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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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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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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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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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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Story Source:
The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.

Anemia in Postmenopausal Women Linked With Poor Nutrition

Emma Hitt, PhD
Anemia is linked to poor nutrition in postmenopausal women, according to a recent observational study of the Women's Health Initiative (WHI).
Cynthia A. Thomson, PhD, RD, with the University of Arizona, in Tucson, and colleagues reported their findings in the April issue of the Journal of the American Dietetic Association.
According to the researchers, nutritional anemia includes those types associated with prolonged inadequate intake of folate, vitamin B₁₂, iron, protein, and vitamin C.
Dr. Thomson and colleagues hypothesized that a greater number of dietary inadequacies of these nutrients would be associated with a greater risk for incident and persistent anemia.
To evaluate their hypothesis, the researchers used data from the WHI observational cohort study (WHI-OS), which contained a longitudinal sample of postmenopausal women. A total of 93,676 postmenopausal women between the ages of 50 and 79 years were recruited at 40 clinical sites across the United States. Women were enrolled from 1993 until 1998, and data collection was completed in 2000.
Diet was assessed by a food frequency questionnaire for iron, vitamin B₁₂, folate, red meat, and cold breakfast cereal. Dietary intake for women older than 50 years was used as a reference to measure inadequacies. Anemia was defined as a blood hemoglobin concentration of less than 120 g/L in women. Persistent anemia was defined as anemia present at each measurement.
Anemia was identified in 3979 (5.5%) of the participants. Inadequate intake of anemia-associated nutrients was less frequent in non-Hispanic whites (7.4%) vs other racial or ethnic groups (14.6% - 16.3%).
Smoking, age, and body mass index were associated with anemia. Women with anemia reported a lower dietary intake of red meat, folate, vitamin B₁₂, vitamin C, and iron. In addition, deficiencies in dietary intake of 1 nutrient were associated with a 21% greater risk for persistent anemia (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05 - 1.41), whereas 3 deficiencies in dietary intake resulted in a 44% increase in the risk for persistent anemia (OR, 1.44; 95% CI, 1.20 - 1.73).
Deficiencies in total intake of 1 nutrient were associated with a 34% increased risk for persistent anemia (OR, 1.34; 95% CI, 1.14 - 1.56). Regarding deficiencies in total intake of 3 nutrients, the risk increased to 56% (OR, 1.56; 95% CI, 1.25 - 1.95).
Editorial: Nutrient Measurements Costly
According to editorialists Lisa Tussing-Humphreys, PhD, RD, with the US Department of Agriculture–Agriculture Research Service, in Los Angeles, California, and Carol Braunschweig, PhD, RD, with the University of Illinois, in Chicago, this study provides "one of the largest prospective assessments of diet and anemia in US postmenopausal women."
They add that the findings "lend credibility to the use of an FFQ [food frequency questionnaire] for large epidemiological studies investigating the relationship between diet and anemia risk."
However, according to the editorialists, the mean nutrient intakes reported indicate that "a portion of the anemia observed in the WHI-OS cohort was not diet-related," they write. "For example, it is well known that decreases in hemoglobin occur from nutrient deficiencies only when stores are nearly exhausted."
In addition, although the accurate assessment of anemia allows clinicians to classify the type of anemia and recommend suitable treatment options, inclusion of these measurements in large epidemiologic studies is "cost-prohibitive and unlikely."

Researchers report gene therapy strategy that improves Beta Thalassemia in mice model

Researchers at Nationwide Children's Hospital report a gene therapy strategy that improves the condition of a mouse model of an inherited blood disorder, Beta Thalassemia. The gene correction involves using unfertilized eggs from afflicted mice to produce a batch of embryonic stem cell lines. Some of these stem cell lines do not inherit the disease gene and can thus be used for transplantation-based treatments of the same mice. Findings could hold promise for a new treatment strategy for autosomal dominant diseases like certain forms of Beta Thalassemia, tuberous sclerosis or Huntington's disease.
Embryonic stem cells have the potential to produce unlimited quantities of any cell type and are therefore being explored as a new therapeutic option for many diseases. Unfertilized eggs can be cultured to form embryonic stem cells, so-called parthenogenetic embryonic stem cells.
"Parthenogenetic embryonic stem cells can differentiate into multiple tissue types as do stem cells from fertilized embryos," said K. John McLaughlin, PhD, principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children's Hospital. Previously, the group demonstrated that blood cells derived from parthenogenetic cells could provide healthy, long-term blood replacement in mice.
"Advantages of parthenogenetic stem cells are not only that fertilization is not needed, but also that the recipient's immune system may potentially not view them as foreign, minimizing rejection problems. Furthermore, since parthenogenetic embryonic stem cells are derived from reproductive cells which contain only a single set of the genetic information instead of the double set present in body cells, they may not contain certain abnormal genes present in the other copy," said Dr. McLaughlin also one of the study authors.

A single copy of an abnormal gene inherited from one parent can cause so-called autosomal dominant diseases such as tuberous sclerosis or Huntington's disease. The affected person has one defective and one normal copy of the gene, but the abnormal gene overrides the normal gene, causing disease. In normal sexual reproduction, each parent provides one gene copy to offspring via their reproductive cells. Therefore, the reproductive cells of a patient with an autosomal dominant disease could either pass along a defective copy or a normal copy.
"As the donor patient has one defective gene copy and one normal, and only one copy is used for normal reproduction, we can select egg-cell-derived embryonic stem cells with two normal copies," said Dr. McLaughlin. "These single-parent/patient-derived embryonic stem cells can theoretically be used for correction of a diverse number of diseases that occur when one copy of the gene is abnormal," said Dr. McLaughlin.
To test this theory, Dr. McLaughlin and colleagues from the University of Pennsylvania, University of North Carolina and University of Minnesota, examined whether parthenogenetic embryonic stem cells could be used for tissue repair in a mouse model of thalassemia intermedia. Thalassemia intermedia is an inherited blood disorder in which the body lacks sufficient normal hemoglobin, leading to excessive destruction of red blood cells and anemia. They used a mouse model in which one defective gene copy causes anemia.
Using approaches developed from a previous study done by this group, Nationwide Children's Research Fellow Sigrid Eckardt, PhD, derived embryonic stem cells from the unfertilized eggs of female mice with the disease, and identified those stem cell lines that contained only the "healthy" hemoglobin genes. These "genetically clean" embryonic stem cell lines were converted into cells that were transplanted into afflicted mice that were carriers of the disease causing gene. Blood samples drawn five weeks after transplantation revealed that the delivered cells were present in the recipients' blood. Their red blood cells were also corrected to a size similar to normal mice and red blood cell count, hematocrit and hemoglobin levels became normal.
"Overall, we observed long-term improvement of thalassemia in this model," said Dr. Eckardt. "Our findings suggest that using reproductive cells to generate embryonic stem cells that are 'disease-free' may be a solution for genetic diseases involving large, complex or poorly identified deletions in the genome or that are not treatable by current gene therapy approaches." Dr. McLaughlin says that this approach also contrasts with typical gene therapy approaches in that it requires no engineering of the genome, which is currently difficult to achieve in human embryonic and embryonic-like (IPS) stem cells.

Source: Nationwide Children's Hospital

Anemia Drugs Could Pose Threat to Some Kidney Patients

Study finds 'poor responders' to meds like Aranesp at higher risk for heart trouble, death

By Serena GordonHealthDay Reporter

When people with chronic kidney disease and type 2 diabetes take certain anemia drugs, the level of hemoglobin cells in their blood should go up.
But a new study finds that if those levels don't increase by much, these "poor responders" experience a significantly increased risk of heart problems and death.
Reporting in the Sept. 16 issue of the New England Journal of Medicine, a team of international researchers says that those who had the worst response to erythropoiesis-stimulating agents (ESAs) -- drugs that include Aranesp, Epogen and Procrit -- had a 31 percent rise in the risk of cardiovascular complications and a 41 percent increased risk of death.
"For people who have chronic kidney disease, I think this is further evidence that we have to be extremely cautious when we use ESAs. There is a potential for harm. The patients who respond poorly are the ones who get the most drug, and we may be putting them at increased risk," said the study's lead author, Dr. Scott Solomon, director of noninvasive cardiology at Brigham and Women's Hospital and an associate professor of medicine at Harvard Medical School in Boston.
"What we can't determine from this study is if these patients had worse outcomes because they were sicker to begin with, or because they got more of the drug, or some combination of the two," added Solomon.
When someone has kidney disease, the kidneys may not produce enough of the hormone erythropoietin to prevent anemia, a deficiency in red blood cells. Symptoms of anemia include fatigue and pale skin, and it can even contribute to heart disease, according to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.
ESAs were developed to replace the missing erythropoietin in kidney patients and stimulate red blood cell production. But these drugs can cause serious, even life-threatening complications in some patients. Because of this, the U.S. Food and Drug Administration requires manufacturers to include a warning about the risks.
The current study is a secondary analysis of a randomized, double-blind, placebo-controlled study done in 24 countries from 2004 to 2009. All of the study volunteers -- 1,872 in all -- had type 2 diabetes and chronic kidney disease.
The study volunteers were randomly assigned to receive either 0.75 micrograms of darbepoietin alfa (Aranesp) per kilogram of body weight or a placebo. In people who didn't respond well to the initial dose of the drug, the dose was repeated after two weeks. After that, hemoglobin levels were monitored and doses adjusted based on an individual's hemoglobin levels, reported the study.
In the initial analysis of these study volunteers, the researchers found no reduction in the risk of death or of cardiovascular or kidney problems in those taking the drug compared to those on placebo. But they did see a significant increase in the risk of stroke. Solomon said there was only a slight, "unimpressive" increase in quality of life for those taking the ESA.
At the same time, other studies have been finding an increased risk of heart problems in people taking ESAs. Solomon's team wanted to know why some people might be at greater risk than others.
In a sub-analysis of the initial study, they divided the group into four smaller groups based on their response to darbepoietin alfa, which is how they found the increased risk of death and cardiovascular events in people who responded poorly to the drug.
Solomon said he thinks this effect would likely be seen in other ESAs, not just darbepoietin alfa. Amgen, the maker of Aranesp, provided funding for the study.
"This study helps clarify some of the confusion from previous studies. When you isolate who are the people who got into trouble, it was people who wouldn't respond to ESAs. I think it helps clarify how to use ESAs. If I see that you don't respond, there may be something else going on with you, and I need to give you some special attention because you're at greater risk of having a bad outcome," said Dr. Robert Provenzano, chair of the department of nephrology at St. John Providence Health System in Detroit.
But, if you respond normally to ESAs, he said, the drugs may improve your quality of life when the medication is adjusted to keep your hemoglobin levels between 10 and 12.5 mg/dL.
Solomon said he wasn't sure if the modest benefit seen in patients was worth the potential increase in stroke risk. Provenzano countered that such a decision needs to be individualized based on the effects of the anemia, along with other aspects of the patient's life.
If you take this medication, Provenzano suggested asking your doctor where you fall on the continuum of response and whether you're in a high-risk group.

H1N1 flu increases complication in children with sickle cell anemia: Study

Children with sickle cell disease are especially hard-hit by the H1N1 flu strain, causing more life-threatening complications than the seasonal flu, according to a study from Johns Hopkins Children's Center.

The study's findings, published online July 23 in an early edition of the journal Blood, should be heeded as a warning call by parents and pediatricians that children with sickle cell anemia are more likely to need emergency treatment and to be hospitalized if they contract the H1N1 flu.

While H1N1 flu in the general population turned out to be much less severe than feared at the start of the 2009 pandemic, children with sickle cell disease remain at greater risk for complications from it, as well as other strains of the flu. A 2009 Hopkins Children's study found that children with sickle cell disease are hospitalized with seasonal flu nearly 80 times more often than other children.

Lead investigator John Strouse, M.D., Ph.D., a hematologist at Hopkins Children's says the study underscores the importance of timely immunization against both the H1N1 and the seasonal flu strains, which this year will be given in a single vaccine.
The Hopkins team analyzed the records of 123 children with sickle cell disease treated for any kind of flu at Hopkins Children's between September 1993 and December 10, 2009. Of them, 29 were infected with the H1N1 virus, a new strain that emerged for the first time in April of 2009.

While both the seasonal flu and the H1N1 virus caused most of the typical flu symptoms — fever, cough and a runny nose — in most of the children, sickle cell patients infected with H1N1 were nearly three times more likely to develop acute chest syndrome, a leading cause of death among such patients, marked by inflammation of the lungs, reduced ability to absorb oxygen and shortness of breath.

H1N1-infected children also were more than five times more likely to end up in the intensive-care unit than those with the regular flu, and they were overall more likely to need a ventilator for breathing.
Named for the unusually sickle-shaped red blood cells caused by an inherited abnormality, sickle cell anemia affects nearly 100,000 Americans, most of them African-American. The cells' abnormal structure reduces their oxygen delivery to vital organs and causes them to get stuck in the blood vessels, leading to severe pain and so-called "sickling crises," which require hospitalization.

The CDC estimates that up to one-fifth of Americans get the flu each year, resulting in 200,000 hospitalizations and 36,000 deaths.
Source : Johns Hopkins Children's Center

New Medicare Rules May Curb Use of Anemia Drugs for Dialysis

By ANDREW POLLACK

Yet more restrictions in the use of anemia drugs are on the way.
Medicare issued final rules Monday that are expected to sharply curtail the use of anemia drugs, particularly Amgen’s Epogen, in the treatment of patients undergoing kidney dialysis.
However, after getting lots of protest, Medicare decided to exempt certain oral drugs from the new system until 2014, which could be good news for Genzyme.
Under the new system, the Centers for Medicare and Medicaid Services will pay a set fee for each dialysis treatment. That so-called bundled payment is supposed to cover both the dialysis service, in which wastes are removed from the body, and the drugs and laboratory tests that accompany it. The new system starts phasing in on Jan. 1.
The new system somewhat resembles concepts in the new health care law, but the dialysis system reform was initiated earlier by Congress, under different legislation.
Until now, Medicare has paid a set fee for the service but certain drugs, like Epogen, are reimbursed separately.
Critics say that gave hospitals and dialysis clinics financial incentives to use a lot of Epogen, which dominates the dialysis market because of Amgen’s patent position. Amgen sells about $2.5 billion of Epogen a year, virtually all for use in dialysis in the United States, and the drug is one of the biggest pharmaceutical expenses for Medicare.

Concern about this system grew stronger when some clinical trials revealed that overuse of Epogen might harm patients, increasing their risk of heart attacks and strokes.
“When drugs remain outside the payment bundle, financial issues can influence both facility and patient behavior, as the over-utilization of EPO to the detriment of patient care in the past has demonstrated,’’ Medicare said in its ruling Monday.
Of course, the new system could have the opposite effect. Epogen will go from being a potential profit source for dialysis clinics to an expense that detracts from profit. So now there will be an incentive to under-use the drug, perhaps subjecting dialysis patients to more anemia and fatigue.
But clinics will have to meet certain standards for quality of care, which Medicare hopes will deter under-use. Medicare said it expects less costly alternatives might be used.
One approach would be to give Epogen by separate injections under the skin. Less of the drug is needed that way than when it is given through the intravenous line now used to deliver dialysis.
When they had a financial incentive to use more Epogen, dialysis clinics resisted giving such separate injections, saying they added to the pain and discomfort for patients. Now, however, many clinics are expected to switch.
Analysts have been expecting the final rules since Medicare first proposed the changes last year, and they have by and large already factored in a reduction in sales of Epogen of as much as 40 percent.
In a note to clients Monday afternoon, however, Jim Birchenough, an analyst at Barclays Capital, said such estimates might be too high and that the transition to giving patients separate injections will occur gradually.
The big suspense in the final rules would be whether Medicare would stick with its original proposal to include certain oral drugs, like Amgen’s Sensipar and Genzyme’s Renvela, in the bundle. These drugs are used to control calcium and phosphorus levels in the patient’s blood.
Opponents of inclusion of the oral drugs argued Medicare had no right to do so, because the drugs typically are not given at the dialysis clinic. Like most other pills, patients get a prescription and Medicare pays for the drugs under its prescription coverage, known as Part D, not under its dialysis program.
The opponents also said that because the drugs were expensive, inclusion in the bundle would curtail their use, to the detriment of patients.
In the final rules issued Monday, Medicare defended its position to include the drugs, but postponed the starting date by three years, until Jan. 1, 2014, to allow time for the study of “operational and safety issues.’’

Anemia and Thrombocytopenia in Pregnancy

Author: Diana Curran, MD, FACOG, Assistant Professor, Residency Program Director, Department of Obstetrics and Gynecology, University of Michigan Health Systems

Thrombocytopenia

Thrombocytopenia in pregnancy is common and is diagnosed in approximately 7% of pregnancies. It is typically defined as a platelet count of less than 150,000/µL. The most common cause of thrombocytopenia during pregnancy is gestational thrombocytopenia, which is a mild thrombocytopenia with platelet levels remaining greater than 70,000/µL.

Patients who are affected usually are asymptomatic and have no history of thrombocytopenia prior to pregnancy. Their platelet levels should return to normal within several weeks following delivery. An extremely low risk of fetal or neonatal thrombocytopenia is associated with gestational thrombocytopenia. Gestational thrombocytopenia may result from increased platelet consumption and can be associated with antiplatelet antibodies. Gestational thrombocytopenia can be hard to distinguish from immune thrombocytopenia purpura (ITP) presenting during pregnancy.


Immune thrombocytopenia purpura
Acute ITP is a disorder occurring in childhood with little implication for women who are pregnant because it resolves spontaneously. Chronic ITP may occur in the second or third decade of life, affecting females 3 times as frequently as males. This condition is characterized by immunologically mediated platelet destruction. Antiplatelet antibodies (immunoglobulin G) attack platelet membrane glycoproteins and destroy platelets at a rate that cannot be compensated by the bone marrow. ITP is usually associated with persistent thrombocytopenia (<100,000/µL), normal or increased megakaryocytes on bone marrow aspirate, exclusion of other disorders associated with thrombocytopenia, and the absence of splenomegaly. Patients may report a history of easy bruising and petechiae or epistaxis and gingival bleeding preceding the pregnancy.
Although worsening of the disease is not typical during pregnancy, when it occurs, the mother is at risk for bleeding complications at the time of delivery. Therapies aimed at improving the maternal platelet count in anticipation of delivery include intravenous immunoglobulin (IVIg) and steroids. The patient may require platelet transfusion during delivery if the platelet count drops below 20,000/µL. Splenectomy is reserved for severe cases only.
Some controversy exists regarding the threat of intracranial hemorrhage (ICH) in neonates born to mothers with ITP. Although as many as 12-15% of infants born to mothers with ITP may develop platelet counts less than 50,000/µL, the risk of ICH is estimated at less than 1% in 2 recent prospective studies.

Neonatal alloimmune thrombocytopenia
In contrast to ITP, neonatal alloimmune thrombocytopenia may pose a serious risk to the newborn. It may occur in 1 in 1000 live births and often is unanticipated when it occurs in first pregnancies. The presentation may be in the setting of an unremarkable pregnancy and delivery. Clinical manifestations in the neonate include generalized petechiae, ecchymoses, hemorrhage into viscera, increased bleeding at the time of circumcision or venipuncture, or, most gravely, ICH. ICH may occur in utero in as many as 25% of cases. Like Rhesus (Rh) disease, neonatal alloimmune thrombocytopenia results from maternal alloimmunization against fetal platelet antigens. The most severely affected antigen is human platelet antigen-1a, which has been described in approximately 50% of cases in white persons. A high risk of recurrence of neonatal alloimmune thrombocytopenia exists, and it tends to worsen with subsequent gestations in a manner similar to Rh disease.
For patients who have a history of the disease and are experiencing their first pregnancy, referral to a maternal-fetal medicine specialist skilled in cordocentesis may be warranted because the fetus may need to have platelet counts or a transfusion while in utero. IVIg has been shown to improve fetal thrombocytopenia. Cesarean delivery is the preferred route of delivery for infants with platelet counts less than 50,000/µL to reduce the risk of ICH secondary to trauma incurred during labor.

Anemia

With normal pregnancy, blood volume increases, which results in a concomitant hemodilution. Although red blood cell mass increases during pregnancy, plasma volume increases more, resulting in a relative anemia. This results in a physiologically lowered hemoglobin (Hb) level, hematocrit (Hct) value, and red blood cell (RBC) count, but it has no effect on the mean corpuscular volume (MCV). Many centers define anemia in a patient who is pregnant as an Hb value less than 10.5 g/dL, as opposed to the reference range of 14 g/dL in a patient who is not pregnant. Treatment with 1 mg folic acid and daily iron is helpful when deficiencies are noted.
Iron deficiency anemia
Iron deficiency anemia accounts for 75-95% of the cases of anemia in pregnant women. A woman who is pregnant often has insufficient iron stores to meet the demands of pregnancy. Encourage pregnant women to supplement their diet with 60 mg/d of elemental iron. An MCV less than 80 mg/dL and hypochromia of the RBCs should prompt further studies, including total iron-binding capacity, ferritin levels, and Hb electrophoresis if iron deficiency is excluded.

Clinical symptoms of iron deficiency anemia include fatigue, headache, restless legs syndrome, and pica (in extreme situations). Treatment is additional supplementation with oral iron sulfate (320 mg, 1-3 times daily). Iron is preferable once daily because more frequent iron supplementation can cause constipation. The clinical consequences of iron deficiency anemia include preterm delivery, perinatal mortality, and postpartum depression. Fetal and neonatal consequences include low birth weight and poor mental and psychomotor performance.1
Folate and vitamin B-12 deficiency
Folate deficiency is much less common than iron deficiency; however, taking 0.4 mg/d to reduce the risk of neural tube defects is recommended to all women contemplating pregnancy. Patients with a history of neural tube defect should take 4 mg/d. An increased MCV can be suggestive of folate deficiency; in this case, determine serum levels of vitamin B-12 and folate. If the levels are low, the patient may require oral folate at a dose of 1 mg 3 times daily. Patients with vitamin B-12 deficiency need further workup to determine the level of intrinsic factor to exclude pernicious anemia. The Schilling test is not recommended during pregnancy because of the radionuclide used in testing. Treatment of vitamin B-12 deficiency includes 0.1 mg/d for 1 week, followed by 6 weeks of continued therapy to reach a total administration of 2 mg.
Infectious causes of anemia
Although rare, anemia can be caused by infections such as parvovirus B-19, CMV, HIV, hepatitis viruses, EBV, malaria, babesiosis, bartonellosis, and clostridium toxin. If the patient's history suggests exposure to any of these infectious agents, appropriate laboratory studies should be performed.

Diamond-Blackfan anemia

This is a rare (7 per 1 million) autosomal dominant disorder of pure red cell aplasia requiring life-long transfusion. Women who are contemplating or who are pregnant require the consultation and care of a hematologist in conjunction with a Maternal Fetal Medicine specialist. Concerns during pregnancy include maintaining adequate hemoglobin while decreasing the risk of fetal exposure to the iron chelating agent (Deferoxamine) used during transfusions.1

Indians at Risk for Rare Blood Disorder Thalassemia

By LISA TSERING
indiawest.com


Indian Americans are at greater risk of contracting thalassemia than many other ethnic groups, according to a study by the Children’s Hospital and Research Center Oakland in Oakland, Calif. To coincide with International Thalassemia Day May 8, the hospital is urging the community to get tested — and to seriously consider banking their infants’ cord blood.

The rare and hereditary blood disorder can result in severe anemia. Children with thalassemia often require frequent blood transfusions and lifelong medical treatment.

Gargi Pahuja, a health care law attorney in New York, was diagnosed with thalassemia when she was 12 months old. “My parents were from India and they hadn’t heard of it,” Pahuja told India-West in a phone interview. “They were shocked to find that they carried the trait.”

Since thalassemia is so rare, some doctors are likely to confuse its symptoms, which include yellow skin, with jaundice. But thalassemia is a much more serious disease.

Thalassemia (also known as Mediterranean anemia) is an inherited blood disorder characterized by less hemoglobin and fewer red blood cells in the body than normal. Since hemoglobin allows red blood cells to carry oxygen, a deficiency leads to anemia, marked by fatigue, pale appearance, shortness of breath and weakness.

Pahuja is 35 years old, and continues to get blood transfusions every two weeks.

“The fact that I’m 35 is an important milestone,” she told India-West. “My parents were told that I would die by the age of 15 … my generation is the first to live into their 30s, 40s and 50s.”

The cause of thalassemia is defects in the genes that make hemoglobin. The only way to contract thalassemia is to inherit one or more defective hemoglobin genes from your parents.

Infants in California are required to receive a test for thalassemia, but California is the only state to require the test, said Pahuja.

Bone marrow transplant is the established treatment to cure thalassemia. Umbilical cord blood stem cells donated by a sibling have been proven to cure 91 percent of cases, according to a 2007 Children’s Hospital study of 40 children.

A Mayo Clinic statement said that most children with moderate to severe thalassemia show signs within the first two years of life. Prenatal testing is also available, at 11 weeks (chorionic villus sampling), 16 weeks (amniocentesis), and 18 weeks (fetal blood sampling).

“People need to be tested so that they can make informed decisions regarding family planning,” said Pahuja.

The Children’s Hospital study showed that in the United States, around two million people are carriers and that around 1,000 people have the full-blown disease. The hospital has one of the largest thalassemia centers on the West Coast, and currently treats around 300 patients.

In the U.S., there are more than 5,000 thalassemia cases, and those numbers are expected

to rise as the trait carrier population increases, said the study; in Alameda County alone, the Asian Indian population is more than 47,000 and has increased by 209 percent in the last decade, according to statistics provided by the Asian American Pacific Islander Health Forum.

According to Pahuja — who says she has devoted her professional and personal life to increasing awareness of thalassemia — people from North India are especially at risk. “If you are Punjabi, or Gujarati, or Sindhi, you need to get tested,” she told India-West. Individuals who are past child-bearing age need not get tested, she added.

In India, as many as one in eight people are believed to be carriers of the thalassemia gene, and in India, it is expected that 1 million people will have the disease in the next 40 years. Babies born there are 80-90 percent likely to die of the disease, said the Children’s Hospital spokesperson. But increasing awareness of the disease there has opened up a market for blood cord banking; a recent Mumbai Mirror article states that there are now three private stem cell banks — one run by Reliance in Mumbai; the CryoCell stem bank in New Delhi; and Life Cell, run in collaboration with Cryo-Cell International, U.S.A., in Chennai.

In India, it costs around Rs. 70,000 ($1,575) to preserve a newborn’s cord blood for 20 years. Here in the United States, the average cost is around $2,000.

Signs of Anemia in an Infant

By:Ashley Waters Gordon
Overview
Anemia is a common blood disorder in infants, affecting normal growth and development. The most common type in babies under two years of age is iron-deficiency anemia. With iron-deficiency anemia, the infant either does not get enough iron or cannot absorb iron. Lack of iron lowers the number of healthy red blood cells. These contain hemoglobin, which carries oxygen to organs and tissues. A growing baby needs this oxygen for organs to develop properly. Signs of infant anemia can be hard to see until the case is more severe, so have your baby tested at routine doctor's appointments. Call your infant's pediatrician right away if you notice any of the below symptoms.

Paleness of Skin, Lips and Nail Beds
Look for paleness in your baby's skin, lips or nail beds. Paleness tells you that not enough red blood cells and oxygen are circulating in your baby's blood. Some babies can even take on a gray or blue tone in very serious cases. You may not be able to notice paleness in infants until they have significant anemia, typically hemoglobin levels greater than 7 grams per deciliter (g/dL). Schedule an appointment for your baby to see his pediatrician if you notice paleness.

Growth or Developmental Delays
Pay attention to any delays in your baby's growth and development. These delays may be signs of anemia. Delayed growth and development can happen when the baby's organs, like the heart or the brain, do not getting enough oxygen to grow properly. Talk with your baby's pediatrician at his next appointment if you feel that your baby is not growing at the same rate or is not reaching normal developmental milestones.

Jaundice
Anemic babies can develop a condition called jaundice. You will be able to see jaundice when the infant's skin or whites of the eyes turn a yellow color. The buildup of a substance called bilirubin causes this yellowing. This happens when the baby's body breaks down too many old red blood cells, making a large amount of bilirubin. The baby's liver can filter out a normal amount of bilirubin each day. When there is a high number of red blood cells broken down and more bilirubin than the liver can handle, your infant's skin begins to turn yellow. Call your baby's pediatrician immediately if you notice any yellowing of the skin so that she can begin treating your baby's jaundice and anemia.

Rapid Heartbeat or New Heart Murmur
Pay attention to heart changes. When not enough oxygen is getting to your baby's tissues and organs, her body may compensate by raising her heart rate. The heart tries to pump more blood and oxygen to tissues throughout her body. Stress on the heart can cause a murmur. Ask the pediatrician if anemia could be causing your baby's increased heart rate or new murmur. If anemia could be the cause, have your infant's blood tested for anemia.

Decreased Appetite
Babies with anemia become tired easily and may be too weak to properly suck. If you notice your baby has a decreased appetite, begin taking notes of how often and for how long your baby nurses. Or, if your baby drinks formula, make note of the volume of formula your baby drinks at each feeding. Share this information with your pediatrician.

Excessive Sleeping or Fatigue
If your baby sleeps an excessive amount, call your pediatrician. This can be a sign of anemia. Because he does not have enough oxygen in his blood, an anemic baby may be too weak to play or remain awake for normal periods of time. Keep a journal of how long your baby sleeps in a 24-hour period. When your baby is awake, make notes on how active he stays. Show the pediatrician your notes to help diagnose and treat any possible anemia.

Irritability
Does your baby seem unusually cranky when she is awake? If she has anemia, your infant may be over-tired, or hungry but too weak to eat. This can make a baby become more irritable than normal. Ask your doctor if your baby's irritability maybe a sign of underlying anemia.

Study Looks at Pregnancy in Thalassemia

A recent study published in Haematologica (Vol. 95, Issue 3) examined pregnancy in women with thalassemia.
Entitled "Pregnancy and Beta-thalassemia: an Italian multicenter experience," the paper examined 58 pregnancies among 47 women with thalassemia major and 17 pregnancies in women with thalassemia intermedia at four centers in Italy. The study reports that conception was spontaneous in all of those with thalassemia intermedia; among those with thalassemia major, gonadotrophin-induced ovulation was required in 33 of the women.
According to the study, 91% of the pregnancies among alassemia major patients resulted in live births (45 single births, 5 sets of twins, one set of triplets). The authors also report that no secondary complications of iron overload developed or worsened during pregnancy. There was a higher prevalence of pre-term births (32.8%), but the authors state that this was primarily related to multiple pregnancies and precautionary measures. Women with thalassemia intermedia who had never been transfused or who had only minimal transfusion prior to pregnancy were found to be at risk of severe alloimmune anemia if transfusions were required during pregnancy. (Decreased hemoglobin levels necessitated transfusion in 11 of the 17 thalassemia intermedia pregnancies.) Of the 17 pregnancies in thalassemia intermedia known to the researchers, 15 resulted in live births.
The authors also state that "cardiac function was not impaired during pregnancy." One patient did experience worsening of T2* scores, but the authors suggest that this was due to the timing of the second MRI reading; as it was taken one month after delivery, the patient was still off chelation. The authors also stated that "it is strongly recommended that thalassemic women wishing to become pregnant undergo a complete evaluation of organ iron overload, including MRI T2* and SQUID, prior to pregnancy." (In the United States, Ferriscan/R2 readings are often used for liver iron rather than those provided by SQUID, together with T2* cardiac assessment.)
The study concludes that "provided a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia." The authors are state the need for larger and more detailed studies, especially in thalassemia intermedia.


Download CAF's "Fertility and Pregnancy in Thalassemia" pamphlet by clicking here