What is the complete blood count (CBC) picture of megaloblastic anemia?

CBC Picture of Megaloblastic Anemia

Megaloblastic anemia presents with macrocytic anemia (MCV >100 fL, often >110-120 fL), accompanied by characteristic peripheral blood findings including macro-ovalocytes, hypersegmented neutrophils (≥5 lobes), anisocytosis, and often pancytopenia with elevated RDW. 1, 2

Peripheral Blood Findings

Red Blood Cell Abnormalities

• Macrocytosis with MCV typically >100 fL, with severe cases often showing MCV >110-120 fL (values >120 fL are usually caused by vitamin B12 deficiency specifically) 3
• Macro-ovalocytes (large oval-shaped red cells) are the most characteristic morphologic feature distinguishing megaloblastic from other causes of macrocytosis 3
• Marked anisocytosis (variation in red cell size) with elevated RDW 3
• Teardrop cells (dacrocytes) may be present 3
• Anemia with hemoglobin often significantly reduced in symptomatic cases 1, 4

White Blood Cell Abnormalities

• Hypersegmented neutrophils are pathognomonic—defined as neutrophils with ≥5 nuclear lobes (normally 2-4 lobes) 2
• Leukopenia is common, particularly neutropenia 4, 2
• Giant metamyelocytes may be seen in severe cases 2

Platelet Abnormalities

• Thrombocytopenia frequently occurs 4, 2
• Platelet count can be severely reduced, sometimes mimicking thrombocytopenic purpura 2

Important Diagnostic Pitfalls

Pancytopenia Presentation

• Pancytopenia (anemia, leukopenia, and thrombocytopenia together) is common in megaloblastic anemia and can mimic myelodysplastic syndrome or other myeloid neoplasms 2
• This triad requires careful evaluation to distinguish megaloblastic anemia from more serious hematologic malignancies 2

Normal MCV at Presentation

• A normal MCV does NOT exclude megaloblastic anemia—this occurs commonly and represents a significant diagnostic trap 2
• Concomitant iron deficiency, thalassemia trait, or inflammatory conditions can mask the macrocytosis 2

Partially Treated Cases

• Partially treated megaloblastic anemia (patients who received some B12 or folate before complete evaluation) creates unique diagnostic challenges with mixed morphologic features 2

Additional Laboratory Features

Indirect Evidence of Ineffective Erythropoiesis

• Elevated indirect bilirubin from intramedullary hemolysis (destruction of abnormal red cell precursors in bone marrow) 1
• Elevated LDH (lactate dehydrogenase) reflecting increased cell turnover 1
• Low reticulocyte count despite anemia (inappropriately low for degree of anemia) 4

Confirmatory Testing

• Serum vitamin B12 <200 pg/mL suggests B12 deficiency 4
• Red blood cell folate <340 nmol/L or serum folate <10 nmol/L indicates folate deficiency 5
• Elevated methylmalonic acid and homocysteine are useful for confirming B12 deficiency when serum B12 is borderline 3
• Bone marrow examination shows characteristic megaloblastic changes with nuclear-cytoplasmic asynchrony, though this is rarely needed when classic peripheral blood findings and vitamin deficiencies are present 6, 1

Critical Clinical Context

Both vitamin B12 and folate deficiency must be evaluated simultaneously because they produce identical hematologic pictures, but B12 deficiency causes neurologic complications that folate supplementation alone will not prevent and may worsen 5, 4. The blood picture may improve with folate treatment while neurological manifestations progress if concomitant B12 deficiency is ignored 5.