Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (308 page)

   Genetic tests are the most definitive approach to diagnosis.

   Elevated levels of LDH and decreased haptoglobin can be seen.

HEREDITARY SPHEROCYTOSIS (HS)

   Definition

HS is a congenital red cell membrane abnormality resulting from defects in one of six genes encoding proteins involved in vertical linkages that tie the membrane skeletal network of the RBCs with the lipid bilayer. The ankyrin gene is the one most commonly involved. HS is inherited as autosomal dominant transmission in 75% of affected individuals. The condition is recessive or presents as a new mutation in the remaining 25%. HS is seen mostly in patients of northern European origin.

   Who Should Be Suspected

   Patients with mild to severe anemia, jaundice, splenomegaly, and cholelithiasis early in life, and a family history of a hereditary hemolytic anemia.

   Exacerbations of anemia may occur in aplastic (infections with parvovirus B19 or other viruses), hemolytic crises (with some viral infections), or due to the development of megaloblastic anemia, usually the result of folate deficiency.

   Laboratory Findings

   CBC: Anemia of varying severity, but with acute exacerbations (see above). Moderately severe anemia occurs in approximately 70% of cases. Approximately 20% have mild, compensated hemolysis. Approximately 10% of HS patients have severe, debilitating anemia and are transfusion dependent, unless splenectomized (splenectomy ameliorates the anemia, but spherocytosis persists). Indices: normal or slightly low MCV (except elevated when the reticulocyte count is very high or if the patient is folate deficient), elevated MCHC (the most helpful red cell index in HS), and RDW.

   Reticulocytosis (5–20%).

   Peripheral blood smear (PBS): Spherocytosis of various degrees is invariably present. Howell-Jolly bodies indicate previous splenectomy. The presence of spherocytes on peripheral blood smear (PBS) is not pathognomonic: it may be due to acquired hemolytic anemias rather than HS.

   Osmotic fragility reveals increased RBC fragility, but it may be abnormal (increased) also in patients with acquired hemolytic anemias.

   Ektacytometry, acidified glycerol lysis test, cryohemolysis test, and especially the flow cytometric eosin-5-maleimide tests have
surpassed the osmotic fragility test in sensitivity and specificity
but may only be available in specialized laboratories.