NORD gratefully acknowledges the Platelet Disorder Support Association and PDSA Medical Advisor Douglas Cines, MD, for assistance in the preparation of this report.
There is some variation in the clinical reaction to having a low platelet count. A child or adult with immune thrombocytopenia may display no symptoms (asymptomatic) or the symptoms may not appear until the platelet count is extremely low. Such symptoms may include:
– Skin that bruises very easily and even spontaneously
– A rash consisting of small red dots (petechiae) that represent small hemorrhages caused by broken blood vessels or leaks in a capillary wall
– Bleeding from the gums
– Frequent and long-lasting nose bleeds
– Blood blisters on the inside of cheeks
– Excessive and prolonged menstrual bleeding
– Bleeding from any area of the body, e.g. in urine or feces
In some cases, frequent bleeding episodes may result in low levels of circulating red blood cells (anemia), which may produce weakness and fatigue. In rare cases of ITP, a serious condition known as bleeding into the brain (intracranial hemorrhage) may occur. Fatigue (even in the absence of anemia), anxiety, and depression are common experiences for people with ITP. In some individuals, these symptoms may be caused by the disease or as a side effect of medication.
Antibodies are normally produced by the body’s immune system to react only to foreign substances, known as antigens. Immune thrombocytopenia belongs to a group of disorders in which the body’s natural immune defenses inappropriately acts against its own cells or tissues (autoimmune disorders). In ITP, an abnormal immune reaction leads to destruction of the individual’s own platelets. For reasons that remain as yet unknown, lymphocytes in the bone marrow, spleen and elsewhere are stimulated to produce antibodies that attach to platelet surfaces. In some individuals, ITP develops in the context of another disorder that might predispose to making autoantibodies. This is called secondary ITP and is discussed below. In most individuals, however, no such connection is evident and the cause of producing anti-platelet antibodies is unknown.
ITP affects normal platelets as they circulate through the spleen, the liver and elsewhere. The antibody-platelet complex is recognized as foreign by the immune system, which then destroys the platelets. After a while, the platelet count in the blood declines and thrombocytopenia (abnormally low numbers of platelets) ensues. In some cases of ITP, platelet production by megakaryocytes in the bone marrow is impaired. Therefore, the mechanisms underlying ITP can be characterized as increased platelet destruction, reduced or inadequate platelet production, or both.
In children, ITP often occurs following an acute viral infection suggesting that antibodies produced to fight foreign viral substances (antigens) may resemble (“cross-react”) with the antigens and, in turn, destroy platelets. It is rare for more than one family member or members of more than one generation to have ITP. When there is a family history of thrombocytopenia, other genetic disorders are more likely.
Some people have secondary ITP, meaning that their ITP is part of another condition. Secondary ITP can be caused by inherited immune disorders (such as autoimmune lymphoproliferative syndrome, ALPS), systemic autoimmunity such as systemic lupus (the body attacks other cells as well as platelets), ongoing infections (such as HIV, Hepatitis C, and the ulcer-causing stomach bacterium, Helicobacter pylori), and lymphoproliferative disorders such as chronic lymphocytic leukemia that impair the immune system. Some cases resembling ITP may result from the use of certain drugs,, after a viral or bacterial infection or in approximately one in 40,000 children after vaccination for measles-mumps-rubella (MMR). A good source of information on this subject is Pathophysiology of secondary immune thrombocytopenia (Cines et. Al. 2009):
Cines DB, Liebman H, Stasi R. Pathobiology of secondary immune thrombocytopenia. Seminars in hematology. 2009;46(1 Suppl 2):S2-14. doi:10.1053/j.seminhematol.2008.12.005. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682438/
The incidence (how many people are diagnosed each year) of immune thrombocytopenia among adults in the USA is estimated to be 3.3 per 100,000 adults/year. The prevalence (how many adults have ITP at any time) is 9.5 cases per 100,000. The annual prevalence is estimated at 5.3 per 100,000 among children; because children in ITP usually recover, the number of children who have ITP at any one time is about equal to those diagnosed annually.
The incidence of ITP increases with age. Among adults (age 30-60) diagnosed with chronic ITP, there are 2.6 cases among women for every case involving a male. In older adults, about the same number of men and women are diagnosed with ITP. Among children diagnosed with acute ITP, the male to female ratio is also almost equal, with 52% male to 48% female. About 40% of all patients diagnosed with one or another form of ITP are children younger than 10 years of age. Among children, the incidence is greatest at ages 2 to 4 years.
The diagnosis of ITP is made by excluding other causes of thrombocytopenia, including certain medications or disorders that affect the bone marrow and reduce platelet production, such as acute leukemia and aplastic anemia. A low platelet count may be detected incidentally by blood tests (CBC: complete blood count) ordered for other purposes and the individual is without apparent symptoms (asymptomatic). Inspection of the blood smear under the microscope will verify the platelets are truly low and not simply clumped, that the platelets are not uniformly very small or very large, and that the red blood cells and white blood cells appear normal which essentially excludes consideration of leukemia and/or aplastic anemia, among other causes of thrombocytopenia. The presence of unusual cells in the blood might indicate the need for a needle biopsy of the bone marrow to exclude other causes of impaired platelet function. In a patient who is otherwise in their usual state of health who has not taken a new medication, has thrombocytopenia and no other abnormality of the CBC or upon inspection of the blood smear, and has no family history of thrombocytopenia, the diagnosis of ITP is considered. There is no definitive test to make the diagnosis or to exclude the diagnosis of ITP. A good response to ITP-specific treatments such as IVIg (Intravenous Immunoglobulin) will confirm the diagnosis.
While there is no well-established cure for ITP, almost all patients find their platelet count improves following treatment. What proves difficult for many ITP patients is finding the treatment that works for them without unwanted side effects. In some individuals, the disease can go into remission for an extended period of time, perhaps for the remainder of a person’s life. ITP can also recur. There is currently no way to predict the course of the disease. Some patients report that changing their diet or lifestyle helps them feel better.
In many children and some adults, therapy may not be necessary at the time they first see the doctor and the disorder may resolve itself (spontaneous resolution). When therapy is necessary, there are many treatments that have been developed for ITP. They all have different risks and benefits and some are toxic. It is important to understand both the success rate and potential side effects before beginning a treatment. Hematologists may even use several treatments at once to increase their success rate.
Initially, treatment with corticosteroid drugs (e.g., prednisone, dexamethasone, methylprednisolone) is usually administered, and this is the mainstay of initial therapy. These drugs function by suppressing the clearance of antibody coated platelets. When very high doses are employed, the goal is to impair the production of anti-platelet antibodies with the hope that the platelet count will remain elevated after the patient stops taking prednisone. Additional studies are needed to affirm the long-term benefit of this approach. If platelet levels do not improve after corticosteroid treatment, or if an individual presents with severe bleeding, affected individuals may be treated with intravenous immunoglobulins (IVIG), usually through monthly infusions, but this does not lead to a cure. The duration and dose of corticosteroids should be minimized because of its immediate and long-term side effects. If an individual requires persistent use of corticosteroids, other treatments should be tried.
The orphan drug anti-D (WinRho SDF, Rhophylac), a form of gamma globulin, was approved by the Food and Drug Administration (FDA) for the treatment of individuals with ITP who are Rh positive and have not received a splenectomy. The drug may be used repeatedly in affected individuals, particularly children, who have the acute or chronic form of ITP. However, concerns have been raised because of a small number of individuals who have had significant side effects soon after infusion.
For information about this drug, contact Emergent BioSolutions: http://emergentbiosolutions.com/contact-us
Tel: 1-800-WINRHO (1-800-494-6746)
Email: Custsvc@ebsi.com Custsvc@ebsi.com
Product Website: http://www.winrho.com/
Anti CD20 antibody, Rituximab (Rituxan) reduces IgG antibody production and is frequently used as second line therapy, i.e. if the individual’s platelet count falls after corticosteroids are tapered and withdrawn.
Because the spleen plays a role in destroying antibody-covered platelets, surgical removal of the spleen (splenectomy) may be recommended in cases where affected individuals fail to respond to steroids or who fail to maintain a remission when steroids are discontinued. Splenectomy improves platelet counts in approximately 70 percent of cases and can achieve a remission in 50 to 60 percent. Response rates are less in patients over 60 years of age. There is a small but real increase in the risk of clotting and potential serious infection in patients who have had a splenectomy that might be weighed against the high long-term success rate.
Other second-line treatments include Imuran (azathioprine), Cytoxan (cyclophosphamide), Sandimmune (cyclosporine), Danocrine (danazol), Cellcept (mycophenolate mofetil), and Vincristine (vinca alkaloids). Other treatments are in clinical trials.
If the patient has antibodies or evidence of Helicobacter pylori infection, treatment with antibiotics and proton pump inhibitors may ameliorate the condition. Antibiotic associated remission of ITP is much more common in Asia and some parts of Europe than in North America.
A relatively new and tertiary line of treatment for ITP patients is the novel thrombopoietic receptor agonists (TPO-RAs). TPO-RAs function by stimulating the body’s production of platelets by megakaryocytes in the bone marrow, which release proplatelets that mature into platelets. By increasing the rate at which platelets are produced in the body, TPO-RAs attempt to overcome the level of platelet destruction caused by antiplatelet antibodies. Two examples of TPO-RAs are Promacta and Nplate.
In 2008, the FDA approved Promacta (eltrombopag) manufactured by GlaxoSmithKline (GSK) for adult patients with chronic ITP to increase platelet counts and reduce bleeding. Novartis Pharmaceuticals Corporation acquired this product from GSK. In 2008, the FDA approved romiplostim (Nplate) for subcutaneous injection. Nplate is manufactured by Amgen Inc. for the treatment of thrombocytopenia in patients with ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
In 2015, Promacta (eltrombopag) was approved for the treatment of children six years and older with ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Other medications are available from different manufactures with the same mechanism of action.
In 2014, Octagam 10%, manufactured from highly purified immunoglobulin, was approved by the FDA as a treatment for adults with chronic immune thrombocytopenia. The medication is marketed by Octapharma USA.
Some patients report success with complementary therapies such as vitamins, supplements, diet changes, herbs, and energy work, such as Reiki. However, there are no controlled trials in ITP patients demonstrating utility or safety with any of these agents.
ITP treatments vary with the severity of the disease, age of the patient, the experience of the hematologist and other factors. Both the American Society of Hematology and the British Society for Haematology have published guidelines for treating ITP. A new International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia was published in January 2010 in the publication Blood. A PDF copy of those new treatment guidelines can be viewed at:
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Algazy KM. Idiopathic Thrombocytopenic Purpura. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:415-16.
Terrell DR, et al. “The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports.” Am J Hematol. 2010 Mar;85(3):174-80.http://www.ncbi.nlm.nih.gov/pubmed/20131303
Chouhan JD, Herrington JD. Treatment options for chronic refractory immune thrombocytopenia in adults: focus on romiplostim and eltrombopag. Pharmacotherapy. 2010;30(7):666-83.
Deane S, Teuber SS, Gershwin ME. The geoepidemiology of immune thrombocytopenic purpura. Autoimmun Rev. 2010;9(5):A34.
Bussel JB. Traditional and new approaches to the management of immune thrombocytopenia: issues of when and who to treat. Hematol Oncol Clin North Am. 2009;23(6):1329-41.
Bennett CM, Tarantino M. Chronic immune thrombocytopenia in children: epidemiology and clinical presentation. Hematol Oncol Clin North Am. 2009;23(6):1223-38.
Fogarty PF. Chronic immune thrombocytopenia in adults: epidemiology and clinical presentation. Hematol Oncol Clin North Am. 2009;23(6):1213-21.
Cines DB, Liebman HA. The immune thrombocytopenia syndrome: a disorder of diverse pathogenesis and clinical presentation. Hematol Oncol Clin North Am. 2009;23(6):1155-61.
Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.
Segal JB, Powe NR. “Prevalence of immune thrombocytopenia: analyses of administrative data.” J Thromb Haemost. 2006;4(11):2377-2383 http://www.ncbi.nlm.nih.gov/pubmed/16869934
Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115:3339-3347.
Kessler CM, Sandler SG, Bhanji R. Immune thrombocytopenic purpura. Medscape. http://emedicine.medscape.com/article/202158-overview Updated: Feb 17, 2014. Accessed October 21, 2015.
Cohen EW. Idiopathic thrombocytopenic purpura (ITP).Medical Encyclopedia, MEDLINEplus. Update Date 2/24/2014. www.nlm.nih.gov/medlineplus/ency/article/000535.htm Accessed October 21, 2015.
Platelet Disorder Support Association. About ITP. http://pdsa.org/about-itp.html Accessed September 30, 2015.
Platelet Disorder Support Association. Information about other platelet disorders. http://pdsa.org/resources/other-platelet-disorders.html Accessed September 30, 2015.
Platelet Disorder Support Association. ITP in Adults: Frequently Asked Questions. http://pdsa.org/images/stories/pdf/itp_adult_web1.pdf Accessed September 30, 2015.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Thrombocytopenic Purpura, Autoimmune. Entry Number; 188030. Available at http://omim.org/entry/188030 Updated 03/24/2009. Accessed October 21, 2015.
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