Platelet Disorders Thrombotic Thrombocytopenic Purpura (TTP)

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TTP is a rare, life-threatening blood disorder. Blood clots form in small blood vessels throughout your body. The clots can limit or block the flow of blood to your organs, such as your brain, kidneys, and heart. This can prevent your organs from working properly and damage them.

TTP can also cause bleeding and bruising because the blood clots use up your platelets (tiny blood cells). These cell fragments stick together to seal small cuts and breaks in your blood vessels to stop bleeding. When your platelets are used up, you do not have enough platelets to form blood clots when necessary.

• Thrombotic refers to blood clots.
• Thrombocytopenic means a low platelet count.
• Purpura refers to purple bruises caused by bleeding under your skin.

TTP usually occurs suddenly and lasts for days or weeks, but it can continue for months. TTP can also cause red blood cells to break apart faster than your body can replace them, resulting in thrombotic microangiopathic hemolytic anemia. Without treatment, TTP can cause long-term problems, such as brain damage or stroke.

The symptoms of TTP are caused by blood clots, a low platelet count, and damaged red blood cells. Your symptoms may include:

• Petechiae, which are small, flat red spots under the skin caused by blood leaking from blood vessels
• Purpura, which is bleeding under your skin that can cause red, purple, or brownish-yellow spots
• Paleness or jaundice (a yellowish color of the skin or whites of the eyes)
• Extreme tiredness
• 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 your urine
• Feeling sick to your stomach, vomiting, and diarrhea

TTP symptoms may happen suddenly. Most people who have inherited TTP begin to have symptoms soon after birth. However, some do not have symptoms until they are adults.

TTP occurs when you do not have the right amount of a protein called ADAMTS13. This protein controls how your blood clots. If you do not have enough ADAMTS13, your body makes too many blood clots.

TTP can be inherited (also called congenital) or acquired. "Inherited" means that your parents passed the gene for the disease on to you. In inherited TTP, the ADAMTS13 gene is faulty. Changes in the ADAMTS13 gene can cause your body to make an ADAMTS13 protein that does not work properly. If you inherit TTP, you are 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 of TTP.

"Acquired" means that you were not born with the disease. This type is much more common than inherited TTP. In acquired TTP, the ADAMTS13 gene is not faulty. Instead, your immune system mistakenly attacks the ADAMTS13 protein. This prevents it from working properly.

The following factors can raise your risk of TTP.

• Age: Acquired TTP mostly occurs in adults, but it can affect children. Congenital TTP mainly affects newborns and children.
• Other medical conditions: Cancer and lupus, and infections such as HIV can cause TTP. Obesity, COVID-19, and pregnancy also can raise your risk.
• Race and ethnicity: Acquired TTP occurs more often in African American people than in other racial groups.
• Sex: Acquired TTP occurs more often in women than men.
• Some medical procedures: Surgery and blood and marrow stem cell transplant can raise your risk of TTP.
• Some medicines: Chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone therapy can cause TTP. Quinine, which is a substance often found in tonic water and nutritional health products, can also raise your risk.

To diagnose TTP, your provider will ask about your medical and family history. They will ask about your symptoms and do a physical exam to look for signs of TTP.

Your provider may order one or more of the blood tests listed below.

• ADAMTS13 assay: A lack of activity in the ADAMTS13 protein 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 protein's activity. Genomic testing may be done for the ADAMTS13 gene to diagnose inherited TTP.
• Bilirubin test: When red blood cells die, they release a protein called hemoglobin into the bloodstream. The body breaks down hemoglobin into a compound called bilirubin. If you have TTP, your bilirubin level may be high because your body is breaking down red blood cells faster than normal.
• Blood smear: For this test, some of your blood is put on a slide. A microscope is used to look at your blood cells. If you have TTP, your red blood cells will look torn and broken.
• Bone marrow tests: These tests check whether your bone marrow is healthy.
• Complete blood count: This test measures the levels of red blood cells, white blood cells, and platelets in your blood.
• Coombs test: This test is used to find out whether TTP is causing hemolytic anemia. In TTP, hemolytic anemia develops because red blood cells are broken into pieces as they try to squeeze around blood clots. The test is negative if TTP is the cause of hemolytic anemia. The test is positive if antibodies (proteins) are destroying your red blood cells.
• Kidney function tests and urine tests: These tests show whether your kidneys are working well. If you have TTP, you may have blood or protein in your urine. Also, your blood creatinine level may be high. Creatinine is a blood product that is normally removed by the kidneys.
• Lactate dehydrogenase (LDH) test: This blood test measures a protein called LDH. Hemolytic anemia causes red blood cells to break down and release LDH into the blood. LDH is also released from tissues that are injured by blood clots because of TTP.
• Tests to see if your immune system is attacking ADAMTS13: If your provider suspects you have acquired TTP, they may test a sample of your blood. The test will see if your immune system is making antibodies (a type of protein) against ADAMTS13.

TTP can cause life-threatening complications if it is not treated right away. Plasma treatments and medicines are the most common ways to treat TTP. If these treatments do not work, you may need surgery. Treatments are done in a hospital.

Plasma treatments

• Therapeutic plasma exchange (plasmapheresis) is used to treat acquired TTP. In this procedure, the liquid part of your blood (plasma) is replaced with donor plasma using a machine that collects the cells in the blood. It removes antibodies (proteins) in your blood that damage your ADAMTS13 protein. Plasma exchange also replaces the ADAMTS13 protein. You will get this treatment daily until any organ problems have gone away, your platelet count is stable, and damage to your red blood cells has stopped.
• The medicine caplacizumab is used along with plasma exchange therapy to treat acquired TTP. Caplacizumab prevents platelets from aggregating and forming clots.
• Plasma infusion is used to treat congenital TTP. For this treatment, donor plasma is given through an IV line inserted into a vein. This is done to replace the missing or faulty ADAMTS13 protein.

A protein called adzynma is administered in the vein to treat patients with congenital TTP or to prevent its symptoms. Adzynma is a genetically engineered form of the ADAMTS13 protein. It replaces low levels of the patient's ADAMTS13 protein. Plasma treatments usually continue until your blood test results and symptoms improve. This can take days or weeks, depending on your condition. You will stay in the hospital while you recover.

Medicines

Many medicines used to treat acquired TTP work by suppressing the immune system. This prevents the immune system from attacking the ADAMTS13 protein. They are commonly used together with plasma treatments. These medicines include corticosteroids, such as prednisone, rituximab, cyclophosphamide, and cyclosporine A.

Caplacizumab is another type of medicine used to treat acquired TTP. It works by preventing tiny blood clots from forming. It is given as an injection (shot) and is typically used with medicines that suppress the immune system and plasma treatments.

ADAMTS13 protein replacement therapy is used to treat inherited TTP. The treatment works by delivering genetically engineered ADAMTS13 protein into your blood through an IV.

Surgery to remove your spleen

The spleen is an organ in your upper left abdomen. Your spleen makes the antibodies that block ADAMTS13 protein activity. Removing your spleen stops your body from making these antibodies. If other treatments for TTP do not work for you, this surgery may be an option, however, it is rarely used.

Some people fully recover from TTP. However, relapses (flare-ups) are common. They can happen in people who have acquired and inherited TTP. If you have frequent relapses, you may need ongoing treatment.

Without treatment, TTP can cause frequent blood clots. These can block blood flow to your organs and cause complications including:

• Brain damage
• Coma
• Problems with your kidneys
• Reduced blood flow to your digestive system, which may cause diarrhea, pain in your abdomen, and other digestive problems
• Reduced blood flow to your heart, which may cause a heart attack
• Seizures
• Stroke
• Problems during pregnancy

Learn how you can manage TTP to avoid serious complications.