Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (307 page)

Basis of diagnosis
:

   Generation of NADPH from NADP as detected by either quantitative spectrophotometric analysis or, more rapidly, by screening tests, such as a fluorescent spot test.

   G6PD levels may be normal during and shortly following a hemolytic episode in type A– cases, because very young RBCs contain sufficient enzyme.
Assays for G6PD should be postponed for at least 6 weeks after an acute episode.

CBC
: Hemolytic anemia: chronic in class 1 and intermittent in classes 2 and 3. It is seen 2–4 days after ingestion of an oxidant drug (primaquine and sulfa drugs are the most common offending agents) or after fava beans consumption. Female carriers: possible mild hemolytic episodes that are difficult to diagnose with conventional methodology; they can be diagnosed by genetic methods.

   Peripheral blood smear (PBS): Heinz bodies in RBCs (require brilliant cre sylblue supravital special stain), nucleated RBCs, spherocytes, poikilocytes, fragmented RBCs, and bite cells.

   Reticulocytosis.

   MCV may be elevated in type A− patients if not supplemented with folic acid.

   Bilirubin is elevated correlating to the degree of hemolysis. Neonatal jaundice develops in 5% of affected newborns of African or Mediterranean ancestry after the first 24 hours of life. Serum indirect bilirubin reaches a peak (often >20 mg/dL) at 3rd to 5th day with resulting kernicterus if not treated promptly.

PYRUVATE KINASE (PK) DEFICIENCY

   Definition

PK deficiency is an autosomal recessive, nonspherocytic
chronic
hemolytic anemia. Affected individuals are either homozygous for a single mutation or heterozygous for two different PK mutations. The mechanism of hemolysis has not been elucidated.

   Who Should Be Suspected?

A patient with chronic, sometimes severe, nonimmune (Coombs negative) hemolytic anemia.

There is a wide range of clinical and laboratory findings. The severity of anemia varies from severe neonatal anemia requiring transfusions to a fully compensated hemolytic process in adults who have 10–20% of the normal enzyme in their RBCs. The severely affected patients may require frequent red cell transfusions and as a consequence develop iron storage overload. The severe cases present with jaundice, pallor, and splenomegaly. Such patients may also develop gallstones. The anemia may worsen after certain infections (aplastic crises). PK deficiency is more common in persons of northern European extraction and possibly in Chinese. The disease is particularly severe among the Amish of Pennsylvania.

   Laboratory Findings

   Peripheral blood smear (PBS) shows no characteristic changes, particularly no spherocytes.

   The laboratory diagnosis is based on demonstrating low erythrocytic PK enzymatic levels. A screening test using crude hemolysate detects heterozygous carriers in persons who are hematologically normal. This assay may miss some variants. Quantitation of the enzyme can be performed in specialized laboratories.