Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura is a rare blood disorder that causes dangerous blood clots to form throughout the body, blocking blood flow to vital organs like the brain, kidneys, and heart. Without urgent treatment, this condition can be life-threatening, but with proper care, most people can recover and manage their health.

Table of contents

• What is thrombotic thrombocytopenic purpura?
• What causes TTP?
• Signs and symptoms
• How is TTP diagnosed?
• Treatment options
• Living with TTP
• Outlook and prognosis

What is thrombotic thrombocytopenic purpura?

Thrombotic thrombocytopenic purpura, or TTP, is a rare blood disorder in which small blood clots form in blood vessels throughout the body^[1]. These blood clots, called thrombi (a single clot is called a thrombus), can restrict blood flow to important organs, including the brain, kidneys, and heart^[2]. When organs don’t get enough oxygen-rich blood, serious medical problems can develop.

The name of this condition gives important clues about what happens in the body^[1]. Thrombotic refers to the blood clots that develop. Thrombocytopenic means the blood has a reduced number of platelets, which are tiny blood cells that help form clots to stop bleeding. With TTP, platelets get used up making clots the body doesn’t need, leaving fewer available for normal clotting. Purpura refers to purplish dots and bruises on the skin that may look like a rash, caused by bleeding beneath the skin.

TTP is a serious condition that comes on quickly and needs urgent medical care^[1]. It affects about 1 to 14.5 per million people each year in the United States, depending on location^[5]. For reasons that aren’t fully understood, the condition occurs more frequently in women than in men^[3]. While onset is typically in adulthood, about 10% of cases begin in childhood^[3].

TTP can also cause red blood cells to break apart faster than the body can replace them, resulting in a condition called thrombotic microangiopathic hemolytic anemia^[2]. This happens when red blood cells collide with blood clots and break into pieces^[1].

What causes TTP?

TTP occurs when there isn’t enough of an enzyme called ADAMTS13 in the blood^[1]. This enzyme normally prevents platelets from forming blood clots when they aren’t needed. When ADAMTS13 is deficient, clots form in small blood vessels throughout the body.

There are two main types of TTP based on what causes the ADAMTS13 deficiency^[1]:

Acquired TTP is the most common form. Also called immune-mediated TTP, this happens when the body mistakenly makes antibodies (proteins made by the immune system) that prevent the ADAMTS13 enzyme from working correctly^[1]. This form usually appears in late childhood or adulthood^[5].

Inherited TTP, also known as congenital TTP or Upshaw-Schulman syndrome, is much rarer^[3]. This happens when both biological parents pass down a faulty gene for making the ADAMTS13 enzyme^[1]. Symptoms often start during infancy or early childhood, though they can appear later in life, especially during pregnancy or when the body is under stress^[5].

Experts aren’t sure exactly what triggers TTP symptoms, but some people experience flares associated with^[1]:

• Viral infections, including HIV
• Autoimmune diseases such as lupus
• Pregnancy
• Certain medications, including chemotherapy drugs, cyclosporine A, quinine, clopidogrel, and ticlopidine^[4]
• Surgery

In about half of cases, a trigger can be identified, while in the other half, the cause remains unknown^[3]. It’s important to note that having a deficiency of ADAMTS13 activity alone doesn’t cause symptoms. Individuals with hereditary ADAMTS13 deficiency can remain without symptoms until a triggering event occurs^[7].

Signs and symptoms

TTP usually comes on quickly, and the symptoms tend to be steady and noticeable^[1]. Many people experience an illness similar to the flu or diarrhea before developing TTP^[3]. The condition won’t improve on its own and always needs treatment.

Blood clots can affect any organ, but the brain is often the first place where symptoms appear^[1]. Symptoms related to the brain and nervous system are very common and can vary greatly in severity. If clots form in the heart, they can cause dangerous heart rhythms or even death^[1].

Common symptoms of TTP include^[1]:

• Altered mental status and confusion
• Headaches
• Fatigue and feeling very tired
• Nausea and vomiting
• Pale or yellowing skin (called jaundice)
• Shortness of breath (also called dyspnea)
• Tiny red or purple dots beneath the skin, called petechiae
• Larger purple bruises on the skin, called purpura^[2]
• Blood in the urine, called hematuria
• Vision changes, like blurred or double vision (also called diplopia)
• Seizures or symptoms similar to a stroke^[3]
• A fast heart rate^[3]
• High blood pressure^[3]

While TTP leads to low platelet levels, some people may have bleeding, but this is less common^[1]. The most common site of bleeding, if it occurs, is from the nose^[3].

How is TTP diagnosed?

Diagnosis of TTP is typically based on symptoms and blood tests^[3]. Because TTP is a medical emergency, doctors may need to start treatment before all test results are available.

Laboratory studies for suspected TTP include a complete blood count, platelet count, examination of blood cells under a microscope (peripheral blood smear), coagulation studies, kidney function tests, and tests to check for red blood cell breakdown^[4].

Most cases of acquired TTP are associated with severe deficiency of ADAMTS13 activity due to autoantibodies against this enzyme^[4]. Measuring ADAMTS13 activity levels may help confirm the diagnosis^[3]. However, because TTP is a medical emergency, treatment is often started before these test results are available.

Doctors look for signs of microangiopathic hemolytic anemia (broken red blood cells, elevated levels of certain enzymes, and changes in bilirubin) and low platelet count without other obvious causes^[4]. Imaging studies and tissue samples are not required for diagnosis^[4].

Only 20 to 30% of patients present with all five classic signs: microangiopathic hemolytic anemia, low platelets with purpura, neurologic abnormalities, fever, and kidney disease^[4]. This means doctors must have a high level of suspicion and start treatment even without all classic signs.

Treatment options

Treatment for TTP depends on the type. Therapy should be initiated as soon as the diagnosis is seriously considered^[9]. Without treatment, TTP can be life-threatening, with mortality rates exceeding 90%^[3]. With proper treatment, the risk of death has decreased to less than 20%^[3].

Treatment for acquired (immune-mediated) TTP

The main treatment for acquired TTP is plasma exchange with fresh frozen plasma^[9]. This procedure removes blood from the body, separates out the plasma (the liquid part of blood), and replaces it with donor plasma containing healthy ADAMTS13 enzyme. Treatment should preferably be started within 4 to 8 hours of diagnosis^[9].

Patients also receive medications to suppress the immune system, preventing it from making antibodies against ADAMTS13^[1]. These medications may include corticosteroids (such as glucocorticoids) and rituximab^[3].

A newer medication called caplacizumab (Cablivi) is approved for treatment of acquired TTP in combination with plasma exchange and immune-suppressing therapy^[4]. This medication works by targeting von Willebrand factor, which is involved in clot formation. It has been shown to reduce the time it takes for platelet counts to return to normal and also to reduce TTP-related death^[4].

When immediate plasma exchange isn’t available, simple plasma infusion can be performed until the patient can be transferred to a facility that performs plasma exchange^[9]. Platelet transfusions are generally not recommended^[3].

Treatment for inherited (congenital) TTP

People with inherited TTP need treatment with infusions of plasma, which provides the ADAMTS13 enzyme their bodies cannot make^[9]. Treatment regimens should be individualized according to the patient’s needs. Some patients require regular infusions, while others with a mild form need only occasional treatment^[9].

In 2023, the FDA approved a recombinant (laboratory-made) form of ADAMTS13 called Adzynma for treatment of congenital TTP^[9]. This can be used for prevention or on-demand treatment in both adults and children.

Monitoring and follow-up care

After treatment for an acute episode, patients may need outpatient treatment to suppress the immune system and prevent another episode^[14]. Monitoring ADAMTS13 levels in the blood is important. If levels are low, treatment with rituximab can be started to prevent a TTP relapse^[14].

Living with TTP

Getting back to normal after a TTP episode is possible, but recovery takes time^[12]. Everyone has a different experience with TTP, so recovery should be guided by how you feel and happen on your own timeline. Take things slowly and listen to your body.

Physical recovery

It’s not uncommon to have neurological problems when recovering from a TTP episode^[12]. You might not realize these problems are TTP-related, especially if you’ve been feeling better. Be on the lookout for memory problems, confusion, loss of concentration, dizziness, lack of balance, headache, or double vision, and let your doctor know if you experience any of them.

Many people feel tired and have low energy during recovery^[1]. Ways to boost your overall energy include eating a healthy diet with lean protein, whole grains, low-fat dairy, fruits, and vegetables; drinking plenty of water; and getting at least seven hours of sleep at night^[1].

Mental and emotional health

After finishing TTP treatment, you will likely feel better physically. However, it’s completely normal not to feel better mentally and emotionally^[12]. A TTP episode can come on suddenly and be very scary. Many people feel anxiety and stress afterward because they’re worried about having another episode.

Checking in about your mental and emotional health after a TTP episode is just as important as monitoring for physical symptoms^[12]. A healthy diet, getting enough sleep and exercise, and connecting with loved ones can all help support mental health. Being open and honest with your care team is most important. If you’re suffering from clinical depression or anxiety, they can make sure you get the help and support you need.

Returning to daily activities

When you can return to work depends on the TTP treatment you’re receiving and how you’re feeling^[14]. This may mean you cannot return to work for at least a few weeks after an acute episode, and sometimes it can take longer. A gradual, phased return to work is recommended.

It is safe to exercise with TTP, but it’s normal to feel tired early on after an acute episode^[14]. Regular exercise is good for you, but don’t push yourself too hard. Good examples include swimming, stationary cycling, or yoga^[16].

Travel considerations

Traveling with TTP is absolutely possible with careful planning^[12]. Before you go, talk to your doctor about the risk of a TTP episode while traveling. They may do a blood test to measure your ADAMTS13 levels to make sure the risk is low. If you feel sick while traveling, contact a doctor right away to make sure you’re not having a recurrence.

Bring important information with you, including contact information for your care team and documents that explain TTP in detail, including your symptoms and care plan^[12]. Having TTP can mean your travel insurance premium will be higher, but some insurance companies offer coverage for patients with TTP^[14].

Pregnancy and TTP

Pregnancy can be a trigger for a TTP episode, but planning with your doctor can help prevent recurrence^[12]. Make sure you talk thoroughly with your care team if you’re planning to become pregnant so you can make the safest decisions. Pregnant women with congenital TTP should attend a specialist center^[9].

Preventing another episode

It is possible to experience more than one episode of TTP^[12]. What you eat will not cause or prevent a TTP episode, but it’s important to eat a healthy balanced diet for your general health^[14]. The best way to prevent another episode is to monitor ADAMTS13 levels in the blood and work closely with your healthcare team^[14].

Outlook and prognosis

With plasma exchange, the risk of death from TTP has decreased from more than 90% to less than 20%^[3]. About 80% of patients respond to initial treatment, and the post-treatment mortality is 10 to 15%^[7].

TTP can come back after treatment. In people with acquired TTP, episodes may occur as a single event or, more commonly, multiple times over the years^[5]. In people with the familial form, symptoms often recur on a regular basis and may return during times of stress, such as during illness or pregnancy^[5].

Without treatment, TTP can cause long-term problems such as brain damage or stroke^[2]. However, with proper treatment and ongoing monitoring, many people with TTP can manage their condition and maintain a good quality of life.