Case Report: Autoimmune Hemolytic Anemia Induced by Enterovirus 71

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Enterovirus infection triggered autoimmune hemolytic anemia (AIHA) — a condition in which the body’s immune system produces self-reactive antibodies that destroy red blood cells — in an 11-year-old boy, a case study has reported for the first time.

Although some signs were consistent with a case of virus-induced cold agglutinin disease (CAD), a type of AIHA, the researchers noted that no direct test for CAD-related self-reactive antibodies was performed to confirm the diagnosis.

Enterovirus infection should be considered as a possible cause of AIHA in all patients with hemolytic anemia, they added.

The case study “Enterovirus 71-induced autoimmune hemolytic anemia in a boy‘ was published in the magazine Insights into clinical medicine: case reports.

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CAD is a type of AIHA, a broad category of diseases in which the immune system mistakenly attacks and destroys red blood cells. In CHD, this attack is fueled by self-reactive antibodies called cold agglutinins, which attach to red blood cells at low temperatures.

AIHA can be triggered by underlying health conditions such as a viral or bacterial infection, cancer, or other autoimmune diseases. Cases caused by enteroviruses are rare, and cases of the Enterovirus 71 (EV71) subtype have not been previously reported.

For the first time, researchers in Thailand described a case of EV71 infection causing AIHA in an otherwise healthy 11-year-old boy.

The boy had a high fever and swelling in the neck for two days and dark-colored urine for a day. He had no cough, loose stools, skin rash, arthritis, difficulty urinating, abnormal bleeding and had not had any vaccinations in the previous month. He was taller than average for his age, conscious, with moderate pallor and yellowish eyes. Examination revealed swollen and tender lymph nodes in his neck.

His liver, heart, lungs and nervous system appeared normal and he had no history of jaundice or low red blood cell counts (anaemia). He reported that no medication was being taken prior to the onset of symptoms and there was no evidence of a family history of underlying blood disorders.

His blood level of hemoglobin, the protein that carries oxygen in red blood cells, was 7 grams per deciliter (g/dL) — well below the normal range of 11.2 to 14.5 g/dL.

The volume percentage of red blood cells in his blood (hematocrit) was 20.9%, also below the normal range of 30-44%. In contrast, its level of immature red blood cells called reticulocytes was slightly elevated (3.4%), indicating red blood cell depletion after maturation. His white blood cells were also elevated, indicating an infection.

Blood levels of LDH and bilirubin were high while haptoglobin was low and all signs of red blood cells were destroyed. Liver function markers ALP and AST were also elevated, a sign of liver inflammation and damage possibly caused by the abnormal clearance of excess damaged red blood cells.

Analysis of the blood smear showed some small, spherical red blood cells, some of different colors, but no red blood cell fragments or signs of red blood cell clumping. Urinalysis showed dark urine with protein that tested positive for red blood cells

“That indicated hemoglobinuria [high hemoglobin levels in the urine] which supports the detection of intravascular hemolysis [red blood cells destruction]’ the researchers write.

AIHA was diagnosed based on a positive direct Coombs test for self-reactive antibodies that target red blood cells.

The boy was first screened for various infectious diseases to identify the possible cause of his AIHA. Genetic screening of a nasal swab that tested positive for enterovirus and further testing revealed elevated blood levels of antibodies to EV71.

treatment strategy

He was treated with the oral anti-inflammatory steroid prednisone, received a blood transfusion, intravenous (into the vein) fluids and other supportive care. His fever resolved within a day and his hemoglobin and reticulocyte counts normalized 35 days after presentation.

Prednisolone was continued and gradually tapered off to complete a 10 week regimen, at which time his hemoglobin, reticulocytes and LDH were normal and he tested negative on the Coombs test.

“This reported case demonstrates the association of EV71 infection and AIHA in a previously healthy young child,” the researchers wrote. “EV71 should be considered as an additional potential cause of virus-induced AIHA in all patients with hemolytic anemia, particularly during the EV71 outbreak season.”

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