Peripheral Blood Smear
Eosin-5-maleimide Binding Test

Common Laboratory Findings
The common findings of lab testing in setting of a patient with hereditary spherocytosis:

Coombs Test: Negative (rules-out autoimmune hemolytic anemia)
Osmotic Fragility Test: Positive (Spherocytes will rupture in liquid solutions less concentrated than the inside of the red blood cell. This is due to increased permeability of the spherocyte membrane to salt and water, which enters the concentrated inner environment of the RBC and leads to its rupture. Although the osmotic fragility test is no longer considered the gold standard for diagnosing hereditary spherocytosis, as it misses ~25% of cases). Acidified Glycerol Lysis Test: Positive (A newer version of the osmotic fragility test that adds glycerol to a hypotonic solution. This produces lysis, a positive test, quicker that the traditional saline version). Supportive blood work:
Mean Cell Volume (MCV): Normocytic (normal range: 80-100fL), or slightly lower. Spherocytes are slightly smaller than normal biconcave red blood cells. Mean Corpuscular Hemoglobin Concentration (MCHC): Increased (normal range: 31-36% Hb/cell). This is secondary to less water being in the cell. Red Blood Cell Distribution Width (RDW): Increased (normal range: 11-15%). The spherocytes create variation in the size of the red blood cells on average, thus expanding the distribution. Red Blood Cell Count (RBC): Sometimes Increased Early (normal range males: 4.3-5.9 million/mm3; normal range females: 3.5-5.5million/mm3). The loss of surface area per cells cause the body to mass produce red blood cells. The spleen will filter spherocytes out and change this value. Reticulocytes: Increased (normal range: 0.5%-1.5% of the RBC listed above).
The body to mass produces red blood cells (reticulocytes being young erythrocytes) even as the spleen filters spherocytes out. This is known as reticulocytosis. Unconjugated Bilirubin: Increased (normal range: 0.2-1.2 mg/dL). This is caused by heme released into the hepatosplenic circulation by macrophages that have phagocytosed erythrocytes. The unconjugated bilirubin is not soluble in water (blood), so it binds to albumin, and is processed in the liver. Haptoglobin (Free): Decreased (normal range: 41–165 mg/dL). This is caused by hemoglobin binding to haptoglobin, thus making it no longer "free." lactate dehydrogenase (LDH): Increased (Normal range: 110-295U/L in children). This is due to extravascular hemolysis. Peripheral Blood Smear: Directly shows spherocytes on microscope. Eosin-5-maleimide Binding Test: Positive (reduced mean fluorescence), as the test will demonstrate a reduced ability of the Eosin-5-maleimide dye to bind to erythrocyte plasma membrane proteins. The process relies upon flow cytometry. Gold standard test that produces results at low cost within ~2 hours.In chronic cases, patients who have taken iron supplementation, have heterozygous hemochromatosis, or received numerous blood transfusions, iron overload may cause additional health issues. Measuring iron stores is sometimes considered part of the diagnostic approach to hereditary spherocytosis in older patients presenting with heart muscle damage of unknown etiology or liver disease without apparent cause. Imaging
Ultrasound is often used to evaluate the dimensions of the spleen, and also the gallbladder in preparation for functionally curative splenectomy with or without cholecystectomy.