What is the appropriate diagnosis and treatment approach for an adult or elderly patient with profound anemia, potentially due to iron deficiency or vitamin deficiency, and a history of chronic disease?

Management of Profound Anemia in Adults

All patients with profound anemia require immediate iron supplementation with ferrous sulfate 200 mg three times daily to correct anemia and replenish body stores, while simultaneously investigating the underlying cause through bidirectional endoscopy (upper GI with small bowel biopsy and colonoscopy) unless there is severe co-morbidity where investigation would not change management. 1

Immediate Treatment Priorities

Iron Replacement Therapy

• Start oral ferrous sulfate 200 mg three times daily immediately as the most cost-effective first-line treatment, regardless of the underlying cause 1, 2
• Ferrous gluconate and ferrous fumarate are equally effective alternatives if ferrous sulfate is not tolerated 1
• Add ascorbic acid (vitamin C) if response is poor, as it enhances iron absorption 1
• Expect hemoglobin to rise by 2 g/dL after 3-4 weeks of treatment 1
• Continue iron supplementation for three months after correction of anemia to replenish body stores 1

When to Use Parenteral Iron

• Reserve parenteral iron only for patients with documented intolerance to at least two oral preparations or confirmed non-compliance 1
• Parenteral iron is painful (intramuscular), expensive, carries risk of anaphylactic reactions, and provides no faster hemoglobin rise than oral preparations 1

Blood Transfusion Criteria

• Consider red blood cell transfusion when hemoglobin is below 7 g/dL, or above this threshold if the patient has symptoms or particular risk factors (e.g., cardiac disease, hemodynamic instability) 1
• Always follow blood transfusions with subsequent intravenous iron supplementation, as transfusions only provide temporary correction without addressing underlying iron deficiency 1

Diagnostic Workup Algorithm

Initial Laboratory Assessment

Order these tests immediately in all patients with profound anemia: 3

• Complete blood count with mean corpuscular volume (MCV) and red cell distribution width (RDW)
• Serum ferritin (most specific test for iron deficiency)
• Reticulocyte count (critical to assess bone marrow response)
• Transferrin saturation
• Vitamin B12 and folate levels
• Urinalysis or urine microscopy
• Serum creatinine

Interpreting Ferritin Levels

• Ferritin <15 μg/L is diagnostic of iron deficiency with 99% specificity 1
• Ferritin <30 μg/L generally indicates low body iron stores 1
• Ferritin <45 μg/L warrants GI investigation, especially with chronic inflammatory conditions where ferritin may be falsely elevated 1
• Ferritin >100 μg/L with transferrin saturation <20% indicates functional iron deficiency in inflammatory states and still requires treatment 3
• Ferritin >150 μg/L makes absolute iron deficiency unlikely even with inflammation 1

Additional Testing Based on Initial Results

• Haptoglobin and lactate dehydrogenase (LDH) if hemolysis is suspected (elevated reticulocytes without obvious blood loss) 3
• Celiac serology (tissue transglutaminase or endomysial antibody with IgA level) in all patients, as celiac disease is found in 3-5% of iron deficiency anemia cases 1, 3
• Hemoglobin electrophoresis if microcytosis is present with normal iron studies, particularly in patients of appropriate ethnic background (to exclude thalassemia) 1

Gastrointestinal Investigation Strategy

Who Requires Bidirectional Endoscopy

90% of patients with iron deficiency anemia and no obvious cause should undergo both upper GI endoscopy with small bowel biopsy AND colonoscopy or barium enema 1

Age-Based Approach

• Patients >45 years: Full investigation with upper and lower GI endoscopy regardless of symptoms 1
• Patients <45 years: Upper GI endoscopy with small bowel biopsy only if upper GI symptoms present; otherwise check celiac serology 1
• Premenopausal women <45 years without GI symptoms: May defer investigation if menorrhagia, pregnancy, or breastfeeding explains the anemia, but maintain low threshold for investigation with any red flags 1

Upper Endoscopy Protocol

• Always obtain small bowel biopsies during upper endoscopy to screen for celiac disease, found in 2-3% of iron deficiency anemia patients 1
• Upper GI endoscopy reveals a cause in 30-50% of patients 1
• If upper endoscopy cannot be performed, obtain barium meal plus celiac antibodies 1

Lower GI Investigation

• Proceed with colonoscopy even if upper endoscopy reveals a lesion (except carcinoma or celiac disease), as dual pathology occurs in approximately 10% of cases 1
• In elderly patients, colonic investigation is more likely to be productive than upper endoscopy 1

When Standard Endoscopy is Negative

• Consider capsule endoscopy for small bowel evaluation if anemia persists or recurs despite treatment, as diagnostic yield is 50-73% in this setting 3
• Video capsule endoscopy is particularly important for detecting angiodysplasia and small bowel tumors 1

Critical Vitamin Deficiency Management

Vitamin B12 Deficiency

Check B12 levels in all patients with profound anemia, as deficiency may be masked in combined deficiency states 1, 3

For B12 deficiency WITH neurological involvement (unexplained sensory/motor symptoms, gait disturbance):

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 1
• Then hydroxocobalamin 1 mg intramuscularly every 2 months for life 1
• Seek urgent specialist advice from neurologist and hematologist immediately 1

For B12 deficiency WITHOUT neurological involvement:

• Administer hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1
• Then maintenance with 1 mg intramuscularly every 2-3 months for life 1

Folate Deficiency

• Never treat folate deficiency before excluding and treating B12 deficiency, as folate supplementation may mask B12 deficiency and precipitate subacute combined degeneration of the spinal cord 1, 3
• Once B12 deficiency is excluded or treated, give oral folic acid 5 mg daily for minimum of 4 months 1

Special Considerations

Anemia of Chronic Disease

• Optimize treatment of the underlying inflammatory condition first before considering erythropoiesis-stimulating agents (ESAs) 1
• ESAs may be considered only for patients with insufficient response to intravenous iron despite optimized disease therapy 1
• Target hemoglobin should not exceed 12 g/dL with ESA treatment 1

Patients with Severe Co-Morbidity or Advanced Age

• Carefully consider whether investigation results would change management before proceeding with invasive testing 1
• Discuss the appropriateness of investigation with patients and caregivers 1
• Treatment with iron supplementation should still be initiated regardless of investigation decisions 1

Monitoring and Follow-Up

Short-Term Monitoring

• Recheck hemoglobin after 3-4 weeks to confirm expected rise of 2 g/dL 1
• Failure to respond indicates poor compliance, misdiagnosis, continued blood loss, or malabsorption 1

Long-Term Monitoring

• Once hemoglobin normalizes, monitor hemoglobin and red cell indices every 3 months for one year, then annually 1
• Give additional oral iron if hemoglobin or MCV falls below normal (check ferritin in doubtful cases) 1
• Resolution of anemia should be achieved by 6 months in 80% of patients 1
• Further investigation is only necessary if hemoglobin and MCV cannot be maintained with iron supplementation 1

Common Pitfalls to Avoid

• Do not accept "normal" ferritin at face value in inflammatory states—ferritin >100 μg/L with transferrin saturation <20% still indicates functional iron deficiency requiring treatment 3
• Do not overlook combined deficiency states—normocytic anemia can result from simultaneous iron and B12/folate deficiency masking each other's typical MCV changes 3
• Do not assume negative endoscopy rules out GI blood loss—persistent or recurrent anemia warrants capsule endoscopy 3
• Do not forget medication review—NSAIDs, anticoagulants, and immunosuppressants can cause anemia through bleeding or bone marrow suppression 3
• Do not rely on faecal occult blood testing—it is insensitive and non-specific for iron deficiency anemia 1
• Do not stop anticoagulants or NSAIDs before investigation—their use should not usually deter diagnostic workup 1