Merck Manual

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Stomatocytosis and Anemia Caused by Hypophosphatemia


Evan M. Braunstein

, MD, PhD, Johns Hopkins University School of Medicine

Reviewed/Revised Jun 2022 | Modified Sep 2022

Stomatocytosis (red blood cells with a transverse slit or stoma across the center) and hypophosphatemia cause red blood cell membrane abnormalities that can result in hemolytic anemia.


Stomatocytosis is a rare condition of red blood cells (RBCs) in which a mouthlike or slitlike pattern replaces the normal central zone of pallor. Stomatocytosis may be

  • Congenital

  • Acquired

Both congenital and acquired stomatocytosis may be asymptomatic or cause hemolysis. Symptoms, if present, result mainly from the anemia.

Congenital stomatocytosis, which shows autosomal dominant inheritance, is rare. It can cause a severe 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 Overview of Hemolytic Anemia presenting very early in life. The RBC membrane is hyperpermeable to monovalent cations (sodium and potassium); movement of divalent cations and anions is normal. The percentage of stomatocytes varies and 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 weeks of alcohol withdrawal.

Anemia caused by hypophosphatemia

Red blood cell pliability varies according to intracellular adenosine triphosphate (ATP) levels. Because the serum phosphate concentration affects RBC ATP levels, a low serum phosphate level Hypophosphatemia Hypophosphatemia is a serum phosphate concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcohol use disorder, burns, starvation, and diuretic use. Clinical features include muscle weakness... read more (< 0.5 mg/dL [< 0.16 mmol/L]) depletes ATP levels in RBCs. The complex metabolic sequelae of hypophosphatemia also include 2,3-diphosphoglyceric acid depletion, a shift to the left in the oxygen 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 (spherocytosis).

Severe hypophosphatemia may occur in

Phosphate supplements prevent or reverse the anemia and are considered for patients at risk of or who have hypophosphatemia.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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