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. The blood clots can cause serious problems if they block the blood vessels and limit blood flow to the brain, kidneys, or heart.

Blood clots form when blood cell fragments 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 on blood vessel walls and stop bleeding.

In TTP, when blood clots form, the result is fewer platelets in the blood. This can cause bleeding into the skin, prolonged bleeding from cuts, and internal bleeding. It also can cause 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 the blood has a lower than normal number of platelets. "Purpura" (PURR-purr-ah) refers to purple bruises caused by bleeding under the skin.

If you have TTP, you also may have bleeding that results in tiny red or purple dots on the skin. These pinpoint-sized dots are called petechiae (peh-TEE-kee-ay). Petechiae may look like a rash.

Purpura and Petechiae

The photograph shows purpura (bruises) and petechiae (dots) in the skin. Bleeding under the skin causes the purple, brown, and red colors of the purpura and petechiae.

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

The two main types of TTP are inherited and acquired (noninherited). "Inherited" means the condition is passed from parents to children through the genes. 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 mostly occurs in adults, but sometimes it affects children.

In acquired TTP, the ADAMTS13 gene isn't faulty. Instead, the body makes antibodies (proteins) that block the ADAMTS13 enzyme's activity.

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

• Some diseases and conditions, such as pregnancy, cancer, HIV, infections, and lupus
• Some medical procedures, such as surgery and blood and marrow stem cell transplant
• Some medicines, such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens
• Quinine, which is a substance often found in tonic water and nutritional health products

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.

TTP usually occurs suddenly and lasts for days or weeks, but it can continue for months. Relapses (or flareups) can occur in up to 60 percent of people who have the acquired type of TTP. Many people who have 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 condition.

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 (TTP). The ADAMTS13 gene controls the enzyme, which is involved in blood clotting.

Not having enough enzyme activity causes platelets to clump together and form blood clots. In TTP, when blood clots form, the result is fewer platelets in the blood.

This can cause bleeding into the skin (purpura), prolonged bleeding from cuts, and internal bleeding. It also can cause 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, the ADAMTS13 gene is faulty, which affects 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 through the genes. A person who has inherited TTP 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 faulty. Instead, the body makes antibodies (proteins) 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 may include:

• Some diseases and conditions, such as pregnancy, cancer, HIV, infections, and lupus
• Some medical procedures, such as surgery and blood and marrow stem cell transplant
• Some medicines, such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens
• Quinine, which is a substance often found in tonic water and nutritional health products

Who Is At Risk for Thrombotic Thrombocytopenic Purpura?

Thrombotic thrombocytopenic purpura (TTP) is a rare condition. Most cases of TTP are acquired. Acquired TTP mostly occurs in adults, but it can affect children. The condition occurs more often in women and in Blacks than in other groups.

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 symptoms until they're adults.

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

• Some diseases and conditions, such as pregnancy, cancer, HIV, infection, and lupus
• Some medical procedures, such as surgery and blood and marrow stem cell transplant
• Some medicines, such as chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens
• Quinine, which is a substance often found in tonic water and nutritional health products

What Are the Signs and Symptoms of Thrombotic Thrombocytopenic Purpura?

Blood clots, a low platelet count, and damaged red blood cells cause the signs and symptoms of thrombotic thrombocytopenic purpura (TTP).

The signs and symptoms include:

• Purplish bruises on the skin or mucous membranes (such as on the mouth) due to bleeding under the skin. These bruises are called purpura.
• Pinpoint-sized red or purple dots on the skin that often are found in groups and may look like a rash. The spots, called petechiae, are due to bleeding under the skin.
• Paleness or jaundice (a yellowish color of the skin or whites of the eyes).
• Fatigue (feeling very tired and weak).
• Fever.
• A fast heart rate or shortness 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, you may be having a relapse (flareup). Talk with your doctor about when to call him or her or seek emergency care.

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 will be involved in your care. A hematologist is a doctor who specializes in blood diseases and disorders.

Medical History

Your doctor will ask about factors that may affect TTP. For example, he or she may ask whether you:

• Have certain diseases or conditions, such as cancer, HIV, infections, or lupus, or whether you're pregnant.
• Have had previous medical procedures, such as a blood and marrow stem cell transplant.
• Take certain medicines, such as ticlopidine, clopidogrel, cyclosporine A, or hormone replacement therapy and estrogens, or whether you've had chemotherapy.
• Have taken any products that contain quinine. Quinine is a substance often found in tonic water and nutritional health products.

Physical Exam

As part of the medical history and physical exam, your doctor will ask about any signs or symptoms you've had. He or she will look for signs such as:

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

Diagnostic Tests

Your doctor also may recommend tests to help find out whether you have TTP.

Complete Blood Count

This test measures the number of red blood cells, 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'll 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. People who have 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. If you have TTP, your bilirubin level may be high because your body is breaking down red blood cells faster than normal.

Kidney Function Tests and Urine Tests

These tests show whether your kidneys are working well. If you have TTP, your urine may contain protein or blood cells. Also, your blood creatinine (kre-AT-ih-neen) level may be high. Creatinine is a blood product that's normally removed by the kidneys.

Coombs Test

This blood test is used to find out 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 because 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 down and release LDH 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 in 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 or weeks, but it can go on for months. Relapses (flareups) can occur in up to 60 percent of people who have the acquired type of TTP. Flareups also occur in most people who have 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 who have inherited TTP, and plasma exchange for people who have 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 inserted into a vein (blood vessel). This is done to replace the missing or altered ADAMTS13 enzyme.

For acquired TTP, plasma exchange (also called plasmapheresis) is done. This is a lifesaving procedure. It removes antibodies (proteins) 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 a vein 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 inserted into 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 take days or weeks, depending on your condition. You'll 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 if plasma infusions or plasma exchange doesn't work well, or if 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) sometimes is needed. This is because cells in the spleen make the antibodies that block ADAMTS13 enzyme activity.

How Can Thrombotic Thrombocytopenic Purpura Be Prevented?

Both inherited and acquired thrombotic thrombocytopenic purpura (TTP) occur 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.)

Talk with your doctor about factors that may trigger TTP or a flareup, including:

• Some diseases or conditions, such as pregnancy, cancer, HIV, infections, or lupus.
• Some medical procedures, such as surgery and blood and marrow stem cell transplant.
• Some medicines, such as ticlopidine, clopidogrel, cyclosporine A, chemotherapy, and hormone replacement therapy and estrogens. If you take any of these medicines, your doctor may recommend a different medicine.
• Quinine, which is a substance often found in tonic water and nutritional health products.

Living With Thrombotic Thrombocytopenic Purpura

Some people fully recover from thrombotic thrombocytopenic purpura (TTP). However, relapses (or flareups) can occur in up 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 bruises on the skin or mucous membranes (such as on the mouth) due to bleeding under the skin. These bruises are called purpura.
• Pinpoint-sized red or purple dots on the skin that often are found in groups and may look like a rash. The spots, called petechiae, are due to bleeding under the skin.
• Paleness or jaundice (a yellowish color of the skin or whites of the eyes).
• Fatigue (feeling very tired and weak).
• Fever.
• A fast heart rate or shortness 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 been treated for TTP, you should talk with your doctor about medicines that may raise your risk of bleeding during a relapse, such as aspirin and ibuprofen.

Also, tell your doctor about all over-the-counter medicines you take, including vitamins, supplements, and herbal remedies. Your doctor may ask whether you're using any products that contain quinine. Quinine is a substance often found in tonic water and nutritional health products. Quinine may trigger TTP or a flareup of the condition.

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 with your doctor about changing medicines that may raise your risk of 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. The blood clots can cause serious problems if they block the blood vessels and limit blood flow to the brain, kidneys, or heart.
• Blood clots form when blood cell fragments called platelets clump together. When this happens, the result is fewer platelets in the blood. This can cause bleeding into the skin, 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.
• The two main types of TTP are inherited and acquired (noninherited). 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 and form blood clots.
• What triggers TTP isn't known, but some diseases or conditions, medical procedures, medicines, and substances may contribute to it.
• Most cases of TTP are the acquired type. The condition occurs more often in women and Blacks than in other groups.
• Signs and symptoms of TTP include purplish bruises on the skin or mucous membranes called purpura, pinpoint red or purple dots on the skin called petechiae, paleness or jaundice (a yellowish color of the skin or whites of the eyes), fatigue (tiredness and weakness), fever, a fast heart rate or shortness of breath, headache, speech changes, confusion, coma, stroke, seizure, a low amount of urine, or protein or blood in the urine.
• Your doctor will diagnose TTP based on your medical history, a physical exam, and test results.
• TTP usually is 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 occur suddenly with no clear cause. You can't prevent either type.
• You should call your doctor right away or seek emergency help 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 with your doctor about changing medicines that may raise your risk of TTP or bleeding.
• Some people fully recover from TTP. However, flareups can occur in up to 60 percent of people who have the acquired type of TTP. They also occur in most people who have inherited TTP.

Links to Other Information About Thrombotic Thrombocytopenic Purpura

NHLBI Resources

• Hemolytic Anemia (Diseases and Conditions Index)

Non-NHLBI Resources

• Thrombotic Thrombocytopenic Purpura (MedlinePlus)

Clinical Trials

• Current Research (ClinicalTrials.gov)
• NHLBI Pediatric Clinical Trials