What Is Thrombotic Thrombocytopenic Purpura?

Thrombotic thrombocytopenic purpura (TTP) is a rare blood condition. It causes blood clots to form in small blood vessels throughout the body. These blood clots can cause serious problems if they block blood vessels and limit blood flow to the brain, kidneys, or heart.

Blood clots form when blood cells called platelets (PLATE-lets) clump together. Platelets are made in your bone marrow along with other kinds of blood cells. They stick together to seal small cuts or breaks and stop bleeding.

In TTP, when blood clots form, there are fewer platelets in the blood. This can cause bleeding into the skin (purpura), prolonged bleeding from cuts, and internal bleeding. It also causes small blood clots to form suddenly throughout the body, including in the brain and kidneys.

Thrombotic (throm-BOT-ik) refers to the blood clots that form. Thrombocytopenic (throm-bo-cy-toe-PEE-nick) means there’s a lower than normal number of platelets in the blood. Purpura (PURR-purr-ah) are purple bruises caused by bleeding into the skin.

Purpura

The photograph show purpura (bleeding) in the skin. Bleeding under the skin causes the purple, brown, and red color of the purpura.

TTP also can cause red blood cells to break apart faster than the body can replace them. This leads to hemolytic anemia (HEE-moh-lit-ick uh-NEE-me-uh)—a rare form of anemia. Anemia is a condition in which a person’s blood doesn’t have enough red blood cells.

A lack of activity in the ADAMTS13 enzyme (a type of protein in the blood) causes TTP. The ADAMTS13 gene controls the enzyme, which is involved in blood clotting. The enzyme breaks up a large protein called von Willebrand factor that clumps together with platelets to form blood clots.

Types of Thrombotic Thrombocytopenic Purpura

TTP has two main types: inherited and acquired (noninherited) TTP.

“Inherited” means the condition is passed from parents to children. This type of TTP mainly affects newborns and children. In inherited TTP, the ADAMTS13 gene is faulty and doesn’t prompt the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or is changed.

Acquired TTP is the more common type. “Acquired” means you aren’t born with the condition, but you develop it. This type of TTP occurs mostly in adults, but it sometimes affects children.

In acquired TTP, the ADAMTS13 gene isn’t changed. Instead, the body makes proteins called antibodies that block the ADAMTS13 enzyme’s activity.

What triggers inherited and acquired TTP isn’t known, but some factors may play a role. These include:

• Diseases and conditions such as pregnancy, cancer, HIV, infection, and lupus
• Medical procedures such as surgery and bone marrow transplant
• Medicines such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens

Outlook

TTP is a rare condition. It can be fatal or cause lasting damage, such as brain damage or stroke, if it’s not treated right away. About 1,200 people develop acquired TTP each year in the United States.

TTP usually occurs suddenly and lasts for days and weeks, but it can continue for months. Most people recover fully from TTP when treated promptly. Relapses (or flareups) can occur in 30 to 60 percent of people with acquired TTP. Many people with inherited TTP have frequent flareups that need to be treated.

Treatments for TTP include infusions of fresh frozen plasma and plasma exchange (also called plasmapheresis (PLAZ-ma-fe-RE-sis)). These treatments have greatly improved the outlook of the disease.

Other Names for Thrombotic Thrombocytopenic Purpura

Inherited Thrombotic Thrombocytopenic Purpura

• Familial thrombotic thrombocytopenic purpura
• Upshaw-Schulman syndrome (USS)

Acquired Thrombotic Thrombocytopenic Purpura

• Moschcowitz disease
• Microangiopathic hemolytic anemia

What Causes Thrombotic Thrombocytopenic Purpura?

A lack of activity in the ADAMTS13 enzyme (a type of protein in the blood) causes thrombotic thrombocytopenic purpura (TPP). The ADAMTS13 gene controls the enzyme, which is involved in blood clotting.

Not having enough enzyme activity causes platelets to clump together, forming blood clots. In TTP, when blood clots form, there are fewer platelets in the blood. This can cause bleeding into the skin (purpura), drawn-out bleeding from cuts, and internal bleeding. It also causes small blood clots to form suddenly throughout the body, including in the brain and kidneys.

TTP also can cause red blood cells to break apart faster than the body can replace them. This leads to hemolytic anemia.

Inherited Thrombotic Thrombocytopenic Purpura

In the inherited form of TTP, changes in the ADAMTS13 gene affect the enzyme’s function. The gene doesn’t prompt the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or is altered.

“Inherited” means that the condition is passed from parents to children. In inherited TTP, a person is born with two copies of the altered gene—one from each parent. Most often, the parents each have one copy of the altered gene, but have no signs or symptoms of the disorder.

Acquired Thrombotic Thrombocytopenic Purpura

In the acquired type of TTP, the ADAMTS13 gene isn’t changed. Instead, the body makes proteins called antibodies that block the ADAMTS13 enzyme’s activity.

“Acquired” means you aren’t born with the condition, but you develop it.

Triggers for Thrombotic Thrombocytopenic Purpura

What triggers TTP isn’t known, but some factors may play a role. These include:

• Diseases and conditions such as pregnancy, cancer, HIV, infection, and lupus
• Medical procedures such as surgery and bone marrow transplant
• Medicines such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens

Who Is At Risk for Thrombotic Thrombocytopenic Purpura?

Thrombotic thrombocytopenic purpura (TTP) is a rare condition. About 1,200 new cases occur each year in the United States.

Most cases of TTP are the acquired type. Acquired TTP mostly occurs in adults, but it can affect children. The condition is seen more often in women than in men.

Inherited TTP mainly affects newborns and children. Most people who have inherited TTP begin to have symptoms soon after birth. Some, however, don’t have their first episode of disease until they’re adults.

What triggers TTP isn’t known, but some factors may play a role. These include:

• Diseases and conditions such as pregnancy, cancer, HIV, infection, and lupus
• Medical procedures such as surgery and bone marrow transplant
• Medicines such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens

What Are the Signs and Symptoms of Thrombotic Thrombocytopenic Purpura?

Signs and symptoms of thrombotic thrombocytopenic purpura (TTP) are due to blood clots, a low platelet count, and damaged red blood cells.

The signs and symptoms include:

• Purplish spots called purpura on the skin or mucous membranes (such as on the mouth) due to bleeding under the skin
• Paleness or jaundice (a yellowish color of the skin or eyes)
• Feeling tired or weak
• Fever
• A fast heart rate or feeling short of breath
• Headache, speech changes, confusion, coma, stroke, or seizure
• A low amount of urine, or protein or blood in the urine

If you’ve had TTP and have any of these signs and symptoms, call your doctor right away.

How Is Thrombotic Thrombocytopenic Purpura Diagnosed?

Your doctor will diagnosis thrombotic thrombocytopenic purpura (TTP) based on your medical history, a physical exam, and test results.

If TTP is suspected or diagnosed, a hematologist (a doctor who specializes in blood diseases) will be involved in your care.

Medical History

Your doctor will ask about factors that may affect TTP, such as:

• Diseases or conditions you may have, such as pregnancy, cancer, HIV, infection, or lupus
• Previous medical procedures, such as a bone marrow transplant
• Medicines you take, such as ticlopidine, clopidogrel, cyclosporine A, chemotherapy, and hormone replacement therapy and estrogens

Physical Exam

Your doctor will do a physical exam and look for signs such as:

• Bruising and bleeding under your skin
• Fever
• Paleness or jaundice (a yellowish color of the skin or eyes)
• A fast heart rate
• Speech changes or changes in awareness that can range from confusion to loss of consciousness, or “passing out”
• Stroke or seizures
• Changes in urine

Diagnostic Tests

Your doctor also may order tests to help find out if you have TTP.

Complete Blood Count

This test measures the number of red and white blood cells and platelets in your blood. For this test, a small amount of blood is drawn from a vein (blood vessel), usually in your arm.

If you have TTP, your platelet count will be low and you will have a lower than normal number of red blood cells (anemia).

Blood Smear

For this test, a small amount of blood is drawn from a vein, usually in your arm. Some of your blood is put on a glass slide. A microscope is then used to look at your red blood cells. In TTP, the red blood cells are torn and broken.

Platelet Count

This test counts the number of platelets in a blood smear (see above). People with TTP have a lower than normal number of platelets in their blood. This test is used with the blood smear to help diagnose TTP.

Bilirubin Test

When red blood cells die, they release a protein called hemoglobin (HEE-muh-glow-bin) into the bloodstream. The body breaks down hemoglobin into a compound called bilirubin. High levels of bilirubin in the bloodstream cause jaundice.

For this blood test, a small amount of blood is drawn from a vein, usually in your arm. In TTP, bilirubin may be high because your body is breaking down red blood cells at a faster than normal rate.

Kidney Function Tests and Urine Tests

These tests are done to see whether your kidneys are working well. In TTP, your urine may contain protein or blood cells. Also your blood creatinine level may be high. Creatinine is a blood product that normally is removed by the kidneys.

Coombs Test

This blood test is used to see whether TTP is the cause of hemolytic anemia. For this test, a small amount of blood is drawn from a vein, usually in your arm.

In TTP, hemolytic anemia occurs when red blood cells are broken into pieces as they try to squeeze around blood clots.

When TTP is the cause of hemolytic anemia, the Coombs test is negative. It's positive when antibodies that bind to red blood cells cause your immune system to destroy the cells.

Lactate Dehydrogenase Test

This blood test measures a protein called lactate dehydrogenase (LDH). For this test, a small amount of blood is drawn from a vein, usually in your arm.

Hemolytic anemia causes red blood cells to break and release this protein into the blood. LDH also is released from tissues that are injured by blood clots as a result of TTP.

ADAMTS13 Assay

A lack of activity of the ADAMTS13 enzyme causes TTP. For this test, a small amount of blood is drawn from a vein, usually in your arm. The blood is sent to a special lab to test for the enzyme's activity.

How Is Thrombotic Thrombocytopenic Purpura Treated?

Thrombotic thrombocytopenic purpura (TTP) can be fatal or cause lasting damage, such as brain damage or stroke, if it’s not treated promptly.

In most cases, TTP occurs suddenly and lasts for days and weeks, but it can go on for months. Most people recover fully when treated right away. Relapses (flareups) can occur in 30 to 60 percent of people with acquired TTP. Flareups also occur in most people with inherited TTP.

Plasma treatments are the most common way to treat TTP. Other treatments include medicines and surgery. Treatments are done in a hospital.

Plasma Therapy

Plasma is the liquid part of your blood. It carries blood cells, hormones, enzymes, and nutrients to your body.

TTP is treated with plasma therapy. This includes fresh frozen plasma for newborns and children with inherited TTP, and plasma exchange for people with acquired TTP. Plasma therapy is started in the hospital as soon as TTP is diagnosed or suspected.

For inherited TTP, fresh frozen plasma is given through an intravenous (IV) line in a vein (blood vessel). This is done to replace the missing or changed ADAMTS13 enzyme.

For acquired TTP, plasma exchange (also called plasmapheresis) is done. This is a lifesaving procedure. It removes antibodies from the blood that damage your ADAMTS13 enzyme. It also replaces the ADAMTS13 enzyme. If plasma exchange isn’t available, you may be given fresh frozen plasma until it is available.

During plasma exchange, an IV needle or tube is placed in your arm to remove blood. The blood then goes through a cell separator, which removes plasma from the blood. The nonplasma part of the blood is saved, and donated plasma is added to it.

The blood is then put back into you through an IV line in one of your blood vessels. The time the procedure takes varies, but it often takes about 2 hours.

Treatments of fresh frozen plasma or plasma exchange usually continue until your blood tests and signs and symptoms improve. This can be days or weeks depending on your condition. You will stay in the hospital during this time.

Some people who recover from TTP have flareups. This can happen in the hospital or after you go home. If you have a flareup, plasma infusion or plasma exchange will be restarted.

Other Treatments

Other treatments are used when plasma infusions or plasma exchange doesn’t work well or when flareups occur often.

Medicines are used to slow or stop antibodies from forming. In acquired TTP, antibodies block the activity of the ADAMTS13 enzyme. Medicines used to treat TTP include glucocorticoids, vincristine, rituximab, and cyclosporine A.

Surgery to remove the spleen (an organ in the abdomen) is sometimes needed. This is because cells in the spleen make antibodies that block the activity of the ADAMTS13 enzyme.

How Can Thrombotic Thrombocytopenic Purpura Be Prevented?

Both inherited and acquired thrombotic thrombocytopenic purpura (TTP) appear suddenly with no clear cause. You can’t prevent either type.

If you’ve had TTP, it’s important to watch for signs and symptoms of a relapse (flareup). (See "Living With Thrombotic Thrombocytopenic Purpura” for more information.)

You also should talk to your doctor about factors that may trigger TTP or a flareup, including:

• Diseases or conditions you may have, such as pregnancy, cancer, HIV, infection, or lupus.
• Any prior medical procedures, such as a bone marrow transplant.
• Medicines you may take, such as ticlopidine, clopidogrel, cyclosporine A, chemotherapy, and hormone replacement therapy and estrogens. Your doctor may change some of these medicines.

Living With Thrombotic Thrombocytopenic Purpura

Most people recover fully from thrombotic thrombocytopenic purpura (TTP) when treated promptly. Relapses (or flareups) can occur in 30 to 60 percent of cases.

If this happens, plasma therapy and/or medicines will need to be restarted.

If you’ve had TTP, you should call your doctor right away if you have signs or symptoms of a relapse. These signs and symptoms include:

• Purplish spots called purpura on the skin or mucous membranes (such as on the mouth) due to bleeding under the skin
• Unexplained or prolonged bleeding
• Paleness or jaundice (a yellowish color of the skin or eyes)
• Feeling tired or weak
• Fever
• A fast heart rate or feeling short of breath
• Headaches, speech changes, confusion, coma, stroke, or seizures
• A low amount of urine, or protein or blood in the urine

If you have been successfully treated for TTP, you should talk to your doctor about using any medicines—such as aspirin and ibuprofen—that can raise your risk of bleeding during a relapse. Also, tell your doctor about all over-the-counter medicines you take, including vitamins, supplements, or herbal remedies.

If your child has inherited TTP, ask the doctor whether you need to restrict your child’s activities.

Report any symptoms of infection, such as a fever, to your doctor. This is very important for people who have had their spleens removed.

Talk to your doctor about changing medicines that may raise your risk for TTP, such as ticlopidine and clopidogrel.

Key Points

• Thrombotic thrombocytopenic purpura (TTP) is a rare blood condition. It causes blood clots to form in small blood vessels throughout the body. These blood clots can cause serious problems if they block blood vessels and limit blood flow to the brain, kidneys, or heart.
• Blood clots form when blood cells called platelets clump together. When this happens, there are fewer platelets in the blood. This can cause bleeding into the skin (purpura), prolonged bleeding from cuts, and internal bleeding.
• TTP also can cause red blood cells to break apart faster than the body can replace them. This leads to hemolytic anemia.
• TTP has two main types: inherited and acquired. Inherited TTP mainly affects newborns and children. Acquired TTP occurs mostly in adults, but sometimes affects children.
• A lack of activity in the ADAMTS13 enzyme (a type of protein in the blood) causes TTP. The ADAMTS13 gene controls the enzyme, which is involved in blood clotting. Not having enough enzyme activity causes platelets to clump together, forming blood clots.
• What triggers inherited and acquired TTP isn’t known, but some diseases or conditions, medical procedures, and medicines may contribute to it.
• About 1,200 new cases of TTP occur each year in the United States. Most cases of TTP are the acquired type. The condition is seen more often in women than in men.
• Signs and symptoms of TTP include purplish spots called purpura on the skin or mucous membranes, paleness or jaundice (a yellowish color of the skin or eyes), fatigue (tiredness) and weakness, fever, a fast heart rate or feeling short of breath, headache, speech changes, confusion, coma, stroke, seizure, a low amount of urine, or protein or blood in the urine. If you have any of these signs and symptoms, call your doctor right away.
• A diagnosis of TTP is based on your medical history, a physical exam, and test results.
• TTP is usually treated with infusions of fresh frozen plasma or plasma exchange. Other treatments, such as medicines and surgery, are used when plasma treatment doesn’t work well or relapses (flareups) occur often.
• Both inherited and acquired TTP appear suddenly with no clear cause. You can’t prevent either type.
• You should call your doctor right away if you have signs or symptoms of a TTP flareup. These are the same as the initial signs and symptoms of TTP.
• You also should report any symptoms of infection. Talk to your doctor about changing medicines that may raise your risk for TTP or bleeding.
• Most people recover fully from TTP when treated promptly. Flareups can occur in 30 to 60 percent of people with acquired TTP. They also occur in most people with inherited TTP.

Links to Other Information About Thrombotic Thrombocytopenic Purpura

Non-NHLBI Resources

• Thrombotic Thrombocytopenic Purpura (MedlinePlus)

Clinical Trials

• Current Research (ClinicalTrials.gov)