ITP Research and Treatments
- New Method for Raising Platelet Counts is in Clinical Trials
- T-cell Abnormalities May Be Involved in Some Cases of ITP
- Anti-D Useful Option for Women With ITP During Pregnancy
- Platelet Microparticles Are Derived Directly from Megakaryocytes, Not Just From Activated Platelets
- ITP Treatment News from Ligand and GlaxoSmithKline (GSK)
Hospitals, Insurance, and Medical Care
- U.S. Congress Revisits Plans to Approve Generic Drugs
- Two Options Emerge for Patients’ Electronic Health Records
- Stimulus Bill Changes Legal Requirements for Patients’ Health Information
General Health and Medicine
- Childhood Stress Increases Risk for Autoimmune Disorders
- Dr. Kuter Clarifies Issue of Coffee’s Effect on Platelets
- Public Access to Clinical Trial Data Expanding
General Health and Medicine
NEW METHOD FOR RAISING PLATELET COUNTS IS IN CLINICAL TRIALS
A new treatment for ITP in clinical trials, R788, is thought to raise platelet counts by selectively blocking the action of macrophages (a type of white blood cell) in the spleen that destroy anti-body coated platelets. Anti-body coated platelets prompt a number of chemical signals in the macrophage and R788 blocks one of them called Syk. In a pilot study of R788 in 16 adults with chronic ITP, including some who had failed several treatments, half achieved a persistent rise in their platelet count above 50,000. The most common side effects were nausea, vomiting, and diarrhea.
Podolanczuk A, Lazarus AH, Crow AR, Grossbard E, and Bussel JB. Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk. Blood, 2 April 2009, Vol 113, No. 14
T-CELL ABNORMALITIES MAY BE INVOLVED IN SOME CASES OF ITP
The production of anti-platelet antibodies is regulated by T-cells, a type of white blood cell, and in some patients with ITP, those regulatory T-cells may be reduced or damaged. Researchers at Newark Beth Israel Medical Center found T-cell abnormalities in seven of their refractory patients and had some success by treating them with therapies that regulated T-cells (ex. rituximab, azathioprine, mycophenolate mofetil, and cyclosporin). The authors suggest that patients with ITP who fail to respond to standard ITP therapy be evaluated for T-cell abnormalities.
Sabnani I and Tsang P, Therapeutic Implications of T-cell clonopathy of unknown significance in chronic immune thrombocytopenic purpura. Platelets, March 2009; 20(2): 135-139
ANTI-D USEFUL OPTION FOR WOMEN WITH ITP DURING PREGNANCY
In a literature review and physician survey, the authors found only a few cases where pregnant women with ITP had been treated with anti-D (ex. Win Rho SDF) to raise their platelet counts. While this is not a licensed indication for the treatment, the pregnant women who received anti-D did not experience any severe reactions. Further investigation of the use of anti-D in pregnant women with ITP is continuing.
Cromwell C, Tarantino M, and Aledort LM. Safety of anti-D during pregnancy, Correspondence in Am J Hematol. 2009 Apr; 84 (4):261-2
PLATELET MICROPARTICLES ARE DERIVED DIRECTLY FROM MEGAKARYOCYTES, NOT JUST FROM ACTIVATED PLATELETS
Platelet microparticles, fragments of their plasma membrane, are the most abundant type of microparticles in circulation and have been implicated in the production of blood clots, sometimes leading to heart attacks and strokes. Scientists in Boston found that microparticles are produced by megakaryocytes, the bone marrow cells from which platelets are released, as well as by activated platelets. (Note: some research shows that splenectomized patients have more microparticles than non-splenectomized patients)
Flaumenhaft R, Dilks JR, Richardson J, et al. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles. Blood. 2009 Jan 29;113(5):1112-21
(Note) Thromb Res. 2008;122 (5):599-603
ITP TREATMENT NEWS FROM LIGAND AND GLAXOSMITHKLINE (GSK)
In December, 2008, Ligand granted GlaxoSmithKline (GSK) full rights to develop and market LGD-4665 as well as other TPO-related molecules discovered by Ligand. According to preliminary clinical trial results, LGD-4665, a pill most likely taken weekly, has the potential for raising the platelet counts in patients with ITP. Also in December 2008, GSK submitted a marketing authorization application in the European Union for another TPO agent, Revolade (eltrombopag) for the treatment of patients with chronic ITP. Eltrombopag is approved by the FDA and marketed as Promacta in the U.S.
Hospitals, Insurance, and Medical Care
U.S. CONGRESS REVISITS PLANS TO APPROVE GENERIC DRUGS
Bills introduced in the U.S. House and Senate would create a standard approval process for generic biologic medicines (drugs). The bills would help promote the development of biologically similar and less expensive versions of biologic treatments currently used to treat cancer and other diseases, including ITP. The bills differ in duration of the market exclusivity for the original biologic drug, the interchangeability of the original and generic biologic, and the handling of clinical trials for generic treatment. The American Medical Association has not taken a position on the bills but is concerned about any measure’s effect on patient safety, incentives for innovation, and physicians’ independence. AMA does not think legislation should compel doctors to treat generic biologics as interchangeable with brand-name biologics.
Trapp D. Congress revisits plan to approve generic biologics, AMNews, March 30, 2009.
TWO OPTIONS EMERGE FOR PATIENTS’ ELECTRONIC HEALTH RECORDS
The two options for storing patients’ electronic health records are 1) individually on platforms provided by Google or Microsoft or 2) a more centralized repository such as those currently used by various physician and hospital groups along with insurance companies. The Obama administration would like all health records stored electronically within the next five years and has offered financial incentives to achieve that goal. For both options, data privacy, data input, and data sharing concerns remain.
Paul C. Tang and Thomas H. Lee, Your doctor’s office or the Internet? Two Paths to Personal Health Records. New England Journal of Medicine (NEJM) March 26, 2009, Vol 360:1276-1278
STIMULUS BILL CHANGES LEGAL REQUIREMENTS FOR PATIENTS’ HEALTH INFORMATION
The recently enacted U.S. government stimulus package contains new requirements for the protection of personal health information. It increases the compliance requirements for those previously covered in the HIPAA regulations and extends privacy and security regulations to “business associates” and “vendors.” The new law strengthens the penalties for breaching the privacy of individuals, restricts marketing, and bans the sale of protected health information.
Nancy L. Perkins, Health data privacy and security: How does the stimulus bill change the legal landscape? HemOnc Today March 10, 2009
General Health and Medicine
CHILDHOOD STRESS INCREASES RISK FOR AUTOIMMUNE DISORDERS
In a study of 15,357 adults (average age: 56), 64% of study subjects reported at least one adverse event during childhood such as physical or emotional abuse or household dysfunction. Individuals with two or more adverse events compared to those with none had a greater than 70% risk for acquiring various autoimmune disorders. The authors suggest that clinicians seeing patients with autoimmune disease be alert for histories of childhood adversity.
Yager J, Childhood Stresses Take a Toll on Adult Immune Health, Journal Watch Psychiatry, March 23, 2009.
Dube, SR et al., Cumulative childhood stress and autoimmune diseases in adults. Psychosom Med. 2009 Feb;71 (2):243-50
DR. KUTER CLARIFIES ISSUE OF COFFEE’S EFFECT ON PLATELETS
In last month’s e-news the article “Cup of Joe Could Lower Platelets” referred to the antiplatelet effect of polyphenols in coffee. We received a letter from Dr. Anaadriana Zakarija, Assistant Professor of Hematology/Ontology at Northwestern University, Chicago, IL. Dr. Zakarija explained that the article does not actually refer to lowering the number of platelets, but rather to an “anti-platelet” effect, which refers to the function of platelets, not the number. The doctor requested that we clarify this point and advise our readers, otherwise patients with a normal platelet count might be afraid they would cause their platelets to drop if they drank coffee. In addition, patients who do have a low platelet count should avoid any substance, including coffee, that has an “antiplatelet” effect so their risk of bleeding is not increased.
For further clarification we contacted one of our Medical Advisory Board members, Dr. David Kuter, a hematologist at Massachusetts General Hospital in Boston, MA. Here is Dr. Kuter’s reply:
“Dr. Zakarija is correct to question the effect of coffee on platelets. It does not alter platelet number or precipitate bouts of thrombocytopenia. It may alter the function of platelets and make those with a reduced platelet count more susceptible to bleeding.”
“It should be remembered that there are two major aspects of the platelet that affect the risk of bleeding. One is the platelet number and the other is the platelet function. While the effects of a low platelet number are familiar to many patients with ITP, the effects of reduced platelet function (and drugs/foods that reduce platelet function, often referred to as an “anti-platelet effect”) are not. Reduced platelet function means that the platelets that are present (irrespective of their number) don't work too well. When we say they don't work well, we mean that they don't bind to sites of injury, don't clump together and don't stop bleeding. This is best illustrated by the effect of aspirin (which most ITP patients with low platelets are encouraged to avoid), which reduces platelet function. By reducing modestly the ability of the platelet to "clot", aspirin provides a beneficial effect to many with heart disease and strokes. This is helpful in a patient with a normal platelet count; but if the count is below 50,000, the combined effect of a low platelet count and the reduced function of the platelet might increase the bleeding risk.”
“Having read the little available data on the effects of coffee on platelet function, it seems that the effects are due to the phenolic acids in the coffee and not the caffeine. In the scientific study mentioned, the investigators were trying to investigate why coffee-drinkers appeared to have a reduced risk of cardiac disease. They tested the platelet function of subjects (with normal platelet counts) after coffee ingestion and found a modest reduction in function.”
“Whether this will be true in ITP patients is unclear. Although this is something that might warrant further study, most of my ITP patients have reported no increased risk of bleeding (even at very low platelet counts) when they drink coffee. What is clear is that the effect is probably minor, but like other medications (e.g., anti-depressants, antibiotics) that reduce platelet function, caution should be used in patients with very low platelet counts (e.g., those under 10,000). There would appear to me to be no concern about drinking coffee if the platelet count is over 30,000. In those who have recovered from ITP there should certainly be no concern about precipitating a subsequent drop in platelet count.”
PUBLIC ACCESS TO CLINICAL TRIAL DATA EXPANDING
Clinical trial data available to the public is gradually expanding as a result of Section 801 of the Food and Drug Amendments Act of 2007. As of December 26, 2007, all companies are required to post their clinical trials on www.clinicaltrials.gov. Since September, 2008, companies are required to post information on the results of the trial within one year of completion and in September, 2009 they will be required to add serious adverse event data. The data requirements expand further in 2010 to include technical and lay summaries and complete protocol information.
Wood A. Progress and deficiencies in the registration of clinical trials. NEJM, Volume 360:824-830, February 19, 2009, Number 8 http://content.nejm.org/cgi/content/full/360/8/824
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