- Megakaryocytes: New Understanding
- Fcγ Receptors Out of Balance in ITP
- Megakaryocytes: FAK’s Role Made Clearer
- PROMACTA (Eltrombopag) Safety and Effectiveness for ITP Presented at ASH Meeting
- Traditional Chinese Medicine Found Effective and Safe for ITP
- Steroid Therapy Increases Risk of Heart Disease and Irregular Heart Rhythms
- Increased Risk of Bleeding for Coumarin Users Also Taking SSRIs
- Celebration of $60 Million Gift for Hematology Division at USC
- Insurers Refuse to Pay for Hospital Errors
- Yoga Reduces Stress for Disaster Survivors
- World’s First Online Database of Integrative Cancer Research
- There May Be No Safe Level for Children’s Exposure to Lead
- Recycling Old Computers and Cell Phones Limits Lead in Landfills
- Study Finds Caffeine Raises Blood Sugar Levels
- Pedometer Use Helps Patients Lower Weight and Blood Pressure
MEGAKARYOCYTES: NEW UNDERSTANDING
In the U.S., about 1.5 million platelet transfusions are administered yearly to patients to reduce their risk of severe bleeding. Yet platelet transfusions are expensive and not an ideal solution. About one third are associated with complications. Therapeutic stimulation of marrow platelet production would be a better solution than transfusion of platelets, according to UCSD’S Kenneth Kaushansky, who provides a detailed tour through research on the origin and role of megakaryocytes and platelet development. New understanding of the origins of platelet development continues to offer advances in the ability to manipulate thrombopoiesis for therapeutic benefit.
Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood, February 1, 2008, 111(3):981-985.
Fcy Receptors Out of Balance in ITP
The current paradigm among researchers is that the balance of activating versus inhibitory Fcγ receptors for IgG contributes to susceptibility to autoimmune disease such as ITP. Researchers in The Netherlands opened a new window into ‘yin and yang’ of Fcγ receptors in ITP. They found that a version of the FCGR2C gene predisposes to ITP. And for the first time, demonstrated a variation in the copy number for the FCGR3A gene. In an accompanying commentary, Steven McKenzie of Thomas Jefferson University calls “exciting” the possibility that these genetic variations contribute to differences in the response to therapy for ITP.
Breunis WB, van Mirre E, Bruin M, Geissler J, de Boer M, Peters M, Roos D, de Haas M, Koene HR, Kuijpers TW. Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura. Blood, February 1, 2008, 111(3):1029-1038.
McKenzie SE. The yin and yang of Fcγ receptors in ITP. Blood, February 1, 2008, 111(3):981-985.
All of the previous articles appeared in the journal Blood. Nonsubscribers can download full articles for $35 each. Articles older than 12 months are available free. http://bloodjournal.hematologylibrary.org/
Patients interested in obtaining a copy of an access-controlled article in Blood that may be helpful to their situation may do so by emailing a request to the Blood Publishing Office . The request should include the following information:
- Article citation information, including author(s), title of article, issue date & page number (example: Rafik Terra et al., T-cell generation by lymph node resident progenitor cells, July 1, 2005, p. 193). All citation information can be found with the article or abstract information online.
- Your name and email address
- Name of treating physician (optional)
MEGAKARYOCYTES: FAK’S ROLE MADE CLEARER
To maintain the high levels of circulating platelets in the adult human—1 trillion platelets—megakaryocytes within the bone marrow must produce about 1 million platelets every second. The protein tyrosine kinase focal adhesion kinase (FAK) was thought to play an important role in megakaryocyte development, but its study in mice has been hampered. Researchers at University of California, San Diego (UCSD), overcame the obstacles, showing that FAK plays a central role in megakaryocyte development and platelet biology, mainly as a negative regulator of megakaryocyte production. In a comment on the paper, Dr. Italiano of Brigham and Women’s Hospital notes that the group’s findings “suggest that manipulation of FAK may provide a way to increase platelet levels in patients with thrombocytopenia or decrease platelet levels in patients with thrombocytosis.”
Hitchcock IS, Fox NE, Prévost N, Sear K, Shattil SJ, Kaushansky K. Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage–specific FAK knockout. Blood January 15, 2008, 111(2):596-604.
Italiano Jr. JE. Megakaryocyte and platelet biology: getting your FAKS straight. Blood. January 15, 2008, 111(2):482-483.
PROMACTA (ELTROMBOPAG) SAFETY AND EFFECTIVENESS FOR ITP PRESENTED AT ASH MEETING
GlaxoSmithKline announced preliminary results of the EXTEND (Eltrombopag eXTENded Dosing) study which showed that in patients with a baseline platelet count lower than 30,000/microliters, over 70 percent achieved a platelet count greater than or equal to 50,000/microliters. Average treatment time was 22 weeks. Starting dose was 50 mg/day, which could be raised to 75 mg in three weeks. Results indicate that PROMACTA (an oral, non-peptide, thrombopoietin receptor agonist that stimulates platelet production in the bone marrow) sustains higher platelet counts during long-term treatment. Findings were presented at the 49th Annual Meeting of the American Society of Hematology held December 8-11 in Atlanta, Georgia. “These long-term results on safety and efficacy are encouraging and suggest that PROMACTA, once approved, may provide physicians with a new treatment option to raise and maintain patients’ platelet levels and alleviate their ITP symptoms,” said James B. Bussel, MD, director of the Platelet Disorders Center of Weill Cornell Medical Center in New York, who led the study.
Bussel JB, Cheng G, Kovaleva L, Saleh MN, et al. Long-Term Safety and Efficacy of Oral Eltrombopag for the Treatment of Subjects with Idiopathic Thrombocytopenic Purpura (ITP): Preliminary Data from the EXTEND study. Presented at the 49th Annual ASH Meeting, Dec 8-11, 2007, Atlanta, GA. Abstract #566, Blood, 2207 Annual Meeting Abstracts, Part 1, Vol. 110, Issue 11, Nov. 16, 2007: p. 174A.
TRADITIONAL CHINESE MEDICINE FOUND EFFECTIVE AND SAFE FOR ITP
Two studies of traditional Chinese medicine treatments for ITP showed that Shengxueling (SXL), a Chinese medicine, helps ITP. In a 2005 study, with 86 patients randomly assigned to two groups, those in the SXL group had a total effective rate of 85.71 percent, while the placebo group on prednisone, had a total effective rate of 83.33 percent for six months. In the SXL group bleeding lessened or stopped, platelet counts improved, platelet associated immunoglobulin (PAIg) and interleukin4 (IL-4) markedly dropped. In a 2007 study, 69 patients with refractory ITP were randomly assigned to two groups. The 37 patients in the SXL group received an oral dose of 60 mg twice a day for four weeks. A group of 32 patients received a placebo. In the treatment group, 27 patients showed improvement in ITP symptoms, while in 10 it was ineffective. The study concluded that SXL is a safe and effective treatment for ITP, few side effects.
Zhou YM, Huang ZQ, Hu MH, Zhou SH, et al. Clinical study on the effect of Shengxueling on idiopathic thrombocytopenic purpura. 2005. Chinese Journal of Integrative Medicine, March 11 (1): 60-64.
Shao KD, Zhou YH, Shen YP, et al. Treatment of 37 patients with refractory idiopathic thrombocytopenic purpura by shengxueling. 2007. Chinese Journal of Integrative Medicine. March 13 (1):33-36.
STEROID THERAPY INCREASES RISK OF HEART DISEASE AND IRREGULAR HEART RHYTHMS
A British study found that cortiosteroids, ex. prednisone, commonly prescribed for various autoimmune disorders including ITP, may pose a 2 ½ times greater risk for cardiovascular disease in patients taking them. A study from The Netherlands found that risk of an irregular heart rhythm, called atrial fibrillation (parts of the heart quiver instead of beat, allowing blood to clot) was six times higher in those who were taking high-dose corticosteroids. Steroids increase blood pressure, lipids, and blood glucose, which are factors that may increase heart disease risk. Steroids also change the potassium balance in heart muscle cells, which may be the root cause of the atrial fibrillation. During the 5-year Netherlands study of nearly 8,000 adults, 435 patients developed atrial fibrillation or died. Researchers showed that those who took high-dose steroids had six times the risk of developing the irregular heart rhythm compared with those who didn’t take steroids.
Heart-Healthy Living, Ed., Jeanne Ambrose, You’re Taking Steroids, Winter 2008, p. 31.
Walker, B. Glucocorticoids and cardiovascular disease. European Journal of Endocrinology, 2007, 157, Issue 5, 545-559.
INCREASED RISK OF BLEEDING FOR COUMARIN USERS ALSO TAKING SSRIs
Patients who are taking coumarins together with selective serotonin reuptake inhibitors (SSRIs) (a class of antidepressant drugs such as Prozac, Paxil and Zoloft) have an increased risk of nongastrointestinal (GI) bleeding according to a study reported in the Archives of Internal Medicine. The coumarins in the study are not used in the U.S., but have similar pharmacodynamics (how drugs interact with cells), so the results may apply to warfarin used in the U.S. Dutch researchers using patient records identified 1,850 patients on coumarin who were admitted to hospitals for bleeding. Patients also taking SSRIs showed higher risk for hospitalization for non-GI bleeding but not for GI bleeds. Patients on non-SSRI antidepressants did not have increased risk. Researchers believe the SSRIs’ ability to inhibit an enzyme that metabolizes coumarins may cause the bleeding effect. They advised intensified monitoring of coumarin patients who are also taking SSRIs.
Schalekamp T, Klungel JH, Souverein PC, de Boer A. Increased Bleeding Risk With Concurrent Use of Selective Serotonin Reuptake Inhibitors and Coumarins. Archives of Internal Medicine, Jan 2008; 168: 180 - 185.
CELEBRATION OF $60MILLION GIFT FOR HEMATOLOGY DIVISION AT USC
The University of Southern California announced Dec. 13 a historic $60 million gift for the Keck School of Medicine’s Division of Hematology and the USC/Norris Comprehensive Cancer Center. The gift from the Jane Anne Nohl estate is one of the largest donations to a hematology program. “This gift will be used to unlock the mysteries of cancer of the blood and other blood disorders. This knowledge will lead to new and better therapies for treating these debilitating diseases,” said USC’s president, Steven B. Sample.
The gift will be used to support research in blood disorders and for recruiting outstanding researchers from around the country. It was coordinated by Larry Kelly, long-time friend and estate trustee for Jane Nohl, who died in July 2007. She chose USC/Norris and the hematology division because of the outstanding care given to Kelly by Dr. Don Feinstein of the Keck School of Medicine.
INSURERS REFUSE TO PAY FOR HOSPITAL ERRORS
Some large health insurance companies, stating they are trying to improve patient safety and reduce health-care costs, are refusing to pay -- and are not letting patients be billed --for medical care linked to errors made by hospital staff. Medicare announced last summer that it would not pay extra costs of treating bed sores, falls, and six preventable injuries and infections that occur while a patient is hospitalized. Next year they will add to the list objects left after surgery, hospital-acquired blood infections, blood clots in legs and lungs, urinary-tract infections from catheters, and pneumonia contracted from a ventilator. Care that insurers are refusing to pay for that they believe hospitals should prevent, include: giving the wrong blood type, operating on the wrong limb, performing the wrong procedure, and using contaminated drugs or devices. Insurers say they are restructuring their contracts with hospitals to make sure hospitals won’t be able to charge patients for care made necessary by a hospital error. However, given the high rate of medical billing errors, patients are advised by consumer advocates to examine their bills carefully and make sure they haven’t been overcharged.
Fuhrmans V. Insurers Stop Paying for Care Linked to Errors.
The Wall Street Journal. Personal Journal. In Depth: Health- Travel, Jan. 15, 2007, D1.
See the National Quality Forum’s list of 28 medical errors for which some insurers may refuse payment, at WSJ’s OnlineToday: http://s.wsj.net/public/resources/documents/WSJ_PRSeriousReportableEvents10-15-06.pdf
YOGA REDUCES STRESS FOR DISASTER SURVIVORS
A one-week yoga program reduced stress and anxiety among survivors of the tsunami that hit several Indian islands in December 2004. Researchers at the Swami Vivekananda Yoga Research Foundation in Bangalore conducted a stress management program for the tsunami survivors one month after the disaster. Self assessment of symptoms and heart and respiratory rate measurements of the 47 adults were carried out before and after the 8-day program. Fear, anxiety, sadness, sleep disturbances, and respiratory rates were significantly reduced following the yoga program. Results appear in the December 2007 issue of eCAM (Evidence-based Complementary and Alternative Medicine). While yoga is considered a relatively safe form of exercise, precautions should be taken if a person is just beginning. The American Academy of Orthopaedic Surgeons recommends: consult your doctor first if you have any medical condition, learn proper techniques from a certified yoga instructor, drink plenty of fluids, warm up before beginning routine, start out slowly, being sure to perform each position correctly, and stop if you feel discomfort or pain.
WORLD’S FIRST ONLINE DATABASE OF INTEGRATIVE CANCER RESEARCH
The first central database of integrative cancer research from around the globe is available online, free for cancer patients, the medical community, and the general public. The Canadian Breast Cancer Foundation awarded InspireHealth (formerly the Centre for Integrated Healing), an integrated cancer care center in Canada, a $142,382 grant to fund the new “Research Information System” for three years. The comprehensive system searches medical databases around the world for the latest cancer care treatments that can be added to conventional treatments on an integrated basis. Areas of interest include: nutrition, supplements, exercise meditation, yoga, emotional and spiritual support, etc. Dr. Hal Gunn, co-founder and CEO of InspireHealth, said, “We need to broaden our emphasis from the current sole focus of treating illness to one which engages people in their own care with a focus on illness prevention through an integrated healthcare approach.”
THERE MAY BE NO SAFE LEVEL FOR CHILDREN’S EXPOSURE TO LEAD
Children exposed to even low levels of lead may experience increase in the release of cortisol—a stress hormone—when they are in a stressful situation, according to a study in Environmental Health Perspectives (EHP). The study involved 169 children, age 9, from the Oswego Children’s Study, who were tested for cortisol levels before and after the stress of having their arm submerged in ice water for one minute. then children were given a simple test following the ice stress, those with high blood lead levels showed a significant release of cortisol. Findings were consistent even in children whose blood lead levels were less than 10 micrograms per deciliter (the action level established by the Centers for Disease Control and Prevention). Researchers said it is important to continue to follow these children to determine the consequences of these early effects of lead exposure on glucocorticoid reactivity.
The full article is online at: http://www.ehponline.org/members/2007/10391/10391.html
RECYCLING OLD COMPUTERS AND CELL PHONES LIMITS LEAD IN LANDFILLS
Now there are new options for keeping toxic trashed computers, cell phones and other electronic products from ending up in our landfills. Some major manufacturers, like Dell and HP, and stores, like Staples and Best Buy, have started recycling programs. Electronic products are a leading source of lead in municipal water supplies and are also a major source of cadmium and mercury, both highly toxic heavy metals. For more information, visit: www.greenerchoice.org which is a service of Consumer Reports.
“Where to recycle all those Computers and Cell Phones.” Ecoprint: newsletter for the responsible print buyer, Jan-Feb 2008. p. 4.
STUDY FINDS CAFFEINE RAISES BLOOD SUGAR LEVELS
For ITP patients already coping with blood sugar problems while taking prednisone here is some useful news. Drinking caffeine in tea, coffee, or soft drinks daily raises blood sugar levels and may hinder efforts to control the condition, according to findings from Duke University researchers. They found that when type-2 diabetes patients consumed caffeine with meals, their average daily sugar levels increased 8 percent. Researchers think caffeine may trigger the release of adrenaline – the ‘fight or flight’ hormone – that is known to boost sugar levels. US diabetes levels increased by one-third during the 1990s. More than 190 million people have the disease now.
Lane JD, Barkauskas CE, Surwit RS, and Feinglos MN. Caffeine impairs glucose metabolism in type 2 diabetes. Diabetes Care. 2004, 27: 2047-2048.
PEDOMETER USE HELPS PATIENTS LOWER WEIGHT AND BLOOD PRESSURE
It’s as easy as clipping on an inexpensive pedometer. Researchers at Stanford University Medical School found in their meta-analysis of 26 earlier studies that patients using pedometers experienced increases in physical activity, and decreases in body mass index (BMI) and blood pressure. The studies involved pedometer use by nearly 2,800 adult outpatients, around age 50, with nearly 85% women. They found that participants’ pedometer use increased physical activity by about 2,500 steps per day (a 27% boost in physical activity) compared to control participants who did not wear them. Participants wearing pedometers reduced their systolic blood pressure by 3.8 mm Hg.
Bravata DM, Smith-Spangler C, Sundaram V, Gienger AL, et al. Using Pedometers to Increase Physical Activity and Improve Health: A Systematic Review. JAMA. 2007. 298(19):2296-2304.
Richardson CR, ,Newton TL, Abraham JJ, Sen A, et al. A Meta-Analysis of Pedometer-Based Walking Interventions and Weight Loss. Annals of Family Medicine. 2008. 6:69-77.