Information on the following diseases can be found in the Related Disorders section of this report:

• Thrombocytopenia
• Purpura
• Allergic Purpura

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 on the brain (intracranial hemorrhage) may occur.

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 fight foreign substances, known as antigens, in the body. In many cases, the exact cause of the production of these anti-platelet antibodies is unknown (idiopathic).

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 collapses 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 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.

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.

Symptoms of the following disorders can be similar to those of ITP. Comparisons may be useful for a differential diagnosis:

Thrombocytopenia may be caused by other blood (hematological) disorders or secondary to a collagen vascular disorder such as systemic lupus erythematosus. Adverse drug reactions (drug-induced thrombocytopenia) are also potential causes of thrombocytopenia. Quinidine, quinine and heparin are three drugs often associated with the development of immune thrombocytopenia.

Thrombotic thrombocytopenia purpura (TTP) is a rare, serious blood disease. Major symptoms may include a severe decrease in the number of blood platelets (thrombocytopenia), abnormal destruction of red blood cells (hemolytic anemia), and disturbances in the nervous system. Affected individuals also exhibit red rash-like areas of skin or patches of purplish discoloration (purpura) resulting from abnormal bleeding into the mucous membranes (the thin, moist layer lining the body's cavities) and into the skin similar to ITP. The exact cause of thrombotic thrombocytopenia purpura is unknown. (For more information on this disorder, choose "thrombotic thrombocytopenia purpura" as your search term in the Rare Disease Database.)

Henoch-Schonlein purpura is a rare inflammatory disease of the small blood vessels (capillaries) and is usually a self-limited disease. It is the most common form of childhood vascular inflammation (vasculitis) and results in inflammatory changes in small blood vessels. The symptoms of Henoch-Schonlein purpura usually begin suddenly and may include headache, fever, loss of appetite, cramping abdominal pain, and joint pain. Red or purple spots typically appear on the skin (petechial purpura). Inflammatory changes associated with Henoch-Schonlein purpura can also develop in the joints, kidneys, digestive system, and, in rare cases, the brain and spinal cord (central nervous system). The exact cause of Schonlein-Henoch purpura is not fully understood, although research suggests that it may be an autoimmune disease or, in some rare cases, an extreme allergic reaction to certain offending substances (e.g., foods or drugs). (For more information on this disorder, choose "Henoch-Schonlein purpura" as your search term in the Rare Disease Database.)

Heparin-induced thrombocytopenia is the most common drug-induced, antibody-mediated thrombocytopenic disorder. Heparin is a drug often used in hospitals that prevents blood clotting (anticoagulant). Heparin-induced thrombocytopenia is characterized by serious thrombocytopenia and the formation of blood clots (thrombosis) often affecting the limbs. In some cases, serious complications may develop including stoke or the formation of blood clots in the lungs (pulmonary emboli) resulting in episodes of chest pain, coughing, difficult or labored breathing (dypsnea ), and coughing up blood (hemoptysis). Skin ulcerations may develop in some cases of heparin-induced thrombocytopenia.
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Diagnosis
The diagnosis of ITP is usually made by excluding other causes of thrombocytopenia, including certain medications or the presence of other 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. If platelet levels do not improve after corticosteroid treatment, affected individuals may require ongoing treatment with intravenous immunoglobulins (IVIG), usually through monthly infusions.

The orphan drug anti-D (WinRho SDF), a new form of gammaglobulin, has been 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)
Baxter Healthcare Corporation
One Baxter Parkway
Deerfield, IL 60015
email: winrho@baxter.com

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.

In some cases, individuals with ITP do not respond to treatment with steroids, immunoglobulins or splenectomy (refractory ITP). Immunosuppressor drugs, such as cyclophosphamide, cyclosporine, and azathioprine, have been used effectively in some cases. Various anticancer (chemotherapeutic) drugs have been used to treat some individuals with chronic ITP. Vincristine and vinblastine are two such drugs that may sometimes be therapeutic. Individuals with ITP have also been treated with danazol, a synthetic androgen (male sex hormone). The response rate of individuals with ITP treated with danazol is approximately 30 percent. The drug colchicine, used for years to treat gout, has been used in the treatment of some individuals with ITP. More research is needed to determine the long-term safety and effectiveness of these various drug treatments for individuals with refractory ITP.

InKine Pharmaceutical Company is developing an experimental steroid drug for ITP known as CBP-1011. The company plans to submit an orphan drug application for the product and will work on a commercially viable oral dosage form. Additional research is needed to determine its long-term safety and effectiveness.

Medarex Inc. is studying MDX-33 for the treatment of ITP. More studies are needed to determine the long-term safety and effectiveness of treatment. The drug is being developed in collaboration with Aventis Behring. MDX-33 is currently undergoing phase II clinical studies.

The drug purified extract of Pseudomonas aeruginosa (ImmuDyn) has received an orphan drug designation for its use in the treatment of immune thrombocytopenia purpura where it is required to increase the platelet counts. More studies are needed to determine the long term safety and effectiveness of this drug for the treatment of immune thrombocytopenia purpura. For more information, contact:

DynaGen, Inc.
99 Erie Street
Cambridge, MA 02139

The Hematology Branch at the National Institutes of Health/National Heart, Lung and Blood Institute (NHLBI) is conducting clinical research studies on immunosuppression using high dose cyclophosphamide followed by autologous peripheral blood stem cell rescue as a treatment for unremitting Idiopathic Thrombocytopenic Purpura. For more information, individuals may contact:

Wanda Zamani
NIH/Hematology Branch, National Heart, Lung and Blood Institute (NHLBI)
Website: http://www.nhlbi.nih.gov/nhlbi/seekpat/hematol.htm
e-mail: zamaniwe@gwgate.nhlbi.nih.gov
Tel: (301) 402-0764
Fax: (301) 402-3088

or

Cynthia Dunbar, M.D.
Richard Hunn, M.D.
Janice Kimball, R.N.
NIH/Hematology Branch, National Heart, Lung and Blood Institute (NHLBI)
Bethesda, MD
Tel: (301) 496-3841

For more information, physicians may contact:
Dr. Neal Young, Chief of the Hematology Branch, or
Dr. John Barrett, Chief of the Bone Marrow Transplant Unit
NIH/Hematology Branch, National Heart, Lung and Blood Institute (NHLBI)
Website: http://www.nhlbi.nih.gov/nhlbi/seekpat/hematol.htm
Tel: (301) 496-5093
Fax: (301) 496-8396

IDEC Pharmaceutical Company and Genentech, Inc., have submitted an Investigational New Drug (IND) application (IND) to the FDA for the monoclonal antibody (Rituxan) as a treatment for ITP. Several initial small clinical trials using Rituxan have demonstrated a potential benefit for individuals with ITP. The companies plan to begin phase III clinical trials upon approval of the IND.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Thrombocytopenic Purpura, Autoimmune. Entry Number; 188030: Last Edit Date; 4/10/2003.

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

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

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

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

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

JOURNAL ARTICLES
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
George JN, Woolf SH, Raskob GE, et al. Idiopathic Thrombocytopenic Purpura: A Practice Guideline Developed by Explicit Methods for The American Society of Hematology. Adopted by the Executive Committee of the ASH, December 1-5, 1995. 67pp.
www.hematology.org/education/idiopathic/cfm

Cohen EW. Idiopathic thrombocytopenic purpura (ITP). Medical Encyclopedia, MEDLINEplus. Update Date: 5/1/2003. 3pp.
www.nlm.nih.gov/medlineplus/ency/article/000535.htm