Causes of stomatocytosis and distinguishing features

Condition	Hematologic parameters	Hemolysis laboratories	Biochemical tests
Hereditary conditions (with associated genes)
Dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis (HX) PIEZO1 KCNN4	Increased MCV, MCH, and MCHC	Increased absolute reticulocyte count, LDH, unconjugated bilirubin Decreased haptoglobin	EMA binding: fluorescence intensity in the range of controls Ektacytometry: Most PIEZO1 variants: leftward shift of the bell-shaped curve compared to controls Most KCNN4 variants: curve unchanged from controls
Overhydrated hereditary stomatocytosis (OHS) RHAG	Increased MCV Decreased MCHC	Increased absolute reticulocyte count, LDH, unconjugated bilirubin Decreased haptoglobin	EMA binding: fluorescence intensity in the range of controls Ektacytometry: rightward shift of the bell-shaped curve compared to controls
Hereditary cryohydrocytosis (CHC) SLC4A1 (encodes Band3)		Slightly increased absolute reticulocyte count, LDH, unconjugated bilirubin Slightly decreased haptoglobin	EMA binding: fluorescence intensity in the range of controls Ektacytometry in Na⁺ buffer: decreased EImax and leftward shift of the curve right arm Ektacytometry in K⁺ buffer: rightward shift
Familial pseudohyperkalemia (FP) ABCB6	Increased MCV In some cases, increased MCH and MCHC	Increased absolute reticulocyte count, LDH, unconjugated bilirubin Decreased haptoglobin	Hyperkalemia EMA binding: fluorescence intensity in the range of controls Ektacytometry: unknown
Southeast Asian ovalocytosis (SAO) SLC4A1 (encodes Band3) specific 27 bp deletion	In infants: Low RBC count Decreased MCV and MCH Increased RDW Abnormalities may resolve with increasing age of the patient	In infants, increased absolute reticulocyte count Reticulocytosis may resolve with increasing age	EMA binding: fluorescence intensity in the range of controls Ektacytometry: large decrease in RBC deformability and leftward shift of the bell-shaped curve compared to controls
Stomatin-deficient cryohydrocytosis with neurodevelopmental disability, seizures, and hepatosplenomegaly SLC2A1	Increased or normal MCV Increased MCHC and RDW		No data
Sitosterolemia ABCG8 ABBCG5	Increased or normal MCV Increased MCHC and RDW Thrombocytopenia with high MPV	Increased absolute reticulocyte count	No data
Acquired conditions
Liver disease and/or excess alcohol	Anemia and other cytopenias may be present. MCV may be increased or decreased depending on whether nutrient deficiencies are present (iron, vitamin B12, folate). Hemolysis is not typically a major feature.		No data
Myelodysplastic syndromes	Anemia and other cytopenias may be present. MCV may be increased, decreased, or normal. Hemolysis is not typically a major feature.		No data
Certain drugs Chemotherapeutic agents Cytosine arabinoside (Ara-C) 6-thioguanine (TG) Vinblastine Immunosuppressive agents Cyclosporine Tacrolimus Sirolimus Medications that interfere with ion channels Chlorpromazine Diazepam Citalopram Arsenic	Anemia and other cytopenias may be present. Hemolysis is not typically a major feature.		No data

Stomatocytosis may be seen as a laboratory artifact related to prolonged storage of blood samples or improper blood smear preparation. Refer to UpToDate for sample handling and details of the evaluation of stomatocytosis.

All of the hereditary conditions are autosomal dominant except for sitosterolemia, which is autosomal recessive or digenic.
The acquired conditions may be transient or chronic.

BP: base pair; EMA: eosin-5-maleimide; K⁺: potassium; LDH: lactate dehydrogenase; MCH: mean corpuscular hemoglobin; MCHC: mean corpuscular hemoglobin concentration; MCV: mean corpuscular volume; MPV: mean platelet volume; Na⁺: sodium; RBC: red blood cell; RDW: red cell distribution width.

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Causes of stomatocytosis and distinguishing features