Answering TTP Canada

Author: John

  • Mina’s Story

    I am 48 years old and Thrombotic Thrombocytopenic Purpura (TTP) has been in and out of my life for the past 17 years. I have always been very healthy, as I workout 3 to 4 times a week, eat well and do not smoke or drink. I have been an advocate of leading a healthy lifestyle, which has helped me deal with my TTP episodes. I was first diagnosed with TTP in January of 1994 at the age of 32. My children were 4 and 6 years old. This disorder affected me physically and mentally. As for the family, they suffered just as much.

    It started with petechiae (small red dots) on my arms. The family physician had me go for blood tests and the results showed that my platelet count had dropped to 16,000. Normal levels should be above 150,000. My family doctor said it was due to my cold virus and I should recover soon. My husband wanted me to get a second opinion with his family physician. A call was made immediately to the emergency department for my admission. The hematologist on call diagnosed me right away by looking at my blood smear. He started treatment including 50 mg of Prednisone and Plasmapheresis the very next day. At that time, Plasmapheresis was done in ICU (Intensive Care Unit). The whole experience was very traumatic, as it included inserting the catheter in my neck and having to be hooked up to all the monitors. I was discharged after 2 weeks and the recovery took a very long time.

    A month later in February of 1994, I was diagnosed with ITP (Idiopathic Thrombocytopenic Purpura). Although not as fatal as TTP, I was given Prednisone at a low dose to keep the platelets up. No hospital admission was required.

    In July of 1994 that year, my TTP relapsed. For these few months, I was going for regular blood work and that is why they were able to detect the relapse. The same hematologist placed me on 200 mg of Prednisone and Plasmapheresis. The side effects of Prednisone were terrible. One of the side effects was vision issues, and at times my husband had to use a wheelchair to get me around. I was discharged after 3 weeks. I had gained 40 lbs from the Prednisone, which took me a year to lose.

    Later that same year in September of 1994, ITP re-surfaced and they decided to remove my spleen. Fortunately, this placed me in remission for 16 years.

    Then in February of 2010, I relapsed again with TTP. When I recognized bruising on my hands, I reported to emergency right away for admission. The medical team started me on 50 mg of Prednisone and Plasmapheresis immediately. I was discharged after 11 days. The Prednisone caused CSR (Central Serous Retinopathy) in my right eye. I could not see very well. This was difficult because I enjoy reading, and my work involves extensive use of the computer. The Retina Specialist performed a laser surgery in September of 2010. By December of 2010, I was finally doing well and was able to resume my normal work hours and routine lifestyle. Throughout the year-long recovery from this more recent TTP crisis, I was thankful once again for the support of my husband, family, friends, work colleagues and the medical staff. Moreover, since my earlier battles with TTP, my kids have grown from toddlers to young adults. Now it is not only their smiling faces that help me fight on, but their shoulders of support.

    My remission was cut much too short. Only a year later, in January of 2011, I relapsed again with TTP. I caught a flu bug and the petechiae appeared on my thigh. Once again, I was admitted immediately and they started the Plasmapheresis treatment. I was not given Prednisone because of my historical vision issues with this drug. This time, the medical team wanted to be more aggressive in the treatment. I was given 3 cycles of Cyclophosphamide but my platelets would not stay up without Plasmapheresis. Next, was 4 cycles of Rituximab but again my platelets would drop without Plasmapheresis. These drugs are used to suppress the immune system. The doctors did more research and decided to do a nuclear ultrasound and discovered that my spleen had either re-grown or not been removed completely. As a result, a laparoscopic surgery was performed to remove the 2.5cm Spleen. After surgery, the platelets dropped again and they started the Plasmapheresis treatment. The Calgary physicians had never experienced this with a TTP patient. This meant going into an unknown territory, which worried me. I had tried to remain positive all along until this time, but now I was scared. My doctor passed on contact details for Answering TTP Foundation and I was happy to connect with other TTP patients for the first time to share experiences and knowledge. Shortly thereafter, a call was made to a couple of US Doctors that have been doing extensive research on TTP. They recommended the drug, Cyclosporine. After a few weeks, my platelets finally stayed up without Plasmapheresis. The plan was to keep me on a high dose of Cyclosporine for 6 months and then taper me off. Cyclosporine has some really nasty side effects. The doctors were not sure what treatments had finally worked on me. They said it could be all of the above.

    Three months later in May of 2011, I was finally discharged. It was physically and emotionally very draining. The hospital staff, family and friends have helped me pull through this. My manager, supervisor and colleagues at work have also been very supportive. I cannot thank everyone enough.

    I realized how important it is to support each other and bring awareness of this disease, so I share my story and try to support other TTP patients.

  • Understanding TTP

    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.