Idiopathic thrombocytopenia purpura
Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder caused by an abnormally low level of blood platelets, small disc-shaped cells essential to blood clotting (coagulation). ITP describes both the cause and symptoms of the condition: idiopathic means that the disorder has no apparent cause; thrombocytopenia refers to a decreased number of blood platelets; and purpura refers to a purplish or reddish-brown skin rash caused by the leakage into the skin of blood from broken capillaries. ITP is as of 2004 often called immune thrombocytopenic purpura rather than idiopathic because studies in the early 2000s have shown the presence of autoimmune antibodies in the blood. Other names for ITP include purpura hemorrhagica and essential thrombocytopenia.
Coagulation, or clotting, is a complex process in which specific proteins found in blood plasma combine with other blood components, including platelets, to form clots and prevent blood loss. Platelets are tiny colorless disc-shaped cells in the blood that collect (aggregate) in blood vessels to form a plug when a vessel is injured. The platelet plug then binds coagulation proteins to form a clot that stops bleeding. A deficiency in platelets or a disorder that affects platelet production can disrupt clotting and severely complicate blood loss from accidental injury, surgery, and specific diseases or conditions in which bleeding can occur. ITP affects the overall number of blood platelets rather than their function. The normal platelet level in adults is between 150,000 and 450,000/mm 3 . Platelet counts below 50,000/mm 3 increase the risk of dangerous bleeding from trauma; counts below 20,000/mm 3 increase the risk of spontaneous bleeding.
ITP may be either acute or chronic. The acute form occurs in children between ages two and six. Although chronic ITP is most common in adult females, 10 to 20 percent of children with ITP have the chronic form.
Acute ITP affects children of both sexes between the ages of two and six years. The chronic form, although most common in adult females between the ages of 20 and 40, is found in 10 to 20 percent of children with ITP. ITP does not appear to be related to race, lifestyle, climate, or environmental factors.
Causes and symptoms
In children, ITP is usually triggered by a virus infection, most often rubella , chickenpox , measles , cytomegalovirus (CMV), or Epstein-Barr virus (EBV). ITP usually begins about two or three weeks after the infection.
Acute ITP is characterized by bleeding into the skin or from the nose, mouth, digestive tract, or urinary tract. The onset is usually sudden. Bleeding into the skin takes the form of purpura or petechiae. Purpura, a purplish or reddish-brown rash or discoloration of the skin, and petechiae, small round pinpoint hemorrhages, are both caused by the leakage of blood from tiny capillaries under the skin. In addition to purpura and petechiae, spontaneous bruises may occur. In extreme cases, ITP may cause bleeding into the lungs, brain, or other vital organs.
Chronic ITP has a gradual onset and may have minimal or no external symptoms. The low platelet count may be discovered in the course of a routine blood test. Most parents consult a pediatrician or primary care doctor after noticing their child has the typical purpuric skin rash, frequent nosebleeds, or bleeding from the digestive or urinary tract.
In adults, ITP is considered an autoimmune disorder, which means that the body produces antibodies that damage some of its own products—in this case, blood platelets. Some adults with chronic ITP may have other autoimmune diseases such as lupus (systemic lupus erythematosus or SLE), rheumatoid arthritis, or scleroderma. Women with ITP may experience unusually heavy or lengthy menstrual periods. Risk factors for the development of chronic ITP in adults include being female, age over 10 years at onset of symptoms, bruising, and having another known autoimmune disease.
When to call the doctor
When a child bruises easily, has frequent nosebleeds, bloody stools, or develops a purplish or reddish-brown rash or tiny spots of hemorrhage, the symptoms should be reported to the pediatrician or family doctor, especially if they are noticed in the weeks following measles or chickenpox or a virus infection such as mononucleosis.
ITP is usually considered a diagnosis of exclusion, which means that the doctor makes a diagnosis by ruling out other possible causes for the symptoms and physical findings. The presence of fever , for example, does not indicate ITP, whereas fever may occur in lupus and some other types of thrombocytopenia. Likewise, the doctor will look for an enlarged spleen by pressing on (palpating) the abdomen; if the spleen is noticeably enlarged, ITP is not absolutely ruled out but is a less likely diagnosis. If ITP is suspected, the doctor will examine the child's skin for bruises, purpuric areas, or petechiae. If nosebleeds or bleeding from the mouth or other parts of the body have been reported, the doctor will examine these areas for other possible causes of bleeding. Individuals with ITP usually look and feel healthy except for the bleeding. If the child has had a recent childhood illness (measles, chickenpox) or a virus, the risk for ITP is greater, and this fact will be considered along with diagnostic testing results.
Diagnostic tests will begin with a complete blood count (CBC), including a platelet count. A blood test for autoantibodies may be performed early in the diagnostic process as well as a test for antiplatelet antibodies. Specific diagnostic tests for autoimmune diseases and viruses (CMV, EBV, and rheumatoid factor or RF) may be performed. Coagulation tests, including clotting time, will be performed to determine the ability of the child's blood to form a clot. Platelet aggregation tests may be performed to evaluate platelet function, particularly if the platelet count is low.
Autoimmune disorder —One of a group of disorders, like rheumatoid arthritis and systemic lupus erythematosus, in which the immune system is overactive and has lost the ability to distinguish between self and non-self. The body's immune cells turn on the body, attacking various tissues and organs.
Clotting factors —Substances in the blood, also known as coagulation factors, that act in sequence to stop bleeding by triggering the formation of a clot. Each clotting factor is designated with a Roman numeral I through XIII.
Idiopathic —Refers to a disease or condition of unknown origin.
Petechia —Plural, petechiae. A tiny purple or red spot on the skin resulting from a hemorrhage under the skin's surface.
Platelet —A cell-like particle in the blood that plays an important role in blood clotting. Platelets are activated when an injury causes a blood vessel to break. They change shape from round to spiny, "sticking" to the broken vessel wall and to each other to begin the clotting process. In addition to physically plugging breaks in blood vessel walls, platelets also release chemicals that promote clotting.
Prednisone —A corticosteroid medication often used to treat inflammation.
Purpura —A group of disorders characterized by purplish or reddish brown areas of discoloration visible through the skin. These areas of discoloration are caused by bleeding from broken capillaries.
Splenectomy —Surgical removal of the spleen.
Thrombocytopenia —A persistent decrease in the number of blood platelets usually associated with hemorrhaging.
Children with ITP will usually have platelet counts below 20,000/mm 3 and a prolonged clotting time. The size and appearance of the platelets may be abnormal, which is observed microscopically. The red blood cell count (RBC) and white blood cell count (WBC) are usually normal, although about 10 percent of individuals with ITP are also anemic (have reduced RBCs and hemoglobin). The bone marrow test yields normal results. Detection of antiplatelet antibodies in the blood usually confirms a diagnosis of ITP.
There is no specific treatment for ITP except to manage symptoms. In most cases, the disorder will resolve within two to six weeks without medications or surgery. Nosebleeds can be treated with ice packs when necessary. General care may include asking parents to watch for bruising, petechiae, or other signs of recurrence. Parents are also advised to avoid giving the child aspirin, ibuprofen, or other over-the-counter pain medications because these drugs are known to lengthen the clotting time of blood.
Children with acute ITP who are losing large amounts of blood or bleeding into their central nervous system require emergency treatment. This may include transfusions of platelets, intravenous immunoglobulins, or prednisone. Prednisone is a steroid medication that decreases the effects of antibodies on platelets and eventually lowers antibody production. If the child has been treated before for ITP and has not responded to prednisone or immunoglobulins, surgery may be required to remove the spleen (splenectomy), an organ that sometimes stores platelets and keeps them out of the general blood circulation. Splenectomy is usually avoided in children younger than five years because of the increased risk of a severe postoperative infection. In older children, however, splenectomy is recommended if the child has been treated for 12 months without improvement, if the ITP is very severe or is getting worse, or if the child begins to bleed into the head or brain.
Children with chronic ITP can be treated with prednisone, immune globulin, or large doses of intravenous gamma globulin. Although 90 percent of those with ITP respond to immunoglobulin treatment, it is an expensive treatment. Response to prednisone therapy is about 80 percent. Platelet transfusions are not recommended for routine treatment of ITP. If platelet levels do not improve within one to four months, or high doses of prednisone are required, splenectomy may be recommended. If the patient is an adolescent female with extremely heavy periods, splenectomy may also be recommended. Adults treated with splenectomy usually experience remission of chronic ITP. All medications for ITP are given either orally or intravenously; intramuscular injection is avoided because of the possibility of causing bleeding into the skin.
The prognosis for recovery from acute ITP is good; 80 percent of those affected recover without special treatment. The prognosis for chronic ITP is also good; most individuals experience long-term remission. In rare instances, however, ITP can cause life-threatening hemorrhage or bleeding into the central nervous system.
Because as of 2004 the exact cause for ITP is unknown, no specific preventive measures are recommended. However, episodes of bleeding can be prevented in children with ITP by discouraging rough contact sports or other activities that increase the risk of trauma. To reduce the risk of ITP associated with other illnesses, children can be immunized against childhood diseases and kept away as much as possible from other children or adults with known or unidentified viruses.
The sudden onset of ITP-like symptoms can be a concern, but the presence of a rash or bruising is not a signal for alarm because there are so many possible causes of these symptoms in childhood. Parents can be generally watchful, but not fearful. The symptoms to be alert for are frequent nosebleeds or frequent bruising with no specific cause, particularly if the child has had a recent illness or virus. It is helpful to remember that ITP, whether acute or chronic, has an excellent prognosis and may cause bleeding but not life-threatening hemorrhage in most cases. Parents can ask the pediatrician when in doubt and understand that simple blood and coagulation tests can be performed to rule out ITP.
Alving, Barbara M. Blood Components and Pharmacologic Agents in the Treatment of Congenital and Acquired Bleeding Disorders. Basel, Switzerland: S. Karger AG, 2000.
"Blood Disorders." The Merck Manual of Medical Information , 2nd Home Edition. Edited by Mark H. Beers et al. White House Station, NJ: Merck & Co., 2003.
National Heart, Lung, and Blood Institute (NHLBI). 6701 Rockledge Drive, PO Box 30105, Bethesda, MD 20824–0105. Web site: http://www.nhlbi.nih.gov.
L. Lee Culvert Rebecca J. Frey, PhD