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Platelets do more than help blood clot when they rush to a wound site. They can release proteins that kill bacteria directly. They also help the body protect against illness by making CD154, a surface protein that stimulates dentritic cells which then stimulate T and B cell growth. The B cells make antibodies that bind to the surface of the offending microbe and promote its destruction.
Speaking about the importance of this work for ITP, John Semple of the University of Toronto said, “Platelet-derived CD154 may be the link that stimulates these pathogenic antibody responses.”
From: “Platelets in blood may guide immune response” Science News, July 26, 2003
Immunity, July, 2003 http://www.immunity.com/content/article/abstract?uid=PIIS1074761303001778
(We are pleased to have John Semple, PhD as one of our medical advisors. To view slides of his presentation at our recent ITP Conference 2003 see: http://www.pdsa.org/conference2003/confprog03.htm
Three ITP patients who previously failed at least six and as many as eleven therapies were given etanercept, an inhibitor of tumor necrosis factor-alpha approved for the treatment of rheumatoid arthritis. All three patients responded promptly to the treatment reported the authors in the American Journal of Hematology. Although etanercept appeared to be effective in these patients, it is important to remember that it is an experimental treatment for ITP. An ITP clinical trial has been established to gather further information about using this drug.
From: American Journal of Hematology, 2003 Jun; 73(2): 135-40
http://www3.interscience.wiley.com/cgi-bin/abstract/104531457/START
See: www.itppeople.com/clinical.htm for clinical trail information
See: www.enbrel.com for more information about etanercept
(Note: please consider the side-effects of this and any medication before making a treatment decision)
The risk of developing ITP within six weeks of an MMR vaccination is estimated to be 1 in 25,000 vaccinations according to a new study by the Department of Public Health, Aberdeen University, UK. The study confirms the increased risk of ITP within six weeks after MMR vaccination.
From: “MMR vaccine and idiopathic thrombocytopaenic purpura” British Journal of Clinical Pharmacology, 2003 Jan: 55 (1): 107-11
Megakaryocytes in the bone marrow produce platelets. To determine if anti-platelet antibodies inhibit megacaryocyte development and influence platelet production, researchers at the Children’s Hospital of Orange County mixed the blood from ITP patients and controls plus other factors in test tubes and measured the number of megacaryocytes produced. The test tubes with ITP patients’ blood produced fewer megacaryoctytes indicating that antibodies in the ITP plasma may also inhibit platelet production.
“Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro” Blood, 1 August, 2003, Vol. 102, No. 3
http://www.bloodjournal.org/cgi/content/abstract/102/3/887
Is your deodorant making you ill? Should you avoid dry cleaned clothes? The National Library of Medicine published a new web site, http://householdproducts.nlm.nih.gov that provides information about the potential health effects of more than 4,000 common household products. On an associated site, http://www.toxtown.nlm.nih.gov you can click around various locations such as a school or a home and find the lurking environmental hazards.
The purpose is to formally evaluate the safety and effectiveness of Rituximab in children and adolescents with severe or refractory ITP. For very general information or a reference guide for parents, see http://www.itpkids.org.
More specific inquiries (from MDs) may be addressed to Pamela Boardman, Study Coordinator, Children's Hospital Boston 617-355-2901; pamela.boardman@tch.harvard.edu (Her info is also on the www.itpkids.org site
See: www.rituxan.com
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After reviewing the charts of thirty-two patients who had both IVIg followed by a splenectomy, researchers at the University of Florida found that 91.3 percent of the patients who had a good to excellent response to IVIg also had an excellent response to splenectomy. Of the patients who had a poor response to IVIg, only 33.3 percent had an excellent response to splenectomy. In their study, other factors such as age, gender, and response to prednisone did not predict splenectomy response.
Hold D, Brown J, Terrill K, et al. “Responses to intravenous immunoglobulin predicts splenectomy response in children with immune thrombocytopenic purpura. Pediatrics. 2003;111:87-90
http://pediatrics.aappublications.org/cgi/content/abstract/111/1/87?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=
&searchid=1063638833119_3277&stored_search=&FIRSTINDEX=0&volume=111&firstpage=87&journalcode=pediatrics
Meditation helped patients improve their moods and stay calmer according to a recent study published in the July/August issue of Psychosomatic Medicine. Researchers Richard Davidson, Ph.D., and John Kabat-Zinn, Ph.D., explained that there is a stress boundary in each person. They reported that after 8 weekly classes in mindfulness meditation, a seven-hour retreat, and daily sessions for an hour six days a week, this threshold began to move in a more positive direction, when compared to a control group. The immune system of meditation group participants produced more antibodies when given a flu shot than the control group, suggesting meditation also helps keep the practitioner healthy.
http://www.psychosomaticmedicine.org/cgi/content/abstract/65/4/564
The National Library of Medicine launched a new web site http://ghr.nlm.nih.gov that helps people who do not have a medical background understand genetics and the impact on disease. It features general genetics and disease specific information plus links to clinical trials. The National Library of Medicine is a part of the National Institutes of Health, included in the US Department of Health and Human Services.
http://www.nlm.nih.gov/
(Note: search on “thrombocytopenia” for some interesting results. You can find out more about genetic causes of low platelets on our new page http://www.itppeople.com/lowplate.htm
Newly diagnosed ITP patients were given a high-dose of dexamethasone, a corticosteroid, for four days by researchers in Hong Kong. An initial good response was achieved by 85% of the patients. Of the patients with a good response, fifty percent sustained an increase in platelet count for at least six months. A platelet count of less than 90,000 on day 10 was associated with a high risk of relapse.
New England Journal of Medicine, August 18, 2003, Vol. 349. No. 9, pp. 831-836
http://content.nejm.org/cgi/content/short/349/9/831?query=TOC
Data from the Framingham Heart Study found that women with the lowest vitamin K intake had significantly lower mean bone density. Vitamin K helps proteins bind to calcium with is required for proper bone growth. Recommended levels of vitamin K can be met by eating leafy green vegetables and vegetable-derived oils and spreads.
Agricultural Research, September 2003, P. 19. http://www.ars.usda.gov/is/AR/archive/sep03/sci0903.htm
For information on vitamin K see:
http://www.anyvitamins.com/vitamin-k-info.htm For information on foods that contains vitamin K see:
http://www.nal.usda.gov/fnic/foodcomp/Data/SR16/wtrank/sr16a430.pdf
(Note: Vitamin K is important for those with ITP for two reasons. Many people have taken prednisone which can contribute to bone density problems. Vitamin K is also needed for your blood to clot.)
An eight year old child with ITP and severe bleeding was helped by administration of recombinant Factor VIIa (rFVIIa; Novoseven). After administration of the treatment her bleeding decreased within a few minutes and stopped within an hour. Recombinant Factor VIIa interacts with tissue factor at the site of the injury and also binds to platelets to increase their effectiveness. Recombinant Factor VIIa is often used to treat hemophilia patients.
British Journal of Haematology 120: 907-915
For more information on Factor VIIa see: http://www.novoseven.com/
Thrombocytopenia can be associated with many viral, bacterial, fungal, and protozoan infections. Patients with this type of thrombocytopenia may not have anti-platelet antibodies or bone marrow suppression. Researchers associated with the University of Massachusetts Medical School studied one of the thrombocytopenia-causing bacterium, Brerelia hermsii (relapsing fever), carried by ticks and found in the mountains and forests of the western United States and southern British Columbia. Using a mouse model, they concluded that thrombocytopenia associated with relapsing fever is the result of the bacteria attaching directly to the circulating platelets resulting in their destruction. (“Blood” 15 October, 2003 Vol. 102, No. 8)
http://www.bloodjournal.org/cgi/content/abstract/102/8/2843
http://www.cdc.gov/ncidod/eid/vol9no9/03-0280.htm
GRANT OPPORTUNITIES HOLD PROMISE
The National Heart Lung and Blood Institute (NHLBI) and the Office of Rare Diseases are collaborating on a new program to support investigators with novel approaches to understanding, treating, and preventing rare heart, lung, and blood diseases. This new program will encourage exploratory projects and allow researchers to obtain support without large amounts of preliminary data (reported in ASH Newslink, October 1, 2003)
http://grants2.nih.gov/grants/guide/pa-files/PA-03-171.html
The NIH awarded nine, 5-year grants, totaling approximately $51 million to expand research on autoimmune diseases. Nine Autoimmunity Centers of Excellence will perform clinical trials and conduct basic research on these diseases that collectively effect 14 – 22 million Americans. The National Institute of Allergy and Infectious Diseases (NIAID) is the lead institute funding the initiative.
Note: ITP is an autoimmune disease. PDSA is a member of the National Coalition of Autoimmune Patient Groups, organized by the American Autoimmune Related Diseases Association (www.aarda.org) promoting increased NIH funding for autoimmune diseases.
ROADMAP REVAMPS NIH APPROACH
Elias Zerhouni, M.D., Director of the National Institutes of Health, presented the new NIH research direction at a briefing for professional and patient support groups on September 29. The research roadmap is designed to create a more efficient and effective research environment leading to more rapid research advances. The three main components of the initiative are “New Pathways to Discovery” (optimizing the genome and computational discovery),”Research Teams of the Future” (encouraging multi-disciplinary participation and innovation), and “Re-engineering the Clinical Research Enterprise (standardizing and streamlining clinical research). For a complete description of the roadmap see http://www.nihroadmap.nih.gov/
ENVIRONMENT AND DISEASE LINKS STUDIED
The National Institutes of Environmental Health Sciences (NIEHS) and the Center for Disease Control are designing a study to collect data on child development. By collecting data as children grow, the centers can help determine the incidence and triggers for various diseases. NIEHS scientists are also examining the differences in the genomes of various populations. They can then create mice with specific genetic configurations and observe the effect of environmental factors on the mice.
Note: PDSA is a member of the NIEHS Public Interest Liaison Group.
Japanese researchers found that the daily consumption of green or yellow vegetables and fruits is associated with a lower total risk of stroke and intracerebral hemorrhage mortality. The researchers administered a food frequency questionnaire as well as collected other information beginning in 1980 from a study population of 39,337 subjects. Daily intake of green or yellow vegetables and fruit was associated with a 26% reduction in the risk of death from stroke. (Stroke, Sept. 18, 2003 as published in Medscape)
http://www.medscape.com/viewarticle/461741?mpid=18842
The records of one hundred thirty consecutive patients with severe ITP treated at the University of Vienna were examined. Most of the patients were given prednisone, IVIg and/or had a splenectomy to keep their counts above 10,000. Of these patients, none died from bleeding, two died from infection, and seven died from other, unrelated causes. The authors conclude that ITP “is a relatively benign disease that does not require aggressive treatment. Bleeding can be prevented if the platelet count can be kept above 10,000 m/ul.” (T. Sailor, et.al, The Hematology Journal (2003) 4, 366-369)
http://www.nature.com/cgi-taf/DynaPage.taf?file=/thj/journal/v4/n5/abs/6200299a.html
H-Pylori is a bacteria that has been shown to cause stomach ulcers. It has also been associated with low platelets. In the past, several researchers reported that using antibiotics to eradicate the H-pylori bacteria raised the platelet counts of some ITP patients who tested positive for the bacteria. Now researchers have shown that some strains of H-pylori can induce platelet aggregation. Immunoglobulin G was also involved in the bacterium-platelet interaction. While there is no evidence that H.Pylori circulates in the blood, there is evidence that it promotes a strong inflammatory response that may pervade the body. Dermot Cox, of the Royal College of Surgeons in Ireland said, “There is also a strong case to be made for screening patients with thrombocytopenia for H-pylori and using eradication as the first step in treating thrombocytopenia.” (Tammy Dotts, Hem/Onc Today October, 2003)
http://www.hemonctoday.com
In an open-label trial of more than 100 patients, H.pylori was cleared in 92% of patients with gatifloxacin (a fluoroquinolone), amoxicillin and rabeprazole. This compares to eradication rates of 80% to 85% with conventional treatment consisting of a proton pump inhibitor, clarithromycin and either amoxicillin or metronidazole. The new regimen is a 7 day treatment with a much lower number of pills. The switch to fluoroquinolone is important because clarithromycin is no longer effective for a growing portion of the population.
Medscape News http://www.medscape.com/viewarticle/462905?mpid=20008
(Note: Eradication of H.pylori has been reported to lead to an increased platelet count for some patients with ITP who have an associated H.pylori infection.)
“Expensive, hard-to-make (bioengineered) drugs are now at the center of one of the drug industry’s hottest new markets: treatments for autoimmune diseases”, reports the Wall Street Journal. In the past year Amgen, Abbott Laboratories, Biogen, Inc, and Genentech, Inc. have launched drugs targeting autoimmune diseases. Abbott estimates the market could reach $14 billion by 2010.
The FDA has already approved the following genetically engineered drugs for treating autoimmune disorders: Enbrel (Amgen) Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis; Remicide (Johnson & Johnson Centocor) Rheumatoid arthritis, Crohn’s disease; Humira (Abbott) Rheumatoid arthritis; Amevive (Biogen) Psoriasis; Raptiva (Genentech) Psoriasis.
“New Battleground for Biotech Drugs: Autoimmune Ills” David P. Hamilton, Wall Street Journal, November 5, 2003
(Note: Many drugs, although developed for one autoimmune disease are tried in others, including ITP. Enbrel, in a limited clinical trial, has been shown to help patients with ITP. See http://www.itppeople.com/enews/enews081803.htm
Medications affect people differently depending on their genetic makeup. Now the Food and Drug Administration (FDA) plans to issue draft guidelines outlining when drug companies must submit information on how medicines affect people with different genetic profiles. This lays the groundwork for tailoring the drugs prescribed to a patient’s individual genetic signature. This type of “personalized medicine” could lead to prescribing drugs to only those who stand to benefit from the treatment and reducing serious side-effects. Already the FDA has begun approving some new drugs with labeling that contains genetic test information.
“FDA Will Issue Rules on New Era of ‘Personalized Medicine’, Anna Wilde Mathews, The Wall Street Journal, November 3, 1003.
Usually scientists describe the immune system as something that distinguishes self from non-self and autoimmune diseases as an error in that process. An alternative theory, proposed by Polly Matzinger, PhD, a researcher at the NIH, suggests that the immune system reacts only to injured cells after they release danger signals. For example, autoimmunity may be triggered by defects in the target cells (such as platelets). Now researchers at the University of Massachusetts report that injured or dying cells release uric acid which activates immune cells. They found that cells damaged by heat, chemicals or radiation increase production of uric acid and it stimulates an immune response to those cells.
“Danger, danger, cry injured cells” Science News, October 18, 2003
Shi, Y., J.E. Evans, and K.L. Rock. 2003. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425(Oct. 2):516-521. Abstract available at http://dx.doi.org/10.1038/nature01991
The danger model of immunity: http://cmmg.biosci.wayne.edu/asg/polly.html
(Note: This may help explain the success of some alternative therapies that are designed to improve tissue health)
The National Heart, Lung and Blood Institute, a part of the National Institutes of Health, recently launched a new web site. One of the features on the site is a section on ITP. See http://www.nhlbi.nih.gov/index.htm to access the new site.
The American Society of Hematology (ASH) 45th Annual Meeting and Exposition was held December 6 – 9, 2003 in San Diego. In addition to days filled with scientific education sessions, there were thousands of posters, hundreds of exhibits, and separate meetings of groups with like interests.
This version of the e-news is devoted to a few of the highlights from the ASH meeting. There is just too much to report in this venue. We will publish additional information in subsequent e-news. The Spring issue of The Platelet News, our quarterly newsletter, will feature a full-length article on the ASH meeting. See www.pdsa.org/joinus.htm to become a member and receive your copy.
You can read the ASH meeting abstracts, view a few of the presentations, and read articles from the ASH daily newspaper on the ASH web site, http://www.hematology.org
Articles:
The European Haematology Association (EHA) has established a working group on thrombocytopenias. The aim of the working group is to standardize and coordinate research projects worldwide. A central research focus will help reduce redundancy and facilitate comparison of research results. One of the working group’s first projects will be to standardize reporting terminology such as ‘complete response’ and ‘chronic’. Other projects include an ITP registry and genomic studies.
See: http://www.hemato.ven.it/EHAWG/home.htm
At our San Diego regional meeting, Dr. Drew Provan, co-chair of the EHA working group, discussed the EHA committee projects and other recent ITP research. We have an audio tape of the meeting. If you would like a copy of Dr. Provan’s presentation at our regional meeting send a $12.00 check and note to PDSA, P.O. Box 61533, Potomac, MD 20859. We thank Nabi for supporting our regional meetings.
Mycophenolate-mofetil (Cellcept ®), a drug used to prevent rejection in kidney and heart transplant patients, is sometimes used to treat ITP. Dr. Drew Provan described a study done by Hou Peng and associates and reported in the European Journal of Haematology. In this study, mycophenolate-mofetil was given to 21 refractory ITP patients. Sixty-two percent of these patients had some response to the treatment including 24% who had a complete response. The response to this treatment is slow and can take a few months. It is unclear what will happen when the medication is discontinued or the long term effects of taking this treatment.
http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601081.html
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12756016&dopt=Abstract
James Bussel, MD, reported on the results of a platelet growth factor (AMG531), an ITP therapy in the very early phase of testing. As in all new treatments, AMG531 was initially given to a few patients during a controlled clinical trial to assess the safety of the treatment. The results of this initial trial demonstrated that AMG531 was well-tolerated at a dose that maintained the platelet count in a normal range. Because of the positive data, a larger clinical trail is being planned.
The platelet count results from the same blood sample can vary widely, depending on the brand of machine used to analyze the sample and the time lag between taking the sample and its analysis. According to Sam Machin, MD, a consultant to several blood analysis machine manufacturers, the algorithms used to differentiate a platelet from other cells in the blood differ between manufacturers. Therefore, the same blood sample analyzed by different machines can produce very different results. Lab conditions can also cause variations in platelet count since platelets swell as they absorb the anti-coagulant mixture in the test tubes. These variations are particularly noticeable in platelet counts below 30,000.
In the corporate Friday program, “The Fifth Annual Review of Immune Thrombocytopenic Purpura, James Bussel, MD, during his talk on “ITP: New Developments in Diagnosis and Clinical Management” updated the audience on several studies on the eradication of H-Pylori in ITP patients. The results of the studies continue to be mixed in that some of them report a positive response in platelet count when H-Pylori positive ITP patients are treated to eliminate H-Pylori and others show no response at all in platelet count. He and others are planning a large scale trial to determine the factors that may be responsible for the variations in results. He also emphasized the desirability of using a breath test in determining if someone is infected with H-Pylori.
Other topics presented during “The “Fifth Annual Review…” are the pathophysiology of ITP and three case presentations on childhood ITP, pregnancy, and refractory ITP. This session was sponsored by Nabi pharmaceuticals. Nabi has donated copies of the handouts from the meeting. This is a 64 page booklet that contains a summary of the presentation and copies of the slides. If you would like a copy of the booklet, please send a note and a check for $7.00 to cover postage and handling to PDSA, P.O. Box 61533, Potomac, MD 20859.
There have been many studies evaluating the effectiveness of splenectomy. The study reported by Dr. Robert McMillan is the first large scale study to look at the outcome of patients whose platelet count relapsed after splenectomy. In his study, the records of 105 patients who failed splenectomy were reported. Seventy-five patients eventually attained a stable platelet count of over 50,000. Fifty-one patients maintained their remission after stopping all therapy, while 24 patients required continued treatment. Of those studied, 36% had additional autoimmune diseases and/or had a high incidence of venous thrombosis. Nine patients developed disorders, possibly associated with ITP, years after their diagnosis.
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British researchers state “age over 40 was identified as the only significant risk factor for response to splenectomy using the Cox multivariate analysis.”
This study evaluated 61 consecutive patients undergoing splenectomy for chronic ITP. Fifty-four patients were followed for an average time of 7.6 years. Thirty-nine (72%) had an immediate complete response (platelet count rose to >100 x 109 / l.) and 9 (17%) had an immediate partial response (platelet count rose to 30 – 100 x 109 / l.). However there was a constant relapse rate during the first 36 months of follow-up and further relapse starting 70 months after surgery. The researchers used a multivariate model to determine any association of sex, age, platelet count, years of thrombocytopenia, associated disease, time of splenectomy , and the response to medical therapy. They state “age over 40 was identified as the only significant risk factor for response to splenectomy using the Cox multivariate analysis.” While the timing pattern of relapse was similar for both age groups, the rate of relapse was significantly greater for those over 40. Two years out, of the initial 48 responders, 8%of the younger group but 25% of the older group relapsed. More alarming, 15 years out 38% of the less than 40 age group relapsed but 75 % of those in the over 40 age group had relapsed. The authors conclude “splenectomy is an effective treatment for chronic ITP but the response rate decreases with time. Choosing splenectomy for ITP treatment requires individual case analysis because only young age seems to be a predictive factor for a good response.
F. Fabris, et al, “Age as the Major Predictive Factor of Long-Term Response to Splenectomy in Immune Thrombocytopenia Purpura”, British Journal of Haematology, 2001, vol. 112 pp 637 -640.
Note: This study was published in March 2001 but came to our attention as part of Dr. Terry Gernsheimer’s presentation during the ITP Conference 2004 in Baltimore. We are contacted frequently by older patients being considered for splenectomy and we wanted to make more people aware of these findings.
The office of New York State Attorney General, Elliot Spitzer, has unveiled a website offering drug price comparisons at pharmacies across New York State.
The prescription drug website (www.nyagrx.org) reports the prices of 25 commonly prescribed drugs at certain pharmacies across the state. Users will be able to search by zip code and distance or by city or county. The survey includes only pharmacies in New York State. While the prices posted on the website are based on a survey of New York State pharmacies, the information can be useful to anyone shopping for prescription drugs.
From News Services
A new drug being developed by Abbott Laboratories with the designation ABT-874 has shown promise in treating Crohn’s disease and may also be effective in treating other autoimmune diseases.
Researchers at the National Institutes of Health (NIH) and elsewhere found that weekly injections of ABT-874 reduced symptoms in as many as 75% of Crohn’s patients, three times as many as placebo injections. The drug might also be effective in treating other autoimmune diseases such as multiple sclerosis and arthritis. Abbott Laboratories has not decided whether to conduct further tests. The study was headed by Peter Mannon of the National Institute of Allergy and Infectious Diseases. It was reported in the November 11, 2004 New England Journal of Medicine.
Washington Post, November 11, 2004, p.A16.
A study drawing on the medical records of more that 360,000 people found that drugs such as Nexium, Pepcid, and Prilosec used to treat heartburn might increase a person’s chance of getting pneumonia.
Drawing on medical records compiled between 1995 and 2002 for more than 360,000 people, researchers found that those using acid blockers were 4.5 times more likely to develop pneumonia as people of the same age and gender who had never used these drugs. The researchers also matched each of 475 individuals using acid blockers with 10 people of the same age, gender, and general health who had stopped taking the drugs at some earlier date. This analysis demonstrated that a person taking an acid blocker has twice the risk of getting pneumonia as does someone who has stopped taking the drug. Stomach acid aids digestion and kills pathogens. Speculation suggests that reducing stomach acid increases stomach bacteria that can migrate up the esophagus and enter the lungs. These findings are particularly worrisome for individuals with compromised or suppressed immune systems or individuals with chronic lung conditions. This research also raises questions about the long-term use of these medications.
N. Seppa, “Affairs of the Heartburn”, Science News, October 30, 2004, p 277.
(Note: Many ITP treatments suppress the immune system)
“Rare but potentially serious” events such as serum sickness, thrombocytopenia, anaphylactic shock, and seizures prompt officials to recommend continued surveillance of the 7-valent pneumococcal conjugate vaccine, Prevnar.
This vaccine was tested and proved effective in 19,000 infants and children in clinical trials prior to FDA approval. During the two years following approval, there were 4,154 events (13.2 per 100,000 doses) reported to the Vaccine Adverse Event Reporting System (VAERS). Most commonly reported were fussiness, rashes, fever, and injection site reactions. Immune mediated events accounted for 31.3% of the reports, anaphylactic reactions occurred in 14 cases, thrombocytopenia was reported in 14 cases and serum sickness in 6 others. Seizures were reported in 393 cases, mostly in individuals with a previous history of the problem. The FDA and the CDC will continue to monitor reports of adverse events for this vaccine and encourage clinicians to report such events to VAERS.
M. Rauscher, “Continued Surveillance of Pneumococcal Vaccine Adverse Events Warranted”, Medscape from JAMA 2004;292:1702-1710.
Phthalates used in certain plastics and floor coverings were identified as a possible source of environmental triggers for allergies.
Phthalates are used in the manufacture of soft plastics and some vinyl flooring. They are also used in cosmetics and plastic toys. These chemicals separate out from the products that contain them and attach to dust particles. Researchers in Sweden, in an effort to determine whether high concentrations of phthalates in dust correlate with allergies, studied children in 400 homes. They found that children exposed to the greatest concentrations of di-ethylhexyl phthalate (DEHP) were almost 3 times more likely to have asthma as were children exposed to the lowest concentrations. Also in homes with the greatest concentrations of butyl benzyl phthalate, children were approximately 3 times more likely as the other children to have rhinitis and eczema. Other phthalates studied were not associated with these three diseases. The study highlights the different phthalate exposures in children with and without allergy related illnesses. The study does not address or demonstrate a causal relationship between phthalates and the several diseases studied. Other important variables such as the humidity and the cleanliness of the homes was not evaluated or studied.
B. Harder, “Dangerous Dust? Chemicals in plastics are tied to allergies”, Science News, July 4, 2004, pp52-53.
Resources and the political will to support safety research and implement safeguards in hospitals and physician’s offices across the nation are lacking.
The 1999 report of the Institute of Medicine warned of outdated and sometimes nonexistent safety practices that were causing widespread errors in physician’s offices, operating rooms, and pharmacies. The report claimed that between 44,000 and 98,000 lives were lost each year as the result of preventable mistakes. Now, five years later, the debate centers on what to measure not on how to save lives. The reluctance of physicians to share authority with other health care professionals may be at the center of the problem. The report recommended physicians, nurses and other health care professional work as a team. The team work aboard aircraft was cited as a model. A 2000 study reported that 50% of surgeons felt the decisions of the leader in their field should never be questioned when making decisions; less than 10% of pilots responded the same way. Much work remains to be done in this area.
T. Zwillich, “Little Progress Seen in Patient Safety Measures”, Medscape, http//www.medscape.com/viewarticle/493127.
“Congenital thrombocytopenias, once considered rare and obscure conditions, are today recognized with increasing frequency….”. It is especially important to distinguish low platelets due to inherited genetic abnormalities from ITP. The treatments used for ITP will be ineffective if the cause of low platelets is genetic reports Dr. Jonathan Drachman in his review article in the journal “Blood.”
Many of the congenital thrombocytopenias have platelet abnormalities that can be recognized by a careful review of a blood smear. In adults, congenital thrombocytopenias are usually mild or moderate with platelet counts above 20,000. Factors such as family history, and tendencies toward easy bruising, prolonged bleeding, or petechiae are important considerations in diagnosis.
If congenital thrombocytopenia is suspected, it is important for the patient to see a hematologist who specializes in inherited platelet disorders.
“Inherited thrombocytopenia: when a low platelet count does not mean ITP” by Jonathan G. Drachman, Blood, 15 January 2004, Vol. 103, No. 2 http://www.bloodjournal.org/
Note that this article contains a long list and description of various inherited thrombocytopenias. See www.itppeople.com/lowplate.htm for a partial list.
See also http://www.familygenetics.net/
Megakaryocytes are bone marrow cells that produce platelets and other blood cells. In the past, studies have shown that 30% to 50% of patients with ITP have a reduced rate of platelet production. Now scientists in the Netherlands have found evidence that the reduced platelet production may be associated with injured megakaryocytes. They found that the megakaryocytes of ITP patients had extensive abnormalities. These megakaryocytes were surrounded by neutrophils and macrophages (types of white blood cells) indicating an inflammatory response against the megakaryocytes. The megakaryocytes also displayed characteristic signals that cells display when they are dying. The authors concluded that the release of platelets into circulation was depressed in some cases of active ITP possibly due to the action of autoantibodies against the megakaryocytes.
Patients with systemic lupus erythematosus (SLE) have an increased prevalence of heart attacks according to studies in the New England Journal of Medicine. In one study 40% of lupus patients had atherosclerotic plaques, a precursor of heart problems. This could be due to the chronic activation of the immune system. Possible SLE-related risk factors include systemic inflammation, autoantibodies to endothelium cells that make up the inside of blood vessels, HDL, phospholipids, circulating immune complexes, activated complement products, nephritis (kidney disease), and dyslipidemia (disorders of HDL and LDL metabolism).
“Systemic Lupus Erythematosus and Accelerated Atherosclerosis”, Bevra Hannahs Hahn, MD, NEJM 349:25, December 18, 2003, P. 2379
“Prevalence and Correlates of Accelerated Atherosclerosis in Systemic Lupus Erythematosus
Platelet microparticles, a marker of platelet activation, are often elevated in ITP patients according to Yeon S. Ahn, MD. In his 2002 study of twenty ITP patients who experience cognitive problems, he observed evidence consistent with small vessel disease. He concluded that thrombic complications can occur in ITP. This could lead to gradual memory loss and vascular dementia. The progression was faster in those with splenectomy and higher platelet counts. At the 2003 American Society of Hematology conference he presented research showing that ITP patients who experienced the dementia had plasma that activated the endothelial cells lining the walls of the blood vessels. This could lead to thrombosis and cause small stroke-like reactions in the brain.
ASH Abstract [1052] Plasma from Patients with ITP-Associated Dementia (ITPAD) Activates Endothelial Cells (EC) and Enhances Transendothelial Migration of Leukocytes (TEML). Session Type: Poster Session 164-I www.hematology.org
“Vascular dementia in patients with immune thrombocytopenic purpura” J Clin Lab Med 119:334,1992; Throm Res 107:337,2002
“People who become partners in their care and view the receipt and delivery of healthcare as a service wherein they are the consumer and the doctor or clinician is the provider, will feel more in control and will likely have better outcomes than people who assume the more traditional role of ‘patient’.” In the past the physician/patient model was considered one of compliance and patients who found it difficult to follow physician directive were considered non-compliant. Now it is recognized that the more active a role a person takes in deciding their treatment protocol, the more likely that the decisions will be carried out.
“Becoming a partner in your healthcare” R. Paper, RN, Haemophilia (2002), 8, 447-449
In most studies of ITP and pregnancy, the focus has been on the infant. In a new retrospective study at McMaster University in Hamilton, Ontario, the records of 119 pregnancies over an 11-year period were reviewed. They revealed that for most women, the pregnancies were uneventful. However 21.5% of the women had moderate to severe bleeding. Most deliveries (82%) were vaginal. The authors concluded that “ITP in pregnancy carries a low risk, but mothers and infants may require therapy to raise their platelet counts.”
“A retrospective 11-year analysis of obstetric patients with idiopathic thrombocytopenic purpura” Blood, 15 December 2003, Vol. 102, No. 13. www.bloodjournal.org
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We are often asked, “How can I assist with ITP research?” One way is to participate in a clinical trial.
We have several major clinical trials listed on our clinical trials page (http://www.itppeople.com/clinical.htm) that are open for enrollment. They include:
AMG 531- Part B of "An Open-label, Dose-finding Study Evaluating the Safety and Efficacy of Amgen Megakaryopoiesis Protein 2 in Thrombocytopenic Subjects With Immune Thrombocytopenic Purpura" is now enrolling patients. There will be 10 study sites participating. For more information and to find a study site near you see http://www.centerwatch.com
Preliminary results from Part A of this study have been promising. See http://www.abstracts2view.com/hem/ and place "AMG 531" in the search box to view the abstract from the 2003 American Society of Hematology meeting.
Rituximab in Children - The purpose of this study is to formally evaluate the safety and effectiveness of Rituximab in children and adolescents with severe or refractory ITP. For general information and a reference for parents, see http://www.itpkids.org.
More specific inquiries (from MDs) may be addressed to Pamela Boardman, Study Coordinator, Children's Hospital Boston 617-355-2901; pamela.boardman@tch.harvard.edu
Daclizumab - Hematologists are testing a new monoclonal antibody treatment (Daclizumab) for people with ITP. The study may help increase platelet counts, reduce bleeding symptoms, and reduce or discontinue immunosuppressive medications. The study takes place at the NIH Clinical Center in Bethesda, Maryland, right outside of Washington, DC. Please call for more information: (301) 496-515. See:http://www.clinicaltrials.gov/ct/gui/show/NCT00049725;jsessionid=C732EB24588
Enbrel - "Prospective Trial of Etanercept (Enbrel) in the Treatment of Chronic Immune Thrombocytopenic Purpura (ITP) in Children and Adults". This a pilot study of a commonly used arthritis drug that may help people with chronic ITP. Study sites include Comprehensive Bleeding Disorders Center, Peoria, IL and Children's Hospital of Orange County, Orange, CA. The treatment phase of the study will last twelve weeks, the observation phase for 6 months. For further information Dr. Michael Tarantino at mdtara@hemophilia-ctr-peoria.com or call 309-692-4533.
Compared with wild salmon, salmon farmed in Europe and North America has significantly more contamination with polychlorinated biphenyls (PCB’s) and 13 other organic chemicals report researchers at Indiana University. The researchers recommend limiting consumption to no more than one serving per month. Farmed salmon now accounts for the majority of salmon available in supermarkets. More than 1 billion kilograms are farmed each year worldwide.
Science News January 24, 2004, Vol 165
(Note: Many pollutants have been shown to exacerbate or potentially cause autoimmune diseases see: http://www.niehs.nih.gov/)
“The ability to pay attention to what you’re experiencing from moment to moment- without drifting into thoughts of the past or the future, or getting caught up in the opinions of what is going on- is called mindfulness” According to the “Harvard Women’s Health Watch” cultivating mindfulness can expand your capacity to cope with illness and possibly improve your health. One form of mindfulness practice is called mindfulness meditation. This type of meditation is the subject on several books and classes.
Harvard Women’s Health Watch, Vol. 11, No. 6, Feb. 2004 http://www.health.harvard.edu/women
See also: http://www.umassmed.edu/cfm/
Researchers at the Weill Medical Center of Cornell University in New York City tested 74 patients with ITP. They found H pylori infection in 16 of the patients. They eradicated H pylori in 15 of the 16 patients. As a result of the treatment for H pylori, the platelet count increased in only one of them. These results conflict with previously published results from other countries showing a positive platelet response in a larger percent of H pylori infected ITP patients when the H pylori is treated successfully. The authors hypothesized several reasons for this discrepancy including variations in the patients’ immune system, different strains of H pylori, and different anti-bodies associated with the H pylori infection. Future studies should be large, randomized and track other parameters that could be important determinants in response.
Marc Michel et al, Blood, 1 February 2004, Vol.103, No. 3
http://www.bloodjournal.org
In a comparison of blood from healthy donors and ITP patients, blood from 12 of 18 ITP patients showed a significant decrease in megakaryocyte production. (Megakaryocytes are cells in your bone marrow that produce platelets) In this test tube experiment, researchers from the Scripps Research Institute found that blood from ITP patients showed a decrease in the total numbers of megakaryocytes produced during the incubation period. They also found an impairment in megakaryocyte maturation resulting in reduced platelet production per megakaryocyte. These results are most likely due to ITP antibodies. The author’s suggest a similar effect may occur in the bodies of ITP patients.
Blood, 15 February 2004, Vol 103, No. 4
Women who consume little vitamin D develop multiple sclerosis (MS) at a rate about 50 percent higher than those who consume a high amount of the nutrient. Researchers from the Harvard School of Public Health analyzed the vitamin D intake from diet and multivitamins in 187,563 women. Of these, 173 developed MS. About 50% more of these women were in the least vitamin D intake group compared with the highest intake group. Previous studies found that many MS patients are deficient in vitamin D. It is not known whether vitamin D deficiency precedes the onset of MS or is the result of the disease. MS is more prevalent far from the equator where less of the sun’s ultraviolet light is available for people’s bodies to make vitamin D.
Science News January 31, 2004, Vol 165
Note: In our May 28, 2002 version of our e-news we reported “Researchers studying autoimmune liver disease report that Vitamin D appears to be an immune system modulator.”
Several people with ITP mentioned to us that they felt better when they spent some time in the sun. If you feel that sunlight has an effect on your ITP (positive or negative), please write to pdsa@pdsa.org
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Inflammation, your body’s response to infection, is increasingly linked to various diseases. It has been found to play a role in heart attacks, strokes, diabetes, Alzheimer’s disease, cancer, and autoimmune diseases. Remicide and Enbrel, drugs used to treat some autoimmune diseases, target specific inflammatory cytokines. In addition to taking drugs or supplements, you can reduce the amount of inflammation in your body by exercising, eating a diet low in fat and high in fruits and vegetables, and flossing your teeth.
“The Fires Within” by Christine Gorman and Alice Park, TIME, February 23, 2004
(An ITP clinical trial for Enbrel is in progress. See www.itppeople.com/clinical.htm)
Multi-tasking, doing too many things in too little time, elevates your cortisol levels, a hormone produced in your adrenal gland. Continued elevation of cortisol can lead to a weakened immune system and deplete other hormones. Dan Beskind, MD, concludes, “Most of us harbor a nagging belief that a slower life is a luxury we can’t afford. Our bodies tell us otherwise. Slowing down is essential to our health.”
“Juggler’s Syndrome: Multitasking isn’t just stressing us out – it’s endangering our health by Dan Beskind, MD, Utne Reaer, March-April 2004
Gamunex ® , a type of IVIg manufactured by Bayer HealthCare, has received approval from Germany’s regulatory authority for biological products. This follows its approval in the United States and Canada. Bayer HealthCare has also received FDA approval for an in-house nucleic acid test for the HIV virus in plasma donations.
News release from Bayer HealthCare. See www.bayerbiologicals.com
Mice treated with Arsenicum Album, a homeopathic remedy, reduced the liver toxicity induced by arsenic poisoning reported researchers in West Bengal, India. Arsenic tainted groundwater is a large problem in India and other countries. Homeopathy, a healing practice used for more than 200 years, treats illness with a minute dilution of the substance believed to cause the disease. In forty other studies that used homeopathic treatments to address toxic exposure, 27 showed positive results.
“Toxic Busters?” by Craig Cox, Utne Reader, March – April, 2004
http://www.newscientist.com/news/news.jsp?id=ns99994305
(Environmental toxins have been shown to exacerbate or potentially trigger autoimmune diseases. Dr. Noel Rose will speak on the subject at our upcoming ITP Conference 2004 www.pdsa.org/conference.htm)
“Platelets…regulate inflammation, tissue repair, and immune responses” report researchers Andrew Weyrich and Guy Zimmerman of the University of Utah. These comments in the March 15 issue of the journal Blood, were in response to two articles on platelets in that issue that dramatically expanded what is known about the proteins produced by platelets as they go about their work. Researchers at the Royal College of Surgeons identified more than 300 proteins that are released by platelets, only 37% of which were previously known. Understanding the proteins produced by platelets could lead to new diagnostic tools and therapies for thrombotic diseases.
“Propelling the Platelet Proteome” by Andrew Weyrich and Guy Zimmerman, Blood, 15 March 2004, Vol. 103, No. 6
“Characterization of the proteins released from activated platelets leads to localization of novel platelets proteins in human atherosclerotic lesions” Judith A. Coppinger, et al. Blood, 15 March 2004, Vol.103, No. 6
See://www.bloodjournal.org
(While this research is directed toward understanding atherosclerosis, it could be useful to those who have few platelets. People with ITP are not protected from getting heart disease, clotting problems, and strokes)
In our February e-news we mentioned a clinical trail using AMG531. The correct name for the trial is "A Dose finding Study Evaluating the Safety and Efficacy of Amgen Megakaryopoiesis Protein 2 [AMP2(AMG 531)] in Thrombocytopenic Subjects with Immune Thrombocytopenic Purpura (ITP)" We apologize for the error.
All of the sites for this clinical trial are now listed at www.centerwatch.com. Search on “ITP”.
In the last issue of our e-news we included an article linking the lack of vitamin D with multiple sclerosis. Since your body synthesizes vitamin D in the presence of sunlight we asked our readers to send an e-mail if they found that sunlight effected their health and platelets.
We received six responses. One person reported their bruising symptoms increased with exposure to the sun. The remaining five responses reported an overwhelmingly positive effect of sunlight on their health.
Researchers in Japan treated twenty ITP patients with escalating doses of an experimental monoclonal antibody that blocks the CD40/CD154 signal. An increase in platelets was seen in three of the five subjects who received 10 mg/kg, the largest dose tested. CD40 on the antigen-presenting cells triggers CD154 (also known as CD40 ligand) on T-cells. Blocking the interaction between these cells is thought to interfere with the antibody production that takes place in autoimmune diseases. This compound is currently being used in clinical studies for various autoimmune diseases. Further studies are necessary to confirm the benefit of anti-CD154 in ITP patients.
“Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thromocytopenic purpura” Blood, 15 February, 2004 Vol 104, No. 4
Encouraging positive thinking when the patient is a natural grouch can lead to unhealthy stress and a decrease in healing response reports Jimmie Holland at Memorial Sloan-Kettering. Patients who stay with their natural coping style rather that striving for a happy disposition have lower cortisol rhythms and natural killer cell counts, measures of stress and immune response.
“Fighting Cancer with a Frown:Research Questions Role of Optimism in Beating the Disease;’the Tyrrany of Positive Thinking’” A.D. Marcus, Wall Street Journal April 6, 2004
Drugs such as Viagra and other less common compounds increase cGMP, a chemical messenger that causes smooth muscles to relax and also interferes with the action of platelets. The new findings revise previous research that suggested increased cGMP lead to increased blood clots.
“Does cGMP mediate platelet inhibition or stimulation?” Wolfgang Siess,Blood, 1 April 2004, Vol. 103, No. 7, p. 2435
Lower levels of exposure to soot particles from diesel exhaust over time reduce the immune system’s capacity to fend off infection more than the same exposure concentrated at one time. A follow-up study by Joseph K. H. Ma of West Virginia University and his colleagues exposed rats to the same level of diesel-derived particles as administered in earlier work but spread the exposure over 5 consecutive days. In this extended exposure, more bacteria survived in the lungs of diesel-exposed animals than in rats that breathed clean air.
“Diesel fumes suppress immune response” Science News, March 13, 2004, p. 174.
Psoriasis, rheumatoid arthritis, and lupus, three distinct diseases, may share the irregular behavior of the same molecule. Three different research efforts have recently reported that these three different disorders seem to be controlled by the same protein, RUNX1 or runt-related transcription factor 1. This work may not quickly lead to new treatments but it does mean that research efforts that have been loosely connected can now converge on a common molecular target.
B. Harder, “All Roads Lead To RUNX”, Science News, April 3, 2004, p216-217.
IVIG (IGIV, Gammaglobulin, IgG) infusions have a long and successful history in treating a wide variety of illnesses including ITP. However there are small but significant differences in the preparations from different manufacturers that can make a difference in the product’s safety and the likelihood of adverse effects. The best way to minimize adverse reactions is to match product characteristics such as osmolarity, sodium content, sugar content, IgA content and pH, among others, with patient profiles. Osmolarity (associated with thrombotic complications) and sodium content have implications for patients with CHF, renal dysfunction, neonates, the elderly, and patients with hypertension and vascular disease. The sucrose in sugar containing preparations has been associated with renal failure.
R. Sacher, “Not all IGIV Preparations Are Created Equal”, Hem/Onc Today, March 2004, pp. 5ff.
http://www.hemonctoday.com/200403/igiv.asp
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