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.
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.