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Calvin’s Story

Quinine-Induced Thrombocytopenia in a 68 Year-Old Man

December 1995

Calvin, a 68-year-old man, was urgently transferred by a Mediflight helicopter from his small regional hospital to a large urban hospital on December 20, 1995. He had developed severe bleeding symptoms with a nose bleed that would not stop, multiple bruises and hundreds of tiny red dots (the red dots, mostly around the feet and legs, are small hemorrhages called petechiae), and blood blisters in his mouth. His platelet count was extremely low, almost unmeasurable, at 2,000 (normal platelet counts are 150,000-350,000). Therefore it was clear that his extremely low platelet count was the cause of his critical bleeding problems. It was assumed that his low platelet count was caused by idiopathic thrombocytopenic purpura (ITP).

The diagnosis was assumed to be ITP because Calvin had been previously diagnosed with ITP in 1988. At that time he had been treated with steroid medications but he did not achieve a sustained response. Therefore surgery to remove his spleen was required in 1988. Calvin had an excellent response to removal of his spleen. After his surgery, his platelet count became normal and he required no more treatment. He had no more bleeding symptoms until this episode on December 20, 1995. Calvin had a heart attack in January, 1995. After he recovered from this he underwent surgery for bypass grafts around the diseased sections of his heart arteries in March, 1995. The surgery had no complications, no bleeding problems, and his platelet count remained normal. The first time Calvin had problems again with his platelets was this bleeding episode on December 20, 1995.

After Calvin arrived at the medical center by helicopter, he required urgent treatment with platelet transfusions and intravenous gammaglobulin. These treatments had no effect on his platelet count for two days, but then his platelet count increased to 44,000 on December 23. He went home that day.

As part of his evaluation during his 3 days in the hospital, Calvin was asked about any medications that may have contributed to the sudden and severe decrease of his platelet count. He had been taking glucotrol to control diabetes, which had been diagnosed 7 years previously at the time of his ITP. He was also taking clonidine and hydrochlorothiazide for high blood pressure. He was taking aspirin as a treatment to prevent further blood clots related to his heart attack. And he was taking multiple medications for arthritis, including advil, cayenne pepper pills, arthrx (which Calvin described as “horse linament”), and occasional quinine tablets for night-time leg cramps. Calvin had taken quinine for malaria during his military service in Okinawa during the Korean War. The next time he took quinine tablets was when had been given a prescription for quinine for his leg cramps in April 1995. He had taken quinine only occasionally over the past 8 months.

Appropriately, Calvin’s doctors told him to stop all of these medications. It is possible to have an allergic reaction to any medicine that can cause thrombocytopenia. His blood pressure was in a normal, safe range so he did not need any further treatment for high blood pressure. He was started on steroid medications for his low platelet count, and the steroids would be effective treatment for arthritis so he did not need the arthritis medicines either. He was given insulin to control his diabetes so that he could stop the glucotrol tablets. When Calvin’s bleeding stopped and his platelet count returned to a safe level, he went home with instructions to take only the insulin injections for his diabetes and prednisone (steroid) tablets for his ITP.

Calvin’s platelet count was normal in his doctor’s office on December 27 (379,000), 4 days after he was discharged from the hospital. But the following day, December 28, Calvin had another critical episode of bleeding symptoms and an extremely low platelet count – 5,000. Again Calvin was urgently admitted to the urban medical center and treated with intravenous gammaglobulin and high doses of steroids. Again he recovered promptly and was able to go home in 3 days, on December 31. Again, he had a perfectly normal platelet count in his doctor’s office – 302,000 on January 3. But again, he had an abrupt, sudden recurrence of severe bleeding symptoms with a platelet count of 3,000 on January 6. Again he was urgently admitted to the hospital.

Because of Calvin’s past diagnosis of ITP 7 years before, which had been serious and had required a splenectomy, and because there were no other apparent causes for the extremely low platelet counts, ITP was still considered to be the correct diagnosis. Therefore additional treatment for the ITP was added, cytoxan, a form of chemotherapy tablets that are effective for ITP.

But Calvin’s intermittent bleeding problems continued. His fourth episode occurred on January 15 with the sudden onset of bruises appearing all over his body and continuing nose bleeding. However this time, after three hospitalizations for the same symptoms, Calvin did not even contact his physician and expected that the bleeding symptoms would stop, even if he just stayed home. He was correct, because the bleeding stopped within two days. Calvin could tell exactly when his bleeding became worse and better by noticing how long it took for the bleeding to stop after he did his own finger pricks with a needle to measure his blood sugar and adjust his insulin. On January 17, 2 days later, he was well again.

At this time his doctor recommended that he see another hematologist, Dr. George in Oklahoma City, even farther from his home, to help investigate this very unusual occurrence of repeated critical episodes of low platelet counts.

Dr. George was very suspicious that the diagnosis of ITP was wrong, because ITP in adults is typically a steady, persistent disease, not a disease with wide, sudden swings of platelet counts, from normal to extremely low, and back and forth. He felt certain that something Calvin was taking, eating, or exposed to was the cause of these sudden low platelet counts. He was suspicious that this was some medication Calvin was taking, and he was particularly suspicious of the quinine tablets that Calvin had taken for leg cramps. This is because quinine is the most common drug that causes allergic reactions that result in low platelet counts, termed drug-induced thrombocytopenia.

Therefore, rather than have Calvin make an appointment to travel the long distance to his office, Dr. George called Calvin on the telephone. They began with a conversation about Calvin’s work as a school bus driver, his general good health, and the details of the serious problems over the previous four weeks. When the doctor asked Calvin what medicines he was taking, Calvin replied, “None. My doctors told me to stop all my medicines. I only take prednisone and insulin”. Then, when Dr. George asked him if he had taken any quinine tablets during the previous four weeks, Calvin replied, “Yes, I have. But I only take quinine when I need it for severe leg cramps.” When Calvin was asked why he had continued to take quinine when his doctors had told him to stop all of his medicines, he replied, “Well, I didn’t think these quinine tablets could hurt me.” Calvin could not recall exactly when he had taken the quinine tablets, and he could not be sure that he had taken the quinine tablets exactly before each episode of bleeding symptoms suddenly began. But Calvin did say that he had taken several tablets during the spring, summer and fall of 1995, after he had been give the prescription in April, and then probably several tablets during the recent weeks when he had his severe bleeding problems. This information supported the previous diagnosis of ITP made 7 years before, when he had not taken any quinine tablets. But it also supported the diagnosis of quinine-induced thrombocytopenia, not ITP, at this time.

Therefore Dr. George told Calvin on January 18 that quinine was the probable cause of his recurrent episodes of severe bleeding and low platelet counts, that he should immediately throw away all of his quinine tablets, and that he should never take quinine again. Dr. George predicted that he would not have any more bleeding problems. If this was true, then he could gradually decrease his steroid tablets and resume the other medicines that he had been taking for diabetes, high blood pressure, and arthritis. And he did not have to travel to Oklahoma City.

Three days later, on January 21, Calvin called Dr. George to say that he had had another episode of bleeding beginning on the morning of January 19. He had seen his doctor in his local community that morning, his platelet count was 4,000, and he had been hospitalized and treated with intravenous gammaglobulin and a platelet transfusion. Dr. George asked Calvin, “Did you take another quinine tablet before this happened?” Calvin, replied, “Yes, I did. On Tuesday night (January 18). My leg cramps were real bad and I thought that just one tablet couldn’t hurt me”.

That finally solved the mystery of Calvin’s severe bleeding problems. Then Calvin actually did throw away all of his quinine tablets and he has never taken one again, and he has never had bleeding problems or a low platelet count again.

Calvin was instructed on nutrition supplements that contain cinchona, the natural tree bark from which quinine is derived, and drinks such as tonic water and Schweppes Bitter Lemon, that contain quinine. Although the quinine concentration in these products is low, it is enough to cause severe low platelet counts and critical bleeding in patients who are sensitive to quinine.

Calvin Update: December 2003

For the past 8 years, Calvin has been well, except for a time in the hospital for heart trouble in January 2003. He says that, “The doctors didn’t need to do any procedures. They controlled it with medicines.” Calvin lives with his wife of 47 years. Calvin says, “My wife takes good care of me. I’m in pretty good shape for a man of my age”. Currently 71 years old, Calvin works at a juvenile prison as a counselor and guard. His job is to maintain discipline and this is a physically demanding job, as it sometimes requires him to break up fights. Recently, Calvin was caught in a fight that resulted in a hip injury. He says, “I have a pinched nerve in my hip and I see both a medical doctor and a chiropractor. I wear a girdle for support and I am on several different kinds of pain pills.” However Calvin has been able to return to his work serving as a counselor. He says, “The job of breaking up fights has been assigned to younger guards”.

During all of this time Calvin since the cause of his bleeding problem was discovered, Calvin has been very careful about his food and drinks, and he takes extra precaution to avoid quinine and quinine-containing products. He says, “When I buy food at the grocery store, I read the label to see what is in it. It takes me longer to go grocery shopping than most people because I read the labels to make sure there is no quinine in it.” Also he does not drink tonic water or Schweppes Bitter Lemon.

Although Calvin clearly understands the danger of quinine for him, and he understands that reactions to quinine caused his severe low platelet counts and bleeding, he refers to these episodes as, “my ITP”. But he makes sure that doctors or pharmacists are always aware that he has had severe allergic reactions to quinine. Calvin says, “I keep a little card that has all the information about my ITP, my diabetic condition, and my heart problems. My little card also lists all the medicines I take. The doctors always make a copy of my card, and they tell me that I’m very well prepared. I tell them that I don’t want no more of that ITP! Whenever I get a new prescription, I ask the doctors about quinine. I’m not a bit bashful when it comes to my body – the doctors are always very cooperative.”

Comments by Dr. George

Calvin’s story is very important. It is important for all patients who have low platelet counts, to recognize that allergic reactions to medicines can cause low platelet counts. It is important because allergic reactions that cause low platelet counts may occur not only with regular prescription medicines, but also with any medicines that people buy themselves at a grocery store and that they regulate themselves. It is important because allergic reactions causing low platelet counts may also occur with herbal remedies, food supplements, and even foods themselves. Calvin’s story is also important for doctors, because questions to their patients asking about medicines, and directions to their patients to stop all medicines, may not be sufficient. Patients may assume that their doctors are only interested in the prescription medicines that they or other doctors, had prescribed. Patients may assume that their doctors are not concerned about medicines that patients buy themselves, or regulate themselves for occasional symptoms.

Because quinine is the most common cause of drug-induced thrombocytopenia, doctors must always specifically ask about quinine, and remedies that contain quinine or the natural substance from which quinine is derived, cinchona. Asking a patient what medicines he takes, and instructing the patient to stop all of his medicines, is not enough.

In my experience, Calvin’s story has been repeated many times in other patients. Doctors have made the diagnosis of ITP when the platelet count is very low and bleeding symptoms have occurred, and when other causes of the low platelet count are not apparent. Doctors have assumed that the routine evaluation, including a question about medicines and directions to stop all current medicines, is enough. But if patients are not asked directly and specifically about quinine tablets, that evaluation is not complete. I am aware of other patient stories where ITP has been the assumed diagnosis, patients have received intensive treatment, and even surgery to remove the spleen has been performed . . . only later to recognize that allergy to quinine was the cause of the low platelet count.

Therefore this is the lesson that Calvin’s story teaches us. Think about quinine.

Update 2010:

We tried to contact Calvin in December 2010, but he had moved again and we could not locate him. We assume that he has had no more quinine-induced thrombocytopenia because he learned to be so careful with any medication, including all non-prescription, over-the-counter medicines, and all drinks.

[First written July 2004. Last updated December 2010.]


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