What is the diagnosis and treatment for a 32-year-old pregnant woman at 13 weeks gestation with anorexia (lack of appetite), skin hyperpigmentation (darkening of the skin), diarrhea, nausea, low hematocrit (34%), anemia (hemoglobin 10.4), and microcytic hypochromic anemia (mean corpuscular hemoglobin 40, mean corpuscular volume 105)?

Diagnosis: Macrocytic Anemia Due to Vitamin B12 and/or Folate Deficiency in Pregnancy

This pregnant woman has macrocytic anemia (MCV 105, which is elevated, not microcytic as incorrectly stated in the question), most likely due to vitamin B12 and/or folate deficiency, with skin hyperpigmentation suggesting possible B12 deficiency. The laboratory values clearly show macrocytosis (MCV 105 fL, normal range 80-100 fL), not microcytosis, which fundamentally changes the diagnostic approach 1, 2, 3.

Key Diagnostic Features

The elevated MCV of 105 fL definitively indicates macrocytic anemia, not microcytic anemia. This is a critical distinction that determines the entire diagnostic and treatment pathway 1, 2, 3.

Laboratory Interpretation

• Hemoglobin 10.4 g/dL and hematocrit 34% indicate anemia in pregnancy (normal Hb >11 g/dL in first trimester) 4
• MCV 105 fL is elevated, indicating macrocytosis (normal 80-100 fL) 1, 2, 3
• MCH 40 pg is elevated (normal 27-33 pg), consistent with macrocytic anemia 1, 2
• The combination of macrocytosis with gastrointestinal symptoms (diarrhea, nausea, anorexia) strongly suggests vitamin B12 or folate deficiency 1, 3

Clinical Features Suggesting B12 Deficiency

• Skin hyperpigmentation is a recognized manifestation of vitamin B12 deficiency, particularly in darker-skinned individuals 5
• Gastrointestinal symptoms (diarrhea, nausea, anorexia) are common in B12 deficiency 5, 6
• Pregnancy increases nutritional demands, making deficiency more likely 4, 5

Diagnostic Workup Required

Immediately measure serum vitamin B12, serum folate, and red blood cell folate levels to confirm the diagnosis. 1, 5, 3

Essential Laboratory Tests

• Serum vitamin B12 level: <200 pg/mL indicates deficiency 5, 3
• Serum folate and RBC folate: Low levels confirm folate deficiency 5, 3
• Methylmalonic acid (MMA) and homocysteine: Elevated MMA is specific for B12 deficiency; both are elevated in B12 deficiency, while only homocysteine is elevated in folate deficiency 5, 3
• Reticulocyte count: Should be assessed to evaluate bone marrow response 4, 1
• Peripheral blood smear: Look for hypersegmented neutrophils (>5% with 5 lobes or any with 6 lobes), which are characteristic of megaloblastic anemia 5, 3

Treatment Approach

Begin immediate supplementation with both folic acid and vitamin B12 while awaiting confirmatory test results, as delays in treatment during pregnancy can harm both mother and fetus. 4, 5

Immediate Treatment Protocol

• Folic acid 1-5 mg orally daily should be started immediately 4, 5
• Vitamin B12 (cyanocobalamin) 1000 mcg intramuscularly daily for 1 week, then weekly for 4 weeks, then monthly if B12 deficiency is confirmed 5, 6
• Alternatively, oral B12 1000-2000 mcg daily can be used if absorption is intact 5, 6
• Continue prenatal vitamins containing iron (30 mg elemental iron daily) as recommended for all pregnant women 4

Monitoring Response

• Recheck complete blood count in 1-2 weeks: Expect reticulocytosis within 3-5 days and hemoglobin increase of ≥1 g/dL within 2 weeks 1, 7, 5
• Monitor hemoglobin every 2-4 weeks until normalized for gestational age 4, 5
• Continue treatment throughout pregnancy and postpartum to maintain adequate stores 4, 5

Investigation of Underlying Cause

After initiating treatment, investigate the underlying cause of vitamin deficiency, particularly malabsorption disorders. 4, 5, 6

Common Causes to Evaluate

• Dietary insufficiency: Particularly in vegetarians/vegans (B12) or poor nutritional intake 5, 6, 3
• Pernicious anemia: Check anti-intrinsic factor antibodies and anti-parietal cell antibodies 5, 6
• Celiac disease: Consider tissue transglutaminase antibodies and small bowel biopsy if indicated 4, 5
• Inflammatory bowel disease: Particularly Crohn's disease affecting terminal ileum (B12 absorption site) 4, 5
• Previous gastric surgery: Impairs B12 absorption 4, 6
• Medications: Metformin, proton pump inhibitors, H2 blockers can impair B12 absorption 5, 6

Critical Pitfalls to Avoid

Never treat with folic acid alone without also addressing potential B12 deficiency, as this can precipitate or worsen neurological complications of B12 deficiency. 5, 3

Key Caveats

• Treating folate deficiency alone in the presence of unrecognized B12 deficiency can mask the anemia while allowing neurological damage to progress 5, 3
• Pregnancy increases folate requirements 5-10 fold, making deficiency common even with adequate dietary intake 4, 5
• Skin hyperpigmentation may take months to resolve even with adequate B12 replacement 5
• If hemoglobin does not increase by ≥1 g/dL within 2 weeks, consider combined deficiencies, ongoing blood loss, or incorrect diagnosis 4, 1, 5

When to Refer

• If hemoglobin <9 g/dL, refer to a physician familiar with anemia in pregnancy for further evaluation 4
• If neurological symptoms develop (paresthesias, ataxia, cognitive changes), urgent hematology consultation is needed 5, 6
• If anemia does not respond to appropriate supplementation within 4 weeks, hematology referral is indicated 4, 5