Diagnostic Criteria
Suggestive Findings EPB42-related hereditary spherocytosis (EPB42-HS) should be suspected in individuals with any of the following clinical and laboratory findings. Clinical findings • Pallor and/or fatigue due to anemia, which is usually of mild-to-moderate severity • Jaundice • Usually intermittent and caused by unconjugated hyperbilirubinemia resulting from exacerbated hemolysis • In rare instances, caused by conjugated hyperbilirubinemia resulting from biliary obstruction • Splenomegaly • Cholelithiasis in the second or third decade of life Laboratory findings • Complete blood count consistent with: • Chronic, nonimmune hemolytic anemia (decreased hemoglobin [Hgb] with reticulocytosis), usually of mild-to-moderate severity • Decreased Hgb level (See for Hgb levels that define the severity of hereditary spherocytosis.) Note: Hgb values in EPB42-HS may also vary depending on the clinical status of the affected individual (baseline or during a hemolytic or aplastic crisis). • Increased percent of reticulocytes as well as increased absolute reticulocyte count (See for percent of reticulocytes that define the severity of hereditary spherocytosis.) Note: Percent of reticulocytes may vary (depending on baseline or crisis status) from 2.5% to greater than 10% (or even normal or low when in aplastic crisis). • High mean corpuscular Hgb concentration. Normal values are typically 31-37 g/dL. Values in individuals with hereditary spherocytosis are usually 35.5-37.5 g/dL. • Negative (i.e., normal) direct anti-globulin test (DAT) Note: DAT should always be evaluated in a person with newly diagnosed hemolytic anemia to evaluate for an acute immune-mediated (acquired) hemolytic anemia. • Peripheral blood smear demonstrating presence of spherocytes and occasionally a few ovalocytes and elliptocytes Note: The term "spherocyte" refers to the sphere-shaped red blood cells (with a decreased surface-to-volume ratio) that characterize the red blood cell membrane skeleton disorders . • Significantly decreased or absent haptoglobin. After age six months normal haptoglobin values are 16-200 mg/dL. In hereditary spherocytosis, haptoglobin is typically undetectable; however, haptoglobin can be normal in the presence of concurrent inflammation (as it is an acute phase reactant). • Mildly increased osmotic fragility (as in Figure 1B of ; see full text) • Decreased maximal deformability index (DImax; also known as elongation index, or EImax) and increased Omin (osmolality at which 50% of red blood cells hemolyze) measured by osmotic gradient ektacytometry, giving a typical hereditary spherocytosis curve Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis. Table 1. Severity of Hereditary Spherocytosis
Severity | Hgb (g/dL) | Reticulocytes | Splenectomy |
|---|
Mild | 11-15 | 3%-8% | Not necessary |
Moderate | 8-11.5 | 8% | Consider if activity level quality of life |
Moderately severe | 6-8 | ≥10% | Indicated at age 5 yrs |
Severe | 6 | ≥10% | Indicated at age 3 yrs |
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Source: GeneReviews — "EPB42-Related Hereditary Spherocytosis"
