Overview of hemolytic anemias in children
- Jenny M Despotovic, DO, MS
Jenny M Despotovic, DO, MS
- Assistant Professor
- Baylor College of Medicine
Anemia is among the most frequent laboratory abnormalities seen by a practicing pediatrician. Anemia is caused by one of three broad mechanisms: decreased production of red blood cells (RBCs), increased loss of RBCs, or premature destruction (hemolysis) of RBCs. A combination of these mechanisms can occur simultaneously in some conditions.
The approach to a child with hemolytic anemia is discussed here. A broader approach to the anemic child is discussed separately. (See "Approach to the child with anemia".)
THE HEMOLYTIC PROCESS
After release from the bone marrow, mature, non-nucleated erythrocytes (red blood cells [RBCs]) generally survive for 100 to 120 days in the circulation . In the steady state, approximately 1 percent of the circulating erythrocytes are destroyed daily and are replaced by an equal number of new erythrocytes (reticulocytes) released from the bone marrow (picture 1 and picture 2). The basic pathophysiology of the hemolytic anemias is a reduced erythrocyte lifespan due to premature destruction, ranging from nearly normal to remarkably shortened. (See "Red blood cell survival: Normal values and measurement".)
In compensation for a reduced RBC lifespan, the bone marrow increases its output of erythrocytes, a response mediated by increased production of erythropoietin. As an example, in adults with hereditary spherocytosis, the bone marrow can increase its output of erythrocytes six- to eight-fold. With this maximal response, erythrocyte survival can be reduced to a value as low as 20 to 30 days without the onset of anemia (ie, fully compensated hemolysis). The limits of erythrocyte production in other hemolytic states have not been determined, particularly in infants and children, but they probably are lower in infants than in adults. (See "Regulation of erythropoiesis".)
As a result of increased RBC production in response to hemolysis, the reticulocyte count often exceeds 2 percent, with an absolute reticulocyte count usually >100,000/microL . When a chronic hemolytic process is present, hyperplasia of the erythropoietic marrow elements occurs, with reversal of the myeloid-to-erythroid ratio from the normal 3:1 to 1:1 or less (picture 3 and picture 4). In the severe, chronic hemolytic processes of childhood (eg, thalassemia major, congenital spherocytosis, sickle cell disease), hypertrophy of the marrow may expand the medullary spaces, producing bony changes, particularly in the skull and hands . (See "Overview of the clinical manifestations of sickle cell disease", section on 'Skeletal complications' and "Diagnosis of hemolytic anemia in the adult", section on 'High reticulocyte count' and "Clinical manifestations and diagnosis of the thalassemias".)
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- THE HEMOLYTIC PROCESS
- DIAGNOSTIC PRINCIPLES
- Time-course of hemolysis
- INTRINSIC HEMOLYTIC ANEMIAS
- Erythrocyte membrane defects
- Enzyme deficiencies
- EXTRINSIC HEMOLYTIC ANEMIAS
- Autoimmune hemolytic anemia
- Systemic disease
- Drugs and toxins
- Mechanical damage
- Wilson disease
- COMBINED MECHANISM
- Paroxysmal nocturnal hemoglobinuria
- DIAGNOSTIC APPROACH
- Laboratory testing
- Peripheral smear
- Serum LDH, haptoglobin, and plasma free hemoglobin
- Reticulocyte count
- Confirmatory testing