Emily’s Story
Severe and Prolonged TTP in a Young Woman, Beginning with Her First Pregnancy and Continuing for 11 Months.
July 2001
In the winter of 1998, Emily was 25 years old; she was in the eighth month of her first pregnancy and she was feeling a little tired. Her job as a physical therapist in a small hospital kept her very busy. Over the next three days, she continued to remain constantly fatigued. She wasn’t very worried until she noticed blood in her urine; she went to her doctor the next morning. The doctor felt that these symptoms were caused by a urinary tract infection, so he prescribed antibiotics.
At work the next day, December 1, Emily experienced a migraine headache. She had had intermittent migraine headaches since she was 13 years old, but this one was more severe. Accompanying the migraine was partial vision loss on her left side and a tingling sensation and clumsiness of her left hand. Her doctor provided symptomatic treatment, as he had when she suffered a similar migraine attack six months earlier. The following day, Emily returned to work, but still felt very tired. On that day she had her routine annual laboratory tests, which were part of her job. She did this because these tests were supposed to be done in December, but also because she did not feel well. No one checked the results until the next day.
That day, December 3, Emily returned to work despite continuing to feel ill. She began to notice new problems, which were scary. "I couldn’t write, and I was not speaking or thinking coherently." She continues, "I even had problems remembering names of people I saw every day". She went home from work to sleep. But then her doctor called her. He had reviewed the results of the lab tests from the previous day, and he was shocked. Emily, whose previous lab tests were normal six months earlier, was now severely anemic (hematocrit 21%, normal over 38%) and had a severely low platelet count (7,000, normal over 150,000). Emily was rushed to a large city hospital 90 miles away. On arrival, everyone felt that the situation was critical. Emily remembers, "There must have been 30 doctors that came in". But she was not very aware of what was happening around her. She states, "I wasn’t with it enough to realize that I was so sick".
Emily received transfusions of red blood cells and platelets, and had an urgent cesarean section. Her baby boy weighed 5 pounds, 1 ounce but he needed urgent attention to start his breathing. He recovered promptly, his platelet count at birth was normal, and he has developed perfectly over the next 4 years.
Emily was seen by a hematologist late that night, just after her cesarean section. He diagnosed TTP because of the severe confusion, low platelet count, anemia, and evidence for red blood cell destruction. Her red blood cells were broken, or fragmented, when seen through the microscope. Also, her blood LDH level was extremely high- 2379; normal is less than 200. LDH is an enzyme that leaks out of red blood cells when they are damaged. Emily did not have other more common complications of pregnancy; she did not have high blood pressure or abnormalities of liver function. She did not have abnormalities of kidney function except for blood and protein in her urine. To begin urgent plasma exchange treatment for the TTP, a central venous catheter was inserted into her groin area. Plasma exchange treatment was begun just after midnight.
When Emily was asked to describe this day, over two years ago, she does not really remember much. But what she does remember is not being able to see her son for three days. As a result of both she and her newborn needing medical attention, the time that they could spend together was limited.
Emily had a lot going on. She was a new mother who was unable to see her son and who was getting intensive medical attention. She was very sick. And while doctors and nurses were taking good care of both of them, Emily and her family were scared. "We didn’t understand what was going on those first few days." And when things seemed as bad as they could get, they got worse.
During one of Emily’s first plasma exchanges, she began to feel a warm sensation spread all over one side of her body. She began to feel a little nervous, and then developed hives and had trouble breathing. This all climaxed with an uncontrollable shaking. She was having an allergic reaction to the plasma exchange. The doctors and nurses were calm, because they knew what was happening and what had to be done. They gave her IV benadryl and hydrocortisone to stop the allergic response. But Emily was frightened. "I was afraid to close my eyes; I thought I was going to die." She continues, "My brother was there, holding my hand, and all I could think about was that my child would grow up without a mother." Soon the IV benadryl and hydrocortisone began to take effect, and the allergic attack came to a halt.
Three days later, although Emily was now fully alert, her platelet count remained extremely low, 8,000. She also continued to be severely anemic, requiring more red blood cell transfusions. Therefore plasma exchange treatments were increased to twice each day and large doses of IV steroids were begun. A new venous catheter was also put in. Only after a week of this intensive treatment did her blood counts begin to recover. On December 15 she went home, and on December 18 she had her last plasma exchange. She seemed to be completely normal.
Emily had received 22 treatments of plasma exchange, and her platelet count had risen to over 300,000. Her central venous catheter was kept in until January 19, in case her TTP became active again and required more plasma exchange treatments. She was in remission. "The funny thing about me," Emily states, "is that about five weeks after my last plasma exchange, my platelets would crash again." This happened first on January 25. Emily felt nauseated and noticed petechiae on her forearms. She went to her local hospital to get her platelet count checked, and it was only 25,000. Her steroids had been stopped, and they were begun again, tablets in large doses. But the next day her platelet count had fallen to 16,000, so she was admitted to the hospital again, a central venous catheter was surgically inserted, and plasma exchange was begun again. Her platelet count rose to over 150,000 after just five plasma exchange treatments. Prednisone and plasma exchange treatments (15 total) were continued until February 13. She was once again in remission. Due to concern for infection, her venous catheter was removed on February 26.
Emily was confused. Her doctor had told her that pregnancy-induced TTP usually doesn’t recur. Yet she had just had another episode. She found herself wondering, "Is there something else wrong with me." It was during this time that she also found "a lump" on her breast. While it turned out to be a normal lump, this is a good example of how Emily felt she had become "too worried about being sick".
But again on March 21, six weeks after her last plasma exchange, Emily noticed a little bruising. This time her platelet count was 44,000. She was once again admitted and plasma exchange was started. Was this her third episode, or was this just one awful long nightmare illness? A central venous catheter was inserted under her collar bone again. As before, her platelet count rose to 151,000 after the fifth plasma exchange treatment. Six more plasma exchanges were administered to Emily during this episode, the last one being on the first of March. Her platelet count was 331,000. Again, she was in remission. Emily went back to work and life as a mother, and everyone including her doctors, hoped that her TTP would not return again. But just to be safe, plans were made to leave the venous catheter in a little bit longer. This catheter, her fourth, had been inserted by a surgical procedure in the operating room, and was tunneled under her skin before penetrating her vein. The tunneled venous catheter was thought to be safer from infection, and with proper care several times every week, could be left in place for several months.
On May 11, however, Emily felt different. She began to experience uncontrollable shaking chills. She also had a fever. She and her husband, Jason, thought this may be another episode of TTP, so she was rushed to the hospital for a platelet count. The results showed that once again her platelets were low at 22,000. The doctors started plasma exchange, but also focused on another problem, which is a worry to all patients who have central venous catheters: a bacterial infection in the blood stream, called sepsis. Emily’s blood cultures were positive for Staphylococcus, a serious infection. Antibiotics were given, as well as plasma exchange treatments. Emily remembers these exchanges well, as she felt "hard chills" during the treatment. After five days of plasma exchange treatments, Emily’s platelet count had risen to 159,000. It was decided that plasma exchange would be stopped, the central line would be pulled out and antibiotics continued to treat the sepsis. The doctors were unsure if this was Emily’s fourth episode of TTP, or whether the low platelet count and anemia were just the result of the serious infection.
Emily’s platelets continued to rise, and on May 17, her platelet count was 502,000. Again it appeared that her trouble with TTP was finally over.
But Emily’s TTP continued to recur, or perhaps never completely resolved. She needed plasma exchange treatments again on May 30, and in an effort to treat her more effectively, plasma exchange treatments were continued twice a week and then once a week until July 10. Emily felt fine. This time her venous catheter was left in for six more weeks; it was removed on August 24.
September 3: nausea, vomiting, stomach ache, emergency room at her hospital, platelet count……. low again! Episode number 5 had occurred. Again Emily responded rapidly to plasma exchange. This time steroids were given again. But this time her platelet count fell almost as soon as the plasma exchange treatments were stopped, and then again when the treatments were stopped again. Something more had to be done to stop the TTP.
A splenectomy was planned. There was also another reason for surgery. Several months earlier Emily had had an ultrasound test to evaluate symptoms of nausea, vomiting, and stomach pain. She had gallstones. Therefore her gall bladder needed to be removed. At that time, her doctors wanted to wait for surgery until she was completely over her TTP. But now it seemed that time may never come. Splenectomy can sometimes help TTP, so it was decided to do laparoscopic surgery to remove both her gallbladder and her spleen. This was done on October 21, two weeks after her last plasma exchange treatment (and more than 10 months since her TTP had begun).
The surgical procedure was successful - but only hours after surgery, Emily’s platelet count fell from 268,000 to 52,000 and then to 15,000. Her LDH increased to 2562. Plasma exchange was begun again; Emily was still on high doses of steroids.
But now the end of Emily’s TTP was near. Again she responded quickly; plasma exchange treatments were continued intermittently for four weeks; then steroids were gradually tapered and discontinued on December 12. A year after it all began, Emily was finally over the TTP and she has been healthy since.
This summer, 2001, Emily remains happy and healthy. She is able to reflect on her experiences with TTP. She received 94 plasma exchange treatments over 50 weeks. For most of these, she did not have to stay in the hospital, but it seemed that her son grew up for his first year in the hospital, staying with Emily. Even though Emily wanted to be at home as much as possible, and not stay in the hospital unless she was very sick, the 90 minute drive to the hospital for plasma exchange treatment was difficult. To add to this, she was also a mother who kept trying to return to work, so constantly having to be at an appointment with the doctor was a problem. And then there is her son’s story.
Jimmy was born a month premature. He was a very sick baby for the first few days of his life. Emily speaks emotionally about the situation, "I almost lost him. I didn’t want to be away from him." So when Emily went for plasma exchange, she took Jimmy with her. "I am sure we probably bugged some people, but I really didn’t care." Emily also states that, "There were many kind, sweet, and understanding nurses, who would play with him". "I just always wanted him with me." Emily also remembers how supportive and helpful her family was during the whole ordeal. "My mother took time off from work to help out."
Emily believes the most frustrating aspect of her illness was "thinking that I was better, then I would get sick again". She then continued, "You think about it every day, and then it is always the topic of conversation." "Your family and friends are always asking about TTP and how you are doing." "And then when you are going on vacation, you start to think, ‘What if I get sick when we are there?’."
When asked how TTP has affected her life, Emily replies, "It has affected my concentration at work. It is harder to understand medical books. And my attention during conversations is less than what it used to be. I was scared because I always wondered if these memory changes were going to be permanent. But it gets better, even though it hasn’t returned to 100%."
But now for Emily, life goes on. Six months after her recovery, Emily was asking her doctor about risks for subsequent pregnancies. Her doctor told her that the information is limited, but the available information indicates that there is a definite risk for recurrence of TTP with a subsequent pregnancy. How great this risk is is unknown, and clearly some women have normal, uncomplicated pregnancies after recovering from severe TTP. Emily’s risks may be greater than some other women, since she had such a long course with so many recurrences. After several long discussions, her doctor advised her to wait at least a year. Now she is pregnant and we hope her current, second pregnancy will be uncomplicated.
Emily Update: October 2001
Emily’s pregnancy was uncomplicated. She had no signs of preeclampsia (no high blood pressure, no abnormalities of her urine). She even had no migraine headaches during her pregnancy. So she not only had no problems during her pregnancy, she was healthier than a year ago, before she became pregnant. Her platelet count, which has been high since her splenectomy (600,000-700,000, a common occurrence after splenectomy) decreased during her pregnancy, but the lowest platelet counts were 371,000 two weeks before delivery and 376,000 on the day of delivery. Because Emily’s severe onset of TTP in her first pregnancy occurred at 36 weeks and the urgent delivery at that time had required a cesarean section, it had been decided to do an elective cesarean section at 36 weeks of her second pregnancy, if the baby seemed mature. The baby was estimated to be 6 pounds at 35 weeks, so the c-section was scheduled for 36 weeks, on September 26, 2001. It was uncomplicated, the baby boy was healthy, weighing 6 lbs, 1 oz., and having Apgar scores of 8 and 9. Emily recovered quickly and was discharged on September 28. Her platelet count was back up to 658,000 on October 3. Therefore her lower platelet counts may simply have been the common occurrence of lower platelet counts near the end of many normal pregnancies. The baby had to stay in the hospital for a week because of respiratory difficulty, a result of prematurity even though he weighed over 6 pounds. By October 3 he was robust and gaining weight.
This wonderful outcome certainly supports Emily’s decision to have another child. A year ago, the risks for another pregnancy seemed great. But the outcomes of subsequent pregnancies after recovery from TTP are uncertain. Some women will have recurrent TTP; others, like Emily, will have no complications. Therefore the decision regarding a subsequent pregnancy, however difficult, cannot be dogmatic.
Emily Update: June 2003
After having five episodes that went into remission by the end of 2000, Emily remains healthy. She reports, “Since the splenectomy [in October 2000], my platelet level has been high.” Emily’s latest platelet count is 569,000 and it is now over three years since she has had any signs of TTP. Emily leads a very active life with her family and work. She enjoys spending time and chasing her two little but very energetic boys, who are also doing very well. The children are keeping her busy, but “my quality of life is good” says Emily.
With respect to her career, Emily worked as a physical therapist at a regional hospital until about six months ago when she transferred to a clinic setting, where her work hours are more flexible. She is very enthusiastic about her job, working three-four days a week. She has no restrictions from TTP. The remainder of the week, she enjoys her children, family, and friends. Emily says, “I learned I am a different person after TTP.” Emily recalls that before TTP she was a hard-working person who dedicates most of her energy into work. However, Emily observes “my experience with TTP made me appreciate life and family more.”
Although she has no restrictions from TTP, she does note that, “I am more anxious and irritable than before I had TTP.” Also, her concentration and memory are not as keen as before TTP. “I have a harder time concentrating and reading medical materials,” says Emily. Additionally, she comments about pain in her hands and joints, which she does not think to be related to TTP.
Reflecting on the factors that have been most helpful in her experience with TTP, Emily recalls that her hematologist has been very supportive and that his knowledge about TTP is reassuring. She also says that “support groups are helpful at first to help me get over the initial fear of not knowing what the disease was.” Throughout the first year of TTP, Emily recalls being very sensitive, even “paranoid,” to the possibility of recurrent TTP “every time I saw bruises or felt bad.” However, after three years without TTP, she doesn’t think about the disease as much. She says, “I think about it weekly, but not daily” as before. Emily further explains that she only gets her platelet counts done annually unless she is feeling bad and having bruises or petechiae.
When asked what advice she has for others going through TTP, she replies, “Read up and understand about the disease. There is not a lot you can do to control the disease. But you will have more control when you understand what’s going on.” Emily admits, “I never heard of it before; but now I understand what it is, I feel more in control.”
Emily Update: November 2006
Thankfully, Emily has had no more episodes of TTP since her remission at the end of 2000. She is in good health, but continues to get her platelet count checked at her annual physical exam. Emily recently sent the following email to let us know how she has been doing over the past few years:
“Since my last update, I have done very well. I have had no episodes of TTP. I still feel that have some problems with memory and concentration, but it seems that this has progressively improved. I only seem to be having difficulty with difficult [medical] literature, and this seems to have improved as well. I have no other difficulty that I attribute to TTP."
“As for my life, everything is going great. We have moved into a new house and I have a new job. I am still working as a physical therapist, but I am now working in the school system. This allows me to have the same breaks as my kids and I am loving it!!! Jason and the kids are doing great, too. They are seven, five, and two now. They are all very smart, of course, and are doing great in school."
“I am not much for advice, but if you or someone you love has TTP, hang in there. Although your life seems crazy now, it will soon get back to normal. I no longer think of TTP everyday. It only crosses my mind periodically. As crazy as it sounds, having TTP had a very positive impact on my life. I am now more thankful than ever for my life and all of those in it. God blessed me greatly when I had TTP, and He continues to bless my life today.”
Emily Update: June 2011
"Everything is going well. I continue to be busy with my multiple careers, working both as a physical therapist in our school system and working maybe a bit harder to keep up with three very busy children, now ages 12, 9 and 7, and all of their ball games. I’m proud of my endurance – especially as I approach age 40. I run to keep in shape and I’ve finished the Oklahoma City Memorial half-marathon for the past two years. In fact, things are going so well I even forgot to tell the story of my third child when I did my last update 5 years ago. She (I was very excited to have a daughter after two boys!) was born in 2004 after a very uncomplicated pregnancy. Things were so uncomplicated that I didn’t even need to be cared for by a “high-risk” obstetrician, as I was for my second child. And I didn’t need to deliver early. I was delivered by my obstetrician in my home town – by C-section, since I've had C-sections twice before. This was a happy ending to all of the previous concerns about pregnancies.
I rarely think about TTP anymore. I get reminders from Dr. George about the meetings of former patients, but I don’t need to attend these. I see Dr. George each summer for a routine follow-up visit, but I turn these into holiday weekends for my husband and I to visit Oklahoma City and leave the children with my parents. TTP will always be part of my medical history, but it’s no longer part of my life. That’s the message for everyone who reads this."Comments by Dr. George
Emily’s course of TTP was extremely complicated. It is unclear to me whether she had one long episode, lasting almost one year, or whether she had an initial episode then four relapses - five separate episodes. Although this distinction may seem arbitrary and unimportant, we think it may be important as patients with relapses of TTP seem to be at greater risk for more relapses. Does Emily have "relapsing TTP"?
Very often, patients whose TTP seems to be in remission (remission is defined by no symptoms and a normal platelet count) get sick again when daily plasma exchange is stopped, or even when just a day or two of plasma exchange is skipped. We call this an "exacerbation", meaning that the TTP is still active, but its activity is controlled and suppressed by plasma exchange. When the plasma exchange is stopped, the TTP is no longer controlled, and the platelet count falls again.
In our experience, TTP always eventually resolves. When this occurs, we use the term "remission" rather than "cure", because we cannot know whether the TTP may only be dormant and will re-activate sometime later. The only way to know if a patient is in remission is to stop the plasma exchange treatments - and see what happens.
We have decided that if a patient remains well and the platelet count remains normal for four weeks without plasma exchange treatments, the TTP has resolved, the patient is in a stable remission, and the venous catheter can be removed. If the TTP has not yet resolved, the patients will almost always have problems very soon after plasma exchange treatments are stopped - almost always within two weeks.
Therefore four weeks is an arbitrary definition of the time to distinguish when one episode of TTP can be called "finished" and a recurrence can then be called a relapse, another new episode. Emily certainly challenged this definition. But this is the rule of medicine and people’s illnesses: "There are no rules"! Every person and every person’s illness has unique aspects.
Even though we cannot predict what Emily’s risk is for future episodes of TTP, we are reassured that she returned completely to normal, and has remained normal for almost eight years. Our optimism about Emily’s future was supported by her uncomplicated subsequent pregnancies.
During pregnancy, especially at the times just before or after delivery, there appears to be an increased risk for TTP. Somehow pregnancy, especially around the time of delivery, triggers the onset of TTP-HUS in susceptible people. We cannot yet define who is susceptible. But also TTP is very difficult to diagnose at this time, because all of the features of TTP can occur with less serious complications of pregnancy, such as preeclampsia. Preeclampsia and related complications get better within a few days after delivery, so often we wait a day or two, or maybe up to three days after delivery to see if the woman will get better and plasma exchange will not be required. However in Emily’s case, she was so sick that we started plasma exchange immediately. What most concerned us was her serious confusion - this is much more likely to be TTP than preeclampsia. Also, she did not have high blood pressure - the usual diagnostic feature of preeclampsia.
Most important, Emily is a very intelligent and careful but determined young woman. She needs information, advice, and support. A doctor cannot just tell her what to do. I was very sympathetic to her strong wish to have another child. Of course there were risks with another pregnancy. But the decision to have another child wasn’t my decision, it was a shared decision but primarily Emily’s decision. Our experience in the Oklahoma TTP-HUS Registry over the past 18 years is that in most women pregnancies following recovery from TTP are uncomplicated.
Update 2007: Emily’s initial treatment in 2007 would be different than our treatment in 1998. We know now, from measurements on Emily’s blood samples that we saved, that her TTP was related to low levels of an enzyme that prevents blood platelets from causing clots. (The name of this enzyme is ADAMTS 13.) The low levels were caused by an antibody that blocked the activity of ADAMTS13. Now we would treat patients like Emily with medicines that would suppress this antibody activity, such as steroids and rituximab.
Update 2011: Emily continues to be in excellent health. For her, TTP is just a bad memory of the distant past. She’s very healthy and happy now.
[First written July 2001. Last updated June 2011.]
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