CASE FILES: BIOCHEMISTRY
A N SW E R S TO C A SE 23: H E M O L Y T IC A N E M IA
A 2-year-old black girl has normocytic anemia, jaundice,
splenomegaly, and peripheral smear showing spiculated cells. A family history
of similar symptoms is possible.
Biochemical mechanism: Pyruvate kinase deficiency usually will
manifest clinical symptoms on red blood cells (RBCs) with no apparent
metabolic abnormalities in other cells. Insufficient adenosine
triphosphate (ATP) is produced in the red cell and its membrane is
affected, is rigid and removed by the spleen.
Inheritance: Autosomal recessive.
C L IN IC A L C O R R E L A T IO N
Hemolytic anemia is not a common cause of anemia, but should be considered
in patients with elevated serum bilirubin or urine bilirubin levels. Lysis of the
erythrocyte can occur from various mechanisms such as medications, antibodies
against red blood cells, infection, coagulopathy, and mechanical processes such
as abnormal heart valves, and enzyme deficiencies of the red blood cell. Patients
may notice fatigue, dizziness from the anemia, and dark colored (classically
“coke-colored” urine) from the bilirubinuria.
Confirmation of hemolysis can be obtained by the peripheral blood smear
revealing fragmented red blood cells, or increased serum bilirubin or
decreased serum haptoglobin. Immunoglobulins can cause red blood cell lysis
by attacking various proteins on the surface of erythrocytes; autoimmune
processes (body attacking itself), or alloimmune (immunoglobulins from out-
side) such as from a blood transfusion or a fetus from the mother. The Coombs
tests can assess for immunoglobulin on the red blood cell or circulating in the
serum. Typically, hemolysis of the erythrocyte is associated with increased
levels of RBC precursors in the bone marrow and thus immature forms of the
erythrocytes in the bloodstream; therefore, an increased reticulocyte concen-
tration supports the increased destruction of red blood cells.
A PPR O A C H TO PYRU VATE M E T A B O L ISM
Understand the role of pyruvate kinase in pyruvate metabolism.
Be familiar with the Embden-Meyerhof pathway of RBC metabolism.
Know how pyruvate kinase deficiency results in anemia.