Differentials
Nonhemolytic anemia
SIGNS / SYMPTOMS
No specific differentiating clinical features.
Jaundice and splenomegaly indicate hemolysis rather than other causes of anemia.
There is more likely to be a family history of HS in patients with HS.
INVESTIGATIONS
CBC and blood smear morphology are typical for each type of anemia.
Iron deficiency anemia (most common cause of anemia): CBC and blood smear reveal a microcytic (low MCV), hypochromic (increased central pallor) anemia; if performed, serum ferritin is low.
HS CBC and blood smear: normal or reduced Hb, increased reticulocytes and presence of spherocytes.
Other causes of hemolytic anemia
SIGNS / SYMPTOMS
May be no specific differentiating clinical features.
There is more likely to be a family history of HS in patients with HS.
INVESTIGATIONS
CBC and blood smear helps to confirm specific diagnosis.
Spherocytes may not be present on the blood smear. Schistocytes are indicative of a microangiopathic process (e.g., disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome) or a traumatic process (e.g., mechanical prosthetic heart valve, march hemolysis). Elliptocytes may indicate elliptocytosis. Blister or bite cells indicate the presence of oxidant damage to the cell. Spur cells may occur with liver disease. Red blood cell inclusions may occur with infections (e.g., malaria, babesiosis, and Bartonella infections).
The direct antiglobulin test (DAT) is usually positive in autoimmune hemolytic anemia. A negative DAT makes autoimmune hemolysis very unlikely.
Hb electrophoresis detects hemoglobinopathy.
Glucose-6-phosphate dehydrogenase deficiency is diagnosed by fluorescent spot test, followed by definitive assay of glucose-6-phosphate dehydrogenase activity by spectrophotometry tests.
Flow cytometry for CD55/CD59 tests for paroxysmal nocturnal hemoglobinuria.
There is abnormal renal function with hemolytic uremic syndrome or thrombotic thrombocytopenic purpura.
Other causes of spherocytosis
SIGNS / SYMPTOMS
May be no specific differentiating clinical features.
There is more likely to be a family history of HS in patients with HS.
INVESTIGATIONS
Blood smear may reveal morphology that is atypical for HS. Further specialist investigation may be required for atypical cases (e.g., quantitative protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis).[16]
The eosin-5-maleimide binding test may be abnormal in other red-cell disorders, particularly congenital dyserythropoietic anemia type II.
Maternal screen and a positive DAT in an infant detects irregular maternal antibody as a cause of neonatal spherocytosis.
Other red-cell membrane disorders
SIGNS / SYMPTOMS
May be no specific differentiating clinical features.
There is more likely to be a family history of HS in patients with HS.
INVESTIGATIONS
Careful exam of the blood smear for morphology of red cells is important. Further specialist investigation may be required for atypical cases.[16]
Other causes of jaundice
SIGNS / SYMPTOMS
May be no specific differentiating clinical features.
There is more likely to be a family history of HS in patients with HS.
INVESTIGATIONS
Abnormal LFTs (various different patterns of specific liver enzyme abnormality depending on the condition) are an indicator of liver dysfunction. LFTs will usually be normal in HS apart from elevated unconjugated bilirubin.
Screening for infectious hepatitis will be positive if this is the cause of jaundice, but negative in HS. However, HS can present during an exacerbation due to intercurrent infection (e.g., infectious mononucleosis), which may be associated with deranged LFTs.
Neonatal blood smears can be difficult to interpret. Review of the blood smear after a period of time may be needed before a definite diagnosis is made. The typical smear appearances of spherocytes in HS are easier to see after a few months.
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