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Perchlorate, the main ingredient of solid rocket fuel was widely dumped at military bases and defense-industry sites during the Cold War. It still lingers in the water supply of 22 states including many of the USA’s fastest-growing population areas such as Nevada, Texas, and Southern California. Perchlorate is also a component of many commercial fertilizers and a by-product during the manufacturing of fireworks.
Perchlorate impedes the production of thyroid hormone. In pharmaceutical form it has been used as a treatment for an overactive thyroid. One of the side effects of treating thyroid disease with perchlorate is aplastic anemia. Aplastic anemia is characterized by bone marrow damage and pancytopenia (decrease in two of the three major cell lines in the blood – red cells, white cells, and platelets). Since, platelets are formed in the bone marrow, any substance that can damage bone marrow is of concern.
Grandipore, an Australian company, received a US Patent for its plasma separation process known as Gradiflow. Unlike other large scale purification technologies, Gradiflow can simultaneously purify proteins and remove viral and bacterial pathogens. This process is an improvement over those currently used which can leave residues of the detergent and killed viruses in the final product. The industrial potential of Gradiflow is under evaluation by leading plasma processing companies such as Cangene and Aventis.
For more information see: www.gradipore.com
Monoclonal antibodies (mab) are a relatively new class of treatment and increasingly being considered for treating ITP. Mab are often developed for treating other diseases, then tried on ITP patients. Last year PDSA added ITP clinical trials of the mab CTLA4 from Repligen (www.repligen.com) and Rituxan (www.rituxan.com) to our clinical trails list. This year we’ve added a listing for Zenapax (www.zenapax.com) also called daclizumab. This new trial is being conducted at the National Institutes of Health in Bethesda, Maryland.
See www.itppeople.com/clinical.htm for our clinical trial listings.
In a six month study, Antegren (natalizumab) a new mab from Biogen and Elan Corp. in Ireland, was reported to significantly reduce the brain lesions in people suffering from the relapsing form of multiple sclerosis. See: http://www.mult-sclerosis.org/Natalizumab.html
Humira, a mab, has been approved for the treatment of rheumatoid arthritis. The drug was developed by the Cambridge Antibody Technology Group in the UK and Abbott Laboratories in the US. See www.humira.com
The symptoms of patients with psoriasis, an autoimmune disease, improved 50% taking daily injections of the protein, interleukin-4, a Dutch-German research team reported in the January issue of Nature Medicine. It was reported that Interleukin-4 caused few side effects in the research subjects. (Science News January 4, 2003)
Korean researchers identified a compound that suppresses the immune system of animals. The research team reports that tautomycetin, isolated from a bacterial strain that grows in the soil of Cheju, an island just south of the Korean peninsula, kills human immune T cells in lab dishes. Mice treated with the compound survived an average of 160 days after a heart transplant vs. two weeks for mice treated with cyclosporin A. Note that cyclosporin A is sometimes used to treat ITP. (Science News August 31, 2002)
Post-transfusion purpura (PTP) is a complication of blood transfusions where platelet counts can plummet to below 10,000. This is a relatively rare condition, but is becoming more widely recognized reported Jan McFarland, MD of the Blood Center of Southeastern Wisconsin at the annual meeting of the American Association of Blood Banks in October, 2002. IVIg is the preferred first-line treatment for PTP. Since there is a risk of recurrence of PTP with subsequent transfusions, it is important for patients to know their diagnosis and future risk. January 2003, Hem/Onc Today (www.hemonctoday.com)
Thrombocytopenia can be induced by GPIIb/IIIa inhibitors, a new class of drugs used to prevent blood clots often following coronary angioplasty. Three GPIIb/IIIa inhibitors, abciximab, tirofiban, and eptifibatide, are approved in the US. In clinical trials 0.5 – 2 percent of patients treated with these agents experienced acute thrombocytopenia. Roxifiban, a new GPIIb/IIIa inhibitor given orally, also produced thrombocytopenia in 2% of patients in a recent clinical trial. From the January 1 issue of Blood (www.bloodjournal.org)
“Heparin induced thrombocytopenia (HIT) is one of the most common and potentially devastating of immune-mediated drug reactions” reports Dr. Barbara Alving in the January 1 issue of the journal, Blood. HIT should be suspected if the patient recently received heparin and has a marked drop in platelets. In HIT Antibodies develop against platelet factor 4 and begin a cascade of events that can end in thrombosis (blood clots). The seven page article in Blood continues with detail recommendations for laboratory testing, treatments, and patient management. (www.bloodjournal.org)
This e-newsletter is published by the Platelet Disorder Support Association, P.O. Box 61533, Potomac, MD, 20859, phone:1-87-Platelet or (301) 294-5967, fax: 301-294-3125, web: http://www.pdsa.org/, e-mail: pdsa@pdsa.org,
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In these volatile times, it is sometimes difficult to know the best course of action. Here’s some information that may help with any decisions you and your family face concerning smallpox vaccine.
“Patients with immune deficiency disorders and their household contacts should not be vaccinated…Any person with a condition that requires the use of prednisone or other immunosuppressive agents should not receive the smallpox vaccine at this time… If there were to be outbreaks of smallpox associated with bioterrorism, these people should check with their doctors before considering smallpox vaccination,” state Dr. Neal Halsey, Department of International Health, Johns Hopkins School of Medicine, and Dr. Noel Rose, Autoimmune Disease Research Center, Johns Hopkins University in a report written for the American Autoimmune Disease Related Association. For the full report see: http://www.itppeople.com/smallpox.htm.
You can receive more smallpox and vaccine information from the National Vaccine Information Center. See: http://www.909shot.com/Newsletters/spsmallpox.htm
The USP Drug Information Listing is a compendium recommending how therapeutics should be reimbursed for different diseases and conditions. The most recent USP Drug Information Listing (Vol. I, January 2003) has accepted Rituxan for the treatment of ITP for the first three doses. Although the FDA has not approved Rituxan for the treatment of ITP, the cost of the first three doses of Rituxan may be covered by managed care based on the USP DI's listing.
See: http://www.nlm.nih.gov/medlineplus/druginformation.html and http://www.usp.org/
Researchers have now linked the action of Sildenafil (Viagra) directly to some deaths from heart attacks. Sildenafil (Viagra) stimulates the production of an enzyme called PKG (cGMP–dependent protein kinase). Researchers have long known that PKG keeps platelets from sticking together. Now researchers at the University of Illinois College of Medicine report that PKG plays a dual role, first promoting platelet aggregation, then later, inhibiting platelet function. They found that PKG made platelets clingier only when natural blood-clotting stimulants were present. After several minutes, platelets became less sticky.
From Science News, January 18, 2003. See: http://www.sciencenews.org/20030118/fob8.asp
(Avoiding substances that inhibit platelet function is fairly obvious for someone with few platelets. However, Viagra can pose a dual problem for patients with ITP, especially those without spleens. A study published in the July 16, 1977 issue of the Lancet “Splenectomy and Subsequent Mortality in Veterans of the 1935-45 war” concluded that the splenectomized veterans they studied had increased mortality due to heart disease. During a meeting associated with the 2001 American Society of Hematology conference, Dr. Ahn from the University of Miami reported on the unusual incidence of small strokes and heart problems among his ITP patients. For more information see The Platelet News, Winter 2001, http://www.pdsa.org/newsletter.htm...ed.)
Loud noise can increase free radicals and damage DNA, according to researchers at the University of Pisa in Italy. They blasted 10 male lab rats with 100 decibel noise, the volume heard in some dance clubs, then analyzed their cells. They found the rats subjected to the loud noise had more broken cell membranes than those held in a quieter environment. “Loud sound sensed by the auditory system can trigger a surge in blood concentrations of the hormone norephephrine, which stimulates heart cells to absorb too much calcium. That can weaken the membranes of the mitochondria and cause them to release free radicals,” notes Pisa geneticist Giada Frenzilli. In the past, loud noise has also been linked to high blood pressure and heart disease. Other researchers suggest that the loud noise causes stress and it is the stress that is responsible for the damage. See: http://www.sciencenews.org/20030201/fob4ref.asp
(At the 2002 American Society of Hematology Meeting, some researchers reported on the link between free radicals and ITP. We will have more information on the ASH conference in our next issue of The Platelet News…ed.)
The World Health Report 2002 – Reducing Risks, Promoting Healthy Life concluded that life expectancy could be increased by five to ten years if government and individuals address the major health risks. The top ten global risks are childhood and maternal underweight; unsafe sex; high blood pressure; tobacco and alcohol use; unsafe water, sanitation, and hygiene; high cholesterol; indoor smoke from solid fuels; iron deficiency, and overweight and obesity. The health risks differ markedly between richer and poorer nations. According to Christopher Murray, MD, PhD, director of WHO’s World Health Report 2002, “Globally, we need to achieve a much better balance between preventing disease and merely treating its consequences.”
From Hem/Onc Today, January 2003, pp. 15-17
The full report is available in all six WHO official languages - English, French Spanish, Arabic, Chinese and Russian –See: http://www.who.int/whr/en/
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Several new research programs sponsored by the National Center for Complementary and Alternative Medicine will explore the mind-body connection in healing. A pilot study at the California Pacific Medical Center suggested that it is possible to measure biological properties of cultured human cells in response to healing intentionality. Also, the University of Arizona’s new Center for Frontier Medicine in Biofield Science will offer doctor training and research opportunities to understand the connection between biofield therapies like qi gong on cellular function.
Ions Noetic Science Review Dec.2002-Feb.-2003 pp. 36 – 38
Patients involved in fibromyalgia research at the University of Louisville and psoriasis research at the University of Massachusetts Medical School Stress Reduction Clinic responded to treatment faster when they learned relaxation techniques such as meditation. (Note: fibromyalgia and psoriasis are autoimmune diseases)
Shape.com March 2003. pp. 103
Rheumatoid arthritis patients reduced their pain and inflammation in 12 weeks after switching from a western diet to a traditional Mediterranean diet, according to Ume University’s Dr. L. Hagfors and his associates. The diet called for a high consumption of fruit, vegetables, cereals, legumes, olive or canola oil, and green or black tea instead of wine. C reactive protein levels and thrombocyte counts were also decreased by this diet. (Note: Rheumatoid arthritis is an autoimmune disease)
“Mediterranean Diet Suppresses Disease Activity in Rheumatoid Arthritis” Reuters Health Information. Feb 19, 2003.
Thrombocytopenia in systemic lupus erythematosus (SLE) patients may indicate a severe familial form of the disease, report researchers at the University of Oklahoma. The associated genetic risk factors therefore need to be identified. Thrombocytopenia was associated with nephritis, serositis, neuropsychiatric involvement, autoimmune hemolytic anemia, anti-double-stranded DNA, and anti-phospholipid antibody.
“Thrombocytopenia identifies a severe familial phenotype of systemic lupus erythematosus and reveals genetic linkages at 1q22 and 11p13” Acofield, Bruner, Kelly, Kilpatrick, Bacino, Nath and Harley, Blood 1 February 2003 Vol. 101, No. 3 pg. 992
See: http://www.bloodjournal.org
Drinking a beer a day alters the structure of fibrinogen, a blood protein involved in blood clotting, report researchers at Hebrew University-Hadassah Medical School in Jerusalem. When the subject’s blood was analyzed ten percent of their fibrinogen disappeared and much of the remaining fibrinogen underwent changes that compromise the blood clotting process. The group suggests that some of the fibrinogen effect may be traced to polyphenols, pigmented antioxidant compounds in beer, green and black tea, red wine, and grape juice .
“Why beer may deter blood clots”, Science News, March 8, 2003, Vol 163, P. 157.
See: http://www.sciencenews.org
Nobel Laureate James Watson, National Human Genome Research Institute Director Francis Collis and others will share their insights in a free program at the National Museum of Natural History in Washington, DC on April 15, 2003 from 9AM to 1PM. A limited number of scholarships are available to defray travel and/or lodging costs for members of the public who otherwise could not attend.
See www.genome.gov/About/April2003. For a scholarship application call 301-402-0955.
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Thrombopoietin treatment may hold promise in raising platelet counts for various types of thrombocytopenia Dr. David Kuter reported at the American Society of Hematology meeting held Dec. 6, 2002. In a limited research study reported in the journal Blood, several patients with ITP had a rise in platelet count after receiving the PEG-rHuMGDF form of thrombopoietin (platelet growth factor). In other studies thrombopoietin raised platelet counts in some patients with thrombocytopenia due to cancer treatments and HIV. The PEG-rHuMGDF form of thrombopoietin is no longer being developed in North America due to anti-body formation. Research here has shifted to rHuTPO, more nearly like native thrombopoietin.
Hem/Onc Today ASH Symposia Highlights April 2003
Blood. 2002; 100(2): 728-730
www.bloodjournal.com
Female rheumatoid arthritis patients might consider consulting a doctor about aggressive monitoring and treatment of heart disease risk factors, according to a study reported in online versions of the February issue of Circulation. Circulation reports women with rheumatoid arthritis, an autoimmune disease, had twice the risk of heart attack compared to those who did not have the disease. The Merck-supported study looked at heart attacks in 114,342 women, 527 of which developed rheumatoid arthritis in 20-year follow-up. Past studies have found that inflammation of the joints can lead to fatty buildup in blood vessels.
Washington Post
(Note: ITP is also an autoimmune disease. Although platelets are low, patients with ITP can still have heart disease)
“Idiopathic Thrombocytopenic Purpura: Pathophysiology and Management” by Yeon S. Ahn and Lawrence L. Horstman published in the International Journal of Hematology is available on the web. See: http://haem.nus.edu.sg/ishapd/2002/827.pdf
Our thanks to one of our discussion group members for finding and posting this link. See http://discuss.pdsa.org
Stress and the “nerve gas pill” (pyridostigmine bromide, PB, NAPS) are two main potentially explanatory factors in the Gulf War cluster of illnesses. The diseases are mostly common ailments occurring at a high level of incidence and possibly the result of the mixture of acute chemical and physiological stressors that could begin an automimmue response in some organs, tissues, or cells. Veterans of the Gulf War were exposed to these elements in a shorter time, in greater intensity, and at a higher percent of exposure than the general population. Studying these experiences may serve to help prevent or possibly treat diseases linked to these risk factors.
Med Hypotheses 2001 Feb;56(2):15
Most Americans carry a whole new set of toxins in their blood compared to 40 or 50 years ago, says Mount Sinai School of Medicine pediatrician Philip Landrigan, commenting on two new studies of the prevalence in the human body of more than 100 chemicals, including phthalates, DDT, lead and other metals. The CDC and the Washington, DC-based Environmental Group performed the studies separately. “As a society, we are still treating chemicals as if they are innocent [safe] until proven guilty [unsafe],” says Tufts University endocrinologist Ana Soto. Children who eat organically grown fruits and vegetables have only one-sixth the concentrations of organophosphate pesticide byproducts in their urine as children who eat conventionally grown produce reports Cynthia Curl of the University of Washington.
Science News February 22, 2003 Vol 163 pg. 120
New technology expert David Bates of the Brigham and Womens’ Hospital in Boston is studying “smart pumps,” or improved IV technology in the hospital’s cardiac units. The devices, intended to reduce medical errors and drug overdoses, can be programmed with hospital guidelines and warn caregivers who violate the guidelines or stop delivering treatments completely. Smart-pump designer Alaris Medical Inc. is offering the market an option for addressing what they count as about one life-threatening IV mistake every two and one half days. The pumps cost $1.2 million for the average hospital, making the technology not yet widely available.
Wall Street Journal 3/26/03 Laura Landro
Almost 100 U.S. hospitals offer alternative or complementary treatments, and that is a number that was fewer than a dozen three years ago. The institutions say they are just responding to patient demand, according to experts, despite some concern that these treatments might only offer false hope. People in the U.S. make about 600 million visits a year to unconventional caregivers, while hospital facilities report a doubling or tripling of patients who seek care for automimmune and other diseases. Treatments include acupuncture, Reiki, aromatherapy, and different forms of meditation.
The Holistic Hospital 3/28/03 pg. W1
On April 3, 2003, the Supreme Court ruled that sates can require managed care health plans to accept any qualified doctor who wants to participate in their health plan, upholding a Kentucky law. While about half the states have “any willing provider” laws most apply only to pharmacies rather than the full range of medical care. States have become more active in passing health care legislation because of the stalemate at the federal level.
New York Times, April 3, 2003
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Intravenous Immunoglobulin (IVIG) is a limited resource, expensive, and since it is a blood product, carries some risks. These qualifications make finding a substitute very attractive. Researchers at St. Michael’s Hospital in Toronto experimented with various monoclonal IgG antibodies using mice with ITP hoping they could find one that worked in a similar way to IVIg. The good news….they found a monoclonal IgG antibody (anti-CD24) that improved the thrombocytopenia of ITP mice.
From “Blood”, 1 May 2003- Vol. 101, No. 9. See: http://www.bloodjournal.org
(Note: Dr. John Freedman, one of the researchers involved in this study, will be speaking at our conference. Our ITP Conference 2003 will be held June 20-22 in Rosemont, IL. See http://www.pdsa.org/conference.htm for more information )
In a literature review of mind-body interventions such as relaxation, meditation, imagery, biofeedback, and hypnosis researchers concluded that there is significant evidence of their efficacy in the treatment of some common diseases. They concluded “There is considerable evidence that an array of mind-body therapies can be used as an adjunct to conventional medical treatment for a number of common clinical conditions.”
Because of time constraints the authors did not examine more body based approaches such as yoga and tai-chi chuan.
See: http://www.medscape.com/viewarticle/452275
(Note: There has been no specific research examining the efficacy of mind-body interventions for ITP. However, our survey showed that several hold promise. See http://www.itppeople.com/surveyres/
Following work that analyzed the genetic makeup of patients with various autoimmune diseases and finding 18 overlapping clusters, researchers at the Center for Genomics and Human Genetics at the North Shore Long Island Jewish Research Institute have initiated a project to identify the genes that some autoimmune diseases have in common. Of the 80 identified autoimmune diseases, they will look at the overlapping genetics in 8 of them. Since the same autoimmune disease can vary considerably, the genetic study can help identify the various ways the disease is characterized and potentially lead to more directed treatment.
Unique disease subclasses can arise as various genetic and environmental elements interact. Frederick Miller, of the National Institute of Environmental Health Sciences (NIEHS) is enrolling twins and siblings for a large study hoping to get a list of environmental factors that effect disease prognosis. They will assess factors like infectious agents, drugs, vaccines, foods, solvents, stress, and others.
(Note: Representatives from PDSA will be working with the director of NIEHS to determine how PDSA can become involved in this work)
Thanks to Enrique Gonzales Vergara, PhD for sending this article.
Thousands of scientists and lay people gathered in Washington, DC the week of April 13, 2003 to celebrate the 50th anniversary of James Watson’s and Francis Crick’s discovery of the structure of DNA.
Coinciding with the celebration, an international six-country consortium of scientists declared that deciphering the genome, the pieces of the DNA, is now complete. The sequencing is just the beginning. Now scientists will be able to identify the approximately 30,000 proteins encoded in the genes and characterize their interactions inside cells and among cells.
With the genome as a tool, researchers may be better able to predict the result of treatments, identify risks, and separate the interaction between genetic and non-genetic factors. This new knowledge will have the potential for preventing or mitigating disease and providing more targeted treatments.
Increased genetic information raises many questions for patients and doctors such as “Does a patient have a duty to warn family members?”, “Will the identification of genetic risk lead to life style change?”, “How can we distinguish from useful and non-useful genetic information?” Genome research also prompts policy questions such as “Can genetic labeling be avoided?” and “How can fair and equitable access to the technology be assured?”
There are many obvious things to learn from the 50-year DNA journey. Some not-so-obvious gleanings are that Watson and Crick didn’t know much about chemistry, although they solved what was essentially a chemistry problem. They were two very good friends who beat two other teams characterized by contentious relationships. Acceptance of their results was slow. Even five years after their results were published may doubted or ignored their work.
A new map of chromosome 7 shows the location of 440 disease-related rearrangements, places where the DNA has shifted. This new map is part of a larger project to represent chromosome abnormalities, genes, and mutations associated with specific diseases. Chromosome 7 is the largest human chromosome to be sequenced and refined to a high degree of accuracy. The work was completed with the help of some 90 researchers around the world.
See: http://www.genomenewsnetwork.org/articles/04_03/chrom7.shtml
You can find out more about the genome project and the DNA discovery in:
Genentech and IDEC have decided not to proceed with company-sponsored clinical development of Rituxan in ITP at this time. The trial was placed on clinical hold by the FDA, not due to concerns regarding patient safety, but due to study design issues. A number of Phase II studies have been published during the past few years showing that Rituxan may be a promising approach in the treatment of ITP.
Genentech remains committed to exploring treatment options for patients with ITP and will continue to support investigator-sponsored trials that extend current knowledge and ask novel questions. Genentech will continue to develop Rituxan for the treatment of other oncologic and autoimmune diseases.
Additionally, there is currently a compendia listing to help patients with ITP secure reimbursement for treatment with Rituxan.
Positive thoughts, even unrealistic positive thoughts, can promote health according to Shelley Taylor, a professor of psychology at the University of California, Los Angeles. In several studies of HIV positive patients she and her team found that patients who found positive meaning in their lives and the lives of others lived longer. She concludes that optimism may improve immune system function. It may also promote a healthier lifestyle, good social relationships, and assist in managing stress.
Opportunities in Science and Theology, Vol. 3 No. 10, June 2003.
(These results are consistent with our survey of Non-Traditional Treatments in ITP. In our survey 38% of the responders reported using positive thinking. Of those, more than 40% reported at least some improvement in their counts and bleeding symptoms from thinking positively. For more information on our survey results see http://www.itppeople.com/surveyres/
A patient who complained of a headache, vomiting, and earache was given various medications including ibuprofen. Ibuprofen is one type of non-steroidal anti-inflammatory drug or NSAID. A week later after the patient continued to complain of a headache and found blood in his urine, he was diagnosed with ITP (platelet count 14,000). He was given prednisone and continued on an ibuprofen drug. Later he developed an enlarged spleen, jaundice and a brain hemorrhage, resulting in a chronic neurologic disorder. After taking into consideration all of the symptoms and additional tests, it was determined that the patients brain hemorrhage was most likely due to infectious mononucleosis.
In a resulting lawsuit the patient’s lawyers argued that giving NSAIDs to someone with ITP was inconsistent with the American Society of Hematology (ASH) practice guidelines for treating ITP. Although the ASH guidelines clearly state they are recommendations, not mandates, physicians are cautioned that legal action could result if NSAIDs are give to patients with ITP.
Hem/Onc Today Vol. 4, No. 6, June 2003, p. 31
ASH ITP Treatment Guidelines are located at http://www.hematology.org/practice/idiopathic.cfm
For a list of NSAIDs and other substances reported to interfere with platelet function see http://www.itppeople.com/warnings.html
The British Society of Haematology has published guidelines on the treatment of ITP.
You can read them at http://www.bcshguidelines.com/pdf/BJH574.pdf
OR in the British Journal of Haematology, 2003, 120, 574-596, titled "Guidelines for the Investigation and Management of Immune Thrombocytopenic Purpura in Adults, Children, and Pregnancy"
There is a link to the guidelines page at http://www.itppeople.com/treatguide.htm
Researchers at the University of Cambridge and other locations studied the genetic make-up of patients with autoimmune thyroid disease and juvenile diabetes. They found that families with these autoimmune diseases had a lower production of CTLA-4, a protein that moderates how aggressive a T-cell will be in attacking pathogens in the immune system. They conclude that autoimmune diseases are caused in part by one from of CTLA-4. CTLA-4 works in tandem with CD28. CD28 enhances immune responses and CTLA-4 slows them. “If we could harness the profound regulatory attributes of CTLA-4 or effectively block CD28, we might be able to modify the immune response” in people with autoimmune diseases says Jeffrey A. Bluestone of the University of California at San Francisco.
Science News May 3, 2003 http://www.sciencenews.org
Nature April 30 (http://dx.doi.org/10.1038/nature01621)
(Note. ITP is an autoimmune disease)
The assumption of distant healing is that the thoughts and intentions of one person can somehow affect the health of another person from a distance. Researchers at the Institute of Noetic Sciences (IONS) are leading an NIH funded study to look at distant healing as it relates to patient knowledge and expectations. The study design will solve some of the problems of previous studies on distant healing by taking into account homogeneity in the patients, documentation of current medications, and consistency in healer background and intervention. Approximately half of the previous studies on distant healing found statistically significant effects.
IONS Noetic Sciences Review June-August, 2003
Many pharmaceutical companies are looking at regulating the signaling pathways of calcium, potassium, sodium and other molecules for new approaches to controlling disease. One of the large pharmaceutical companies is working on a compound named PAC, a type of disubstituted cyclohexyl (DSC) that inhibits the Kv1 family of potassium channels thereby inhibiting the action of T-cells. That means that compounds in the DSC family could be useful in turning off the immune system in the treatment of autoimmune diseases.
BSG BioNewsletter #15 2003 See: http://www.bioseeker.com
Schjmalhofre WA et al. Biochemistry 2002, 41, 7781-7794
For parts of the United States, summertime brings damp, warm weather-and the risk of West Nile virus. Spread by mosquitoes, which thrive in wet areas and high temperatures, West Nile is a concern, albeit a slim one. As of late June 2003, the Centers for Disease Control (CDC) had no reported human cases of West Nile for 2003.
However, if you are over the age of 50 or have an impaired immune system, you should take precautions to avoid mosquito bites and the possibility of West Nile. The CDC suggests the following:
Know the symptoms. If you experience fever, headache, body aches, a skin rash on the trunk of the body, or swollen lymph glands, contact your physician.
Clean out areas where mosquitoes live and breed. Standing water and clogged gutters are breeding places for mosquitoes.
Be aware. Alert local authorities of any dead birds and standing water in public places, and stay updated on local West Nile prevention tactics.
Prevent bites. Wear protective clothing (such as long sleeves and pants) when outdoors. Apply insect repellent containing DEET to all exposed skin, especially in the early morning and evening hours-peak mosquito times. (If you prefer to avoid DEET, I recommend Geraniol-based products, some of which can be found at hensonsales.com.)
Published with permission from www.DrWeil.com
Editor Note: PDSA recommends wearing protective clothing and using as gentle a mosquito deterrent as possible. While, there have been no studies directly linking ITP and pesticides there has been research linking pesticides and other autoimmune diseases. See http://www.niehs.nih.gov/oc/news/autoim.htm
Today the Washington Post reports the West Nile virus is spreading much more quickly than last year. According to the CDC there are more states reporting the presence of the virus and at least four human cases have been confirmed to date. Since the virus can be spread through blood transfusions, blood banks have begun screening donations for the virus.
“West Nile Spreading Rapidly” The Washington Post, Wednesday, July 16, 2003.
Mosquito coils consisting of spiral-shaped strips of insecticide treated material are sometimes burned to control the pests. Now researchers from Rutgers University report that the particles released by these coils can carry toxic carcinogenic compounds such as formaldehyde to the lungs. Since the amounts and types of pollutants emitted by various brands of these coils differ widely, systematic testing is needed to help consumers make informed choices.
“Antimosquito coils release toxic fumes” Science News July 12, 2003, Vol 164
Common drugs used to reduce cholesterol call statins can have an effect on your T-cells reports Sawsan Youssef, PhD of the Beckman Center for Molecular Medicine. Atorvastatin (Lipitor, Pfizer) was shown to prevent or reverse autoimmune encephalomyelitis in mice models by promoting the differentiation of T-lymphocyte cells (a type of white blood cell) into Th2 cells (T helper cells type 2). The author concluded that atorvastatin has immunomodulatory effects involving both the antigen presenting cells and T-cells.
From: “Should statins be tried as therapeutic adjuncts to aplastic anemia?” July 2003/Hem/Onc today (www.hemonctoday.com). See also “Nature”2002 Nov. 7;420 (6911):39-40 and http://www.rndsystems.com/asp/g_sitebuilder.asp?bodyId=224
Editor Note: This is important because many researchers consider ITP a T-cell mediated disease.
We have received e-mails from several people who feel that taking a statin has either caused their ITP or made it worse. If you have ITP and are also taking or have taken statins please send an e-mail to pdsa@pdsa.org describing your experience (positive, negative or neutral).
Green tea polyphenol extract suppressed inflammation in mice that are bred to mimic an intestinal autoimmune disease. More study is required to determine if a smaller amount of green tea will have similar anti-inflammatory benefits since the extract used in these experiments was comparable to 100-200 cups of green tea per day. In prior experiments a smaller amount green tea extract was shown to reduce the symptoms of inflammatory arthritis. Green tea extract is now available in health food stores.
See: http://www.nutrition.org/cgi/content/full/131/7/2034
According to one estimate, difficulties in physician/patient communication cost the US Healthcare system $73 billion dollars a year. When patients don’t understand their condition and the suggested treatments they are more likely to make medication errors, comply with treatment less often and suffer with their chronic condition for a longer time. A new health literacy program sponsored by the Partnership for Clear Health Communication, a coalition that includes the American Medical Association Foundation, the American Public Health Association, the National Coalition for Literacy and Pfizer, Inc. aims to help patients and physicians bridge the communication gap.
The Partnership suggests that patients always ask: “What is my main problem? What is it important for me to do? And why is it important for me to do this?”
See www.ASKme3.org for more information about the Partnership. See http://www.mlanet.org/resources/medspeak/index.html and http://www.medlineplus.gov to help translate medical terms
.From: “The Informed Patient” by Laura Landro, “Doctor’s Orders Are Useless If They’re Befuddling. Wall Street Journal, July 3, 2003.
The growing field of ‘personalized medicine’ hopes to eliminate the trial and error approach to treatments. Roche Holding AG is launching AmpliChip CYP450, a test to help predict how a patient will react to some medications. Using a drop of blood or smear from the inside of a patient’s cheek, the test checks for variations in two genes known to play a critical role in metabolizing about one-fourth of the prescription drugs on the market. Roche will make the test available to 400 specially certified laboratories. By late 2004 Roche hopes to have FDA approval to distribute it more widely.
“Roche Test Promises to Tailor Drugs to Patients” by Vanessa Fuhrmans, Wall Street Journal, June 25, 2003.
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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
Contents:
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.