Hereditary Disorders of Red Cell Permeability Workup

Updated: Jan 30, 2019
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Workup

Laboratory Studies

Peripheral blood smear

As many as 3% of RBCs may be stomatocytes in a normal smear. Stomatocytes have a mouth-shaped (stoma) area of central pallor, and the cells are large and osmotically fragile. In overhydrated hereditary stomatocytosis (OHSt), this amount rises to 5-50%.

In dehydrated hereditary stomatocytosis (DHSt), target cells and echinocytes may be observed, as well as dense erythrocytes that have hemoglobin puddled at the periphery. Stomatocytes are usually not seen, and most RBCs have normal morphology.

CBC count

A CBC count reveals the degree of anemia, if present. In OHSt, there is usually macrocytosis with a mean cell volume (MCV; mean corpuscular volume) of 110-150 fL and a decreased mean cell hemoglobin concentration (MCHC; mean corpuscular hemoglobin concentration). In DHSt, macrocytosis is also seen (>100 fL), but the MCHC is elevated and this is often diagnostic.

The WBC and platelet counts are typically normal.

Reticulocyte count

The reticulocyte count is usually elevated, and in OHSt can be as high as 50% during active hemolysis, and in DHSt higher than expected for the degree of anemia (3-30%).

Osmotic fragility tests

The stomatocytes or hydrocytes of OHSt are osmotically fragile, whereas xerocytes in dehydrated hereditary stomatocytosis are resistant to osmotic lysis.

Although osmotic fragility tests are not required to establish the diagnosis, in patients in whom the peripheral blood smear has not been reviewed carefully, OHSt may be misdiagnosed as hereditary spherocytosis.

Miscellaneous tests

The eosin-5′-maleimide (EMA)–binding test detects the band 3 complex in red blood cells, which is normal or increased in OHSt and DHSt, but decreased in hereditary spherocytosis. [11]

RBC sodium, potassium, and 2,3-DPG levels are useful but not always available in clinical laboratories. In OHSt, the intracellular sodium concentration and total cation content is high, but potassium and 2,3-DPG levels can be low. In DHSt, the intracellular potassium and the total cation content are low.

Although ektacytometry detects characteristic red blood cell deformability profiles in stomatocytosis syndromes, access to this technique remains limited, reducing its utility. [20]

Genetic mutations can be detected in kindreds with familial pseudohyperkalemia (FP), cryohydrocytosis (CHC), and DHSt. Unfortunately, the wide variety of mutations has precluded genetic screening thus far.

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Imaging Studies

Perform abdominal ultrasonography in symptomatic patients to assess for pigment gallstones.

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