depression compared to the non-anemic group. It took five years for the iron stores to reach normal levels. "The quality of life of women with heavy periods is plural, but the treatment of anemia is important to get good results," concludes Dr. Peuranpää. "Our findings suggest that clinicians should screen for anemia in women with heavy menstrual bleeding and recommend early iron supplementation as part of the treatment process."

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The above story is based on materials provided by Wiley. Note: Materials may be edited for content and length.

Acetate supplements speed up red blood cell production, anemia research shows

UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

 Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

"Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy," said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.

Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.

"Our study shows that acetate functions as a biochemical 'flare,' linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway," Dr. Garcia said.

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.

Gene mutation discovered in blood disorder aplastic anemia

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which three generations had blood disorders, the researchers discovered a defect in a gene that regulates telomeres, chromosomal structures with crucial roles in normal cell function.

 "Identifying this causal defect may help suggest future molecular-based treatments that bypass the gene defect and restore blood cell production," said study co-leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia (CHOP).

Hakonarson and CHOP colleagues collaborated with Australian scientists on the study, published online Sept. 9 in the journal Blood.

"We're thrilled by this discovery which has advanced our understanding of certain gene mutations and the causal relationship to specific diseases," said study co-leader Tracy Bryan, Ph.D., Unit Head of the Cell Biology Unit at the Children's Medical Research Institute in Westmead, New South Wales, Australia.
The research team studied an Australian family with aplastic anemia and other blood disorders, including leukemia. Hakonarson and lead analyst Yiran Guo, Ph.D., along with genomics experts from BGI-Shenzhen, performed whole-exome sequencing on DNA from the families and identified an inherited mutation on the ACD gene, which codes for the telomere-binding protein TPP1.

Telomeres, complex structures made of DNA and protein, are located on the end of chromosomes, where they protect the chromosomes' stability. They are sometimes compared to plastic tips at the end of shoelaces that prevent the laces from fraying.

Telomeres shorten after each cell division, and gradually lose their protective function. Aging cells, with their shortened telomeres, become progressively more vulnerable to DNA damage and cell death. Separately from the aging process, certain inherited and acquired disorders may shorten telomeres and injure rapidly dividing blood-forming cells produced in bone marrow. This leads to bone marrow failure, one example of which is aplastic anemia.

Bryan's team investigated the function of the ACD gene. They determined that the mutation shortened telomeres and interrupted the ability of telomeres to attract the enzyme telomerase, which counteracts telomere shortening and thus protects cells.

In the current study, the researchers showed that the mutation in ACD alters the telomere-binding protein TPP1, disrupting the interactions between telomere and telomerase. Without access to telomerase to help maintain telomeres, blood cells lose their structural integrity and die, resulting in bone marrow failure and aplastic anemia.
Nine other genes were previously found to play a role in bone marrow failure disorders. The current study adds ACD to the list, the first time the gene has been shown to have a disease-causing role.
"This improved understanding of the underlying molecular mechanisms may suggest new approaches to treating disorders such as aplastic anemia," said Hakonarson. "For instance, investigators may identify other avenues for recruiting telomerase to telomeres to restore its protective function."

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Adults stop anti-rejection drugs after partial stem-cell transplant reverses sickle cell disease

NIH trial success suggests a new treatment option for older, sicker patients

Half of patients in a trial have safely stopped immunosuppressant medication following a modified blood stem-cell transplant for severe sickle cell disease, according to a study in the July 1 issue of the Journal of the American Medical Association. The trial was conducted at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, by researchers from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Heart, Lung, and Blood Institute.
The transplant done in the study reversed sickle cell disease in nearly all the patients. Despite having both donor stem-cells and their own cells in their blood, the patients stopped the immunosuppressant medication without experiencing rejection or graft-versus-host disease, in which donor cells attack the recipient. Both are common, serious side effects of transplants.
"Typically, stem-cell recipients must take immunosuppressants all their lives,” said Matthew Hsieh, M.D., lead author on the paper and staff clinician at NIH. “That the patients who discontinued this medication were able to do so safely points to the stability of the partial transplant regimen.”
In sickle cell disease (SCD) sickle-shaped cells block blood flow. It can cause severe pain, organ damage and stroke. The only cure is a blood stem-cell, or bone marrow, transplant. The partial transplant performed in the study is much less toxic than the standard “full” transplant, which uses high doses of chemotherapy to kill all of the patient’s marrow before replacing it with donor marrow. Several patients in the study had less than half of their marrow replaced.
Immunosuppressant medication reduces immune system strength and can cause serious side effects such as infection and joint swelling. In this study, 15 of 30 adults stopped taking the medication under careful supervision one year after transplant and still had not experienced rejection or graft-versus-host disease at a median follow up of 3.4 years.
“Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease,” said John F. Tisdale, M.D., the paper’s senior author and a senior investigator at NIH. “Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem-cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition.”
“One of the most debilitating effects of sickle cell disease is the often relentless pain,” added Dr. Hsieh. “Following the transplant, we saw a significant decrease in hospitalizations and narcotics to control that pain.”
The partial transplant used donor stem-cells from healthy siblings. It effectively reversed SCD in 26 of 30 patients and allowed them to achieve stable mixed donor chimerism, a condition in which a person has two genetically distinct cell types in the blood. The study includes patients from an NIH study reported in 2009, in which partial stem-cell transplants reversed SCD in 9 of 10 people.
In the United States, more than 90,000 people have SCD, a genetic disorder found mainly in people of African ancestry. Worldwide, millions of people have the disease.
“The devastating complications associated with sickle cell disease can deeply affect quality of life, ability to work and long-term well-being,” said NIDDK Director Griffin P. Rodgers, M.D., a co-author on the paper. “This study represents an important advance in our efforts to make a potentially transformative treatment available to a wider range of people, especially those who could not tolerate a standard stem-cell transplant or long-term use of immunosuppressants.”
People with sickle cell disease interested in joining NIH blood stem-cell transplant studies may call 1-800-411-1222 or visit http://www.clinicaltrials.gov for more information.
The Sidney Kimmel Cancer Center at Johns Hopkins Medical Institute provided input into trial design.

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Part of the NIH, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. The institute also administers national health education campaigns on women and heart disease, healthy weight for children, and other topics. NHLBI news releases and other materials are available online at: http://www.nhlbi.nih.gov.
The NIDDK, part of the NIH, conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases. For more information, visit http://www.niddk.nih.gov.
The NIH Clinical Center (CC) provided clinical laboratory and transfusion medicine support and care for stem-cell donors and recipients. The CC is the clinical research hospital for the NIH. Through clinical research, physician-investigators translate laboratory discoveries into better treatments, therapies and interventions to improve the nation's health. For more information, visit http://clinicalcenter.nih.gov.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.