A 6-day-old girl is seen in the newborn unit for persistent jaundice. She was born at 39 weeks gestation to a primigravid 17-year-old woman with O+ blood type, who had an unremarkable pregnancy and normal prenatal laboratory results. On the first day of life, the infant developed jaundice on the face that has now spread to below the umbilicus and to the palms. Phototherapy was initiated, but repeated attempts at stopping therapy have resulted in rebound hyperbilirubinemia. The infant is feeding well, has normal urine output, and is passing soft, yellow stool. Temperature is 36.7 C (98 F). Vital signs are normal. On examination, the patient is asleep but easily aroused. The sclerae are icteric. The abdomen is soft and nontender, the liver is nonpalpable, and the spleen is enlarged. The skin shows generalized jaundice. Laboratory results at 24 hours of life showed hemoglobin of 15.7 g/dL, total bilirubin of 13 mg/dL, and direct bilirubin of 0.2 mg/dL. Current laboratory results are as follows:
| Complete blood count | ||
| Leukocytes | 10,000/mm3 | (9,400-34,000/mm3) |
| Hemoglobin | 12 g/dL | (14.5-22.5 g/dL) |
| Mean corpuscular volume | 98 µm3 | (95-121 µm3) |
| Mean corpuscular hemoglobin concentration | 42% Hb/cell | (29%-37% Hb/cell) |
| Platelets | 230,000/mm3 | |
| Red cell distribution width | 18% | (11.5%-14.5%) |
| Reticulocytes | 6% | (1.8%-4.6%) |
| Hematology | ||
| Blood type | A+ | |
| Direct Coombs test | negative | |
Which of the following is the most likely cause of this patient's anemia?
Hereditary spherocytosis | |
Epidemiology |
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Clinical presentation |
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Laboratory findings |
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Treatment |
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MCHC = mean corpuscular hemoglobin concentration. | |
This infant has anemia, jaundice, and splenomegaly, concerning for hereditary spherocytosis, a common cause of hemolytic anemia in persons of Northern European descent. It is typically an autosomal dominant disorder caused by a defect of red blood cell membrane proteins (most commonly ankyrin), resulting in unstable, round (rather than biconcave) red blood cells.
These fragile spherocytes cannot traverse through tight spaces in the microcirculation, such as the spleen, which leads to the classic triad of hemolytic anemia, jaundice, and splenomegaly. Patients can have symptoms at any time of life, including the newborn period. Specifically, neonates may present with jaundice on the first day of life and persistent jaundice refractory to standard management (eg, phototherapy).
Laboratory findings in spherocytosis include anemia, increased mean corpuscular hemoglobin concentration (MCHC), indirect hyperbilirubinemia, and negative Coombs test. The increased MCHC is due to membrane loss and cellular dehydration. Reticulocytes are elevated to compensate for hemolysis, and spherocytes are usually present on peripheral smear. The diagnosis is confirmed by abnormal acidified glycerol lysis (osmotic fragility) and eosin-5-maleimide binding tests.
(Choices A and F) Isoimmune hemolytic disease of the newborn (eg, ABO incompatibility) and autoimmune hemolytic anemia can cause anemia, reticulocytosis, and indirect hyperbilirubinemia. However, antibody-mediated hemolysis typically causes a positive direct Coombs test, not seen in this patient.
(Choices B and E) Most alpha and beta thalassemias are microcytic anemias and are unlikely in an infant with normal mean corpuscular volume. Some thalassemias (eg, alpha thalassemia minima) are mild and may not cause microcytosis; however, these conditions are typically asymptomatic.
(Choice D) Pyruvate kinase deficiency and glucose-6-phosphate dehydrogenase deficiency can cause hemolytic anemia due to inherited defects of erythrocyte glycolytic enzymes. However, MCHC would not be elevated.
(Choice G) Folate deficiency can cause macrocytic anemia. Patients with hemolytic anemia are at risk of folate deficiency due to high cell turnover; however, this is uncommon in the neonatal period, and laboratory results would show an elevated mean corpuscular volume.
Educational objective:
Hereditary spherocytosis, caused by a defect of red blood cell membrane proteins, often presents with refractory jaundice and splenomegaly on examination and laboratory evidence of a hemolytic anemia with an increased mean corpuscular hemoglobin concentration.