Idiopathic Thrombocytopenic Purpura

Idiopathic Thrombocytopenic Purpura

National Organization for Rare Disorders, Inc.

Important

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Synonyms

  • ITP
  • autoimmune thrombocytopenic purpura
  • primary thrombocytopenic purpura

Disorder Subdivisions

  • None

General Discussion

Idiopathic thrombocytopenic purpura (ITP) is a not infrequent autoimmune bleeding disorder characterized by the abnormally low levels of blood cells called platelets, creating a condition known as thrombocytopenia. Platelets are specialized blood cells that help prevent and stop bleeding by inducing clotting. In many ITP cases, there are no readily apparent causes or underlying disease (idiopathic), but frequently there are associated collagen vascular diseases or underlying neoplasms, most frequently lymphoid. The cells of the immune system, lymphocytes, produce anti-platelet antibodies that attach to the platelets. The presence of antibodies on platelets leads to their destruction in the spleen. The disorder is characterized by abnormal bleeding into the skin resulting in bruising, which is what the term purpura means. Bleeding from mucous membranes also occurs, and may subsequently result in low levels of circulating red blood cells (anemia).



ITP presents as a brief, self-limiting form of the disorder (acute ITP) or a longer-term form (chronic ITP). Acute ITP accounts for about 50% of cases, and chronic ITP accounts for the remainder. Eighty percent (80%) of the children with ITP have the acute form while the chronic form affects mostly adults. The acute form usually resolves without treatment (spontaneously) within three to six months. When thrombocytopenia lasts for more than six to 12 months, ITP is classified as the chronic form. Onset of acute ITP is often rapid, while the onset of the chronic form may be gradual.

Symptoms

A child or adult with idiopathic thrombocytopenic purpura may display no symptoms (asymptomatic). Symptoms of ITP may not appear until the platelet count is extremely low. Such symptoms may include:



- Skin that bruises very easily

- A rash consisting of small red dots (petechiae) that represent small hemorrhages

- Bleeding from any area of the body made obvious by blood in urine or feces

- Bleeding from the gums

- Frequent and long-lasting nose bleeds

- Abnormal menstruation



In some cases, frequent bleeding episodes may result in low levels of circulating red blood cells (anemia), which may produce weakness and fatigue. Additionally, people with this disorder may experience fevers and abnormal enlargement of the spleen (splenomegaly). Some women with ITP may experience prolonged and heavy menstrual bleeding. In rare cases of ITP, a serious condition known as bleeding into the brain (intracranial hemorrhage) may occur.

Causes

Idiopathic thrombocytopenic purpura belongs to a group of disorders in which the body's natural immune defenses inappropriately act against the body's own tissues (autoimmune disorders). In ITP, an abnormal immune reaction appears to lead to destruction of certain blood cells known as platelets. For reasons that remain as yet unknown, lymph tissues and the spleen are stimulated to produce anti-platelet antibodies that mistakenly attach to platelets, forming an "antibody-platelet complex". Antibodies are produced by the body's immune system to react to foreign substances, known as antigens. In many cases, the exact cause of the production of these anti-platelet antibodies is unknown (idiopathic), but in some underling collagen vascular/rheumatologic conditions as well as malignancy may stimulate antibody production



ITP affects normal platelets as they circulate through the spleen. The antibody-platelet complex is recognized as foreign by the immune system, which then goes to work to destroy it. After a while, the platelet count in the blood declines and thrombocytopenia (abnormally low numbers of platelets) ensues.



In children, ITP often occurs following an acute viral infection or upper respiratory illness suggesting that antibodies produced to fight foreign viral substances (antigens) may cross- react with the antigens and, in turn, destroy platelets.



Some cases resembling ITP may result from the use of certain drugs. According to the medical literature, Helicobacter pylori, a bacterium that has been shown to cause stomach ulcers, is associated with the development of ITP in some cases.

Affected Populations

The incidence of idiopathic thrombocytopenic purpura among adults annually in the USA has been estimated at 66 cases per million. The annual incidence among children has been estimated at about 50 cases per million of population. Chronic ITP is thought to make up about 10 cases per million per year.



The incidence varies from country to country with studies in Denmark reporting 10-40 cases per million per year. Other studies in Kuwait report 125 cases per million per year.



Among adults diagnosed with chronic ITP, there are 2.6 cases among women for every case involving a male. Among children diagnosed with acute ITP, the male to female ratio is almost equal, with 52% male to 48% female.



Among adults, the incidence is greatest at ages 20 to 50 years. Among children, the incidence is greatest at ages 2 to 4 years. About 40% of all patients diagnosed with one form of ITP are children younger than 10 years of age.

Standard Therapies

Diagnosis

The diagnosis of ITP is usually made by excluding other causes of thrombocytopenia, including certain medications or the presence of disorders such as acute leukemia and aplastic anemia. The disorder is commonly without apparent symptoms (asymptomatic). Low platelet counts may be found after routine blood tests ordered for other purposes.



Blood tests to determine platelet counts and the presence of platelet antibodies are commonly ordered. Normal appearing red blood cells or white blood cells will rule out or exclude leukemia and/or aplastic anemia from the diagnosis. The presence of unusual cells in the blood will call for the use of a needle biopsy of the bone marrow.



Treatment

In some cases, especially with the acute from of ITP, no therapy may be necessary and the disorder may resolve itself (spontaneous resolution). When therapy is necessary, treatment with corticosteroid drugs (e.g., prednisone) is usually administered, and this is the mainstay of therapy. If platelet levels do not improve after corticosteroid treatment, affected individuals may require ongoing treatment with intravenous immunoglobulins (IVIG), usually through monthly infusions, but this does not lead to a cure.



The orphan drug anti-D (WinRho SDF), a form of gammaglobulin, 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. For information about this drug, contact:



1-800-4WINRHO (1-800-494-6746)

Cangene bioPharma, Inc.

Baltimore, MD 21230

Email: CustomerService@cangene.com

Product Website: www.winrho.com



Anti CD20 antibody, Rituximab (Rituxn) reduces IgG antibody production and is frequently used in patients refractory to other therapies.



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.



If the patient has antibodies or evidence of Helicobacter pylori infection, antibiotics and proton pump inhibitors may ameliorate the condition. (This is much more common in Asia)



In 2008, the FDA approved Promacta manufactured by GlaxoSmithKline (GSK) for patients with chronic immune thrombocytopenic purpura to increase platelet counts and reduce bleeding. According to GSK, Promacta is the first pill to treat the condition. Other medications are available from different manufactures with the same mechanism of action.



In 2008, the FDA approved romiplostim for subcutaneous injection (Nplate, made by Amgen Inc.) for the treatment of thrombocytopenia in patients with ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Romiplostim is a thrombopoietin (TPO) receptor agonist that stimulates bone marrow megakaryocytes to produce platelets.

Investigational Therapies

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:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Algazy KM. Idiopathic Thrombocytopenic Purpura. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:415-16.



Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:923.



Fauci AS, et al, eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:732.



Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:980-2.



Frank MM, et al. Samter's Immunologic Diseases, 5th ed. Boston, MA: Little, Brown and Company; 1995:919-25.



JOURNAL ARTICLES

Chouhan JD, Herrington JD. Treatment options for chronic refractory idiopathic thrombocytopenic purpura 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.



Ahn YS, Horstman LL. Idiopathic thrombocytopenia purpura: pathophysiology and management. Int J Hematol. 2002;76:123-31.



Todisco M, Rossi N. Melatonin for refractory idiopathic thrombocytopenic purpura: a report of 3 cases. Am J Ther. 2002;9:524-6.



Ancona KG, et al. Randomized trial of high-dose methylprednisolone versus intravenous immunoglobulin for the treatment of acute idiopathic thrombocytopenic purpura in children. J Pediatr Hematol Oncol. 2002;24:540-4.



Giagounidis AA, et al. Treatment of relapsed idiopathic thrombocytopenic purpura with the anti-CD20 monoclonal antibody rituximab: a pilot study. Eur J Haematol. 2002;69:95-100.



Pamuk GE, et al. Overview of 321 patients with idiopathic thrombocytopenic purpura. Retrospective analysis of the clinical features and response to therapy. Ann Hematol. 2002;81:436-40.



Yenicesu I, et al. Virus-associated immune thrombocytopenic purpura in childhood. Pediatr Hematol Oncol. 2002;19:433-7.



Michel M, et al. Autoimmune thrombocytopenic purpura and helicobacter pylori infection. Arch Intern Med. 2002;162:1033-6.



Adams JR, et al. Pharmacoeconomics of therapy for ITP; steroids, i.v.Ig, anti-D, and splenectomy. Blood Rev. 2002;16:65-7.



McMillan R. Classical management of refractory adult immune (idiopathic) thrombocytopenic purpura. Blood Rev. 2002;16:51-5.



Blanchette V. Childhood chronic immune thrombocytopenic purpura (ITP). Blood Rev. 2002;16:23-6.



Caplin C, et al. Is bone marrow aspiration needed in acute childhood idiopathic thrombocytopenic purpura to rule out leukemia? Arch Pediatr Adolesc Med. 1998;152:345-57.



Law C, et al. High-dose intravenous immune globulin and the response to splenectomy in patients with idiopathic thrombocytopenic purpura. N Engl J Med. 1997;336:1494-8.



Demiroglu H, et al. High-dose pulsed dexamethasone for immune thrombocytopenia. N Engl J Med. 1997;337:425-7.



Figueroa M, et al. Combination chemotherapy in refractory immune thrombocytopenic purpura. N Engl J Med. 1993;328:1226-9.



FROM THE INTERNET

Kessler CM, Sandler SG, Bhanji R. Immune thrombocytopenic purpura. eMedicine. http://emedicine.medscape.com/article/202158-overview. Updated December 28, 2010. Accessed February 15, 2011.



Cohen EW. Idiopathic thrombocytopenic purpura (ITP). Medical Encyclopedia, MEDLINEplus. Update Date: 3/28/2010. 3pp.

www.nlm.nih.gov/medlineplus/ency/article/000535.htm. Accessed February 15, 2011.



McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Thrombocytopenic Purpura, Autoimmune. Entry Number; 188030: Updated 3/20/2009. Accessed February 15, 2011.



National Cancer Institute/Cancer Drug Information. http://www.cancer.gov/cancertopics/druginfo/fda-romiplostim. Reviewed November 26, 2010. Accessed February 15, 2011.

Resources

American Autoimmune Related Diseases Association, Inc.

22100 Gratiot Ave.

Eastpointe, MI 48021

Tel: (586)776-3900

Fax: (586)776-3903

Tel: (800)598-4668

Email: aarda@aarda.org

Internet: http://www.aarda.org/



NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

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Tel: (301)592-8573

Fax: (301)251-1223

Email: nhlbiinfo@rover.nhlbi.nih.gov

Internet: http://www.nhlbi.nih.gov/



ITP People Place

133 Rollins Avenue, #5

Rockville, MD 20852

USA

Tel: (301)770-6636

Fax: (301)770-6638

Tel: (877)528-3538

Email: info@pdsa.org

Internet: http://www.pdsa.org/



NIH/National Heart, Lung and Blood Institute ~ Hematology Branch

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3-5140, MSC-1202

Bethesda, MD 20892-1202

Tel: (301)496-5093

Fax: (301)496-8396

Tel: (800)644-2337

Email: YoungNS@mail.nih.gov

Internet: http://dir.nhlbi.nih.gov/labs/hb/index.asp?



Platelet Disorder Support Association

133 Rollins Avenue, Suite 5

Rockville, MD 20852

USA

Tel: (301)770-6636

Fax: (301)770-6638

Tel: (877)528-3538

Email: pdsa@pdsa.org

Internet: http://www.pdsa.org



ITP Foundation

30 Old Kings Hwy South Suite 275

Darien, CT 06820

USA

Tel: (203)655-6954

Fax: (203)548-9182

Email: itpf@itpfoundation.org

Internet: http://www.itpfoundation.org



ITP Support Association

Synehurst

Kimbolton Road

Bolnhurst

Bedfordshire, MK44 2EW

United Kingdom

Email: info@itpsupport.org.uk

Internet: http://www.itpsupport.org.uk



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

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Madisons Foundation

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Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Autoimmune Information Network, Inc.

PO Box 4121

Brick, NJ 08723

Fax: (732)543-7285

Email: autoimmunehelp@aol.com



European Society for Immunodeficiencies

1-3 rue de Chantepoulet

Geneva, CH 1211

Switzerland

Tel: 410229080484

Fax: 41229069140

Email: esid@kenes.com

Internet: http://www.esid.org



AutoImmunity Community

Email: moderator@autoimmunitycommunity.org

Internet: http://www.autoimmunitycommunity.org



For a Complete Report

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