LOS ANGELES – Acute anemic events were associated with significantly increased risk for "silent" strokes not only in children with sickle cell disease but also in children with acute anemia due to other causes, a controlled study of 52 patients found.

Prospective screening of all children who were admitted to one hospital during a 30-month period found that 398 were having acute anemic events – accounting for nearly 1% of all admissions and 12% of children admitted with sickle cell disease. Diffusion-weighted MRI in 52 of these children showed evidence of acute silent infarction in 4 (18%) of 22 patients with sickle cell disease and in 2 (7%) of 30 patients without sickle cell disease, Dr. Michael M. Dowling and his associates reported at the International Stroke Conference.

"I didn’t initially plan a controlled study," but funders insisted, and the comparison yielded unexpected information, said Dr. Dowling, a pediatric neurologist at the University of Texas Southwestern Medical Center, Dallas. "I didn’t think these children [without sickle cell disease] would be having silent infarctions." The Children’s Medical Center of Dallas funded the study.

In addition, three patients with sickle cell disease showed evidence of what looked like remote silent infarctions on MRI (14%). Dr. Dowling said he was "fascinated" to also find evidence of remote silent infarctions in seven of the control patients (23%).

"These are not children with sickle cell disease. I’m worried that a lot of these children with acute anemic events were prone to recurrent anemic events from dysfunctional uterine bleeding, cancer, or repeat GI bleeds. I’m worried that at previous admissions they may have had an acute silent infarction in the setting of an acute anemic event that was missed," he said at the conference, which was sponsored by the American Heart Association.

Overall, 31% of all MRIs were abnormal, including both acute and remote silent infarctions.

"I think we can’t simply look at a severely anemic child in an emergency room and say he’s hemodynamically stable, because I think these kids are losing brain cells. We need to respond to them more quickly," he said.

He hopes that a future study will monitor these kinds of children at home via a pulse oximeter so that when their hemoglobin level falls, they can be brought in sooner for transfusion. "I think we can prevent injury," he said.

Previous studies suggest that approximately 10% of children with sickle cell disease will have a clinically evident stroke unless they get prophylactic therapy, and up to 35% will have silent infarctions.

"It’s a bad term because they’re not silent," Dr. Dowling said. "They cause significant cognitive impairment," educational delays, and increased risk for new or progressive silent infarctions and overt stroke.

His working definition of silent infarction is an MRI lesion consistent with infarction without a focal deficit lasting more than 24 hours. The study defined an acute anemic event as either a hemoglobin level no higher than 5.5 g/dL or, for children with sickle cell anemia whose "normal" hemoglobin level may be 6 g/dL, a decline of at least 30% from baseline hemoglobin level.

Follow-up imaging in four patients with acute silent infarctions showed signals consistent with permanent brain injury in three of them, but not in the fourth. "Some of these might be reversible," Dr. Dowling said.

He estimated that the incidence of acute silent infarction during acute anemic events is 633 per 100 patient-years in children with sickle cell disease, and 243 per 100 patient-years in children without sickle cell disease, based on the study’s findings. His estimates are much larger than are those from the SIT (Silent Infarct Transfusion) study, which suggested an incidence of 43 per 100 patient-years in children with sickle cell disease as a whole, he said.

"We have identified unsuspected silent infarctions occurring during acute anemic events in 18% of children with sickle cell disease and 7% of controls. I think these events may be telling us" that children with acute anemia may need closer observation, he said.

The etiologies of acute anemia were a bit surprising in both the sickle cell and control groups. There were more oncology patients than anticipated among the 294 children who were admitted without sickle cell disease. Aplastic or hemolytic anemias were the leading etiology. Others included GI bleed or liver problems, leukemias, lymphomas, and other cancers. Among patients with sickle cell disease and acute anemia, fewer than expected had acute chest syndrome, aplastic crisis, or splenic sequestration, although these still accounted for the majority. Some simply had infection, GI bleed, or other problems.

Dr. Dowling said he had no relevant conflicts of interest. He has received research support from First American Real Estate Services Inc.

Silent Strokes Common in Pediatric Acute Anemia