SAN ANTONIO — It was 4 a.m. on a Sunday when Dana Jones heard an ominous sound, barely audible over the whirring of box fans, like someone struggling to breathe. She ran down the hall and found her daughter Kyra, age 12, lying on her back, gasping for air. Terrified, she called 911.
A police officer, the first to arrive, dashed into Kyra’s bedroom, threw the slender girl over his shoulder and laid her on a leather sofa in the living room. He asked her mother, an oral surgery technician, to give her CPR.
Kyra’s lips were ice-cold. An ambulance whisked the girl to Methodist Children’s Hospital, where staff members swarmed her and put her into a medically induced coma.
Kyra, who has sickle cell, had suffered a devastating stroke — her second — a common complication of this inherited disease, which afflicts 100,000 Americans, most of them Black. She most likely would never have had the strokes if she had been given an annual screening test and treatment proven more than two decades earlier to prevent nine out of 10 strokes in children with the disease and recommended by the National Institutes of Health. But like countless other children with sickle cell, she was never screened.
This is a paradoxical moment for people who have this painful, deadly disease. For the first time, gene therapies that have advanced through clinical trials offer the real possibility of a cure.
But Dr. Francis Collins, director of the National Institutes of Health, said the lack of attention paid to sickle cell historically “is one more reflection of the fact that we do not have equity in our country.”
Some doctors and researchers believe the national reckoning on race sparked by the pandemic’s devastating impact on people of color, and the Biden administration’s pledge of a broad assault on racial inequities in American medical care, could make this a singular moment for advancing the fight against sickle cell.
Even so, Kyra’s strokes are a striking case study of the broad national failure to provide even the most basic treatments to people with sickle cell. Faulty care and sluggish research are symptoms of what sickle cell specialists say is the deplorable legacy of neglect of Americans with the disease.
A third as many Americans have cystic fibrosis, a genetic disease that is of comparable seriousness to sickle cell but that primarily affects white children, yet it gets “seven to 11 times the research funding per patient, which results in disparate rates of development of medications,” according to a recent opinion piece in The New England Journal of Medicine. Only four medications are approved by federal regulators for sickle call, and 15 for cystic fibrosis.
The screening test for strokes in children with sickle cell has been proven for decades, as has the treatment if it detects markers for stroke risk.
“It’s such a simple, painless and harmless test,” said Dr. Robert Adams, the neurologist whose study, published in The New England Journal of Medicine in 1998, proved the effectiveness of a scan of the head known as Transcranial Doppler ultrasound and blood transfusions for those at high risk for strokes. “It’s not rocket science.”
The National Institutes of Health issued a statement in 2002 recommending that children with sickle cell get screened every year. Then, in 2014, a consensus panel of experts convened by the National Institutes of Health issued guidelines repeating the advice.
But the message often did not get through, said Dr. Peter Lane, director of the sickle cell disease program at Children’s Healthcare of Atlanta and a pediatrics professor at Emory University. “There’s often a gap between the development of improved treatments and delivery of those treatments to the patients who need them.”
With sickle cell, he said, the gap is even bigger. “A big part of the challenge of sickle cell is that it impacts predominantly disadvantaged folks,” he said.
Kyra’s mother has learned, to her eternal regret, about the system’s failings. Ms. Jones said she was shocked when a new doctor told her about the screening test that could have prevented disabling strokes that struck both of her daughters, Kyra, who turns 16 this weekend, and Kami, now 17.
Kyra’s strokes, in 2015 and 2017, severely damaged her brain and caused a learning disability that meant she had to repeat sixth grade and years later still needed a tutor to shadow her in school. Her mother said that no one informed her until recently about the ultrasound test that was offered by a hospital just a 45-minute drive from their home — and that could have helped prevent the damage to both girls.
She still feels guilt and anger. She tosses in bed at night thinking, “What if?” How could the girls’ original doctor not have mentioned it?
“I took everything he said as Bible,” she said.
Researchers have repeatedly found that many children with the disease do not get the test or do not get it annually, as recommended. A new study, based on a survey of the largest group of children with sickle cell to date and recently published in The Journal of Pediatric Hematology/Oncology, again documented the dire situation.
Dr. Julie Kanter, a hematologist at the University of Alabama at Birmingham and director of the university’s adult sickle cell clinic, reviewed medical records of 5,347 children at 28 medical centers large and small, including academic sites as well as smaller medical centers. Only 30 to 75 percent of the children had gotten the recommended screening, depending on the center. On average, just 48.4 percent got the ultrasound. The rates were independent of the medical center’s size or academic affiliation.
“The rate is terrible, actually worse than we thought it would be,” Dr. Kanter said.
The researchers surveyed parents and caregivers and learned that some doctors failed to tell parents about the screenings. Some parents, even if told, had not understood their critical importance. (Dr. Kanter wants to rename the test “stroke screen” rather than Transcranial Doppler ultrasound so its purpose is clearer.) Some medical centers with special sickle cell clinics failed to consistently follow up with families who missed appointments.
There were also logistical obstacles. Sometimes medical centers offering the test were far from the homes of children with the disease. Some parents had trouble getting time off from work to take their children for testing. And the centers that did the tests were sometimes out of a family’s insurance network.
Ultrasound screens aren’t the only needed medical care inconsistently given to children with sickle cell. Hydroxyurea, an inexpensive generic drug, around since the 1980s, can reduce the risk of irreversible damage to organs and the brain. But it is woefully underused. Guidelines from the National Institutes of Health published in 2014 say all children and adolescents should take it, as should adults with three or more pain crises in a year or other serious complications.
A recent survey funded by the National Institutes of Health of 2,200 sickle cell patients from eight sites found that just 48 percent of patients were taking hydroxyurea regularly. Interviews with doctors who did not prescribe the drug revealed that many were unfamiliar with it while others were afraid hydroxyurea, which is also a cancer treatment at much higher doses, might cause cancer, although at the lower sickle cell dose it does not.
Another recent study, of Medicaid patients in North Carolina, found that only 32 percent of 2,790 Medicaid patients with sickle cell even had a prescription for hydroxyurea and just 31 percent of those patients took the drug regularly.
“To have teenage patients who never heard the word hydroxyurea — that’s preposterous,” said Dr. Patrick McGann, a sickle cell specialist at Cincinnati Children’s Hospital who puts all his patients on the drug.
In sharp contrast, chronic diseases whose patients are predominantly white, including type 1 diabetes and cystic fibrosis, are typically assigned to a nurse case manager who keeps in touch and manages the multiple medical appointments needed to prevent complications.
In sickle cell, said Dr. Michael DeBaun, a sickle cell specialist at Vanderbilt University, “the model of medical care is often reactionary to medical problems.”
The burden falls on parents to navigate the nation’s complicated, fragmented health care system.
‘Where’s the responsibility here?’
The idea for the stroke screening test occurred to Dr. Adams 30 years ago when he was a young neurology faculty member at the Medical College of Georgia in Augusta. One night, a 3-year-old boy with sickle cell was admitted to the hospital with a massive stroke that had destroyed most of his brain. The toddler’s red blood cells, shaped like sickles instead of disks, had gotten stuck in blood vessels to his brain, injuring their fragile linings and blocking blood flow.
“I tried to explain to this mother why her beautiful son had had this terrible stroke,” Dr. Adams said. “I tried to prepare her for what I knew was the eventuality — he had no chance to survive.”
Dr. Adams thought of how he would have felt if this tragedy had struck his own son, Christopher, who was then 9. That night, he determined to find a way to prevent such strokes.
He hypothesized that Transcranial Doppler ultrasound, or TCD, could detect children at high risk before they had strokes. The ultrasound test could measure the rate of blood flow into the brain and detect blood vessels that were partly obstructed by sickle cell. Then blood transfusions might prevent the strokes in the endangered children.
The N.I.H. tested his idea with a study that began in 1994. Children whose ultrasounds indicated high risk were randomly assigned to have transfusions or not.
The study was abruptly stopped in 1997, ahead of schedule, because children at risk who got transfusions had an annual stroke rate of less than 1 percent. Those who did not get transfusions had a 10 percent per year chance of having a stroke. Sickle cell experts were elated.
But decades later, Dr. Adams, now a distinguished professor of neurology at the Medical University of South Carolina, is alarmed that the health care system has failed to consistently use this knowledge that could have prevented so much suffering.
Hospitals must make a concerted effort to reach families with children who have sickle cell, he said.
“Where’s the responsibility here?” he asked.
“My BMW dealer knows when I am due for an oil change,” he said. Surely, he said, clinic staffs can be just as vigilant in contacting families.
“If you know who your patients are,” he said, “you have to keep track of them.”
Life with sickle cell
Ms. Jones and her former husband, the girls’ father, both carried the mutated hemoglobin gene that causes sickle cell if a child inherits it from both parents. Both their daughters were born with the disease.
Their symptoms began when they were babies, screaming in fierce pain when the distorted cells got caught in blood vessels.
When Kami was 2 years old, Ms. Jones found a caring hematologist, Dr. Mahendra Patel. But Ms. Jones said he never told her about the screening test to detect whether her daughters were at risk for strokes.
The girls’ new doctor, Dr. Melissa Frei-Jones, a pediatric hematologist at the University of Texas Health Science Center at San Antonio, confirmed that the girls had never gotten the test, and Methodist Hospital, where Dr. Patel practiced, confirmed that it did not offer the test.
Dr. Patel declined repeated requests for interviews through his office assistant, who said that the girls were no longer his patients and that he did not have time to discuss their care, including whether he ever mentioned the TCD test.
Kyra had her first stroke at age 10 on a steamy night in 2015 as she watched a basketball game with her mother and sister. She had been complaining for weeks of headaches, but that night, the pain was so bad that she screamed in agony.
Ms. Jones rushed her to the hospital. As Kyra slept that night, her mother tapped her. Kyra opened her eyes, but Ms. Jones recalled, “she looked through me like I wasn’t there.”
Terrified, Ms. Jones ran into the hall and cornered a nurse, begging for help. The nurse called a code blue, a life-threatening emergency. Medical personnel rushed into the room, pushing Ms. Jones aside.
Doctors at the hospital put Kyra in a medically induced coma for a week and a half to allow her brain to heal.
When she woke, Ms. Jones was at her bedside. Kyra looked up and said, “Hi, Mommy.”
Ms. Jones wept in relief.
But Kyra had large gaps in her memory. Her reading level had plummeted. She had forgotten how to tell time.
“I couldn’t remember anything,” Kyra said. “Like math. I didn’t even know what 1+1 is. I didn’t know how to divide.”
And she was unable to walk. She stayed in the hospital for a month, working with a physical therapist, progressing from using a walker to wobbly steps on her own.
With determination and special tutoring, she managed — barely — to get through fifth grade, but sixth grade defeated her. She had to repeat it.
Two years later when she was 12, Kyra had her second stroke deep in the middle of that night when her mother heard her gasping for breath.
Kyra, still struggles in school, with a learning disability so severe that — before Covid forced her to do remote schooling — she had a tutor who shadowed her and helped in her classes. She also had two special study periods a day with a teaching assistant standing by to help with schoolwork
A year older than the other students in her grade, Kyra said she found it hard to fit in.
During a tutoring session on a Friday afternoon last year, a chatty girl sitting across the table from Kyra told her, “I have come to the conclusion that I am not smart enough to do eighth-grade science.”
“Neither am I, in all honesty,” Kyra replied. “But I refuse to give up.”
If it weren’t for the medical staff at Methodist Hospital, where Kami and Kyra have long received care, Ms. Jones might never have learned about the TCD ultrasound test. One day in 2019 a doctor there handed Ms. Jones a Post-it note with Dr. Frei-Jones’s name and phone number on it.
At their appointment, Dr. Frei-Jones ordered M.R.I. scans of the girls’ brains to look for stroke damage. Kami’s showed little white spots in her frontal lobes, signs of a silent stroke that had destroyed brain cells. The results explained why she has trouble with organization. She uses every planning tool available to compensate for her losses, including lists and color coding with highlighters.
Kyra, too, had those white spots on her frontal lobes, but she also had big areas toward the back of her brain where tissue had been destroyed by her strokes.
A year ago, Dr. Frei-Jones showed Kyra’s brain scan to Kyra and her mother.
Seeing it, Ms. Jones said, her eyes welled with tears. Kyra was shocked and silent.
Dr. Frei-Jones told Kyra that it was this brain damage that explained why she struggled in school and why, at times, she was unable to find the words to say what she meant.
Dr. Frei-Jones advised — and Kyra agreed — that she should have transfusions every three weeks to reduce her stroke risk and that Kami should have them too.
Transfusions are a major commitment — an all-day ordeal. The girls have to miss school and Ms. Jones misses work. Kyra and Kami both feel tired and slightly ill after getting one.
Ms. Jones is so terrified they will have another stroke that she sleeps with a baby monitor in the girls’ room so she can hear if anything goes wrong in the night.
She knows, to her everlasting regret, that if she had been seeing Dr. Frei-Jones from the start, her daughters would most likely never have had the strokes that damaged their brains.
“I believe that wholeheartedly,” she said. “If things had been handled differently, their strokes could have been prevented.”
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