What is the best course of action for a patient with severe anemia (low hemoglobin levels), consistently below 7 g/dL, without evidence of gastrointestinal (GI) bleeding and a normal colonoscopy result?

Management of Severe Anemia (Hemoglobin <7 g/dL) Without Gastrointestinal Bleeding

You should transfuse this patient immediately with packed red blood cells (one unit at a time, reassessing after each unit) to achieve a hemoglobin of 7-8 g/dL, while simultaneously investigating non-GI causes of iron deficiency anemia and initiating intravenous iron supplementation. 1, 2

Immediate Transfusion Management

Blood transfusion is almost always indicated when hemoglobin is below 7 g/dL, particularly when anemia is causing symptoms or the patient has cardiovascular comorbidities. 1, 2

• Transfuse one unit of packed red blood cells at a time, then reassess clinical status and hemoglobin before administering additional units. 1, 2
• Each unit should increase hemoglobin by approximately 1-1.5 g/dL. 1, 2
• Target a post-transfusion hemoglobin of 7-8 g/dL in most patients, as higher targets (>10 g/dL) have not shown benefit and may increase complications including volume overload, transfusion-related acute lung injury, and infections. 1, 2
• For patients with known cardiovascular disease, consider a slightly higher threshold of 8 g/dL. 1, 2

Diagnostic Workup for Non-GI Causes

Since colonoscopy is normal and there is no evidence of GI bleeding, you must pursue upper GI endoscopy with small bowel biopsies and evaluate for non-GI causes of iron deficiency. 3

Upper GI Evaluation

• Perform upper GI endoscopy with small bowel biopsies to evaluate for celiac disease, which accounts for 2-3% of iron deficiency anemia cases. 3
• Upper GI endoscopy reveals a cause in 30-50% of patients with iron deficiency anemia. 3
• Even if upper GI pathology is found (such as erosions, esophagitis, or peptic ulcer), do not assume this is the sole cause—dual pathology occurs in 10-15% of patients. 3

Small Bowel Investigation

• If both upper and lower endoscopy are negative and the patient remains transfusion-dependent, proceed to video capsule endoscopy. 3
• Capsule endoscopy has a diagnostic yield of 47-66% in patients with iron deficiency anemia after negative bidirectional endoscopy. 3
• Small bowel investigation is particularly indicated when hemoglobin continues to drop despite iron supplementation, requiring repeated transfusions. 3
• Enteroscopy may be helpful to detect and treat small bowel angiodysplasia in transfusion-dependent patients. 3

Non-GI Causes to Evaluate

• Check for urinary tract bleeding by testing for hematuria, as urinary tract tumors occasionally present with iron deficiency anemia. 3
• Obtain family history for hereditary conditions including thalassemia, sideroblastic anemia, and bleeding disorders. 3
• Review medication history for aspirin and NSAIDs, which should be stopped whenever possible. 3
• Assess dietary iron intake, though borderline deficient diets should not be presumed as the sole cause without full investigation. 3

Iron Replacement Strategy

After transfusion, initiate intravenous iron supplementation to address the underlying iron deficiency and replenish stores. 1, 4

• Intravenous iron is preferred over oral iron in patients with complex medical disorders, severe anemia requiring transfusion, or those who have failed oral therapy. 4, 5
• Oral iron (100-200 mg elemental iron daily) requires 3-6 months to normalize hemoglobin and replenish stores, whereas IV iron works faster. 5
• Continue iron supplementation for three months after correction of anemia to replenish body stores. 3
• Iron therapy alone requires 3-4 weeks minimum to show hemoglobin response, which is why transfusion is needed acutely. 1

Monitoring and Follow-Up

• Monitor hemoglobin concentration regularly after initiating iron therapy. 3
• If hemoglobin cannot be restored to normal and stores cannot be replenished despite adequate iron supplementation, reconsider further evaluation including repeat capsule endoscopy or other small bowel imaging. 3
• For patients with negative initial capsule endoscopy who experience ongoing bleeding, repeat studies have a diagnostic yield of 37.5-62.5%. 3

Critical Pitfalls to Avoid

• Do not accept upper GI findings like erosions or peptic ulcer as the sole cause without also investigating the colon, as dual pathology is common. 3
• Do not perform faecal occult blood testing, as it is insensitive and non-specific in this context. 3
• Do not pursue liberal transfusion strategies targeting hemoglobin >10 g/dL, as restrictive strategies (7-8 g/dL) have shown significant reductions in mortality, rebleeding, acute coronary syndrome, and infections. 1
• Do not delay small bowel investigation if the patient remains transfusion-dependent after negative bidirectional endoscopy. 3
• Do not rely on oral iron alone in patients with severe anemia requiring transfusion—IV iron is more effective in this population. 4, 5