What is the workup for a healthy 20-year-old with a family history of colon cancer who develops anemia (Hemoglobin (Hb) of 10 g/dL) after a bout of pneumonia?

Workup for Anemia in a 20-Year-Old with Family History of Colon Cancer

This 20-year-old male with hemoglobin of 10 g/dL requires immediate comprehensive laboratory evaluation followed by urgent gastrointestinal investigation, particularly given the family history of colon cancer, despite his young age.

Initial Laboratory Workup

The minimum essential laboratory tests must include 1, 2:

• Complete blood count with red cell indices: MCV, MCH, and RDW to classify the anemia as microcytic, normocytic, or macrocytic 1
• Reticulocyte count: To distinguish between impaired red cell production (low/normal reticulocytes) versus increased destruction or blood loss (elevated reticulocytes) 1, 3
• Iron studies: Serum ferritin, transferrin saturation (TfS), and total iron-binding capacity 1, 3
• Inflammatory markers: CRP to assess for anemia of chronic disease or ongoing inflammation 1, 3
• Peripheral blood smear: Essential for identifying morphologic abnormalities not apparent from automated indices 1, 2

Extended Laboratory Panel

Additional tests should be obtained to exclude other correctable causes 1, 2, 3:

• Vitamin B12 and folate levels: To exclude nutritional deficiencies that can present with normocytic anemia or mask microcytosis in combined deficiencies 1, 3
• Renal function tests: Creatinine and estimated GFR to assess for chronic kidney disease 1, 2, 3
• Lactate dehydrogenase and haptoglobin: If reticulocyte count is elevated, to evaluate for hemolysis 1
• Bilirubin: To further assess for hemolytic process if indicated 1

Critical Interpretation Points

Iron deficiency criteria depend on inflammatory status 1, 3:

• Without inflammation: Serum ferritin <30 μg/L indicates iron deficiency 1, 3
• With inflammation present: Ferritin up to 100 μg/L may still be consistent with iron deficiency 1, 3
• Transferrin saturation <30% supports iron deficiency diagnosis 3

Reticulocyte count interpretation 1:

• Low or normal reticulocytes suggest impaired erythropoiesis from deficiencies or bone marrow disease 1
• Elevated reticulocytes indicate increased red cell production, suggesting hemolysis or acute blood loss 1

Mandatory Gastrointestinal Investigation

Despite the patient's young age, gastrointestinal evaluation is essential given the family history of colon cancer and new-onset anemia 1, 3, 4:

• Upper endoscopy (OGD): To exclude gastric cancer, peptic ulcer disease, angiodysplasia, and celiac disease 1, 3
• Duodenal biopsies: Should be obtained during upper endoscopy, ideally with celiac serology (tissue transglutaminase antibody) performed beforehand 1
• Colonoscopy: To exclude colonic cancer, polyps, and inflammatory bowel disease 1, 3

The rationale for aggressive GI investigation includes 4, 5:

• Right-sided colon cancers present with anemia in 57.6% of cases and often at higher stages 4
• Anemia may be the only presenting sign of asymptomatic colorectal malignancy 1, 3
• Family history increases risk, warranting complete evaluation regardless of age 3

Post-Pneumonia Considerations

While the recent pneumonia may contribute to anemia of chronic disease, this does not exclude concurrent GI pathology 1, 3. The CRP level will help distinguish:

• Elevated CRP with normal/elevated ferritin suggests anemia of chronic disease from recent infection 1, 3
• However, GI investigation should not be deferred based on the pneumonia history alone 3

Common Pitfalls to Avoid

• Do not assume the anemia is solely from recent pneumonia without excluding GI blood loss, especially with family history of colon cancer 1, 3
• Do not delay investigation because hemoglobin is "only" 10 g/dL—any degree of anemia with iron deficiency warrants investigation in males 1, 3
• Do not skip duodenal biopsies if celiac serology is negative but not yet available; approximately 5% of IDA patients have celiac disease 1
• Do not overlook combined deficiencies: Concurrent iron and B12/folate deficiency can neutralize each other, resulting in normal MCV despite significant abnormalities 1, 3

Hematology Referral

Consultation with a hematologist is appropriate if the cause of anemia remains unclear after comprehensive laboratory workup and GI investigation 1, 2.