Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare disorder in which blood clots form in small blood vessels throughout your body. These clots can cause serious, potentially life-threatening complications if they completely block blood vessels, or if they reduce or block blood flow to organs such as your brain, kidneys, or heart.
Most cases of aTTP occur in adults, but the disease can also affect children. Symptoms typically develop suddenly, and it’s important to seek medical treatment right away to reduce the risk of serious complications or death. If left untreated for too long, aTTP can cause lasting organ damage, including brain damage, according to the National Heart, Lung, and Blood Institute (NHLBI).
“Acquired” means you’re not born with the condition. “Thrombotic” means you have blood clots, and “thrombocytopenic” means you have a lower than normal platelet count in your blood. “Purpura” describes purple bruises due to bleeding under the skin.
Signs and Symptoms of aTTP
The symptoms of aTTP may be caused by three main factors:
- Blood Clots The out-of-control blood clots that develop in aTTP can directly cause a variety of symptoms.
- Low Platelet Count When aTTP develops, your blood’s clot-forming platelets are “used up,” leading to a low platelet count throughout your body.
- Damaged Red Blood Cells Since aTTP can destroy red blood cells faster than your body replaces them, you may develop symptoms related to anemia (inadequate red blood cells).
Symptoms of aTTP usually develop suddenly, and may include:
- Petechiae (small, flat red spots on your skin)
- Purpura (larger red, purple, or brown bruising on your skin)
- Pale skin
- Jaundice (yellow skin)
- Fatigue or weakness
- Nausea, vomiting, or diarrhea
- Low urine volume
- Fast heart rate
- Shortness of breath
- Slight or partial paralysis
- Speech changes
People with aTTP may also experience signs that show up on certain lab tests, such as:
- Proteinuria (protein in your urine)
- Hematuria (red blood cells in your urine)
- Hyperkalemia (high potassium level in blood)
- Elevated creatinine level in blood
Elevated creatinine indicates worse kidney function, and a high blood potassium level may indicate that your kidneys are failing due to aTTP. Research shows that about half of all people with aTTP have acute kidney injury.
Causes and Risk Factors of aTTP
Out-of-control blood clotting in aTTP is caused by not having enough of an enzyme known as ADAMTS13, which limits clotting. This happens when your body makes antibodies (proteins that are part of the immune system) that stop the ADAMTS13 enzyme from working as it should.
Scientists aren’t sure exactly why or when a person’s immune system creates antibodies that target the ADAMTS13 enzyme, leading to aTTP, according to the Cleveland Clinic. But they have identified risk factors that make this process more likely, including several health conditions.
The following factors may raise the risk of developing aTTP:
- Being an adult
- Being of African descent
- Being female
- Having had a stem cell or bone marrow transplant
- Taking certain medications, including chemotherapy (cancer treatment), clopidogrel (Plavix), cyclosporine (Gengraf, Neoral), or ticlopidine
- Hormone therapy, including estrogen therapy
- Taking quinine (a substance found in tonic water and some dietary supplements)
Aside from lupus, other autoimmune diseases may also raise the risk of developing aTTP, according to the National Organization for Rare Disorders (NORD).
How Is aTTP Diagnosed?
As with many health conditions, the process of diagnosing aTTP begins with your doctor asking questions about your medical history and symptoms. The doctor will also perform a physical exam, taking note of any visible signs of aTTP such as purpura (areas of bruising).
If your doctor suspects you may have aTTP, the following tests may help diagnose the disorder:
- Complete Blood Count This blood test involves measuring levels of your platelets and red blood cells, both of which are lower in people with aTTP.
- Bilirubin Test When red blood cells break down due to aTTP, they release a protein called hemoglobin, which your body breaks down into a chemical called bilirubin. Bilirubin levels tend to be elevated in people with aTTP.
- Blood Smear Looking at your blood under a microscope may reveal torn and broken red blood cells due to aTTP.
- Urine Tests Your doctor may order tests to look for protein or blood in your urine, both of which may indicate aTTP.
- Creatinine Test Elevated levels of creatinine in your blood indicate worse kidney function, which may be due to aTTP.
- ADAMTS13 Assay This test measures activity of the ADAMTS13 enzyme in your blood. A lack of this enzyme’s activity may indicate aTTP.
- Lactate Dehydrogenase (LDH) Test This test measures LDH, an enzyme found in cells throughout your body. Higher levels of LDH indicate that cells are being destroyed, which occurs in aTTP.
- Coombs Test This test can help determine whether anemia (inadequate red blood cells) is caused by aTTP or another health condition.
Any single blood or urine test may not definitively show that you have aTTP, but a combination of tests — along with your health history and physical signs and symptoms — is likely to point to, or rule out, the condition.
Duration and Prognosis of aTTP
Left untreated, aTTP may last for days or weeks, or even months in some cases. During that time, you may experience severe complications and damage to your organs, including brain damage. The condition may also be fatal.
Without any treatment, aTTP has a 90 percent mortality rate, according to the Cleveland Clinic. But with prompt and appropriate treatment, the mortality rate is between 10 and 20 percent.
When you receive successful treatment for aTTP, your recovery time will depend on the severity of your condition and your overall health, among other factors. Recovery times can range from a few days to a few weeks after undergoing typical treatments for aTTP, according to the Cleveland Clinic.
People who develop aTTP once are more likely to develop the condition again. Relapses, or flare-ups, of aTTP occur in about 60 percent of people with the condition, according to the Genetic and Rare Diseases Information Center.
Treatment and Medication Options for aTTP
Getting treatment for aTTP as soon as possible is essential in order to prevent life-threatening complications. The most common treatments for aTTP are plasma treatments and drug treatments, though surgery may be needed if those treatments aren’t enough, according to the NHLBI.
Plasma Treatments for aTTP
There are two main types of plasma treatments for aTTP:
- Plasma Exchange In this procedure, your blood is sent through an intravenous line to a centrifuge (separation device), where your plasma is removed and replaced with donor plasma. Your blood is then returned to your body.
- Plasma Infusion If plasma exchange is not an immediate option at the facility where you’re being treated, you may receive donor plasma by itself through an intravenous line. This is typically done only until you can receive a plasma exchange, according to the Cleveland Clinic.
The purpose of plasma exchange for aTTP is to remove antibodies from your blood that are damaging your ADAMTS13 enzyme, while also giving you functional ADAMTS13 through donor plasma. Treatment is typically given daily until any organ function problems are resolved, your platelet count is stable, and your red blood cells are no longer being damaged.
Drug Treatments for aTTP
It is a common practice to treat aTTP with medications at the same time as plasma treatments. The main drug treatment for aTTP is corticosteroids, which work to stop your body from forming antibodies that attack the ADAMTS13 enzyme.
Other drugs that may be used to stop your body’s attack on ADAMTS13 include:
- Rituximab (Rituxan)
- Vincristine (Oncovin)
- Cyclophosphamide (Cytoxan)
Caplacizumab (Cablivi) was approved in 2019 by the U.S. Food and Drug Administration as the only treatment specifically indicated for adults with aTTP. It is used in combination with plasma exchange and other drug treatments.
In a clinical trial involving 145 adults with aTTP, participants who received caplacizumab were 55 percent more likely to see their platelet count return to normal than those who received a placebo (inactive injection). They were also 74 percent less likely to experience a combination of poor outcomes during their plasma treatment or in the next 30 days, and 67 percent less likely to have a recurrence of aTTP during the trial or during a 28-day follow-up period.
Surgery for aTTP
For severe cases of aTTP, surgery to remove your spleen (splenectomy) may be needed. That’s because your spleen creates the antibodies that attack the ADAMTS13 enzyme in aTTP.
Your spleen is an organ located in the upper left area of your abdomen. Splenectomy is recommended as a treatment for aTTP only when other treatments are unsuccessful in stopping the disease process.
Prevention of aTTP
Since aTTP develops suddenly and there are no screening procedures to detect the condition before it causes symptoms, aTTP is not considered to be preventable.
If you’ve already had aTTP, talk to your doctor about how to reduce your risk of a recurrence or flare-up of the condition. If you experience frequent flare-ups, you may need ongoing treatment to prevent frequent blood clots, according to the NHLBI.
Complications of aTTP
Blood clots due to aTTP can reduce or block the flow of blood to different areas of your body, leading to a number of possible complications, according to the NHLBI:
- Brain damage
- Kidney problems
- Digestive problems (including diarrhea and abdominal pain)
- Heart problems, including heart attack
According to NORD, acute kidney failure requiring kidney dialysis occurs in about 10 percent of individuals with aTTP.
Getting prompt treatment for aTTP is essential to reduce your risk of serious complications due to the condition.
Research and Statistics: Who Has aTTP?
There is limited data on how common aTTP is in the United States. According to the National Library of Medicine, both aTTP and a far less common related condition (inherited TTP) are estimated to affect between 1.7 and 14.5 out of every one million people each year. Based on an estimated U.S. population of about 330 million in 2020, that works out to between 561 and 4,785 cases of aTTP (and inherited TTP) each year. Two-thirds of people with aTTP are women, according to NORD.
A study of aTTP in German hospitals, published in 2019, found that the annual incidence of the condition in Germany was projected to be 2.1 for every one million people. That is in line with previous estimates in European countries that ranged from 1.5 to 6.0 cases per million people.
The “a” in aTTP stands for acquired, meaning you’re not born with the condition.
There is also a form of TTP that is genetic and is caused by mutations in the ADAMTS13 gene. It’s inherited in an autosomal recessive pattern, meaning that an individual must inherit one abnormal gene for the disease from each parent. In most of these cases, each of the parents has only one copy of the gene for the disease and no symptoms of TTP, according to the NHLBI.
Inherited TTP results in an ADAMTS13 enzyme that does not work properly, and symptoms typically first occur in infancy or early childhood, according to NORD. But inherited TTP may also not cause any problems until adulthood, such as during a first pregnancy.
Treatment for inherited TTP is similar to treatment for aTTP, except that a direct infusion of donor plasma is used instead of a plasma exchange.
Resources We Love
If you want to learn more about aTTP or get involved in related causes, the websites of these organizations can help:
This division of the U.S. National Institutes of Health offers extensive information about aTTP and related platelet disorders — including detailed descriptions of the disease process, symptoms, and treatments.
This resource from the National Library of Medicine provides an overview of aTTP, as well as links to information and resources on related conditions, support for patients, clinical trials, and scientific journal articles.
This Canada-based support and advocacy group offers virtual support groups for people with aTTP (and inherited TTP), a quarterly newsletter, and educational brochures, and it raises funds for research grants related to TTP, among other activities.