idiopathic thrombocytopenia purpura

What Is ITP?

ITP, or immune thrombocytic purpura (THROM-boe-see-tic purr-PURR-uh), is a disease that destroys platelets in the blood. Platelets are the blood cells that help form clots to stop bleeding and close up wounds. When the platelet count is low, bleeding too much can be a problem. ITP can also stand for idiopathic thrombocytopenic purpura. “Idiopathic” means that we do not know what causes it. “Thrombocytopenic” means that there are not enough platelets in the blood. “Purpura” means bruises in the skin. The immune system usually fights germs or infections. If your child has ITP, their immune system instead attacks the body’s platelets and destroys them. The platelets are mostly destroyed in the spleen.

ITP in Children

Any child can get ITP. Even though we are not sure what causes it, ITP sometimes happens when children get some kinds of viruses or take some kinds of medicines. It can be more likely in children with certain kinds of immune disorders. Even though ITP can start with a virus, it is not an infection. Your child cannot not catch ITP from someone else. For most children with ITP, it goes away within six months. Platelet count usually goes back to normal in four to six weeks. When ITP lasts longer than 12 months, it is called chronic ITP. Chronic ITP happens in about one in four children with ITP.

Symptoms of ITP

Having ITP means your child has fewer platelets than normal. Most symptoms of ITP are from bleeding problems:

Bleeding more easily than usual

Bruising or purplish areas on the skin (purpura). These are caused by bleeding under the skin.

Tiny round red spots on the skin (petechiae, or puh-TEE-key-eye) that may look like a rash. These are also caused by bleeding under the skin.

Nosebleeds

Bleeding from the gums and blood blisters in the mouth

Blood in your child’s pee (urine) or bowel movements (stool)

Any bleeding that is difficult to stop

Heavy menstrual bleeding

ITP Diagnosis

Because there are other health problems that can cause low platelet levels, your child’s healthcare team will talk to you in detail about your child’s health. They will need to know more than your child’s platelet level before they know whether your child has ITP. Your child’s provider will ask about your child’s symptoms, recent illnesses and medicines that may affect platelets. They will also ask about any immune problems that your child might have.

Your child’s healthcare provider will also do the following to find out if your child has ITP:

Look for signs of bleeding, bruising or petechia, or other health problems

Do blood tests

Sometimes, they may need to do a bone marrow test.

Bone marrow tests

If your child needs a bone marrow test, they will get medicine to make them sleep so that they do not feel pain during the procedure. Then, a member of the healthcare team will place a needle into the hip bone and use a syringe to take out a small amount of bone marrow (aspiration). Sometimes, they may also need to take out a very small piece of bone (biopsy). There may be a little soreness in the hip for one to two days after the procedure.

ITP Treatment Options

Many children with ITP do not need treatment. It often goes away on its own in a few weeks or months.

For more serious cases, your child’s provider may recommend treatment. This will not cure ITP, but it will help your child make more platelets and slow down the speed that platelets get destroyed. Here are the main ITP treatment options:

Intravenous gamma globulin (IVIG)

IVIG is made from blood plasma. It may help block the antibodies that cause platelet destruction. It is given into the vein over several hours. IVIG can cause nausea, headache, and other side effects.

WinRho SDF

This is also made from blood plasma. It causes the spleen to destroy some of your child’s red blood cells instead of platelets. This medicine may cause a temporary drop in red blood cells (anemia), but may help to raise the platelet levels. It is given into the vein over about 15 minutes. Your child’s healthcare team will watch your child for several hours after treatment.

Corticosteriods

These medicines may help slow down the speed that the spleen takes platelets out of the blood. They are usually taken by mouth. Steroids, like prednisone or dexamethasone, have several side effects. They make your child gain weight, feel hungrier than usual, have an upset stomach or feel moody. If your child gets this treatment, their provider will talk with you about how to manage side effects.

Taking out the spleen (splenectomy)

For some very serious or long-lasting cases of ITP, healthcare providers might recommend a splenectomy. This surgery has long-term effects, so it is important to talk with your child’s medical provider about what to consider and what to expect.

Other treatments

Other medicines are sometimes used for ITP, especially when it is very serious or chronic. Your child’s provider may talk with you about these if your child may need them.

Many people wonder about using transfusions as a treatment. We almost never use platelet transfusions in ITP treatment because the transfused platelets are destroyed by the spleen as quickly as the child's own platelets.

Your child’s provider will talk with you about when and how often your child’s platelet count should be checked. Right after treatment for ITP, we will check your child’s platelet count often (every two to three

days). If there are no problems, we may check weekly for the next month. After that, we will check less often. When the platelet count is normal and stable, we can stop checking platelet levels.

If your child does not need treatment, or if they have ITP longer than four to six weeks, they may not need to be checked so often. But if your child develops new symptoms or has problems like bruising again, that is usually a time to check the platelet count.

Your child’s provider will talk with you about the plan to monitor your child. This plan will depend on your child’s individual needs. We will work with you and with your primary care provider to decide where to have those blood tests done and whom to talk to about the results.

Idiopathic Thrombocytopenic Purpura (ITP)

What is ITP?

ITP stands for idiopathic thrombocytopenic purpura. "Idiopathic" means that the cause of the condition is unknown. "Thrombocytopenic" means the blood doesn't have enough platelets (platelets are also called thrombocytes). "Purpura" means a person has excessive bruising. ITP is also sometimes called "immune thrombocytopenic purpura."

In people who have ITP, all of the blood cells are normal except for the platelets. Platelets are the tiny cells that form blood clots and seal minor cuts and wounds. A person who has too few platelets bruises very easily and can bleed for a long time after being injured. When the platelet count is very low, a person who has ITP might have nosebleeds that are hard to stop, or they might have bleeding in the intestines, or even bleeding in the brain with minor trauma.

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What are the symptoms of ITP?

The symptoms of ITP include:

•Easy or excessive bruising

•Petechiae (tiny reddish purple dots on the skin that are caused by bleeding under the surface of the skin) on the body, especially on the lower legs

•Cuts or minor wounds that take a very long time to clot or stop bleeding

•Blood in the urine or stools

•Unusually heavy menstrual flow in women

•Unexplained bleeding from the nose or gums

What causes ITP?

The cause of ITP is not known. People who have ITP form antibodies that destroy their blood platelets. Normally, antibodies are a healthy response to bacteria or viruses. In people who have ITP, however, the antibodies attack the body's own blood platelets.

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How is ITP diagnosed?

Your doctor can begin to diagnose ITP by asking questions about your health and doing a physical exam. Your doctor may take a blood sample for a test that counts blood cells and platelets (called a CBC) or look at it under a microscope (called a blood smear). Your doctor may also want you to get a bone marrow exam to rule out other possible causes of your symptoms.

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Who gets ITP?

There are 2 types of ITP. One type affects children, and the other type affects adults. In children, the usual age for getting ITP is 2 to 4 years of age. Most adults with ITP are young women, but it can occur in anyone. ITP does not seem to be hereditary (run in families). ITP is not contagious (you can’t “catch it” from someone else).

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How does ITP affect children?

ITP in children is usually mild and runs it course without the need for treatment. About 80% of children recover completely from ITP within about 6 months.

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How is ITP treated in children?

Because most children recover with no treatment, many doctors recommend just watching them carefully and taking care of the bleeding symptoms. Children don't have to go to the hospital if good care is available at home. However, some doctors recommend a short treatment with prednisone pills or intravenous infusions (given in a vein) of gamma globulin to increase the platelet count more quickly. Both medicines have some side effects.

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How does ITP affect adults?

In most adults, ITP lasts much longer than it does in children. At the time of diagnosis, most adults have noticed increased bleeding and easy bruising for several weeks or even months. In women, increased menstrual blood flow is a common sign.

Many adults have only mild thrombocytopenia. In fact, quite a few people have no bleeding symptoms. They are only diagnosed with ITP when their blood is checked for another reason and a low blood platelet count is found. Mild cases of ITP may not require treatment, just regular monitoring of the platelet levels.

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How is ITP treated in adults?

Treatment of ITP in adults is aimed at increasing the blood platelet count. This is not the same as curing the disease. Your doctor may recommend that you get high doses of immune globulin (through a needle). Some patients might take prednisone for several weeks or months. Prednisone raises the level of your platelet count. As your count rises and reaches a safe level, your doctor may gradually decrease your medicine until you no longer take the prednisone. However, when the medicine is stopped, your platelet count may decrease again.

If prednisone doesn't help enough, your doctor may recommend that your spleen be removed. The spleen makes most of the antibodies that destroy the blood platelets. It also destroys old or damaged blood cells. In an otherwise healthy person, removal of the spleen is not a serious operation. Laparoscopic removal of the spleen is now possible, further reducing surgical risk. However, this treatment is done less often than it once was. Removing the spleen will permanently reduce your body’s ability to fight infection. Some people can also relapse (have the condition return) even after the spleen is removed.

Other treatments for ITP include another kind of steroid medicine called danazol or other medicines that work to hold the immune system in check, such as rituximab. Some people with certain blood types may have anti-RhD therapy, which is a shot or series of shots that also work to reduce antibodies in the blood. Another option includes filtering antibodies from the blood.

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What about ITP in pregnant women?

Many of the medicines used to treat ITP should not be taken by women who are pregnant. Talk to your doctor if you are taking medicine and want to become pregnant.

Diagnosing ITP during pregnancy can be difficult, because platelet counts may be low for other reasons. About 5% of women have mildly low platelet counts at the end of a normal pregnancy. The cause of this is unknown. The platelet count goes back to normal right after delivery.

A baby born to a mother who has ITP may have a low blood platelet count a few days to a few weeks after birth. These babies are usually kept in the hospital for several days for observation (watching to make sure they are okay) before they go can home. If the baby's platelet count is very low, treatment is available to speed recovery.

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What can I do if I have ITP?

If you have ITP, you should avoid medicines that increase risks for bleeding, such as warfarin (a medicine often used to treat an abnormal heart rhythm called atrial fibrillation) and over-the-counter drugs like aspirin and ibuprofen (some brands: Advil, Motrin). You should also limit alcohol because it can decrease the ability of your blood to clot.

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Idiopathic thrombocytopenic purpura (ITP)

Definition

By Mayo Clinic staff

Idiopathic thrombocytopenic purpura (ITP), also called immune thrombocytopenic purpura, is a blood-clotting disorder that can lead to easy or excessive bruising and bleeding. ITP results from unusually low levels of platelets — the cells that help your blood clot.

Idiopathic thrombocytopenic purpura affects both children and adults. Children often develop idiopathic thrombocytopenic purpura after a viral infection and usually recover fully without treatment. In adults, however, the disorder is often chronic.

Treatment of idiopathic thrombocytopenic purpura depends on your symptoms and platelet count. If you don't have signs of bleeding and your platelet count isn't too low, treatment for idiopathic thrombocytopenic purpura usually isn't necessary. More serious cases may be treated with medications or, in critical situations, with surgery.

Symptoms


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Petechiae

Idiopathic thrombocytopenic purpura (ITP) may have no symptoms. When signs and symptoms do occur, they may include:

■Easy or excessive bruising (purpura) — your skin naturally bruises and bleeds more easily as you age, but this shouldn't be confused with ITP

■Superficial bleeding into your skin that appears as a rash of pinpoint-sized reddish-purple spots (petechiae), usually on your lower legs

■Prolonged bleeding from cuts

■Spontaneous bleeding from your gums or nose

■Blood in urine or stools

■Unusually heavy menstrual flows

■Profuse bleeding during surgery

When to see a doctor

If you or your child has abnormal bleeding or bruising, or develops a rash of pinpoint-sized red spots, see your doctor. It's also important to seek medical advice if you're a woman and suddenly develop significantly increased menstrual bleeding, as this may be a sign of ITP.

Serious or widespread bleeding indicates an emergency and requires immediate care.

Causes


The exact cause of ITP isn't known. That's why it's referred to as idiopathic, which means "of unknown cause." It is known, however, that in people with idiopathic thrombocytopenic purpura, the immune system malfunctions and begins attacking platelets as if they were foreign substances.

Antibodies produced by your 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 normal.

Ordinarily, you have anywhere from 150,000 to 450,000 platelets per microliter of circulating blood. Adults and children with ITP often have platelet counts below 20,000. As the number of platelets 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 despite a lack of any injury.

In most children with ITP, the disorder follows a viral illness, such as the mumps or the flu. It may be that an infection sets off the immune system, triggering it to malfunction.

Risk factors


ITP is a fairly common blood disorder and can occur in anyone at almost any age, but these factors increase your risk:

■Your sex. Women are about twice as likely to develop ITP as men are.

■Age. Once considered a young person's disease, ITP is actually far more common in people older than 60 than it is in younger adults.

■Recent viral infection. Many children with ITP develop the disorder after a viral illness, such as mumps, measles or a respiratory infection. In most children, ITP clears on its own within two to eight weeks.

Complications


The biggest risk associated with idiopathic thrombocytopenic purpura is bleeding, especially bleeding into the brain (intracranial hemorrhage), which can be fatal. Major bleeding is rare with ITP, however. Complications are more likely to arise from the treatments — corticosteroids and surgery — used for chronic or severe ITP. In fact, many therapies pose more serious potential risks than does the disease.

Long-term use of corticosteroids can cause serious side effects, including:

■Osteoporosis

■Cataracts

■Loss of muscle mass

■Increased risk of infection

■High blood sugar, even diabetes

Removal of your spleen (splenectomy), which may be performed if corticosteroids aren't working, also makes you permanently more vulnerable to infection, although the risk of an overwhelming infection in a healthy person who has had a splenectomy is low.

Pregnancy

Pregnant women with mild ITP usually have a normal pregnancy and delivery, though antibodies to platelets can cross the placenta and affect the baby's platelet count. In some cases, a baby may be born with a low number of platelets. If this happens, your baby's doctor will want to monitor your child for several days, because your baby's platelet count may drop before it starts to rise. It's likely that your baby's platelet count will improve without treatment, but if the count is very low, treatment can help speed recovery.

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.

Preparing for your appointment


Because a low platelet count may not cause symptoms, the problem is often discovered when you have a blood test for another reason. If your doctor thinks you might have ITP, you are likely to have further blood tests that require drawing a small amount of blood from a vein in your arm. You are also likely to be referred to a doctor who specializes in blood disorders (hematologist) for further evaluation and treatment.

Appointments, even with specialists, can be brief, and there's often a lot of ground to cover, so it can help to be prepared. Here are some tips to help you get ready for your appointment:

What you can do

■Write down all your symptoms — even those that seem unrelated to your current problem. Include key personal information, such as major stresses or recent life changes.

■Make a list of all medications, including vitamins, herbs and over-the-counter drugs, that you're taking. Even better, take the original bottles and a written list of the dosages and directions.

■Take along a family member or friend. It can be difficult to absorb all the information provided during an appointment. The person who accompanies you may remember something that you forgot or missed.

■Write down questions for your doctor. Don't be afraid to ask questions or to speak up when you don't understand something your doctor says. Start with the problems that concern you most. If you run out of time, ask to speak with a nurse or physician's assistant or leave a message for your doctor.

Questions you may want to ask include:

■What tests are needed to confirm the diagnosis?

■Is this condition temporary or long-lasting?

■What treatments are available and what do you recommend?

■What will happen if I do nothing?

■What are the possible side effects of the treatments you're suggesting?

■How can I avoid those side effects?

■Can you refer me to a website or other source, so I can learn more about this condition?

Tests and diagnosis


Doctors usually diagnose idiopathic thrombocytopenic purpura by excluding other possible causes of bleeding and a low platelet count, such as an underlying illness or medications you may be taking. If no other underlying problem is causing your signs and symptoms, then a diagnosis of ITP may be made.

To diagnose ITP, your doctor may need a:

■Physical exam, including a complete medical history. Your doctor will look for signs of bleeding under your skin, and will ask you about previous illnesses you've had and the types of medications and supplements that you've recently taken.

■Complete blood count. This common blood test is used to determine the number of white and red blood cells and platelets in a sample of your blood. With ITP, white and red blood cell counts are usually normal, but the platelet count is low.

■Blood smear. A sample of your blood is placed on a slide and observed under a microscope. This test is often used to confirm the number of platelets observed in a complete blood count.

■Bone marrow examination. Another test that may help identify the cause of a low platelet count is a bone marrow exam. Platelets are produced in your bone marrow — soft, spongy tissue in the center of your large bones. In some cases, a sample of solid bone marrow is removed in a procedure called a bone marrow biopsy. Or, you may have a bone marrow aspiration, which removes the liquid portion of your marrow. In many cases, both procedures are performed at the same time (bone marrow exam). Both the liquid and solid bone marrow samples are frequently taken from the same place on the back of one of your hipbones. A needle is inserted into the bone through an incision.

If you have ITP, your bone marrow will be normal because your low platelet count is caused by the destruction of platelets in your bloodstream and spleen — not by a problem with the bone marrow.

Treatments and drugs


The goal of treating ITP is to ensure a safe platelet count and prevent bleeding complications while minimizing treatment side effects.

In children, idiopathic thrombocytopenic purpura usually runs its course without the need for treatment. About 80 percent of children with idiopathic thrombocytopenic purpura recover completely within six months. Even in children who develop chronic ITP, complete recovery may still occur, even years later.

Adults with mild cases of ITP may require nothing more than regular monitoring and platelet checks. But if your symptoms are troublesome and your platelet count remains low, you and your doctor may opt for treatment. Treatment usually consists of medications and sometimes surgery (splenectomy). Your doctor may also have you discontinue certain drugs that can further inhibit platelet function, such as aspirin, ibuprofen (Advil, Motrin, others) and the blood-thinning medication warfarin (Coumadin).

Medications

Common medications used to treat idiopathic thrombocytopenic purpura include:

■Corticosteroids. The first line of therapy for ITP is a corticosteroid, usually prednisone, which can 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, including cataracts, high blood sugar, increased risk of infections and loss of calcium from your bones (osteoporosis). You and your doctor will want to weigh the benefits of the medication against these risks. If you've taken corticosteroids for longer than three months, your doctor will likely recommend that you take calcium and vitamin D supplements to help maintain your bone density.

■Intravenous immune globulin (IVIG). If you have critical bleeding or need to quickly increase your blood count before surgery, you may receive medications, such as immune globulin, given intravenously. These medications are quick and effective, but the effect usually wears off in a couple of weeks. Possible side effects include headache, nausea and vomiting.

■Thrombopoietin receptor agonists. The newest medications approved to treat ITP are romiplostim (Nplate) and eltrombopag (Promacta). These drugs help your bone marrow produce more platelets, which helps prevent bruising and bleeding. Possible side effects include headache, joint or muscle pain, dizziness, nausea or vomiting, and an increased risk of blood clots.

Surgery

If you have severe ITP and an initial course of prednisone hasn't helped, surgical removal of your spleen (splenectomy) may be an option. This eliminates the main source of platelet destruction in your body and improves your platelet count within a few weeks. Splenectomy for ITP is not as routinely performed as it once was, however. Serious post-surgical complications sometimes occur, and not having a spleen permanently increases your susceptibility to infection. What's more, some people relapse even after splenectomy.

Splenectomy is rarely performed in children because of their high rate of spontaneous remission.

Emergency treatment

Although rare, severe bleeding can occur with ITP, regardless of age or platelet count. Severe or widespread bleeding is life-threatening and demands emergency care. This usually includes transfusions of platelet concentrates, intravenous methylprednisolone (a type of corticosteroid) and intravenous immune globulin.

Other treatments

If neither the initial round of corticosteroids nor a splenectomy has helped you achieve remission and your symptoms are severe, your doctor may recommend another course of corticosteroids, usually at the lowest effective dose.

Other possible treatments include:

■Immunosuppressant drugs. Medications that suppress the immune system, such as rituximab (Rituxan) — the most commonly used of this group — cyclophosphamide (Cytoxan) and azathioprine (Imuran, Azasan), have been used to treat ITP, but they can cause significant side effects, and their effectiveness has yet to be proved.

■Experimental drugs. New medications that increase platelet production, especially eltrombopag and AMG 531, are being studied in clinical trials. Although they appear to be well tolerated, questions about long-term side effects remain, and relapse is possible when the drugs are stopped.

■H. pylori treatment. Some people with ITP are also infected with Helicobacter pylori, the same bacteria that cause most peptic ulcers. Eliminating the bacteria has helped increase platelet count in some people, but the results for this therapy are inconsistent and need to be studied further.

Because of the potential complications of both the disease and its treatment, it's important for you and your doctor to carefully weigh the benefits and risks of treatment. For example, some people find that the side effects of treatment are more burdensome than the effects of the disease itself. Treatment decisions are usually based on:

■Severity of signs and symptoms (active bleeding is usually an indication for treatment)

■Platelet count — even relatively low counts (less than 30,000 platelets per microliter of blood) may not merit treatment, especially if you have no active bleeding and have a fairly sedentary lifestyle

■Your age and willingness to undergo treatment

■Risk of bleeding relative to lifestyle, such as participation in sports or other vigorous physical activities that may predispose you to injury

■Risk of bleeding based on other medical conditions (high blood pressure, infections, alcoholism, chronic liver disease, peptic ulcer) or needed medications, such as aspirin

■Potential side effects of ITP therapies

Lifestyle and home remedies


If you have idiopathic thrombocytopenic purpura, the following steps may help control your risk of bleeding and other complications:

■Avoid platelet-impairing medications. Over-the-counter drugs, such as aspirin and ibuprofen (Advil, Motrin, others), can impair platelet function.

■Limit alcohol. Excessive alcohol intake can adversely affect blood clotting.

■Choose low-impact physical activities. Your doctor may recommend avoiding competitive sports or other activities that might increase the risk of injury and bleeding.

■Watch for signs of infection. If you've had your spleen removed, be alert for any signs of infection, including fever, and seek prompt treatment. Infection in someone who's had a splenectomy may be more severe, last longer and have more serious implications than in someone who still has an intact spleen.

Introduction

Background

Idiopathic thrombocytopenic purpura (ITP), also known as primary immune thrombocytopenic purpura and autoimmune thrombocytopenic purpura, is defined as isolated thrombocytopenia with normal bone marrow and the absence of other causes of thrombocytopenia. The 2 distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults.

ITP is a decrease in the number of circulating platelets in the absence of toxic exposure or a disease associated with a low platelet count.

Pathophysiology

ITP is primarily a disease of increased peripheral platelet destruction, with most patients having antibodies to specific platelet membrane glycoproteins. Relative marrow failure may contribute to this condition, since studies show that most patients have either normal or diminished platelet production.

Acute ITP often follows an acute infection and has a spontaneous resolution within 2 months. Chronic ITP persists longer than 6 months without a specific cause.

Frequency

United States

The incidence of ITP in adults is approximately 66 cases per 1,000,000 per year.

An average estimate of the incidence in children is 50 cases per 1,000,000 per year.

New cases of chronic refractory ITP comprise approximately 10 cases per 1,000,000 per year.

International

According to studies in Denmark and England, childhood ITP occurs in approximately 10-40 cases per 1,000,000 per year. A study in Kuwait reported a higher incidence of 125 cases per 1,000,000 per year.

Mortality/Morbidity

•Hemorrhage represents the most serious complication; intracranial hemorrhage is the most significant. The mortality rate from hemorrhage is approximately 1% in children and 5% in adults. In patients with severe thrombocytopenia, predicted 5-year mortality rates from bleeding are significantly raised in patients older than 60 years versus patients younger than 40 years, 47.8% versus 2.2%, respectively.

•Older age and previous history of hemorrhage increase the risk of severe bleeding in adult ITP.

•Spontaneous remission occurs in more than 80% of cases in children but is uncommon in adults.

Sex

•In chronic ITP (adults), the female-to-male ratio is 2.6:1. More than 72% of patients older than 10 years are female.

•In acute ITP (children), distribution is equal between males (52%) and females (48%).

Age

•Peak prevalence occurs in adults aged 20-50 years.

•Peak prevalence occurs in children aged 2-4 years.

•Approximately 40% of all patients are younger than 10 years.

Clinical

History

•Focus on the symptoms of bleeding (eg, type, severity, duration) and on symptoms that may exclude other causes of thrombocytopenia.

•Elicit risk factors for HIV and systemic symptoms linked to other illnesses or to medications (eg, heparin, alcohol, quinidine/quinine, sulfonamides) that may cause thrombocytopenia. Medications can be a common etiology for inducing thrombocytopenia, and patients should have their medications carefully reviewed. One study used 3 distinct methods to document drugs that may be associated with drug-induced immune thrombocytopenia (DITP).1,2 Approximately 1500 drugs are associated with thrombocytopenia, but, using this analysis, 24 drugs had evidence of causing thrombocytopenia by all 3 methods.

•Address risk factors for increased bleeding, such as GI disease, CNS disease, urologic disease, or active lifestyle, as these may determine the aggressiveness of management.

•Common signs, symptoms, and precipitating factors include the following:

◦Abrupt onset (childhood ITP)

◦Gradual onset (adult ITP)

◦Purpura

◦Menorrhagia

◦Epistaxis

◦Gingival bleeding

◦Recent live virus immunization (childhood ITP)

◦Recent viral illness (childhood ITP)

◦Bruising tendency

•Limited data are available on the recurrent form of the disease. One study showed a 6% prevalence of recurrent ITP with most patients (69%) having only one recurrence. Though one third of patients had

their recurrent episode within 3 months of their initial one, the remainder of patients had at least a 3-month interval between episodes.

Physical

Evaluate the type and the severity of bleeding and try to exclude other causes of bleeding. Seek evidence of liver disease, thrombosis, autoimmune diseases (eg, nephritis, cutaneous vasculitis, arthritis), and infection, particularly HIV.

Common physical findings include the following:

•Nonpalpable petechiae, which mostly occur in dependent regions

•Hemorrhagic bullae on mucous membranes

•Purpura

•Gingival bleeding

•Signs of GI bleeding

•Menometrorrhagia, menorrhagia

•Retinal hemorrhages

•Evidence of intracranial hemorrhage, with possible neurologic symptoms

•Nonpalpable spleen: The prevalence of palpable spleen in patients with ITP is approximately the same as that in the non-ITP population (ie, 3% in adults, 12% in children).

•Spontaneous bleeding when platelet count is less than 20,000/mm3.

Causes

•Immunoglobulin G (IgG) autoantibodies on the platelet surface

Differential Diagnoses

Disseminated Intravascular Coagulation

HIV Infection and AIDS

Thrombocytopenic Purpura

Other Problems to Be Considered

Pseudothrombocytopenia (platelet clumping in the presence of ethylenediaminetetraacetic acid [EDTA])

Liver disease

Myelodysplasia

Lymphoproliferative, autoimmune, or infectious diseases

Pregnancy-associated thrombocytopenia

Drug-induced immune thrombocytopenia (alcohol, heparin, quinine/quinidine, sulfonamides)

Infection/sepsis

Acute leukemia

Myelodysplastic syndrome

Malignancy

Megaloblastic anemia

Isoimmune neonatal purpura

Transfusion

Factitious

Workup

Laboratory Studies

•CBC

◦Isolated thrombocytopenia is the key finding regarding laboratory evaluation.

◦Truly giant platelets on peripheral smear suggest congenital thrombocytopenia.

◦The WBC count and hemoglobin typically are normal, unless severe hemorrhage has occurred.

•Coagulation studies are normal, and a bleeding time is not useful.

Imaging Studies

A CT scan of the head is warranted if concern exists regarding intracranial hemorrhage.

Treatment

Prehospital Care

•Prehospital care focuses on the ABCs, which include providing oxygen, controlling severe hemorrhage, and initiating intravenous (IV) fluids to maintain hemodynamic stability.

•Prehospital airway control may be necessary for a large intracranial hemorrhage.

•EMS providers should be aware of the potential for serious bleeding complications in patients with idiopathic thrombocytopenic purpura (ITP).

Emergency Department Care

•Life-threatening bleeding requires conventional critical care interventions.

•In the patient with known ITP, high-dose parenteral glucocorticoids and IV immunoglobulin (IVIg), with or without platelet transfusions, are appropriate.

•Platelet transfusion is indicated for controlling severe hemorrhage. Send a blood specimen to the lab for type and screen in case platelet transfusion is necessary.

•Platelet survival is increased if the platelets are transfused immediately after IVIg infusion.

•A consultation with a hematologist may be required to make a decision regarding the transfusion of platelets.

•Guidelines for transfusion dosage

◦6-8 U of platelet concentrate, or 1 U/10 kg

◦1 U of platelets to increase count of a 70-kg adult by 5-10,000/mm3 and an 18-kg child by 20,000/mm3

•Splenectomy is reserved for patients in whom medical therapy fails. Emergent splenectomy is indicated in patients with life-threatening bleeding in whom medical therapy fails.

•In patients without life-threatening complications, focus ED care on confirming the diagnosis, if possible, and initiating therapy as needed.

•Most patients with undiagnosed thrombocytopenia and purpura will need admission for further evaluation and treatment, since ITP is a diagnosis of exclusion.

Consultations

•Consult a hematologist for assistance in confirming the diagnosis or, in the patient with known ITP, arranging disposition and follow-up care, if appropriate.

•Consult a neurosurgeon for intracranial hemorrhage. Consultation by other surgical specialists may be required for extensive hemorrhage at other sites.

Medication

Glucocorticoids and IVIg are the mainstays of medical therapy. Indications for use, dosage, and route of administration are based on the patient's clinical condition, the absolute platelet count, and the degree of symptoms. Consultation with a hematologist may be needed prior to starting therapy.

Children who have platelet counts >30,000/mm3 and are asymptomatic or have only minor purpura do not require routine treatment. Children who have platelet counts <20,000/mm3 and significant mucous membrane bleeding and those who have platelet counts <10,000/mm3 and minor purpura should receive specific treatment.

Adults with platelet counts >50,000/mm3 do not require treatment. Treatment is indicated for adults with counts <50,000/mm3 with significant mucous membrane bleeding. Treatment also is indicated for those adults with risk factors for bleeding (eg, hypertension, peptic ulcer disease, vigorous lifestyle) and in patients with a platelet count <20,000-30,000/mm3.

IV anti-(Rh)D, also known as IV Rh immune globulin (IG), was not recommended by the 1996 American Society of Hematology practice guidelines. However, recent studies using higher dosages of IV RhIG in acute ITP in children and adults show platelet count increases at 24 hours faster than medicating with steroids and at 72 hours similar to IVIg. Although generally less toxic than IV steroids, IV RhIG is more expensive than IV steroids. Studies in children with chronic ITP show that escalating or elevated doses of IV RhIG have comparable responses to those of high-dose IVIg therapy in children. This therapy is not appropriate for patients who have undergone splenectomy. Acute intravascular hemolysis after infusing IV RhIG has been reported, with an estimated incidence of 1 in 1115 patients.

Steroid use and immunosuppressives and splenectomy may be undesirable because of their associated complications. For long-term steroid use, this includes osteoporosis, glaucoma, cataracts, loss of muscle mass, and an increased risk of infection. For immunosuppressive therapy and splenectomy, risks include worsening immunosuppression and infection or sepsis. Studies of the use of multiagent therapies in refractory patients are ongoing. Some small studies have shown limited success. According to one study3 , using a combination of weekly vincristine, weekly methylprednisolone, both until platelet

counts reached 50,000/mm3, and cyclosporine orally twice daily until the platelet count is normal for 3-6 months seems promising, though larger prospective studies are needed.

Other therapies, such as cyclophosphamide, danazol, dapsone, interferon alfa, azathioprine, vinca alkaloids, accessory splenectomy, and splenic radiation have been studied. Many case series discussing these treatments are too small to show sufficient evidence of a clinically significant reduction in bleeding or mortality rate; however, they serve as additional therapeutic measures in ITP refractory-to-primary therapy (eg, glucocorticoids, IVIg immunoglobulin, splenectomy). Newer studies on rituximab suggest that this agent is an effective treatment option in splenectomized refractory or relapsed ITP patients.4,5

Clinical trials have shown promise for agents that directly stimulate platelet production, such as thrombopoietin (TPO) receptor-binding agents. Two new agents, eltrombopag and romiplostim, are available to patients with chronic ITP who have failed other therapies.6,7 Both of these agents require registration in a database. While they show promise for raising platelet counts, there are potential safety concerns such as thrombocytosis and rebound thrombocytopenia. It is unlikely that emergency physicians should be prescribing these agents without being under the recommendation of a hematologist.

Glucocorticoids

These agents are used to treat idiopathic and acquired autoimmune disorders. They have been shown to increase platelet count in ITP.

Prednisone (Deltasone, Orasone, Sterapred)

Useful in treating inflammatory and allergic reactions; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. DOC for all adult patients with platelet counts <50,000/mm3. Asymptomatic patients with platelet counts >20,000/mm3, or patients with counts 30,000-50,000/mm3 with only minor purpura, may not need therapy; withholding medical therapy may be appropriate for asymptomatic patients, regardless of count.

DosingInteractionsContraindicationsPrecautionsAdult

1-2 mg/kg/d PO

Pediatric

4-8 mg/kg/d PO for severe, life-threatening bleeding with platelet counts <50,000/mm3, or for all patients with platelet counts <30,000/mm3

DosingInteractionsContraindicationsPrecautionsEstrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

DosingInteractionsContraindicationsPrecautionsDocumented hypersensitivity; viral, fungal, or tubercular skin infections

DosingInteractionsContraindicationsPrecautionsPregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

PrecautionsMay cause severe infections, hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, and growth suppression; abrupt discontinuation may cause adrenal crisis

Methylprednisolone (Solu-Medrol, Depo-Medrol)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased permeability. Used as alternative glucocorticoid of choice for all patients with severe, life-threatening bleeding or children with platelet counts <30,000/mm3. Careful observation without medical treatment may be appropriate in some asymptomatic children.


Loading dose: 125-250 mg IV

Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d

Pediatric

Loading dose: 2 mg/kg IV

Maintenance dose: 0.5-1 mg/kg/dose IV q6h for up to 5 d

DosingInteractionsContraindicationsPrecautionsCoadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking concurrent diuretics

DosingInteractionsContraindicationsPrecautionsDocumented hypersensitivity; viral, fungal, or tubercular skin infections

DosingInteractionsContraindicationsPrecautionsPregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

PrecautionsHyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications

Blood products

Administration of IVIg may temporarily increase platelet counts in some children and adults with ITP. Consider IVIg if the situation requires a rapid, temporary rise in platelet count.

Intravenous immune globulin (IVIg)

DOC for severe, life-threatening bleeding or for children with platelet counts <20,000/mm3 with minor purpura; can be used alone or in addition to glucocorticoid therapy.


1-2 g/kg IV administered over 1-5 d

Pediatric

1 g/kg once

DosingInteractionsContraindicationsPrecautionsNone reported

DosingInteractionsContraindicationsPrecautionsDocumented hypersensitivity; IgA deficiency and anti-IgE/IgG antibodies


PrecautionsCheck serum IgA before IVIg (use IgA-depleted product, eg, Gammagard S/D); may increase serum viscosity and thromboembolic events; may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d postinfusion)

Increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, or preexisting kidney disease; changes in lab findings associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Thrombopoietic Agent

These agents directly stimulates bone marrow platelet production.8

Eltrombopag (Promacta)

Oral thrombopoietin (TPO) receptor agonist. Interacts with transmembrane domain of human TPO receptor and induces megakaryocyte proliferation and differentiation from bone marrow progenitor cells. Indicated for thrombocytopenia associated with chronic idiopathic thrombocytopenic purpura in

patients experiencing inadequate response to corticosteroids, immunoglobulins, or splenectomy. Not for use to normalize platelet counts but used when clinical condition increases bleeding risk.

Prescribers must enroll in Promacta Cares program. Only available through restricted distribution program. Program phone number is (877) 9-PROMACTA (877-977-6622).


50 mg PO qd 1 h ac or 2 h pc

East Asian ancestry or moderate-to-severe hepatic insufficiency: 25 mg PO qd

Use lowest dose to achieve and maintain platelet count ≥50 X 109/L to reduce risk of bleeding; not to exceed 75 mg/d; discontinue if platelet count not increased after 4 wk at maximum dose or if platelet count increases substantially

Pediatric

Not established

DosingInteractionsContraindicationsPrecautionsCYP1A2, CYP2C8, UGT1A1, and UGT1A3 substrate; OATP1B1 inhibitor; UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 inhibitor

Coadministration with moderate or strong CYP1A2 (eg, ciprofloxacin, fluvoxamine) or CYP2C8 (eg, gemfibrozil, trimethoprim) inhibitors may inhibit eltrombopag's oxidative metabolism and increase toxicity

Coadministration with UGT1A1 or UGT1A3 inhibitors or inducers may affect glucuronidation of eltrombopag

Inhibits OATP1B1 and may increase exposure to OATP1B1 substrates (eg, benzylpenicillin, atorvastatin, fluvastatin, pravastatin, rosuvastatin, methotrexate, nateglinide, repaglinide, rifampin)

Inhibits UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 enzymes and therefore may increase systemic exposure of substrates (eg, acetaminophen, narcotic, NSAID)

Chelates polyvalent cations; allow 4-h interval for administration of other medications, calcium-rich foods, or supplements containing polyvalent cations (eg, antacids, aluminum, calcium, iron, magnesium, selenium, zinc)

DosingInteractionsContraindicationsPrecautionsNone known


PrecautionsMay cause hepatic impairment, monitor ALT, AST, and bilirubin, and discontinue if levels increase; may cause bone marrow fibrosis because of reticulin fiber deposition; excessive dose may increase platelet counts and produce thrombotic/thromboembolic complications (discontinue if platelet count >400 X 109/L after 2 wk at lowest dose); may increase risk for hematological malignancies; monitor CBC count weekly during dose adjustment, monthly following stable dose, and at least 4 wk after discontinuation

Romiplostim (Nplate)

An Fc-peptide fusion protein (peptibody) that increases platelet production through binding and activation of the thrombopoietin (TPO) receptor, a mechanism similar to endogenous TPO. Indicated for chronic immune (idiopathic) thrombocytopenic purpura in patients who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Only available through the Nplate NEXUS (Network of Experts Understanding and Supporting Nplate) program, a program designed to promote informed risk-benefit decisions before initiating treatment. For more information, see www.nplate.com or call (877) NPLATE1 (877-675-2831).


1 mcg/kg (actual body weight) SC initially; adjust in increments of 1 mcg/kg SC qwk to achieve platelet count of 50 X 109/L or greater (median dose in clinical trials was 2 mcg/kg); not to exceed 10 mcg/kg/wk

If platelet count not adequate to control bleeding after 4 wk at maximum dose, discontinue and continue monitoring platelet count for 2 wk

Pediatric

<18 years: Not established

Follow-up

Further Inpatient Care

•Rule out other potential causes of thrombocytopenia.

•Emergency splenectomy may be necessary if severe bleeding complications due to thrombocytopenia do not respond to medical therapy.

•Observe for life-threatening bleeding.

•Consult with a hematologist, as further treatments (eg, steroids, IVIg, platelet transfusion) may be indicated.

Further Outpatient Care

•Close follow-up care with a hematologist is required.

•Elective splenectomy may be necessary if medical therapy fails.

Transfer

Transfer may be necessary under the following conditions:

•A hematologist is not available.

•Blood bank support is insufficient.

•A higher level of intensive care is needed.

Complications

Complications of idiopathic thrombocytopenic purpura may include the following:

•Intracranial or other major hemorrhage

•Severe blood loss

•Adverse effects of corticosteroids

•Pneumococcal infections if the patient must have a splenectomy

Prognosis

•Children

◦Approximately 83% of children have a spontaneous remission, and 89% of children eventually recover.

◦More than 50% of patients recover within 4-8 weeks.

◦Approximately 2% of patients die.

•Adults

◦Only 2% of adults have a spontaneous recovery; however, approximately 64% of adults eventually recover.

◦Approximately 30% of patients have chronic disease, and 5% of patients die from hemorrhage.

Patient Education

•Instruct patients to return for follow-up in order to assess for a potentially reduced platelet count.

•Emphasize close outpatient follow-up care.

•Because of the increased risk of bleeding, instruct patients to avoid aspirin products.

Miscellaneous

Medicolegal Pitfalls

•Failure to consider other causes of thrombocytopenia

•Failure to initiate therapy

Special Concerns

•Pregnancy

◦Gestational thrombocytopenia and thrombocytopenia due to preeclampsia are more common than ITP in pregnancy.

◦Pregnancy does not increase the incidence of ITP, and it does not exacerbate a preexisting disease.

◦The pregnant patient with ITP is treated the same as other patients with ITP.

◦Concerns about thrombocytopenia increase as term approaches, and the risks of thrombocytopenia to the newborn must be considered. This is because antiplatelet IgG antibodies can cross the placenta and can induce fetal thrombocytopenia.

◦The perinatologist and the hematologist make the ultimate decisions regarding cesarean section (for protection of the newborn against intracranial hemorrhage), percutaneous umbilical blood sampling, prednisone, and IVIg therapy.

•Geriatrics: Patients older than 60 years may be at greater risk of severe bleeding than younger patients (<40 y) at equivalent platelet counts.

idiopathic thrombocytopenia purpura

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