Hemolytic Anemia Case File

https://medical-phd.blogspot.com/2021/03/hemolytic-anemia-case-file.html

Eugene C.Toy, MD, William E. Seifert, Jr., PHD, Henry W. Strobel, PHD, Konrad P. Harms, MD

❖ CASE 23
A 2-year-old black girl is being seen by the hematologist after her pediatrician found her to be
severely anemic with splenomegaly and jaundice. Her mother gives a possible history of a “blood
problem” in her family but doesn’t know for sure. Her hemoglobin electrophoresis was normal, and
the complete blood count (CBC) revealed a normocytic anemia. The platelet and white blood cell
counts are normal. On the peripheral smear, there are many bizarre erythrocytes, including
spiculated cells. A diagnosis of pyruvate kinase deficiency is made.

◆ What is the biochemical mechanism for this disorder?

◆ How is this disorder inherited?

ANSWERS TO CASE 23: HEMOLYTIC ANEMIA

Summary: 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.

CLINICAL CORRELATION
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 outside) 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 concentration supports the
increased destruction of red blood cells.

APPROACH TO PYRUVATE METABOLISM

Objectives
1. Understand the role of pyruvate kinase in pyruvate metabolism.
2. Be familiar with the Embden-Meyerhof pathway of RBC metabolism.
3. Know how pyruvate kinase deficiency results in anemia.

Definitions

Hemolytic anemia: A pathologic condition in which there is an abnormally lowered number of

circulating RBCs caused by rupture of RBCs as a result of membrane abnormalities or deficient
enzyme(s) level within the red blood cell.

Glucose 6-phosphate dehydrogenase: The enzyme that catalyzes the rate regulating step of the
hexose monophosphate shunt, which produces NADPH required for inactivating oxygen radicals
and thereby protects the RBC membrane from radical attack and rupture.

Pyruvate kinase: Last ATP-producing step in glycolysis and critical in the RBC for maintaining
energy supply (ATP levels).

Methemoglobin reductase: Red blood cell enzyme that uses nicotinamide adenine dinucleotide
(NADH) to convert the iron of oxidized hemoglobin (methemoglobin) from the ferric (Fe 3+) to
reduced ferrous state (Fe2+) hemoglobin, which alone is capable of binding O 2.