What work‑up and management are indicated for a 46‑year‑old woman with microcytic anemia (MCV 69 fL), high red cell distribution width (RDW 20.7 %), normal mean corpuscular hemoglobin concentration (MCHC 30.6 g/dL), elevated alkaline phosphatase, mildly elevated aspartate aminotransferase (AST 45 U/L) and alanine aminotransferase (ALT 43 U/L), hypercholesterolemia (total cholesterol 272 mg/dL), hypertriglyceridemia (triglycerides 228 mg/dL), elevated low‑density lipoprotein (LDL 131 mg/dL), and pre‑diabetes (hemoglobin A1c 6.0 %)?

Workup and Management of Microcytic Anemia with Multiple Metabolic Abnormalities

Immediate Diagnostic Priority: Confirm Iron Deficiency

Order serum ferritin, transferrin saturation (TSAT), and C-reactive protein (CRP) immediately as the first-line tests to confirm iron deficiency anemia, which is the most likely diagnosis given the severe microcytosis (MCV 69 fL) and markedly elevated RDW (20.7%). 1

Interpretation of Iron Studies

• Ferritin < 30 μg/L confirms iron deficiency, while a cut-off of 45 μg/L provides optimal sensitivity and specificity in routine practice 1
• TSAT < 16–20% confirms iron deficiency, particularly when ferritin may be falsely elevated by inflammation 1
• The combination of low MCV (69 fL) with elevated RDW (20.7%) strongly favors iron deficiency over thalassemia trait, which typically presents with RDW ≤ 14% 1, 2
• CRP must be measured concurrently because ferritin is an acute-phase reactant that can be falsely elevated in inflammatory, infectious, malignant, or hepatic conditions 1

Critical Pitfall to Avoid

Do not assume all microcytic anemia is iron deficiency—if iron studies show ferritin > 100 μg/L with TSAT < 20%, this indicates anemia of chronic disease rather than true iron deficiency 1. However, given the extreme microcytosis (MCV 69) and very high RDW (20.7), iron deficiency is by far the most likely diagnosis 1, 2.

Mandatory Investigation for Source of Iron Loss

Once iron deficiency is confirmed, gastrointestinal evaluation with both upper endoscopy (with duodenal biopsies) and colonoscopy is mandatory in a 46-year-old woman, as GI blood loss—including from malignancy—must be excluded even when menstrual bleeding appears explanatory. 1

Specific Investigations Required

• Upper endoscopy with duodenal biopsies to exclude celiac disease (present in 2–3% of iron deficiency anemia patients), gastric malignancy, NSAID-induced gastropathy, and peptic ulcer disease 1
• Colonoscopy to exclude colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease 1
• Celiac serologic screening (tissue transglutaminase antibody with total IgA) should be performed before endoscopy 1
• Gynecologic evaluation for menorrhagia, including pelvic ultrasound and consideration of endometrial sampling if indicated 1

Why Both Upper and Lower GI Evaluation Are Required

Do not accept upper GI findings (such as esophagitis or peptic ulcer) as the sole cause without also examining the lower GI tract, because dual pathology is present in approximately 10–15% of patients. 1

Immediate Treatment While Workup Proceeds

Start oral ferrous sulfate 200 mg three times daily immediately while diagnostic evaluation proceeds—severe iron deficiency should be treated without delay. 1

Treatment Details and Monitoring

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least 3 months after correction of anemia to replenish iron stores 1
• Alternative formulations (ferrous gluconate or ferrous fumarate) can be used if ferrous sulfate is not tolerated 1
• Ascorbic acid (vitamin C) can be added to enhance iron absorption 1
• Expected response: hemoglobin should rise ≥ 10 g/L within 2 weeks if iron deficiency is the cause 1
• If no response within 2–4 weeks, consider non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders such as IRIDA (iron-refractory iron deficiency anemia) 1

When to Consider Intravenous Iron

If malabsorption is confirmed (e.g., celiac disease) or the patient fails oral therapy despite compliance, switch to intravenous iron (iron sucrose or iron gluconate) with expected hemoglobin increase of at least 2 g/dL within 4 weeks. 1

Evaluation for Combined Deficiencies

The markedly elevated RDW (20.7%) may indicate combined deficiencies—iron deficiency can coexist with vitamin B12 or folate deficiency. 1, 3

• Check vitamin B12 and red blood cell folate levels if the patient does not respond appropriately to iron therapy or if macrocytic cells are seen on peripheral smear 3
• Do not give folic acid without ensuring B12 is repleted or given concomitantly, to avoid masking B12 deficiency while allowing irreversible neurologic damage to progress 3

Management of Other Metabolic Abnormalities

Pre-diabetes (HbA1c 6.0%)

• Initiate lifestyle modifications including medical nutrition therapy, weight loss if BMI ≥ 25 kg/m², and 150 minutes/week of moderate-intensity physical activity
• Recheck HbA1c in 3 months to assess progression

Hyperlipidemia (Total cholesterol 272, Triglycerides 228, LDL 131)

• Calculate 10-year ASCVD risk using the pooled cohort equation
• Initiate moderate-intensity statin therapy (e.g., atorvastatin 10–20 mg daily) given the presence of multiple risk factors (pre-diabetes, hyperlipidemia)
• Address hypertriglyceridemia with lifestyle modifications (weight loss, reduced refined carbohydrates, increased omega-3 fatty acids); consider fibrate therapy if triglycerides remain > 500 mg/dL after statin initiation

Mildly Elevated Liver Enzymes (AST 45, ALT 43, Alkaline Phosphatase 152)

• These mild elevations are likely secondary to non-alcoholic fatty liver disease (NAFLD) given the metabolic profile (pre-diabetes, hyperlipidemia)
• Obtain right upper quadrant ultrasound to assess for hepatic steatosis
• Recheck liver enzymes in 3 months after addressing metabolic risk factors
• Do not attribute iron deficiency to liver disease—the liver abnormalities are too mild to cause anemia

When to Consider Rare Genetic Causes

Genetic disorders of iron metabolism (such as IRIDA) should be considered only if there is failure to respond to both oral and intravenous iron, remarkably low TSAT with low-to-normal ferritin, or family history of refractory anemia. 1

• IRIDA is characterized by remarkably low TSAT with low-to-normal ferritin and fails oral iron but may respond to IV iron 1
• Hemoglobin electrophoresis should be ordered if microcytosis persists with normal iron studies or if MCV is disproportionately low relative to degree of anemia, to exclude thalassemia trait 1
• Referral to hematology is appropriate only if the cause remains unclear after comprehensive GI evaluation and trial of iron therapy 4

Summary Algorithm

1. Order ferritin, TSAT, CRP immediately 1
2. Start oral ferrous sulfate 200 mg three times daily 1
3. Arrange upper endoscopy with duodenal biopsies AND colonoscopy 1
4. Check vitamin B12 and folate if RDW remains elevated or poor response to iron 3
5. Monitor hemoglobin in 2 weeks—expect rise ≥ 10 g/L 1
6. Continue iron for 3 months after anemia correction to replenish stores 1
7. Address metabolic abnormalities (pre-diabetes, hyperlipidemia, NAFLD) with lifestyle modifications and pharmacotherapy as indicated
8. Consider IV iron or hematology referral only if failure to respond to oral therapy despite compliance and negative GI workup 1