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Red blood cells (RBCs) have a normal life span of approximately 120 days. An operational definition of hemolysis, therefore, is accelerated RBC destruction with premature removal from the circulation, which usually causes anemia. Hemolytic anemia can occur in a wide range of clinical settings featuring various etiologies; signs and symptoms reflect the location and severity of hemolysis. Intravascular hemolysis occurs when erythrocytes are destroyed in the blood vessel itself, whereas extravascular hemolysis occurs in the hepatic and splenic macrophages within the reticuloendothelial system. Intravascular hemolysis is often dramatic, with free hemoglobin released into the plasma leading to hemoglobinuria (positive blood on urine dipstick but few erythrocytes on microscopic examination). Examples of intravascular hemolysis include enzyme defects such as glucose-6-phosphate dehydrogenase (G6PD) deficiency or certain immune-mediated processes. Extravascular hemolysis usually results from more subtle RBC destruction, typically with chronic splenic enlargement and jaundice. Extravascular hemolysis is more common with RBC membrane disorders such as hereditary spherocytosis. Some forms of hemolytic anemia feature both intravascular and extravascular hemolysis. The degree of anemia depends on how rapidly the erythrocytes are being removed from circulation and how well the bone marrow compensates with increased reticulocytosis.

The clinical presentation of hemolytic anemia is highly variable, ranging from mild anemia with asymptomatic splenomegaly, to jaundice with splenomegaly and dark urine, to acute severe anemia as a consequence of a parvovirus-induced aplastic crisis. Symptoms of hemolysis may include pallor, fatigue, abdominal pain, dark urine, and “yellow” eyes. On physical examination, patients may have a cardiac flow murmur, splenomegaly, and scleral icterus. Some children have a relatively benign physical examination and medical history.

The classic laboratory finding of hemolysis is anemia with an elevated reticulocyte count. The reticulocytosis reflects normal bone marrow function and occurs in response to the premature RBC destruction; reticulocytes are larger than older erythrocytes and have a blue-purple color known as polychromasia (Fig. 433-1). Reticulocytosis generally occurs 3 to 5 days after a sudden drop in hemoglobin concentration but is relatively constant in children with congenital hemolytic anemia. Making the diagnosis of hemolytic anemia begins with recognizing the constellation of signs and symptoms, then obtaining a complete blood count with reticulocyte count, and finally examining the peripheral blood smear. Additional laboratory findings supporting the diagnosis of hemolysis include elevated total serum bilirubin and lactate dehydrogenase (LDH; LDH being released from RBCs during hemolysis). Intravascular hemolysis also causes decreased or undetectable levels of haptoglobin, but this test is not specific so is not generally helpful. Dipstick urinalysis may reveal bilirubin, protein, or blood; the presence of blood without erythrocytes on microscopic analysis indicates hemoglobinuria reflecting intravascular hemolysis.

Figure 433-1.

Reticulocytes. Compared to mature erythrocytes, reticulocytes just entering the circulation are larger and have a bluish-purple hue. The presence of reticulocytes indicates a bone marrow response to anemia and is often found in children with hemolytic anemia.

Hemolytic anemia ...

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