What is the cause of leukopenia and potential anemia or nutritional deficiency in an adult patient with low MCH and MCHC values?

Microcytic Hypochromic Anemia with Leukopenia: Diagnostic Approach

This patient has iron deficiency anemia (IDA) as the primary diagnosis, evidenced by low MCH (25.7 pg) and MCHC (30.8 g/dL) with borderline low WBC (3.7 K/uL), requiring immediate iron studies (ferritin and transferrin saturation) and investigation for underlying blood loss or malabsorption. 1

Understanding the Laboratory Findings

The CBC reveals several key abnormalities that point toward a specific diagnostic pathway:

• Low MCH (25.7 pg, reference 27.0-33.0) and low MCHC (30.8 g/dL, reference 31.6-35.4) are the hallmark findings of iron deficiency 1, 2
• MCH is more reliable than MCV for detecting iron deficiency because it's less affected by storage conditions and machine variability 1, 2
• The normal MCV (83.3 fL) does not exclude iron deficiency—this is a critical pitfall, as normal MCV can occur in early or mild iron deficiency 1, 3
• Mild leukopenia (3.7 K/uL) may indicate nutritional deficiency affecting multiple cell lines, particularly folate or B12 deficiency 4, 5

Immediate Diagnostic Workup Required

First-Line Iron Studies

Order serum ferritin and transferrin saturation immediately to confirm iron deficiency: 6, 1, 2

• Ferritin <15 μg/L is highly specific (99%) for absent iron stores 6, 1
• Ferritin <30 μg/L indicates low body iron stores 6, 1
• Ferritin <45 μg/L provides optimal sensitivity/specificity trade-off for iron deficiency in practice 6, 1
• Transferrin saturation <20% supports iron deficiency diagnosis 1, 2

Additional Nutritional Assessment

Given the leukopenia, check vitamin B12 and folate levels to exclude combined nutritional deficiencies: 6, 5

• Folate deficiency can cause macrocytic anemia but may coexist with iron deficiency 7, 8
• B12 deficiency causes macrocytic anemia and leukopenia, and can mask iron deficiency 9, 5
• Never give folic acid before excluding B12 deficiency, as folic acid may correct anemia but allow progression of irreversible neurological damage (subacute combined degeneration of the spinal cord) 9

Investigating the Underlying Cause

Mandatory Evaluation for Blood Loss

In adults with confirmed iron deficiency, investigation for gastrointestinal or genitourinary blood loss is mandatory: 6, 1

• Urinalysis or urine microscopy to exclude urinary blood loss 6
• Detailed menstrual history in premenopausal women (heavy menstrual bleeding is the most common cause) 1
• Gastroscopy and colonoscopy should be first-line investigations in men and postmenopausal women with newly diagnosed IDA 6
• Screen for celiac disease serologically, as it's found in 3-5% of IDA cases and causes malabsorption 6

Risk Stratification for Malignancy

Age, sex, hemoglobin concentration, and MCV are independent predictors of GI cancer risk in IDA: 6

• Approximately one-third of men and postmenopausal women with IDA have underlying pathological abnormalities, most commonly in the GI tract 6
• Fast-track secondary care referral is indicated for unexplained IDA in at-risk individuals due to potential GI malignancy 6

Treatment Algorithm

If Iron Deficiency Confirmed (Ferritin <45 μg/L)

Start oral iron supplementation immediately: 1

• Ferrous sulfate 200 mg three times daily for at least 3 months after correction of anemia to replenish iron stores 1
• Alternative formulations (ferrous gluconate or ferrous fumarate) if ferrous sulfate not tolerated 1
• Add ascorbic acid to enhance iron absorption 1
• Expected response: hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency 6, 1, 2

If No Response to Oral Iron After 2-4 Weeks

Consider the following causes of treatment failure: 1

• Non-compliance with medication
• Ongoing blood loss (requires investigation)
• Malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery) 6, 1
• Switch to intravenous iron if malabsorption present, with expected hemoglobin increase ≥2 g/dL within 4 weeks 1
• Rare genetic disorders of iron metabolism (IRIDA, SLC11A2 defects) if extreme microcytosis (MCV <70) or family history 1

If B12 or Folate Deficiency Identified

For B12 deficiency with neurological symptoms: 9

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 6
• Then hydroxocobalamin 1 mg intramuscularly every 2 months lifelong 6

For B12 deficiency without neurological symptoms: 6

• Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 6
• Then maintenance 1 mg intramuscularly every 2-3 months lifelong 6

For folate deficiency (only after excluding B12 deficiency): 6

• Folic acid 5 mg orally daily for minimum 4 months 6

Monitoring and Follow-Up

Monitor hemoglobin and red cell indices: 1

• Recheck at 2 weeks to confirm response to iron therapy 1, 2
• Monitor at 3-monthly intervals for one year, then after a further year 1
• Provide additional oral iron if hemoglobin or MCV falls below normal 1

Critical Pitfalls to Avoid

• Do not assume normal MCV excludes iron deficiency—MCH and MCHC are more sensitive early markers 1, 2, 3
• Do not give folic acid before excluding B12 deficiency—this can precipitate irreversible spinal cord damage 9
• Do not overlook combined deficiencies—iron deficiency can coexist with B12 or folate deficiency 1, 5
• Do not fail to investigate the source of iron loss in adults—GI malignancy must be excluded 6, 1
• Do not use hemoglobin electrophoresis unless microcytosis persists with normal iron studies—this suggests thalassemia trait 6, 1