(See also Overview of Hemolytic Anemia Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span ( read more .)
G6PD deficiency, a defect in the hexose monophosphate shunt pathway, is the most common disorder of red blood cell (RBC) metabolism. The G6PD gene is located on the X chromosome and exhibits a high amount of variation (polymorphism), resulting in a range of G6PD activity from normal to severely deficient. Variants are classified I through V by the amount of activity of the G6PD enzyme. Because the gene is X-linked, males are more likely to present with clinically significant hemolysis, although females who are homozygous, or who are heterozygous with skewed X inactivation that results in a high proportion of affected X chromosomes (see Mosaicism Mosaicism Certain situations represent aberrant inheritance, often because genes or chromosomes are altered. However, some of these alterations, such as mosaicism, are very common; others, such as polymorphisms... read more ) may also be affected.
This defect occurs in about 10% of black males and in < 10% of black females in the US and in lower frequencies among people with ancestors from the Mediterranean basin (eg, Italians, Greeks, Arabs, Sephardic Jews) and people with ancestors from Asia.
Pathophysiology of G6PD Deficiency
G6PD deficiency renders RBCs susceptible to oxidative stress, which shortens RBC survival. Hemolysis occurs following an oxidative challenge, commonly after fever, acute viral or bacterial infections, and diabetic ketoacidosis Diabetic Ketoacidosis (DKA) Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with... read more . Hemolysis is episodic and self-limited, although rare patients have chronic, ongoing hemolysis in the absence of oxidative challenge.
Less commonly, hemolysis occurs after exposure to drugs or to other substances that produce peroxide and cause oxidation of hemoglobin and RBC membranes. These drugs and substances include primaquine, salicylates, sulfonamides, nitrofurans, phenacetin, naphthalene, some vitamin K derivatives, dapsone, phenazopyridine, nalidixic acid, methylene blue, and, in some cases, fava beans. The amount of hemolysis depends on the degree of G6PD deficiency and the oxidant potential of the drug.
Symptoms and Signs of G6PD Deficiency
In most cases, hemolysis affects < 25% of RBC mass and causes transient jaundice Jaundice Jaundice is a yellowish discoloration of the skin and mucous membranes caused by hyperbilirubinemia. Jaundice becomes visible when the bilirubin level is about 2 to 3 mg/dL (34 to 51 micromol/L)... read more and dark urine. Some patients have back and/or abdominal pain. However, when the deficiency is more severe, profound hemolysis may lead to hemoglobinuria and acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more .
Diagnosis of G6PD Deficiency
The diagnosis is considered in patients with evidence of acute hemolysis, particularly males with a direct antiglobulin–negative hemolytic anemia (see Diagnosis of Hemolytic Anemia Diagnosis At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span ( read more ). Anemia, jaundice, and reticulocytosis develop during hemolysis.
The peripheral smear may reveal RBCs that appear to have had one or more bites (1-micron wide) taken from the cell periphery (bite or blister cells) and RBCs with inclusions termed Heinz bodies, which are particles of denatured hemoglobin, which can be recognized only by special stains. These cells may be visible early during the hemolytic episode but do not persist in patients with an intact spleen, which removes them.
Testing for G6PD activity is available. However, during and immediately after a hemolytic episode, tests may yield false-negative results because of destruction of the older, more deficient RBCs and the production of reticulocytes, which are rich in G6PD. Thus, testing may need to be repeated several weeks after the acute event. Several screening tests are available, including point-of-care tests; positive results should be confirmed with a quantitative test.
Treatment of G6PD Deficiency
Avoidance of triggers, removal of offending drug or agent, and supportive care
During acute hemolysis, treatment is supportive; transfusions are rarely needed. Patients are advised to avoid drugs or substances that initiate hemolysis.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited disorder of red blood cell metabolism and can cause hemolysis in the presence of triggers.
Incidence is higher in certain ethnic groups (eg, American blacks, people from the Mediterranean basin, people with Asian ancestry).
Triggers include acute illnesses (eg, infections), drugs (eg, salicylates) and other substances (eg, fava beans) that cause oxidative stress.
Diagnose using peripheral smear and G6PD assay; false negative G6PD assays are possible during acute hemolysis so repeat testing after several weeks if initial G6PD assay is negative.
Avoid triggers to limit hemolytic episodes.