What are the initial investigations and management steps for a patient presenting with severe anemia?

Investigations for Severe Anemia

For severe anemia, immediately obtain a complete blood count with indices, reticulocyte count, peripheral blood smear, and iron studies (serum ferritin, transferrin saturation, TIBC), while simultaneously initiating iron replacement therapy without waiting for test results if iron deficiency is suspected. 1, 2

Initial Laboratory Workup

Essential First-Line Tests

• Complete blood count with MCV: Defines severity and classifies anemia as microcytic, normocytic, or macrocytic 1, 3
• Serum ferritin: The single most powerful test for iron deficiency; <15 μg/L is diagnostic (specificity 0.99), though values <45 μg/L warrant investigation especially with inflammation 1
• Transferrin saturation: Calculate as (Serum Iron/TIBC) × 100; <16% confirms iron deficiency, <20% suggests it 1, 4
• Reticulocyte count: Distinguishes between decreased production (inappropriately low) versus increased destruction or blood loss (elevated) 5, 3
• Peripheral blood smear: Identifies red cell morphology abnormalities, hemolysis, or hematologic malignancies 3, 6

Critical Caveats About Iron Studies

• Ferritin is an acute phase reactant: In patients with chronic inflammation, malignancy, or hepatic disease, ferritin may be falsely elevated above 12-15 μg/L despite true iron deficiency 1
• Use higher thresholds with inflammation: Ferritin <45 μg/L provides optimal sensitivity/specificity trade-off in inflammatory states; values >150 μg/L essentially exclude iron deficiency even with inflammation 1
• Response to iron therapy is diagnostic: A hemoglobin rise ≥10 g/L within 2 weeks strongly confirms iron deficiency even when iron studies are equivocal 1

Mandatory Additional Screening

Rule Out Common Non-GI Causes

• Urinalysis or urine microscopy: Excludes urinary tract bleeding as a rare but important cause 1, 2
• Celiac disease screening: Found in 3-5% of iron deficiency anemia cases; obtain tissue transglutaminase antibodies or perform small bowel biopsy during upper endoscopy 1, 2
• Serum creatinine and GFR: Identifies chronic kidney disease as a cause of anemia of chronic disease 1
• Vitamin B12 and folate levels: Essential if MCV is elevated or normal (combined deficiency can mask microcytosis) 1, 7

Gastrointestinal Investigation Algorithm

Who Requires Urgent GI Evaluation

All men and postmenopausal women with newly diagnosed iron deficiency anemia require bidirectional endoscopy (gastroscopy + colonoscopy) unless there is obvious non-GI blood loss. 1, 2

• Upper endoscopy identifies bleeding sources in 30-50% of cases: Common findings include peptic ulcers, gastric erosions, angiodysplasia, and malignancy 2
• Mandatory small bowel biopsies during gastroscopy: Must be performed even if mucosa appears normal, as 2-3% have celiac disease 1, 2
• Colonoscopy is non-negotiable: Must be performed regardless of upper endoscopy findings because dual pathology occurs in 10-15% of patients 2
• CT colonography is acceptable alternative: Use if patient unsuitable for colonoscopy 1

Premenopausal Women Exception

• GI investigation threshold is lower but not zero: Generally not warranted if menstrual blood loss or recent pregnancy explains the anemia, but maintain low threshold if GI symptoms, family history of GI pathology, or failure to respond to iron therapy 1

When to Investigate Small Bowel

Small bowel evaluation is NOT routinely needed initially. 2 Further investigation is warranted only if:

• Patient becomes transfusion-dependent 1, 2
• Persistent visible blood loss continues 1, 2
• Failure to respond to iron therapy after correcting dietary deficiency and stopping NSAIDs 2
• Capsule endoscopy is the preferred modality, with CT/MRI enterography as alternatives 1, 2

Immediate Management Priorities

Start Iron Replacement Without Delay

• Begin oral iron immediately: Use 100-200 mg elemental iron daily without waiting for endoscopic evaluation 2
• Standard regimen: Ferrous sulfate 200 mg three times daily, or equivalent ferrous gluconate/fumarate 4
• Continue for 3 months after hemoglobin normalization: Required to fully replenish iron stores 2
• Consider ascorbic acid: Enhances absorption when response is suboptimal 4

Stop Offending Medications

• Discontinue NSAIDs and aspirin immediately: These are common culprits for occult GI bleeding 2

Critical Pitfalls to Avoid

• Never assume dietary deficiency alone: Full GI investigation is mandatory even with positive dietary history if overt blood is present 2
• Never stop after finding single upper GI lesion: Complete lower tract evaluation due to 10-15% dual pathology rate 2
• Never rely on fecal occult blood testing: It is insensitive and non-specific for risk stratification 1, 4
• Never ignore mild anemia: There is no evidence that mild anemia is less indicative of important disease than severe anemia 1

Risk Stratification Factors

Age, sex, hemoglobin concentration, and mean cell volume are all independent predictors of GI cancer risk and must be considered holistically. 1

• Non-anemic iron deficiency (low ferritin, normal hemoglobin) carries low cancer risk and generally does not warrant GI investigation in premenopausal women 1
• Men and postmenopausal women with non-anemic iron deficiency should have low threshold for investigation, especially with GI symptoms or family history 1