THROMBOTIC THROMBOCYTOPENIC PURPURA

Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body, resulting in low platelet counts. These small blood clots, called thrombi, can damage many organs including the kidneys, heart, brain, and nervous system. In the era before effective treatment with plasma exchange, the fatality rate was about 95%. With plasma exchange, this has dropped to 10% at six months. Because the disease generally results from antibodies that activate the immune system to inhibit the ADAMTS13 enzyme, agents that suppress the immune system, such as glucocorticoids, rituximab, cyclophosphamide, vincristine, or ciclosporin, may also be used if a relapse or recurrence follows plasma exchange. Platelets are not transfused unless the patient has a life-threatening bleed, since the transfused platelets would also quickly be consumed by thrombi formation, leading to a minimal increase in circulating platelets.
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.

Types of Thrombotic Thrombocytopenic Purpura

Inherited Thrombotic Thrombocytopenic Purpura

Acquired Thrombotic Thrombocytopenic Purpura

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

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 overactive blood clotting. In TTP, blood clots form in small blood vessels throughout the body. These 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 many of the blood’s platelets. 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.
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 inherited TTP, the ADAMTS13 gene is faulty. It doesn’t prompt the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed. “Inherited” means that the condition is passed from parents to children through genes. A person who inherits TTP is born with two copies of the faulty gene—one from each parent. Most often, the parents each have one copy of the faulty gene, but have no signs or symptoms TTP.

Acquired Thrombotic Thrombocytopenic Purpura

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.

Risks for Thrombotic Thrombocytopenic Purpura

It’s unclear 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

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 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.

Headache, speech changes, confusion, coma, stroke, or seizure.

A low amount of urine, or protein or blood in the urine.

Thrombotic Thrombocytopenic Purpura 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.

Thrombotic Thrombocytopenic Purpura Treatment

Thrombotic thrombocytopenic purpura (TTP) can be fatal or cause lasting damage, such as brain damage or a stroke, if it’s not treated right away. 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 acquired 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 people who have inherited TTP

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. This is done to replace the missing or changed ADAMTS13 enzyme. Plasma exchange (also called plasmapheresis) is used to treat acquired TTP. This is a lifesaving procedure. It removes antibodies (proteins) from the blood that damage your ADAMTS13 enzyme. Plasma exchange 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 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. Then, the blood is put back into you through an IV line inserted into one of your blood vessels. The time required to complete the procedure varies, but it often takes about 2 hours. Treatments of fresh frozen plasma or plasma exchange usually continue until your blood tests results and signs and symptoms improve. This can take days or weeks, depending on your condition. You’ll stay in the hospital while you recover. Some people who recover from TTP have flareups. This can happen in the hospital or after you go home. If you have a flareup, your doctor will restart plasma therapy.

Other Treatments

Other treatments are used if plasma therapy doesn’t work well or if flareups occur often. For acquired TTP, medicines can slow or stop antibodies to the ADAMTS13 enzyme from forming. Medicines used to treat TTP include glucocorticoids, vincristine, rituximab, and cyclosporine A. Sometimes surgery to remove the spleen (an organ in the abdomen) is needed. This is because cells in the spleen make the antibodies that block ADAMTS13 enzyme activity.

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