Severe TTP with a Prolonged Four Month Course in a Middle-Aged Man
On a Thursday evening in September, Ralph noticed that he was feeling a little more tired than usual. As a member of the law enforcement community, working hard and feeling tired were not abnormal. But this time it felt different to this slightly overweight, yet active, middle-aged man. By the next morning the feeling of being tired had developed into exhaustion and a total lack of energy. Ralph arose and attempted to begin his daily routine of preparing himself for the workday. But on this Friday morning, he recalls, "I was barely able to shave and I was too tired to even shower." Ralph called in sick and decided to rest.
Throughout that Friday the exhaustion persisted, and Ralph began to develop a stomach ache. This stomach ache advanced over the course of three days, until Sunday evening when he and his wife, Sherrie, made the decision to visit the 24 hour clinic. He complained only of pain in his belly and exhaustion; he did not have any nausea, vomiting, diarrhea, fever, or cough. And with the exception of aspirin, he was not taking any medications.
Once at the clinic the physician did a blood test, which revealed a severely low platelet count; he directed Ralph to go immediately to the local hospital emergency room. Upon arrival at the emergency room, Ralph began to experience trouble with his memory. He had blood in his stool and urine samples. He remembers, "Blood was coming from everywhere!" His CBC (complete blood count) showed that his hematocrit was 32% (hematocrit is a measure of the number of red blood cells, normal is over 41%). Other lab tests showed that his platelets were 2,000 (normal is over 150,000), and his LDH (an enzyme in the blood plasma; increased LDH levels indicate damage to red blood cells and other tissues) was greater than 2,000 (normal is less than 200). The doctors did not know what to do. Ralph remembers being "scared to death by the reaction of the doctors around me." The doctors decided to give Ralph a platelet transfusion, and then another.
With the order of the platelet transfusions came a stroke of luck. When the hospital called the regional blood center to restock the platelets that had been administered, a doctor at the blood center called the doctors at the distant emergency room to ask why they had given two platelet transfusions to Ralph. The ER doctors described the symptoms and lab results, which they could not figure out. And from this information, the blood center doctor was able to suggest the possibility of a rare disease known as TTP (thrombotic thrombocytopenic purpura). After further telephone discussion with a hematologist, the diagnosis of TTP was confirmed by the presence of severe thrombocytopenia (low platelets) and hemolytic anemia (anemia caused by the destruction of red blood cells) in association with neurologic (Ralph's trouble was with his memory) and kidney abnormalities (increased blood level of creatinine, a chemical normally excreted by the kidneys).
Treatment with plasma exchange was planned to begin that Sunday evening by sending a team to the hospital where Ralph was. It was felt that this was the quicker way to begin this potentially life-saving treatment, rather than transferring Ralph to a city hospital. Plasma exchange is a procedure where a pump is used to pull out the plasma (liquid part of the blood) and the cells are returned with an equal amount of fresh frozen plasma (FFP) obtained from normal donors. In order to do this, a surgeon was called in to put in a large diameter catheter into one of Ralph's large veins close to his heart. The catheter is needed to pump fluids both in and out of the patient’s blood system. In the case of Ralph, the venous catheter was inserted into his subclavian vein (just below his right collar bone). The team from the city arrived at the intensive care unit at midnight to begin the plasma exchange.
Sherrie, Ralph's wife, remembers the doctor telling them that Ralph had TTP. Sherrie and Ralph had no idea what that meant, and they felt that the doctors were just as ignorant of the disease as they were. Sherrie also remembers being told that the average course of this disease was two or three weeks. They had no idea what they were dealing with, but they were about to live it out.
The next day Ralph was transported to a larger hospital in the city. It was then that Ralph and Sherrie were introduced to doctors who not only knew about TTP, but they were able to explain and provide information about the disease. The doctors worked hard to try to correct Ralph's blood problem. Ralph was given a unit of red blood cells, 100 mg of prednisone (steroid) each day, and plasma exchange was done daily. Ralph remembers feeling "a chill sensation" during plasma exchange. And to avoid an allergic reaction to the new plasma, the doctors also gave Ralph IV Benadryl before each plasma exchange treatment.
The next day, while Ralph was receiving plasma exchange therapy, his doctor came to visit him. As they were discussing his treatment, Ralph began to hear "a ringing in my ears". He thought nothing of it, dismissing it as simple machine noise. He then remembers that as his doctor continued to speak, he did not hear anything, just saw the moving of his lips. The last thing Ralph remembers was "my head drawing back". All of this happened in seconds before the onset of a grand mal seizure. Luckily, Sherrie was not in the room to witness this terrible event. The next thing Ralph remembers was "waking up tied to the bed". He then drifted right back to sleep. Then he awoke and was untied but was also "unaware that several hours had passed." Later he was told that it took several people to hold him in the bed during the seizure, it had been so violent.
After the seizure, Ralph was given plasma exchange therapy twice a day. And over the next few days, Sherrie and Ralph both noted that he was behaving differently. For example, Sherrie would walk into the room and "see him staring at the wallpaper from about six inches away and shuffling along the wall". Ralph actually remembers looking at the wall and "watching electrodes jumping out of it."
Three days after his seizure, Ralph awoke at 6:30 in the morning and was unable to speak. He had a drooping of his right mouth and remembers thinking, "My God, I’ve had a stroke!" The doctors ordered plasma exchange therapy to begin right away, and with the treatment, the symptoms began to subside.
TTP is a disease where the platelets begin to clump together and obstruct blood flow in small vessels. It is important to say that Ralph did not have a stroke. His symptoms were caused by what is called a transient ischemic attack, or TIA. Basically, this means that platelet clumps transiently blocked a critical blood vessel in his brain, and therefore stopped the oxygen flow (ischemia) to that area. There was no permanent damage, as may occur in a stroke.
During the plasma exchange (which took about four hours) the symptoms of the TIA began to disappear. Ralph's speech returned to normal, and he regained total control of his facial movements. But with the good came the bad. He had another seizure toward the end of the plasma exchange session. While this one was not as bad as the first one, Ralph was extremely frightened by this, especially after one week of intensive therapy with twice daily plasma exchange plus prednisone. A CT scan of his head was done to make sure that he did not have any bleeding. He did not, and a couple of days later, he remembers waking up "totally mentally intact".
During this time, Ralph was not the only patient in the hospital with TTP. A woman down the hall, close to Ralph's age, was also receiving treatment for TTP. The onset of her TTP had been just 5 days before Ralph's. As the treatment progressed, so did the bond between the two couples who were going through the same experience. The two couples became quite close and shared information about their symptoms and treatments. Then one day, while Sherrie and Ralph were waiting for the plasma exchange, they got word that their friend had had a severe reaction to the plasma exchange therapy. In fact, she had stopped breathing for a short time and was rushed to the intensive care unit. As soon as they heard this bad news, "They wheeled the (plasma exchange) machine right in". Ralph describes the experience, "I was spooked real bad". Their friend recovered completely and was back on the same hospital floor three days later. But for every plasma exchange session after that, Ralph "sweated it big-time, everytime I sat in that (plasma exchange) chair."
Over the next few weeks, things were less eventful, thankfully. Ralph and Sherrie remember these times as "counting platelets and taking treatments". He dreaded seeing them "roll in the machine" for plasma exchange. He always wondered whether he would have another seizure, or an allergic reaction like his friend down the hall. They also remember it as sort of a "depressing time", as the highlight of each day was looking forward to the results of the CBC and LDH levels.
Ralph was released from the hospital in the middle of October, after being in the hospital for a little more than twenty days. And while his platelets were up to 170,000, he still received intermittent outpatient treatments of plasma exchange and steroids taken by mouth. Just because he was no longer in the hospital did not mean that Ralph was free and clear. And as he continued to take the steroids (prednisone), he began to notice some side effects.
Ralph and Sherrie remember the side effects of the steroids quite well. They were unprepared for the variety of side effects that would accompany the steroid treatment. It seemed to them that when they noticed something unusual, it would usually be categorized by the doctors as a side effect of the steroids. The first side effect he noticed was a blurring of his vision. He also remembers getting "the shakes for no reason". His appetite was insatiable. He ate everything and gained several pounds. He also recalls trouble sleeping, waking up 3 or 4 times per night. But "worse than anything, I would go off at Sherrie for no reason". His mood swings were the most distressing of all of the side effects of the steroids. As an example, he said that he would come "in and out of depression". But as soon as steroid treatment was discontinued, the side effects "eased off".
Also tiresome to Ralph and Sherrie was the maintenance of the venous catheter. The catheter was necessary in order to pump the plasma in and out during the plasma exchange sessions. Since the catheter is in direct contact with Ralph's blood, it was vital to always keep it dry and clean. It seemed to Ralph that he was always wrapping and taping it in order to keep it clean.
In the same way he was eased off of steroid treatment, Ralph was also eased off of plasma exchange treatment. When he did receive a treatment, he would drive up to the city. As an outpatient, he was still worried when he would begin the treatment. On one occasion he had a severe allergic reaction which he refers to as "hives and hotdogs". “Hives,” the itchy red bumps all over his body, and "hotdogs" describing the swelling of his lips. On another occasion, the plasma exchange machine "blew up, spewing blood all over," when one of the tubes came loose. He thinks it was probably more traumatic for the nurse, who was responsible for running the machine, than for him.
After more than three months, it began to seem that the TTP would never end. Each time the plasma exchange treatments were spread out or stopped, his platelet count fell and LDH rose. Then the daily plasma exchange treatments were resumed again. Although these times were not critical, Ralph had no more seizures or TIAs, frustration was severe. His doctor discussed other treatments: resume steroids or consider surgery to remove the spleen. Ralph absolutely refused to resume steroids; he said, "I’d rather have surgery." But just as the surgeon was consulted, four months after the TTP began, Ralph's platelet counts and LDH levels finally held at normal values without plasma exchange. He was in remission.
It is now almost a year since his last plasma exchange. Ralph has returned to his normal activities. His platelet counts remain normal. However, long term effects of his illness are present. He feels that it has "zapped my strength and concentration". He also feels that he has developed problems remembering things that just happened. He explains this further by telling examples of times where he has had difficulty in recalling names or specific words.
When asked for advice to give to those who have recently been diagnosed with TTP, he quickly responded with, "Don’t get discouraged…there is an end". He also suggests that one should ask for a definition of the disease in laymen’s terms. When asked about the illness, Ralph feels that he "has lost a chunk of his life." But he also states that, "There is treatment available, and I am still here to bitch about it!" And finally he suggests that it is okay "to think about it, but don’t dwell on it."
Ralph Update: July 2003
Over the last two years, life for Ralph, in general, “hasn’t been too bad.” Ralph is currently working full time at his job as a member of the law enforcement community. “I have no restrictions on my activities. I do what I need to do.” Although Ralph mentions that, “I haven’t recovered the strength and stamina I had before TTP.” At the house, Ralph mows the lawn and works in the yard. Afterward Ralph says, “I would get tired but that could be due to my age.”
Ralph also says, “I would occasionally have a memory problem. My memory has not been back to normal, but that could also be due to age.” Ralph’s memory problem did not become apparent until about 3 months after his TTP was in remission, when “I noticed I had a problem with memory and word choice. I can’t find the right words to express myself.” Ralph acknowledges that some days his memory, word choice, and recall are better than others.
Ralph had been visiting his doctors quarterly to monitor his high blood pressure and platelet counts. “My platelet count has been low a couple of times but within the normal range (greater than 150,000), although it was scary at times.” After Ralph finished his plasma exchange treatments in December 2000, “I developed gall bladder problems in February.” Ralph’s gall bladder was taken out and a colonoscopy was done for mild colitis. He was prescribed a sulfonamide for his colitis. Unfortunately, Ralph had a reaction to the sulfa and “rashes appeared on my arms.” His doctor discontinued the treatment. Ralph was then treated with asacol, which helped, but he would develop stomach aches. When Ralph stopped the asacol, “the stomach ache went away.” He checked with his doctor, who then discontinued Ralph’s asacol and recommended citrusol or metamucil.
Now, Ralph has his check-up twice a year. Ralph’s most recent platelet count was 163,000 in June 2003. His average platelet count has been about 210,000. Out of habit, Ralph finds himself checking his forearms and legs almost every morning for red spots (petechiae). Ralph says, “I think about TTP once or twice a week.” He also notes that the worst things about re-thinking about his experience with TTP are the steroids, which induced cataracts in both of his eyes. Also he gained a lot weight as result of the prednisone. “At one point I was at 210-250 lbs.” The worst side effects of all for Ralph were “the personality change and mood swings.”
When asked what advice would be helpful for newly diagnosed TTP patients, Ralph replies, “It is important for the family to get explanation of what is happening.” The patient is usually very ill, so he does not know what’s going on with his disease. So when the family can explain what the disease is and what is happening to him, patients can better understand. For Ralph, “My first week in the hospital, I would wake up in the morning and try to talk to my wife but I was just talking gibberish. I was in and out with my state of mind. I was too sick to be scared. I recall having two full-blown grand mal seizures and when I woke up, I was tied to the bed. I would think, ‘What is happening to me?’” Ralph feels that if he had been provided with more information about some of the things that could have happened with TTP, “I wouldn’t have been so scared. I remember being so sick that I could not remember what was going on for a whole week. When I was tied to my bed, I felt as if I had no control with my life. It was pretty scary and I don’t know what I would do if my wife wasn’t there to help me.”
In answering the question, what was most helpful in your experience with TTP, Ralph replied, “One of the most helpful things, aside from trying to understand what TTP was, was the support from my wife, my work, and my boss. In the hospital, I was so happy to recover from TTP and just get back to my life.” Ralph feels that his hematologist was very helpful and reassuring with his compassion and knowledge. Ralph feels that the support he had received from his wife, his boss, and the TTP support group at the Oklahoma Blood Institute has been very helpful in his experience with TTP.
Ralph Update: December 2003
Shortly after the July 2003 update to Ralph’s story, he had a relapse of his TTP, his second episode.
The first sign that the TTP was coming back was the appearance of the little red or purple dots (petechiae) around his feet. Ralph noted them while he was getting dressed for work on Friday morning, August 15. His wife had already left for work and he didn’t call her. He felt perfectly well, so he continued to get dressed and went on to work. He worried about these purple dots and of course TTP immediately crossed his mind, but he was able to suppress the idea of TTP because he felt so well.
That afternoon, when he and his wife got home from work, he took off his shoes and socks; he says, “They were still there, in fact the red spots had traveled up a little bit to above my ankles”. Ralph and his wife wondered whether this could be an allergic reaction to lamisil, a medicine started for a fungus infection around his toes and toenails 30 days before. He had had blood tests for liver function to check for a reaction to lamisil on August 11, and these were normal. Blood counts, including a platelet count, were not done at that time. So Ralph’s wife called the dermatologist’s office; they told her that it seemed too long since the lamisil had been started for an allergic rash to appear. She was told that if the rash didn’t go away by Monday, to come into their office for a checkup.
Ralph and his wife felt comfortable enough to put off any other decision until the next day, Saturday. Ralph says that, “When I woke up Saturday, the purple spots were real obvious. They had traveled up a little further, I was nervous and my wife was too. We didn’t talk about TTP to each other. I think we were both thinking about it. We just didn’t want to admit it yet. I asked my wife, ‘What do you think they could be?’ Still, neither one of us talked about TTP. I guess we just had a false sense of security since it had been 3 years since my TTP. I just didn’t believe it could come back. We ended up looking at the purple spots all day Saturday.”
Ralph’s wife says that when she saw that the purple spots were still there on Saturday morning, and traveling up towards Ralph’s knees, she thought, “Oh boy. Here we go again. We were both kind of hoping it was the lamisil thing.”
Sunday morning Ralph still felt perfectly well, but the red spots had traveled up to his thigh. Ralph’s wife suggested, “Why don’t we call Dr. George?”, and immediately Ralph said, “That’s a good idea”. So they called Dr. George about noon on Sunday and reported the description of the petechiae and the absence of any other symptoms. They described the petechiae as not thicker than the day before, but not fading. Dr. George asked if there were any other symptoms of bleeding; there were none. He asked if the petechiae were anywhere else on Ralph’s body except for his legs up to his thighs; there were none. Dr. George also initially hoped that this could be just only low platelets, thrombocytopenia, caused by a drug reaction, and not recurrent TTP. But he was certain that Ralph was describing petechiae and thought that the platelet count would probably be very low. So he asked Ralph to go immediately to the hospital in his town and he called the hospital laboratory to arrange for a CBC. Ralph and his wife waited while the CBC was run, and then the technician came out and told them that the platelet count was 3,000. Ralph says, “We were very surprised that the platelet count was that low. That was as low as it had ever been with my first time with TTP. We were pretty certain that it was TTP then.”
Dr. George asked the technician to look at a blood smear through the microscope, and she reported that there were very few red blood cell fragments seen. Ralph’s hemoglobin and hematocrit were only slightly below normal, but certainly lower than they had been at the time of his previous blood count two months before. Dr. George also asked the laboratory to check the blood chemistry levels for evidence of hemolytic anemia, the other major component of TTP. These numbers were reported in about 30 minutes, and the LDH and bilirubin levels were very high, indicating that hemolysis (destruction of the red blood cells) was occurring. Therefore Dr. George was confident that Ralph’s problem was recurrent TTP.
Ralph says, “We were extremely disappointed, apprehensive, fearful, mad, all of those emotions. We asked Dr. George, ‘Can we go home and get some things before we got to the hospital?’. He said ‘No’, so we went straight to the city. In some ways, I think that made me feel better. We just got on with what we had to do. You could describe it as we got into an ‘attack mode’. When we got to the hospital, a doctor came down and got me and put me in a wheel chair and took me up to my room. There was some discussion about putting in the line for the plasma exchange, who was going to do it, and whether my low platelet count was a problem. By this time, Dr. George was there and told the surgeon there would be no problem, then the surgeon was just real confident and moved ahead. He put the large catheter in my groin and then put a heavy weight on top of it to prevent bleeding. There wasn’t any problem.”
“In addition to Dr. George, we saw another doctor at the hospital whom we had known three years ago. And then when the OBI nurse came to begin the plasma exchange treatment, she was the same nurse who had taken care of me before. It was just as if we had our friends back again. It was just like deja vu.”
Ralph rested well that night. He still had no symptoms other than the petechiae. The only other thing he described was some ringing in his ears, which he was concerned about because a similar sensation had happened three years ago just prior to his seizures. But this disappeared after a short time in the hospital and never recurred again. Ralph never had other signs or symptoms that can be associated with TTP. He never had confusion or any other neurologic symptoms. He never had abdominal pain, nausea, vomiting, or diarrhea. He never had weakness. The only symptom he had was the petechiae.
Because Ralph had had severe allergic reactions to plasma during his first episode, and because his first episode had been so difficult and prolonged, he was started on very high doses of steroids, at first 250 mg each day of IV methylprednisolone, increasing to 500 mg per day the following Monday. In spite of this Ralph had severe itching, hives, and redness of his skin after the plasma exchange treatments. After the third treatment these became worse and his skin was all bright red even 24 hours after the plasma treatment. His wife says that, “He was as red as a lobster. He wouldn’t let the OBI nurse hook him up. The regular nurse knew how to work with Ralph. The new lady didn’t know Ralph or how to work him through it. Ralph was convinced that something bad would happen if he began the plasma exchange. I think that the high doses of steroids made him more jumpy and fearful.” Dr. George finally convinced Ralph that he needed the plasma exchange. It was clear that Ralph was very agitated, almost paranoid from the high doses of steroids. But they were continued, with multiple doses of benadryl in addition, to control the allergic reactions.
Ralph’s platelet count began to respond after the second plasma exchange and was normal in 5 days, the following Wednesday. Then Ralph’s steroid dose was decreased again to 250, then to 100, then to 50 milligrams when he went home on August 25. He had had 9 plasma exchange treatments. The femoral intravenous catheter in his groin had been in for 8 days, and his platelet count had been normal for 4 days. It was thought that the risk for infection was too great to leave the catheter in any longer. There was discussion about whether to put in a new catheter in Ralph’s chest vein, which would have less risk of infection and could be left in place longer, but it was decided that this may not be necessary. It was decided not to put in a new catheter and not to give more plasma exchange treatments unless the TTP came back and Ralph’s platelet count fell again.
However Ralph’s platelet count stayed up; his steroid dose was gradually decreased; the steroids were stopped on October 8, 6 weeks after he left the hospital.
Ralph says, “I felt pretty good when I left the hospital. I didn’t go back to work for a couple weeks even though I didn’t feel as weak as the last time. I wanted to be sure that I was OK, and I wanted to wait until the steroid dose was manageable. The steroids make me cranky and I get mad and fly off easily. I didn’t want to go to work and blow up at any co-workers or the public.”
Ralph says, “There was no real scary stuff with this episode. Maybe we caught it earlier, though the platelets were as low as the last time. But there were no other symptoms. Maybe the real high doses of steroids really worked. It was easier this time because we didn’t have to explain everything to my family and friends. We didn’t have to go through all that again. We could just say, ‘OK, guys, it’s back’.”
“Now, I just tell people that I’m in remission. I’m doing fine again and feel well. But that second episode shatters any false sense of security. This could always happen again, but I think it may never happen again. It was bad to have a second episode, but it was good that we knew what was happening, the doctors were ready for us, and we got through this second episode a lot easier than the first time.”
Ralph Update: January 2007
We recently asked Ralph to update his patient perspective for this website. The following is his response:
“On September 17, 2003, I returned to work after my second episode of TTP. I was on a decreased dosage of prednisone a day. In dealing with the public, the lower daily dosage of prednisone allowed me to pretty much function as normal without most of the side effects."
“On October 8, 2003, I stopped taking prednisone and began living life as normal as possible again. I continued to have the same memory problems that I experienced after my first episode of TTP. I have days when I feel ‘right on’ as far as not experiencing memory problems or struggling for words that I want to use in conversation. Other days, I am just a little ‘off’ in memory and I struggle to remember specific words or phrases I want to use. Before the first episode of TTP, I always considered my memory to be above average. After TTP, it seemed my memory was average or below average. My memory has never seemed the same after the first episode of TTP."
“I seem to have a general overall lack of energy and initiative to do anything. I just seem to feel tired all the time. This generally goes on for extended periods. Then I will have a burst of energy and I really feel like doing things for a couple of days. Then the lack of energy and initiative begins again. It seems to be a cycle that repeats itself over and over again."
“In late April of 2005, I noticed what looked like a rash or petechiae just below the knee on my left leg. Since the petechiae I experience with TTP begins on my ankles, my wife and I decided that I would check it during the day and see how it looked when I got home from work. When I arrived home that afternoon, the rash or petechiae was about the same. It didn’t appear to be spreading but it wasn’t fading either. I was not experiencing any of the other symptoms".
“We immediately made the decision to call Dr. George. My wife called Dr. George and described the rash or petechiae. My wife also told Dr. George that there were no other symptoms present. Again, Dr. George made arrangements with a local hospital and the ER physician to do a CBC. My wife and I went to the hospital ER and I went through all the admittance paperwork just to have a CBC done. I was completely frustrated by the time I finally got a CBC. I finally met with the ER doctor and gave her my TTP history. The doctor commented that my wife and I were certainly knowledgeable about TTP!"
“The doctor then left the room to check on the results of my CBC. When she returned, she said she had good news! My platelet count was 187,000 and she believed the red spots were just a rash. My wife and I felt a relief that I can’t put into words! Instead of going to Oklahoma City to the hospital to deal with another round of TTP, we were going back home."
“I go to my regular doctor in Shawnee for regular quarterly follow-up visits for high blood pressure and other related lab work. A CBC has been a routine part of the lab work since my first episode of TTP. My last follow-up visit was in December 2006. My platelets were 170,000, which made me a little nervous. My doctor said all the other numbers looked good. But, it always makes me a little nervous when the platelets are below 200,000. I just try to put it out of my mind and avoid rushing to the lab for the several days to get a CBC."
“I retired on April 1, 2006, after over thirty years in law enforcement. I then went back to work in law enforcement on a part-time basis and will continue to work part-time for at least four years or more. Overall, I don’t have any severe medical problems and I feel good other than the lack of energy. My wife and I continue to live life pretty much as we did before TTP. I don’t consciously think about TTP that much, but I do check my ankles and forearms every day for petechiae. It has just become a habit.”
Ralph Update: October 2011
Since our last update of Ralph’s story in January 2007, he has had two further episodes of TTP.
On a Thursday in June 2008 he noted chills and fever. He had no other symptoms and assumed this was minor and transient. The following day he had chills and fever again, but again it was only transient. However that evening he noticed what may have been petechiae on his lower legs - but they were not clearly distinguishable from his chronic lower leg purpura related to his venous problems. He waited until Monday morning to go to his doctor’s office for blood counts. One reason he waited is that twice before, in 2005 and 2007, he had called his doctor for what he thought were petechiae and his platelet counts had been normal. However this time his platelet count was low at 31,600 and he was also mildly anemic, with a hematocrit of 38%. The low platelet count clearly indicated that his symptoms were caused by a relapse of TTP, Ralph’s third episode. However because he had no symptoms and the platelet count was only moderately low, we chose to treat him on the first day just with an infusion of plasma and high doses of steroids. Then the next day, when his platelet count fell to 11,000, it was clear that treatment with plasma exchange would be required. Ralph recovered quickly from this episode, requiring only seven plasma exchanges to get his platelet count back to normal.
Ralph’s fourth episode of TTP occurred seven months later, in January 2009. At this time he was extremely tired because of the effort that was required for him and his wife to move to a new home. Again he noted petechiae. His platelet count was 17,000. He required only eight plasma exchange treatments to achieve a normal platelet count. But this time in addition to steroids we used rituximab as a more intensive immunosuppressive medicine to try to prevent further relapses.
During the following two and one-half years, Ralph has had no further problems with TTP. However he has had other health problems. Most important has been heart failure. In May 2008, before Ralph’s third episode of TTP, he was evaluated for extreme fatigue and shortness of breath. An echocardiogram documented that the blood pumped out by his heart, described as the “ejection fraction” was only 10-15% (it should be over 50%). There were no blocks in his coronary arteries; therefore he did not have the typical plaques associated with heart attacks. Rather he seemed to have problems with circulation through the small vessels throughout his heart. This made us wonder whether these small vessel obstructions were related to his previous two episodes of TTP. This has not been described in other patients with TTP, but it seems to be a rational interpretation. Because of the persistent heart failure which causes a risk for heart rhythm problems and even heart arrest, Ralph had a “defibrillator” placed in April 2009. This is like a heart monitor, with wires from a battery under the skin of his chest to his heart to provide electric current required to restart his heart if an arrest occurs.In spite of these health problems, Ralph continues to work and when we visited together this month, he appears very healthy and happy.
Comments by Dr. George:
Ralph’s first episode of TTP was very severe. I was very worried during those first two weeks when he did not respond. I shared my concern in long discussions with Ralph and Sherrie. But then he began to respond – what an enormous relief. But then relief became frustration, as it seemed that we could never completely stop the plasma exchange treatments. I was very impressed by the severity of side effects that Ralph experienced with steroids. I was impressed that, given a choice, he preferred splenectomy to resuming daily prednisone! But the splenectomy was not necessary. I wonder how many other patients may have avoided splenectomy if their doctors had just persisted with plasma exchange treatments.
Eventually this episode of TTP resolved. We all hope Ralph does not have a relapse of TTP, but we know that his risk for relapse over the next several years may be as high as 30%.
The story of their good friends down the hall is poignant. The woman with TTP had come into the hospital the week before Ralph, and was doing well. She was at home and only in the hospital for plasma exchange treatment that Saturday when her cardiac arrest occurred. I thought she would die, but she also has recovered completely. These two couples remain close friends.
Update 2003: Ralph’s story of his relapse covers all the emotions that occur with the relapse of any illness. After recovery from a first episode, patients feel they have escaped. They are hopeful but a bit apprehensive. And with the passage of time, the apprehension diminishes and confidence grows. A relapse is a confidence shattering event. However for Ralph, the successful treatment of his second episode helps to rebuild confidence. In addition to the effect of this relapse on Ralph, it is important to appreciate the effect on his friend, the woman who also had TTP at the same time as Ralph’s first episode. This woman and her husband have been good friends of Ralph and his wife ever since that first episode. They visited Ralph in the hospital last August. Ralph says that he and his wife have never talked directly to their friends about whether his relapse caused them great concern that she could also relapse. This is the same as Ralph and his wife not talking directly to each other about TTP on the Saturday morning, when the petechiae were more evident. Sometimes things like this are just too difficult to talk about. Sometimes it may even be better if they are not said. But sometime reality has to be faced.
At this time Ralph and his wife are doing fine. I think they are very comfortable with their situation. Ralph has recovered completely. They are busy with their careers and they don’t dwell on the risk for another episode. But if they see petechiae again, they probably won’t wait two days the next time.
Update 2007: Ralph continues to do well. We visit at the patient meetings that we have at the OBI, and we keep up to date with occasional emails. Although we are all alert for another episode of TTP, everything now seems almost back to normal. However on some days Ralph still senses that his balance is not quite right and he has trouble remembering things or finding words.
With serum that we saved from the beginning of his TTP episodes, we have determined that Ralph’s TTP was associated with a severe deficiency of an enzyme that normally prevents clumping and clotting of blood platelets, the abnormality of TTP that blocks blood circulation through the smallest blood vessels. (This enzyme is called ADAMTS13.) This type of TTP sometimes requires more than just plasma exchange to achieve a durable remission. If we were treating Ralph’s initial episode today, we would add additional medicines, such as rituximab, and hopefully the TTP would respond more quickly.
Our experience now is that about half of patients like Ralph, whose TTP is associated with a severe deficiency of the enzyme, ADAMTS13, will have a relapse, another episode of TTP. Almost all of these relapses occur within the first four years. Fortunately most patients have had only one relapse. So we are hopeful that Ralph and Sherrie have seen the last of TTP.
[First written September 2001. Last updated October 2011.]
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