ITP in a woman who experienced severe bleeding, severe problems with steroid treatment, and then responded to splenectomy
In December of 2000, Rosie, a 46 year-old mother of three, was preparing for Christmas and the wedding of her only daughter. She had, for several months, noticed increasingly heavy menstrual periods. Sometimes the periods were so heavy that it "was difficult to leave the house for a couple of days". Rosie attributed this to her age and approaching menopause, but her friends had never heard of such heavy bleeding. Then she began to notice bruises on her thighs. The bruises were round and eventually began to form on her hands and forearms as well. "I would take a bath at night and there would be no bruises, but in the morning they would be all over my thighs." "I just thought I was anemic," Rosie admits. She never had other bleeding symptoms, such as nosebleeds or gum bleeding when she brushed her teeth.
When Rosie realized that her next menstrual period would be at the same time as the wedding of her daughter, she went to her gynecologist. Her doctor was concerned by the excessive bleeding and bruising, so a complete blood count (CBC) was performed, which revealed very low platelets (17,000, normal is over 150,000). At this point, Rosie was referred to her internist, who had known her for many years. Because all of her other blood tests were normal and because Rosie was in otherwise excellent health, he appropriately made the diagnosis of ITP (idiopathic/immune thrombocytopenic purpura). Rosie was then referred to a hematologist. The hematologist provided information and described the treatment plan for people with ITP. Treatment begins with steroids, typically prednisone, which usually increases the platelet count. If the patient does not respond to prednisone, or if the platelet count falls again when the prednisone dose is decreased, then a surgeon can perform a splenectomy (remove the spleen).
On Thursday, the 11th of January, Rosie began steroid treatment with prednisone, 80 mg once daily. Rosie expressed her concern to her doctor about the possible side effects of steroids, as she was in the last week of preparations for the wedding of her daughter, on Saturday, January 20th. Her doctor expressed sympathy for her situation but stressed to Rosie the importance of beginning the treatment, as her platelet count was now only 11,000, and she had had symptoms of excessive bleeding and bruising.
Rosie claims that the side effects of steroids were the "worst part" of her illness. She says, "The biggest thing was not being able to sleep." She would only sleep for an hour at a time, causing her to stay awake for long periods during the night hours. With nothing to do, and being unable to sleep, she began to take on night projects around the house. One example was the reorganization of the kitchen cabinets. Her "inability to stay focused" would then cause her to leave the project unfinished. The end result of one project was a kitchen with the cabinets emptied into a pile in the middle of the floor, leaving the reorganization for her husband upon his waking for work, at 6:30 am the next day. Other side effects of the steroids began to develop after a few weeks to months. She was "unable to remember things." She "felt hot all of the time", and developed blood pressure as high as 195/120. The high blood pressure resulting from the steroid treatment was a particular concern because high blood pressure increases the risk for brain hemorrhage, even in people with normal platelet counts. In Rosie, the combination of high blood pressure and very low platelets was dangerous, so additional treatment to control her high blood pressure was begun. Also she began to develop some physical changes associated with the steroid treatment. A condition she refers to as moon-face, and the development of a small hunch-like hump between her shoulders, on her back. She describes these effects as "very disruptive" to her lifestyle. However the prednisone did cause a modest increase of her platelet count to 43,000
With all of this going on, Rosie managed to prepare for her daughter’s wedding. Everything went as planned and was wonderful. The only inconvenience was that her menstrual period had begun on schedule and was very heavy; "I was excusing myself to the restroom often." Then on Sunday, the day after the wedding, Rosie spent the entire evening in the bathtub due to extremely heavy menstrual bleeding. Her doctor called in a prescription for progesterone to stop the menstrual bleeding; it slowed down the next day. On Monday she saw her doctor: her platelet count, which had slowly risen to 43,000 with the prednisone, had dropped to 5,000. Her doctor gave her a new steroid, methylprednisolone, 1000 mg in an IV solution each day for three days. After this treatment, her platelet count increased to over 100,000, but within three days, Rosie’s platelets began to drop again.
In an attempt to avoid splenectomy, Rosie’s doctors prescribed an IV infusion of anti-Rh(D) on February 2. This is a type of immune globulin, similar to the Rhogam given to Rh(D)-negative pregnant women, which can decrease platelet destruction in the spleen and increase platelet counts in patients with ITP. Rosie responded better than expected. Her platelet count increased from 3,000 to 128,000 after three days, and then kept going up for 4 weeks reaching a high of 223,000. Her doctor thought that this might be a long-term remission and that she might not need splenectomy. At this time, Rosie insisted that her prednisone dose be decreased due to the extremely disruptive and overwhelming side effects. Even though Rosie had had severe problems with menstrual bleeding, she felt that the side effects of the prednisone were worse than the ITP itself. The prednisone dose was decreased and on March 5, when her platelet count was 223,000, she took her last dose.
The following day, Rosie began to notice symptoms suggesting a crash in her platelets. She had spontaneous bruising, vaginal spotting, and bleeding gums. It was decided to try a second round of the anti-Rh(D) immune globulin. This time, her platelets began to rise, but not as dramatically as the first time. Her platelet count rose from 9,000 to 65,000 on March 21.
On March 27, 11 days after the second anti-Rh(D) dose, Rosie awoke late at night with an extremely painful headache. She describes this as "the worst headache of my life". The headache began in her temple, on the right side of her head, and became "progressively worse". Rosie was in so much pain that she says that she was not worried about brain hemorrhage, she just needed the pain to go away. Her husband was very frightened. They were aware that the most terrifying risk to any patient with ITP is the possibility of an uncontrolled brain hemorrhage, so Rosie’s husband rushed her to the local emergency room.
She remembers being worried on the way to the hospital, but what worried her most was the notion that she may have to take steroids again. Upon arrival, "the doctors did not know how to treat me". Her platelet count was only 2000. After some confusion and some phone calls, Rosie was given 250 mg of IV methylprednisolone and a platelet transfusion. She then had a CT scan of her head, which was normal; she had not had any brain hemorrhage. When asked about the scan, Rosie downplays how scary the whole situation was to everyone. Her major concern was not the results of the scan and she did not care what was going on, as she was overwhelmed by the pain. She was admitted to the hospital, her pain was controlled. Six hours after she arrived at the ER, the platelets, which had been requested for urgent transfusion, finally arrived. It took that long for them to be driven from the city to her hospital. The pain was almost gone the next morning. The cause was not known; just a very severe headache, probably unrelated to ITP or its treatment.
The next day, she returned to the hospital in the city as an outpatient, where she received treatment with IVIg (intravenous immune globulin). During the administration of the IVIg, Rosie began to have a severe headache again. This time it occurred in the back of her head. It quickly grew into "the worst headache of my life," even worse than the headache the night before. In addition to headache, the back of Rosie’s neck became uncomfortably stiff. Because of the headache, the treatment infusion had to be slowed down and could not be completed. The next day she completed the IVIg treatment.
Because of Rosie’s serious symptoms, and her decreasing responses to treatments, she had a splenectomy on March 30. The splenectomy was done by laparoscopy, avoiding a large open incision in her abdomen and allowing her to recover from surgery more quickly. Her platelet count, which was at 64,000 just before surgery, increased to 346,000 over six days. Was this a response to splenectomy, or only to the IVIg? Rosie had her platelets checked often after the surgery, and she was very sad as they steadily decreased, reaching 51,000 on April 25. It was clear that the very high platelet counts after surgery were only a response to the IVIg. She wanted to believe her doctor when he told her that a normal platelet count was not so important, that she only needed to have a safe platelet count. Her doctor also told her that patients who respond to splenectomy do so within a week or two; now it was almost a month after surgery, and her platelet count was going steadily down. But then a surprising thing happened. Her platelet count turned around, increased, and became normal!
When asked about the changes in her life caused by ITP, Rosie had some very optimistic responses. "I am a lot more thankful for every healthy day," she replied with a smile, "although I am still often tired." Rosie also exclaims that ITP has made her "more compassionate, more appreciative, and a better person". She is thankful for all of the friends and family who have supported her, and she is also thankful for the new friends she has met throughout the experience.
Advice that Rosie would offer to someone with a new diagnosis of ITP: "Be patient." She believes that it is only a matter of time before "they’ll get you on a right combination, and you will get better." She also adds, "Avoid steroids if you can, they are the worst part."
Rosie update: June 2003
Since the laparoscopic splenectomy and her platelet count reaching normal values (over 150,000), Rosie has been doing well. Her platelet counts remain high with the last count at 395,000. In her daily activities, Rosie said, “I am cautious” to avoid bruises. Family life has been good with an addition to the family, a grandson, whom Rosie is very excited about.
When asked what has been most helpful in her experience with ITP, Rosie recalls that her hematologist has been most supportive. Rosie believes that it is important to have a calm, helpful, and knowledgeable doctor who would work with her throughout her treatments. She feels that having a calm and caring physician who provides consistent reassurance makes that process easier.
It has been over two years since her splenectomy and Rosie has not had any recurrence of ITP. In fact, her lowest platelet count has been 344,000, but she averages around 390,000. Rosie gets her platelet count done with her annual physical exam. In addition to the annual tests, she would go for a check-up if she feels sick or if bruises appear, but that hasn’t happened. Rosie says that “now I don’t think of ITP much;” whereas in 2001, she notes that she was a lot more sensitive to the possible recurrence of ITP.
Given her experience with ITP, Rosie offers two suggestions to others with ITP. First, it is important to be educated about ITP. Rosie adds, “With more knowledge about ITP, the less you’ll be afraid of it.” Also, she notes that “ITP patients should try to understand the information about the disease and don’t be so alarmed by it.” Rosie expresses the value of a supportive and calm doctor who could provide the education to patients about ITP. Rosie’s other advice is to get to know someone or to read about someone who also has had ITP. For Rosie, these examples make the information on ITP more understandable and relevant.
Rosie update: September 2006
Happily, Rosie has little ITP-related news to report since her last update in June 2003. Rosie gets her platelet count checked annually, and her platelets have remained normal since June 2001.
The symptom that led to Rosie’s diagnosis of ITP, heavy menstrual bleeding, continues to be a problem. This led Rosie to undergo an endometrial ablation in January 2006. This is a procedure in which the lining of the uterus is removed in order to greatly reduce or eliminate menstrual flow. Endometrial ablation is an alternative to having a hysterectomy (surgical removal of the uterus) for heavy menstrual bleeding. Since having the ablation, Rosie is happy to report that she no longer has to schedule her life around her periods!
When Rosie was diagnosed with ITP she began taking steroids. This is the usual treatment for people with ITP. One of the side effects of steroid use is loss in bone density (also known as osteoporosis). After three of Rosie’s teeth cracked three years ago, she underwent a bone mineral density test that showed that she did have some bone density loss. This wasn’t necessarily completely due to the steroids she took for her ITP, but the steroids could have contributed to the problem. Women and men can gradually start to lose bone density as they age. To prevent any further loss in bone density and to try to prevent any bone fractures, Rosie started taking a bisphosphonate. Bisphosphonates are drugs that slow bone loss while increasing bone mass, and may prevent bone fractures.
Rosie no longer thinks about ITP often, but she is aware of how long a scrape or cut bleeds. She states that when her counts were low, any cut or scrape would bleed for a long time. “Now, I gauge my platelet count by how quickly I stop bleeding,” she says. Rosie had a splenectomy in March 2001 in an effort to increase her platelet count. After her surgery, she was concerned about getting sick since people who have had their spleen removed are at a higher risk of infection than they were previously. This year, she had her first illness (an upper respiratory tract infection) since her splenectomy five years ago. It was very minor and resolved promptly.
Rosie and her family are doing well. Her daughter is about to have her first baby, so Rosie’s fourth grandchild is on the way. She states, “My family is wonderful and my life is better than I deserve. I am a blessed woman.”
Comments by Dr. George
Rosie’s story contains many important lessons for patients with ITP.
First, the onset of her symptoms of excessive bleeding and bruising were gradual and easily ignored. Rosie felt perfectly well; ITP causes no symptoms except for increased bleeding and bruising. The only function of blood platelets is to prevent bleeding, and having too few platelets increases the risk for bleeding. That’s all. Rosie’s gradual onset of bleeding symptoms is typical for adults with ITP, but different from the onset of ITP in young children. Childhood ITP usually occurs before age 6 and the beginning is usually abrupt; an active healthy child is suddenly covered by bruises and petechiae. Sometimes a day-care aide, school teacher, or nurse my suspect child abuse; this is a wrong impression that creates extreme stress. Childhood ITP is also distinct from ITP in adults because most children will recover without any treatment, within several weeks to several months. In adults, ITP is typically a long-term illness.
Second, the diagnosis is usually straightforward, even though there are no laboratory tests that specifically document ITP and exclude other causes of a low platelet count (thrombocytopenia). In an otherwise healthy person who is taking no medicines or health food supplements, whose routine physical examination is normal (except for possibly bruises and other signs of bleeding), and whose routine laboratory data are normal except for a low platelet count, ITP is the appropriate diagnosis. No further evaluation is required. Signs of bleeding are typically on the skin and the mucous membranes of the nose and mouth and excessive menstrual bleeding - which was so dramatic in Rosie. Skin bleeding is described as "purpura" (bruises, often occurring without any remembered bumps), "ecchymoses" (also a term for extensive bruises), and "petechiae" (the tiny red hemorrhagic dots caused by leakage of blood from a small blood vessel, leaks normally sealed by platelets).
Perhaps the most important part of the laboratory evaluation is the direct examination of the blood cells. This is done by preparing a thin film of blood on a glass slide, staining the blood film with a mixture of dyes that develop specific colors for each type of blood cell, and examining the stained blood film with a microscope. In ITP, the blood should be normal except for the decreased number of platelets. The red blood cells and white blood cells are normal in number and appearance. The remaining platelets are normal in size; the presence of giant platelets suggests the possibility of an inherited problem of platelet production. Occasionally, perhaps in 1 of 1000 normal people, platelets clump in the tube used to collect blood for routine counts, and the reported platelet count is falsely low. Without examination of the blood film to actually see the clumped platelets, this harmless occurrence can be mistaken for ITP.
If all of these observations and results are consistent with the diagnosis of ITP, a bone marrow aspiration may not be necessary. If there are unexplained abnormalities of the red blood cells or white blood cells, a bone marrow aspiration is appropriate to be certain that the production of blood cells is normal. In patients with ITP, the bone marrow examination is normal. Although an important cause of the low platelet counts in ITP is increased destruction of circulating platelets, the bone marrow production of platelets is often also insufficient. Normally the bone marrow should increase platelet production to compensate for the more rapid destruction. In patients with ITP, platelet production is often not as effective as it should be.
The third lesson is Rosie’s experience with a severe headache at a time when her platelet count was very low. This is the most feared symptom for all patients with ITP. Although the ER doctors in her small community hospital had no experience with ITP, their management was exactly correct: urgent platelet transfusion and IV steroid (IVIg would also have been given if it had been available) followed by a CT scan to diagnose or exclude brain hemorrhage.
The final important lesson from Rosie’s story is her experience with the treatment. The story of Rosie’s treatment is familiar to most all patients with ITP. Prednisone pills or an equivalent steroid preparation are always the initial treatment for adults - inexpensive and simple to take. Most patients respond with an increased platelet count, but Rosie responded only incompletely and transiently. In most patients, thrombocytopenia recurs when the prednisone dose is decreased. The side effects of the steroids are not immediately dangerous, but they can be devastating. Rosie’s experience is common, and it is echoed in the experiences of several other patients in this series of Patient’s Perspective Stories, both with ITP and TTP.
It is an important lesson for physicians that patients often feel that the treatment of ITP is worse than the disease itself. Since the goal of the treatment is not to cure ITP, but only to prevent the risk for major bleeding, patients whose platelet counts are not severely decreased may be better off with no treatment - managed only with reassurance and careful follow-up. The key phrase in this recommendation is: "…whose platelet counts are not severely decreased". How low can a platelet count be without causing risk for dangerous bleeding? In an otherwise healthy young person, platelet counts as low as 10,000 to 20,000 may be safe. Therefore it is commonly recommended that patients with ITP and platelet counts greater than 30,000 (to provide an additional margin of safety) may not require treatment. But older patients who may have other diseases, such as high blood pressure, which can increase the risk for bleeding in the brain, may need higher platelet counts to provide safety.
Rosie’s experience with treatment documents (1) the emotional disturbance caused by steroids, (2) the optimum response with the first dose of anti-Rh(D) but only a brief response to the second dose, (3) the response to IVIg but also the common side effect of a severe headache and neck stiffness, symptoms which can cause alarm because they may suggest brain hemorrhage, and finally (4) what appears to be an excellent response to splenectomy. Typically excellent responses to splenectomy occur promptly after surgery, within two weeks. Rosie’s delayed response caused concern, but now her platelet count is normal. We hope it will remain normal, and it most likely will, but there is always a chance that her ITP will return.
Since 2001 there are new treatments for ITP. Although the sequence of treatments Rosie received is still the most common treatment plan today, a drug called rituximab is increasingly used for patients who do not have a durable platelet count response to initial steroid treatment. Rituximab is a relatively safe drug that suppresses the antibody that is destroying platelets. Initial experience suggests that it is not as effective as splenectomy. Several new medicines that increase platelet production in patients with ITP are being developed. When they are approved they will be helpful for patients like Rosie.