In the latest Case Record of the Massachusetts General Hospital, a 29-year-old man was admitted to the hospital because of anemia, jaundice, fatigue, and diffuse body aches. He had returned from a 3-month trip to North Africa 1 month before presentation. A diagnostic test was performed.
Obtaining a thorough family history with particular attention to hereditary diseases, a detailed patient history that includes antecedent illnesses and exposures (travel and drug consumption), and a review of the peripheral-blood smear should lead to the correct cause of most cases of hemolysis.
It has been suggested that hemolytic anemia be categorized as either an inherited or an acquired disorder of red cells. When considering potential acquired causes of hemolysis, one should attempt to rule out hypersplenism, immune-mediated hemolysis, microangiopathy, infection, and other uncommon disorders, such as paroxysmal nocturnal hemoglobinuria and paroxysmal cold hemoglobinuria. Inherited hemolytic anemias can be classified on the basis of the red-cell abnormality that is responsible for their destruction; hence, hereditary hemolysis can be caused by a membrane defect (e.g., hereditary spherocytosis or hereditary elliptocytosis), an enzymatic defect (e.g., pyruvate kinase deficiency or glucose-6-phosphate dehydrogenase deficiency), or hemoglobin defects intrinsic to red cells (e.g., sickle cell anemia or thallesemia)
G6PD deficiency is an X-linked recessive disorder found mostly in men of Asian, African, Mediterranean, and Middle Eastern descent. Unlike the other inherited hemolytic anemias, G6PD deficiency is most often a self-limited disease that presents shortly after an oxidative insult to red cells, such as infection, drug exposure, or ingestion of certain foods. Signs and symptoms of hemolysis develop in patients with this enzyme deficiency, but patients typically have normal erythrocyte indexes and few laboratory abnormalities.
Morning Report Questions
Q: How is G6PD deficiency diagnosed?
A: The diagnosis of G6PD deficiency can be made on the basis of a well-documented history, evidence of hemolysis, a peripheral-blood smear showing Heinz bodies (erythrocytes with denatured hemoglobin), and bite cells, and the measurement of the level of G6PD activity. G6PD deficiency should be considered in patients with acute, nonspherocytic hemolytic anemia and a negative Coombs’ test, especially those who are men of African, Mediterranean, or Asian descent. It is important to remember that the level of enzyme activity may remain normal during an acute hemolytic episode because only nonhemolyzed, freshly produced, younger red cells are assayed. If G6PD deficiency remains a concern after normal activity is measured, the assay must be repeated a few weeks later, once hemolysis has ceased and cells of all ages are again present.
Q: How is hemolysis secondary to G6PD deficiency treated?
A: The disease is self-limited, and treatment is directed toward halting hemolysis by identifying, removing, or treating the agent that is responsible for the increased oxidative stress. Therapeutic goals are aimed at maintaining a level of hemoglobin that is apt for hemodynamic stability, and transfusions are required only on rare occasions when severe hemolysis and inappropriate reticulocytosis are present.