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Stomatocytosis and Anemia Caused by Hypophosphatemia

By Alan E. Lichtin, MD, Cleveland Clinic;Cleveland Clinic Lerner College of Medicine

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Stomatocytosis (presence of cup- or bowl-shaped RBCs) and hypophosphatemia are RBC membrane abnormalities causing hemolytic anemia.


Stomatocytosis is a rare condition of RBCs in which a mouthlike or slitlike pattern replaces the normal central zone of pallor. These cells are associated with congenital and acquired hemolytic anemia. The symptoms result from the anemia.

The rare congenital stomatocytosis, which shows autosomal dominant inheritance, causes a severe hemolytic anemia presenting very early in life. The RBC membrane is hyperpermeable to monovalent cations (Na and K); movement of divalent cations and anions is normal. About 20 to 30% of circulating RBCs are stomatocytic; RBC fragility is increased, as is autohemolysis with inconstant correction with glucose. Splenectomy ameliorates anemia in some cases.

Acquired stomatocytosis with hemolytic anemia occurs primarily with recent excessive alcohol ingestion. Stomatocytes in the peripheral blood and hemolysis disappear within 2 wk of alcohol withdrawal.

Anemia caused by hypophosphatemia

RBC pliability varies according to intracellular ATP levels. Because the serum phosphate concentration affects RBC ATP levels, serum phosphate level < 0.5 mg/dL (< 0.16 mmol/L) depletes RBC ATP; the complex metabolic sequelae of hypophosphatemia also include 2,3-diphosphoglyceric acid depletion, a shift to the left in the O2 dissociation curve, decreased glucose utilization, and increased lactate production. The resultant rigid, nonyielding RBCs are susceptible to injury in the capillary circulatory bed, leading to hemolysis and small, sphere-shaped RBCs (microspherocytosis).

Severe hypophosphatemia may occur in alcohol withdrawal, diabetes mellitus, refeeding after starvation, the recovery (diuretic) phase after severe burns, hyperalimentation, severe respiratory alkalosis, and in uremic patients receiving dialysis who are taking antacids. Phosphate supplements prevent or reverse the anemia and are considered for patients at risk of or who have hypophosphatemia.

* This is the Professional Version. *