G₆PD Hemolytic Anemia

Nejm 1991;324:169

Cause:

A hereditary, nonspherocytic anemia

Type I: Genetic; sex-linked recessive (women show only some decreased reducing power)

Type II: genetic plus drug precipitants like antimalarials, eg, primaquine, sulfonamides, nitrofurans, ASA and aminopyrines, sulfones, dimercaprol, naphthalene, phenylhydrazine, probenecid, vitamin K, chloramphenicol, fava beans (only in whites), -MeDopa (Nejm 1967;276:658), etc. In 11% of US blacks; much higher prevalence in several Near-Eastern groups, eg, Kurds (62%). This type exists because of balanced polymorphism from selective advantage in female against falciparum malaria

Pathophys:

In Caucasians, G₆PD is decreased in all rbc's leading to profound anemia through vulnerability to oxidative damage because G₆PD reduces NADP and thus provides the cell-reducing power to maintain sulfhydryl (SH) groups and thus help detoxify free radicals and peroxides. A deficiency also exists in other body cells (Nejm 1969;281:60). In contrast, G₆PD is decreased in only older (>60-day-old) rbc's in blacks

Drugs are all redox catalysts taking TPNH TPN, Hgb Ø met-Hgb. Cell membranes injured by oxidizing thiols (SH SS). Injured cells then phagocytized by liver and spleen

Racial prevalence: blacks, 15%; Sardinians, 14%; Jews (Nejm 1967;277:1124), Sephardic up to 20%, Ashkenazi (Polish-Russian), <1%; Greeks; Egyptians.

Sx:Acute jaundice and anemia with infection or drug use in type II. Newborn jaundice can cause kernicterus

Si:Anemia, color blindness

Sickle trait protects and vice versa (Nejm 1972;287:115)

Lab: Hem:Hemolytic anemia with increased reticulocytes, bilirubin, and marrow red cell series; low haptoglobin. Peripheral smear shows Heinz bodies (precipitated hemoglobin—Nejm 1969;280:203), helmets. G₆PD enzyme assay

Rx:Stop drug; avoid infection and other sources of aplastic crisis; vitamin E no help (Nejm 1983;308:1014). Exchange transfusion in neonates with icterus