Investigations
1st investigations to order
peripheral blood smear
Test
Macrocytic anaemia and hypersegmented polymorphonuclear neutrophils are classically seen in folate and vitamin B12 (cobalamin) deficiencies. Macro-ovalocytes are seen in early folate deficiency.[Figure caption and citation for the preceding image starts]: Megaloblastic macrocytic anaemia: A. Peripheral blood smear of a patient with megaloblastic anaemia. B. Peripheral blood smear of healthy individualPhotomicrograph from Mark J. Koury, MD; used with permission [Citation ends].
Result
macrocytosis, anisocytosis, poikilocytosis, hypersegmented neutrophils
FBC
Test
Elevated mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) can precede anaemia by a few weeks; thrombocytopenia and neutropenia are seen in advanced cases.[30]
Result
low haemoglobin, elevated MCV and MCH; increased MCV and MCH may be absent or less than expected in combined folate and iron deficiency; thrombocytopenia, neutropenia in advanced cases
reticulocyte count
Test
Low count indicates decreased production.
Result
low corrected reticulocyte count
Investigations to consider
serum folate
red blood cell folate
Test
Better indicator of tissue folate status than serum folate.[47] Can help detect the 5% of folate deficient patients with normal serum folate.
May be normal in acute folate deficiency.
Red blood cell folate is low in >50% of patients with vitamin B12 (cobalamin) deficiency.
A more complex and expensive test than serum folate.
Result
low
serum vitamin B12
Test
Underlying vitamin B12 (cobalamin) deficiency should be ruled out before implementing therapy with folic acid, because such therapy may mask neurological complications of untreated vitamin B12 deficiency.
Result
normal
serum LDH
Test
Sign of ineffective erythropoiesis, present in advanced anaemia.
Not useful to rule in or rule out folate deficiency.
Result
elevated
serum unconjugated bilirubin
Test
Sign of ineffective erythropoiesis (i.e., intramedullary haemolysis), present in advanced anaemia.
Not useful to rule in or rule out folate deficiency.
Result
elevated
serum iron panel
Test
Sign of ineffective erythropoiesis.
Not useful to rule in or rule out folate deficiency.
Result
elevated serum iron, ferritin, transferrin
plasma or serum methylmalonic acid
plasma homocysteine
Test
Useful in borderline folate levels, suspected combined deficiency states, and folate-deficient patients with normal serum folate.[46]
Elevated in >95% of patients with vitamin B12 (cobalamin) deficiency.
Sensitivity is only 86% in detecting clinical folate deficiency states.[49]
Level affected by renal function.
Result
elevated
bone marrow aspirate/biopsy
Test
Classic findings of megaloblastic erythropoiesis seen in both folate and vitamin B12 (cobalamin) deficiencies.
Not required to confirm diagnosis.[Figure caption and citation for the preceding image starts]: Megaloblastic marrow cellsPhotomicrograph from Mark J. Koury, MD; used with permission [Citation ends].
Result
megaloblastic changes, erythroid hyperplasia, abnormal nuclear appearance
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