Thrombotic thrombocytopenic purpura, acquired

Other Names: Purpura, thrombotic thrombocytopenic; TTP; Moschowitz syndrome; Idiopathic thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP), acquired is a blood disorder characterized by low platelets (i.e., thrombocytopenia), small areas of bleeding under the skin (i.e., purpura), low red blood cell count, and hemolytic anemia. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop.

The increased clotting that occurs in TTP also uses up platelets (PLATE-lets) in the blood. Platelets are blood cell fragments that help form blood clots. These cell fragments stick together to seal small cuts and breaks on blood vessel walls and stop bleeding.

With fewer platelets available in the blood, bleeding problems can occur. People who have TTP may bleed inside their bodies, underneath the skin, or from the surface of the skin. When cut or injured, they also may bleed longer than normal.

"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.

Bleeding under the skin also can cause 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.

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 the body has a lower than normal number of red blood cells. Hemolytic anemia can lead to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate

Acquired TTP usually begins in adulthood, but can affect children. An episode of TTP usually occurs suddenly and lasts for days or weeks, but it may continue for months. Relapses (or flareups) can occur in up to 60 percent of people who have the acquired TTP.

Cause

Acquired TTP usually begins in adulthood, but can affect children. An episode of TTP usually occurs suddenly and lasts for days or weeks, but it may continue for months. Relapses (or flareups) can occur in up to 60 percent of people who have the acquired TTP. In acquired TTP, the ADAMTS13 gene isn't faulty. Instead, the body makes antibodies (proteins) that block the activity of the ADAMTS13 enzyme.

"Acquired" means you aren't born with the condition, but you develop it sometime after birth.

Risk factors

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder. 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 Black people than in other groups. It isn't clear what triggers inherited and acquired TTP, but some factors may play a role. These factors may include:

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

Symptoms

The signs and symptoms of thrombotic thrombocytopenic purpura, acquired (acquired TTP) may include:

• Purplish bruises on the skin or mucous membranes (such as in the mouth). These bruises, called purpura, are caused by bleeding under the skin
• Pinpoint-sized red or purple dots on the skin. These dots, called petechiae, often are found in groups and may look like a rash.Bleeding under the skin causes petechiae.
• 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.
• Nausea or vomiting
• Headache, speech changes, confusion, coma, stroke, or seizure
• A low amount of urine, or protein or blood in the urine.

Acquired TTP usually presents as severe low red blood cell count due to destruction of red blood cells (microangiopathic hemolytic anemia or MAHA) and low platelet count (thrombocytopenia) in a previously healthy individual. Due to earlier diagnosis and improved treatments, fewer people with acquired TTP become critically ill. TTP affects the central nervous system and/or gastrointestinal system in over 1/3 of cases. Kidneys may also be damaged by TTP, but severe kidney damage is no longer common. Other organs such as the heart may be affected, but the lungs are rarely affected.

Diagnosis

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 diagnosing and treating blood 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, lupus, or infections (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 therapy and estrogens, or whether you've had chemotherapy. Have used 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 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 sample of blood is drawn from a vein, usually in your arm. If you have TTP, you'll have a lower than normal number of platelets and red blood cells (anemia).

Blood Smear For this test, a sample 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 sample of blood is drawn from a vein, usually in your arm. The level of bilirubin in the sample is checked. 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 sample 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. The test is positive if antibodies (proteins) are destroying your red blood cells.

Lactate Dehydrogenase Test This blood test measures a protein called lactate dehydrogenase (LDH). For this test, a sample 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 sample 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.

Treatment

The main treatment for people with thrombotic thrombocytopenic purpura, acquired (acquired TTP) is daily plasma exchange (PEX or plasmaphoresis). PEX removes antibodies (proteins) from the blood that damage the ADAMTS13 enzyme and replaces the ADAMTS13 enzyme. Corticosteroids are usually given in addition to PEX. Some doctors may also give rituximab, but others use this medication only in cases that are not responding to treatment well or are more severe. Both corticosteroids and rituximab help slow or stop the making of the antibody which is attacking the ADAMTS13 enzyme, but both medications can have serious long term side effects. PEX is recommended to be continued daily until the platelet count has returned to normal. Once the person continues to be stable, corticosteroids will be decreased over a 2-3 week period. Since relapses can occur, doctors will continue to check for signs of TTP, especially during the first several years after an episode.

In about 10% of cases, acquired TTP does not respond well to these treatments. Other medications including certain chemotherapy drugs may be tried, or the doses of the corticosteroids may be increased. As medical researchers continue to learn more about the antibodies that attack the ADAMTS13 enzyme, new treatments are being developed. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Caplacizumab (Brand name: Cablivi)February 2019, caplacizumab (Cablivi) was approved for the treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy.

Prognosis

The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for people with idiopathic TTP diagnosed and treated early with plasmapheresis.

NIH genetic and rare disease info

• NIH info on Thrombotic thrombocytopenic purpura, acquired

Thrombotic thrombocytopenic purpura, acquired is a rare disease.

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