The 38-year-old woman made it to her car before she broke down in tears. A wife and mother of three, she was about to start her third year as a medical student at the University of Maryland in Baltimore. But before that, in just a few days, she was supposed to defend her dissertation to complete the research component of her combined M.D.-Ph.D. program. Now one of her doctors, a hematologist, had just suggested she postpone everything. She needed a bone-marrow biopsy right away. And the results of that biopsy, the doctor told her ominously, could have major implications for her career and her life.
He wouldn’t say what he was worried about, but the answer seemed clear: cancer. What else could merit such a dramatic suggestion? She allowed herself a few minutes to feel sad and briefly mourn everything she could lose. Then she dried her face, blew her nose and, as she drove home, came up with a plan. From her driveway she called her uncle — a cardiologist in town — to get his advice.
Perilously Low White-Blood-Cell Count
Six months earlier, she told her uncle, she went to a new primary-care doctor, who sent off some routine blood work. A couple of days later, she received a call saying that one part of her white-blood-cell count — her neutrophils — was low. It was probably a lab error, or maybe she’d had a viral infection that knocked it down; she should be retested in a few weeks. But then Covid-19 hit, and everything came to a standstill.
She finally got around to having the recommended test months later. When her doctor called with the results, he also had a referral. She needed to see a hematologist. Her white count was now dangerously low.
If white blood cells are the armed forces defending the body from outside invaders, the cells she was missing, the neutrophils, are the Marines, the fiercest first-line defenders against almost any infection. A normal count is over 1,500. Her first count had been low at 1,000. Now it was 400. The risk of infection skyrockets in patients with counts below 500. She saw the hematologist, she told her uncle, and he had told her to hold everything — indefinitely.
Her uncle was quiet for a moment. She needed a second opinion; he would call her right back. An hour later, he called with a name and a number: Dr. Sandrine Niyongere, a relatively new hematologist at the university, who came very highly recommended.
When the woman called Niyongere’s office to make an appointment, the doctor herself got on the phone. She had reviewed the patient’s records and had a few questions. How did she feel? Was she sick? Tired? Did she feel bad at all? No, the patient reported; she felt fine. That was why it all seemed so strange. How could she have whatever terrible thing this doctor thought she had and feel just fine? The doctor asked again if she was tired. Of course she was tired! She had three children and had been working crazy hours to complete her research and her dissertation so she could continue her medical training on time. But did that mean she had a life-threatening disease?
“Go defend your dissertation,” Niyongere encouraged the woman. She would see the patient after her dissertation defense. “We’ll figure this out,” she said.
Just One Medication
The student’s defense was on the following Tuesday. She thought it went well. Then, just before 5 p.m. that Friday, she arrived at the university’s cancer center. Despite the airy modern lobby, just entering the building felt oppressive and heavy with unthinkable possibilities. And because of Covid-19 restrictions, she would have to face them alone.
In Niyongere’s office, she first spoke with a trainee, who disappeared after taking a full history and performing an exam and then returned with the young doctor the patient had spoken to over the phone. A distant part of her brain observed that her doctor was younger than she was.
The hematologist sat across from the patient and slowly laid out what she knew. In someone who is otherwise healthy, whose other types of blood are fine, this kind of severe drop in neutrophils — what’s known medically as neutropenia — is usually caused by a medication. There were other possibilities, of course. Nutritional deficiencies could do this. Insufficient vitamin B12 or copper could affect blood counts. Some viral infections — H.I.V., mono, hepatitis — could, too. And they would look for those. But her money was on a medication. The doctor knew that the only medication the patient took regularly was Adderall; she had a history of A.D.H.D. And Niyongere hadn’t found anything in the medical literature linking this drug with neutropenia. Still, the hematologist insisted, it was the most likely cause of her isolated neutropenia.
They would look for infections. They would check her levels of vitamins and minerals. And if all these were normal, the next step would be a bone-marrow biopsy. The doctor expected it to be normal — with lots of blood cells of all types being made and released. Her first hematologist was right that a cancer or disease process affecting the production of these vital defenders was possible — but it was very unlikely, in Niyongere’s opinion, given how healthy the patient looked and felt. Meanwhile, she should stop the Adderall.
The Tests Come Back
The following week was busy as the student prepared to restart the medical-school part of her education. In just a few days, she would be in the hospital learning to care for sick patients, and she needed her immune system to be up to the task. She watched as the test results came back. The vitamin levels were normal. She didn’t have any of the viruses. And so that Friday the student went back to Niyongere’s office for a bone-marrow biopsy. The doctor suggested doing it in the hospital operating room with sedation. No, the patient insisted. They would do it in the office. It was a tough procedure, but the patient wanted to get it over with. She needed an answer and some more neutrophils before she could safely be around the sick patients she would see in the hospital.
The results came back faster than she expected. A wave of weakness forced her to sit down as she read the results: normal. There was no sign of leukemia or any of the other processes that could affect her body’s ability to make neutrophils. And she was making a healthy amount of all the white blood cells, including neutrophils. That meant that whatever was happening to those warrior cells was happening after they left the safety of the bone marrow and entered the bloodstream. That’s what you would expect if this was a reaction to a medication. Many medications can cause neutropenia. Some drugs destroy these fighter cells directly. Some trigger an immune response so that other parts of the body’s defense system mistake these cells for invading pathogens and attack them.
If it were a reaction to a medication, then stopping it would allow the cell count to rebound, sometimes almost immediately. Neutrophils have a very short life span, and a full complement of new cells is released from the bone marrow every day. The student waited anxiously for her next blood count. Could just stopping her Adderall get her back to normal?
The answer was a resounding yes. Her neutrophils had doubled from their lowest point weeks earlier. They weren’t quite back to normal, but she was well above the most dangerous range. She started her rotation on the hospital wards as scheduled.
After a few weeks, the patient decided to try a different version of the medication. She had been on Adderall for years with breaks only for pregnancy and nursing and never had a problem. Without it her A.D.H.D. made the hard work of learning to be a doctor even harder. But when her neutrophils dropped again, she stopped — this time, she figures, for good.
The patient has now turned to cognitive behavioral therapy to help her manage her disorder. She’s working hard to come up with systems to help manage the demands of work and family more effectively. She says it’s about time she did that anyway.
Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share with Dr. Sanders, write her at [email protected]
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