What is TTP?
Thrombotic Thrombocytopenic Purpura (TTP) is a rare blood disorder: only about 3-4 people in a million will get it each year.
It is a medical emergency when a TTP attack occurs: the platelets in your blood will start to form clots, which can restrict blood flow to your vital organs, risking damage. Then as the platelets form these clots, they are not available in the blood for their normal function, which is to seal injuries and prevent excess bleeding, which puts you at risk of bleeding and blood loss.
TTP is caused by a deficiency in the ADAMTS13 enzyme, which is involved in regulating the blood clotting system. Specifically, ATAMTS13 cleaves von Villebrand factor (VWF), which regulates platelet clotting. Most cases (>99%) of TTP happen when the immune system creates antibodies that attack the ADAMTS13 enzyme, this in turn allows VWF to clump up and bind to platelets, causing the platelets to form clots where they are not wanted, and depriving the blood of platelets.
It’s a complicated process that can happen quite quickly (symptoms appear in a matter of days, and death can follow soon if not treated).
Symptoms
During a TTP attack, many potential symptoms can appear, including:
- fatigue
- fever
- skin that bruises easily
- thrombocytopenia (bruising, purpura, petechiae)
- bleeding (from nose, gums)
- diarrhea
- chest pain
- abdominal pain
- neurological symptoms (confusion, headaches, visual changes)
After an attack, there can be many lingering symptoms from the organ damage that may have occurred from the clots and then bleeding, as well as from the life-saving treatments themselves (e.g., high-dose steroids may have long-term side effects).
Diagnosis
A medical history and a physical exam, in combination with a complete blood count (CBC), lactate dehydrogenase level (LDH) and blood smear are used to determine a diagnosis of TTP. More recently an ADAMTS 13 enzyme level test may be used to help confirm the diagnosis. Importantly, diagnosis and immediate treatment should not await the results of an ADAMTS 13 assay.
Treatment
Most patients receive steroids (e.g., predisone) to slow the immune system and the autoimmune process that is depleting the body of ADAMTS13. The high dose of steroids can be challenging and lead to future problems (though the first step is to save the patient’s life from the TTP crisis!).
Plasma exchange is then used as the treatment of choice. This involves a machine that filters out the plasma from the patient’s blood, and replaces it with plasma from blood donors, with each treatment taking several hours. Most TTP patients require daily plasma exchange for several weeks or even months. The antibodies targeting ADAMTS13 will be removed with the old plasma, and the donor plasma helps replenish some plasma proteins.
For the minority (<1%) of patients with hereditary TTP, prophylactic (preventative) plasma exchange is sometimes used to maintain functioning levels of ADAMTS13.
For some patients, rituximab is used. This drug was originally developed as a treatment for lymphoma, and targets immune cells called B-lymphocytes.
An emerging therapy is caplacizumab, an antibody-based treatment designed specifically for TTP. It blocks the platelet clumping by targeting VWF, which can not only help save lives (which was demonstrated in clinical trials) but likely also helps prevent the organ damage that can occur while patients wait for plasma exchange to reverse a TTP attack (based on our understanding of its mechanism of action and our patient testimonials). Though it was approved by Health Canada in 2020, caplacizumab is not currently available for Canadian TTP patients to use
Prognosis
Without treatment, 95% of patients will die, however plasma exchange combined with other therapies will see that 80-90% of patients will survive their TTP attack and achieve remission. Remission is when the antibodies that mysteriously formed to attack the ADAMTS13 proteins stop being produced, the ADAMTS13 levels rise (though not always back to normal), and the platelet levels are restored, and the patients can begin to recover from their episode.
However, once someone has had an attack of TTP, they are at at much increased risk of having it happen again: about 30% of people who survive their attack will have a relapse, many will have multiple relapses through their lives. Vigilance and early detection of another flare-up are critical to minimize the risk of death or irreversible injury to vital organs.
It is not entirely clear what can trigger a relapse. In some cases, infection may be a trigger. Pregnancy is a known trigger, so women who survive a TTP episode should discuss their individual cases with their care team, and consider careful monitoring of ADAMTS13 levels for early detection of a relapse, and potentially consider prophylactic treatment.
A growing percentage of patients are recognized with anxiety, depression and neurocognitive deficits after recovering from an episode of TTP.
Support
TTP is a terrifying event. The first attack comes out of nowhere, and in part because it is so rare, often involves many mis-diagnoses before it is caught and treatment starts. By then patients are often very sick, and will have to spend a long time (weeks or months) in a hospital for plasma exchange and rehabilitation. Because it is such a rare disease, it may be nearly impossible to find someone else with a similar story. Please feel free to read our patient and family stories, and to reach out to us at answeringttp.ca@gmail.com.