Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Resulting complications can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.
Blood clots normally form to prevent excess blood loss at the site of an injury. In people with thrombotic thrombocytopenic purpura, clots develop in blood vessels even in the absence of injury. Blood clots are formed from clumps of cell fragments called platelets, which circulate in the blood and assist with clotting. Because a large number of platelets are used to make clots in people with thrombotic thrombocytopenic purpura, fewer platelets are available in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura.
This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.
There are two major forms of thrombotic thrombocytopenic purpura, an acquired (noninherited) form and a familial form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or they may recur over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood. In people with the familial form, signs and symptoms often recur on a regular basis.
Idiopathic thrombocytopenic purpura can occur in anyone at almost any age, but these factors increase the risk:
- Your sex. Women are two to three times more likely to develop ITP than men are.
- Recent viral infection. Many children with ITP develop the disorder after a viral illness, such as mumps, measles or a respiratory infection.
A rare complication of idiopathic thrombocytopenic purpura is bleeding into the brain, which can be fatal.
In pregnant women with ITP, the condition doesn't usually affect the baby. But the baby's platelet count should be tested soon after birth.
If you're pregnant and your platelet count is very low or you have bleeding, you have a greater risk of heavy bleeding during delivery. In such cases, you and your doctor may discuss treatment to maintain a stable platelet count, taking into account the effects on your baby.
Idiopathic thrombocytopenic purpura may have no signs and symptoms. When they do occur, they may include:
- Easy or excessive bruising (purpura)
- Superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple spots (petechiae), usually on the lower legs
- Bleeding from the gums or nose
- Blood in urine or stools
- Unusually heavy menstrual flow
In some people thrombocytopenia is caused by the immune system mistakenly attacking and destroying platelets. If the cause of this immune reaction is unknown, the condition is called idiopathic thrombocytopenic purpura. Idiopathic means "of unknown cause."
In most children with ITP, the disorder follows a viral illness, such as the mumps or the flu. It may be that the infection triggers the immune system malfunction.
Increased breakdown of platelets:
In people with ITP, antibodies produced by the immune system attach themselves to the platelets, marking the platelets for destruction. The spleen, which helps your body fight infection, recognizes the antibodies and removes the platelets from your system. The result of this case of mistaken identity is a lower number of circulating platelets than is normal.
A normal platelet count is generally between 150,000 and 450,000 platelets per microliter of circulating blood. People with ITP often have platelet counts below 20,000. Because platelets help the blood clot, as their number decreases, your risk of bleeding increases. The greatest risk is when your platelet count falls very low — below 10,000 platelets per microliter. At this point, internal bleeding may occur even without any injury.
Platelet defects can be considered either as a decreased number of platelets (thrombocytopenia) or as defective platelets. Platelet aggregation tests are useful in differentiating various disorders of platelet function. Spurious thrombocytopenia can occur due to aggregates forming in the specimen. Also, dilutional thrombocytopenia may occur in situations of fluid replacement or blood component replacement without platelet support. In all cases of thrombocytopenia, the peripheral blood smear must be reviewed to confirm the thrombocytopenia. This review is crucial.
Thrombocytopenia can be further divided into increased destruction or decreased production. Thrombocytopenia resulting from increased destruction occurs either by an immune mechanism or increased consumption. Platelets are consumed intravascularly by the activation of the coagulation process (diffuse intravascular coagulation [DIC]) or by deposition on damaged endothelial cells (microangiopathy). Production defects result from those diseases that cause bone marrow failure, such as aplastic anemia, infiltration by leukemia or another malignancy, fibrosis or granulomatous disorders, or tuberculosis. Functional disorders of platelets can be inherited (rare) or acquired (common).
Disorders of platelet function are as follows:
- Disorders of platelet adhesion (von Willebrand disease, Bernard-Soulier syndrome)
- Disorders of aggregation (Glanzmann thrombasthenia)
- Disorders of secretion
- Disorders of thromboxane synthesis
- Acquired disorders of platelet function (drugs, eg, aspirin, NSAIDs, alcohol)
- Fibrin degradation products
- Myelodysplasia or a myeloproliferative syndrome
You can't prevent immune thrombocytopenia (ITP), but you can prevent its complications.
- Talk with your doctor about which medicines are safe for you. Your doctor may advise you to avoid medicines that can affect your platelets and increase your risk of bleeding. Examples of such medicines include aspirin and ibuprofen.
- Protect yourself from injuries that can cause bruising or bleeding.
- Seek treatment right away if you develop any infections. Report any symptoms of infection, such as a fever, to your doctor. This is very important for people who have ITP and have had their spleens removed.
To diagnose idiopathic thrombocytopenic purpura, your doctor will try to exclude other possible causes of bleeding and a low platelet count, such as an underlying illness or medications you or your child may be taking.
Your doctor will also ask you about your or your child's medical history, perform a physical exam and run one or more of the following tests:
- Complete blood count (CBC). This common blood test is used to determine the number of blood cells, including platelets, in a sample of blood. With ITP, white and red blood cell counts are usually normal, but the platelet count is low.
- Blood smear. This test is often used to confirm the number of platelets observed in a complete blood count. A sample of blood is placed on a slide and observed under a microscope.
- Bone marrow exam. This test may be used to help identify the cause of a low platelet count, though the American Society of Hematology doesn't recommend this test for children with ITP.
Platelets are produced in the bone marrow — soft, spongy tissue in the center of large bones. In some cases, a sample of bone tissue and the enclosed marrow is removed in a procedure called a bone marrow biopsy. Or your doctor may do a bone marrow aspiration, which removes some of the liquid portion of the marrow. In many cases, both procedures are performed at the same time (bone marrow exam).
In people with ITP, the bone marrow will be normal because a low platelet count is caused by the destruction of platelets in the bloodstream and spleen — not by a problem with the bone marrow.
With treatment, the chance of remission (a symptom-free period) is good. In rare cases, ITP may become a long-term condition in adults and reappear, even after a symptom-free period.
People with mild idiopathic thrombocytopenic purpura may need nothing more than regular monitoring and platelet checks. Children usually improve without treatment. Most adults with ITP will eventually need treatment, as the condition often becomes severe or long-term (chronic) ITP.
Treatment may include a number of approaches, such as medications to boost your platelet count or surgery to remove your spleen (splenectomy). Talk with your doctor about the risks and benefits of your treatment options. Some people find that the side effects of treatment are more burdensome than the effects of the disease itself.
Your doctor will talk with you about medications or supplements you take and whether you need to stop using any that might inhibit platelet function. Examples include aspirin, ibuprofen (Advil, Motrin IB, others), ginkgo biloba and warfarin (Coumadin).
Your doctor may prescribe one or more of the following medications to treat ITP:
- Drugs that suppress your immune system. Your doctor will likely start you on an oral corticosteroid, such as prednisone. This drug may help raise your platelet count by decreasing the activity of your immune system. Once your platelet count is back to a safe level, you can gradually discontinue taking the drug under the direction of your doctor. In general, this takes about two to six weeks. The problem is that many adults experience a relapse after discontinuing corticosteroids. A new course of corticosteroids may be pursued, but long-term use of these medications isn't recommended because of the risk of serious side effects. These include cataracts, high blood sugar, increased risk of infections and thinning of bones (osteoporosis).
- Injections to increase your blood count. If corticosteroids don't help, your doctor may give you an injection of immune globulin (IVIG). This drug may also be used if you have critical bleeding or need to quickly increase your blood count before surgery. The effect usually wears off in a couple of weeks. Possible side effects include headache, vomiting and low blood pressure.
- Drugs that boost platelet production. Thrombopoietin receptor agonists — such as romiplostim (Nplate) and eltrombopag (Promacta) — help your bone marrow produce more platelets. Possible side effects include headache, dizziness, nausea or vomiting, and an increased risk of blood clots.
- Other immune-suppressing drugs. Rituximab (Rituxan) helps reduce the immune system response that's damaging platelets, thus raising the platelet count. Possible side effects include low blood pressure, fever, sore throat and rash.
Although rare, severe bleeding can occur with ITP. Emergency care usually includes transfusions of platelet concentrates, intravenous corticosteroid (methylprednisolone) and intravenous immune globulin.
Treatments for resistant disease:
If your condition persists despite treatment, your doctor may suggest other drugs that suppress the immune system or boost platelet production:
- Removal of your spleen. If your condition is severe or persists despite initial drug treatment, your doctor may suggest surgical removal of your spleen (splenectomy). This quickly eliminates the main source of platelet destruction in your body and improves your platelet count, though it doesn't work for everyone. Serious post-surgical complications sometimes occur, and not having a spleen permanently increases your susceptibility to infection. Splenectomy is rarely a treatment choice for children with ITP because they often get better without treatment.
- Other drugs. Azathioprine (Imuran, Azasan) has been used to treat ITP. But it can cause significant side effects, and its effectiveness has yet to be proved. Possible side effects include fever, headache, nausea and vomiting, and muscle pain.
Refer to Research Publications.