Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (289 page)

   CBC:

   Anemia with oval macrocytes, poikilocytosis and anisocytosis, small tear-drop cells

   High RDW

   Thrombocytopenia and leukopenia in severe cases

   Hypersegmented polymorphonuclear cells and giant metamyelocytes in megaloblastic anemias

   Reticulocyte count: inadequate for the degree of anemia.

   Serum or RBC folate and serum cobalamin are obtained if another etiology is not obvious. The specific metabolites methylmalonic acid and homocysteine accumulate in these deficiencies; they are additional assays and may help discriminate between cobalamin and folate deficiencies and other etiologies for macrocytic anemias. These assays, as well as RBC folate, are more expensive and should be reserved for patients with borderline folate or cobalamin values but strong suspicion of one or the other.

   Serum cobalamin if <200 pg/mL is consistent with vitamin B
₁₂
deficiency.

   Serum folate if <2 ng/mL is consistent with folate deficiency.

   Serum or urine methylmalonic acid if increased confirms vitamin B
₁₂
deficiency. It may be normal in folate deficiency.

   Homocysteine (total) if elevated is compatible with either cobalamin or folate deficiency. If normal, both can be excluded.

   Documentation of cobalamin deficiency does not establish the diagnosis of PA, an autoimmune disease characterized by deficiency of intrinsic factor (IF) and lack of HCl gastric secretion. PA was traditionally diagnosed by the absorption of orally administrated radiolabeled cobalamin, the Schilling test (no longer available in the United States). In its absence, the assays mentioned above are helpful, but not specific for PA. Fifty percent to 70% of PA patients will have positive serum anti-IF antibodies, thus documenting PA (100% specificity). The patients who are negative for IF antibodies cannot be distinguished from non-PA cases of cobalamin malabsorption but will respond to oral vitamin B
₁₂
if not PA. Antiparietal antibodies are less sensitive or specific. Recently, chronic
Helicobacter pylori
infection has been implicated in the etiology of PA and the lack of IF.