What additional investigations are warranted for a patient with chronic anemia, previously diagnosed with a neuroendocrine tumor (NET) of the jejunum, with normal Vitamin B12, Thyroid-Stimulating Hormone (TSH), bilirubin, peripheral smear, Serum Protein Electrophoresis (SPEP), reticulocyte count, haptoglobin, Lactate Dehydrogenase (LDH), and liver enzymes, presenting with symptomatic anemia and no overt bleeding?

From the Guidelines

For a patient with chronic anemia requiring transfusions despite extensive workup and a history of resected jejunal neuroendocrine tumor, additional investigations should focus on potential causes not yet explored, including iron studies, evaluation for hemolysis, and assessment for rare causes such as hemoglobinopathies or myelodysplastic syndrome, as recommended by the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1.

Key Considerations

• The patient's history of resected neuroendocrine tumor and extensive GI workup suggests the need for further investigation to rule out underlying pathology, such as small bowel lesions or malabsorption, as highlighted in the guidelines 1.
• Iron studies, including serum iron, ferritin, TIBC, and transferrin saturation, should be considered to rule out iron deficiency, which can occur with occult bleeding, as noted in the guidelines 1.
• Evaluation for hemolysis with direct and indirect Coombs tests, as well as assessment for rare causes with hemoglobin electrophoresis, may help identify underlying causes of anemia, as suggested by the clinical practice guidelines for the use of video capsule endoscopy 1.

Additional Investigations

• Consider CT enterography or MR enterography to detect small bowel lesions missed by endoscopy, as recommended by the guidelines 1.
• Test for celiac disease with tissue transglutaminase antibodies, as malabsorption can contribute to anemia, as noted in the guidelines 1.
• Evaluate renal function with creatinine and eGFR, as chronic kidney disease can cause anemia, as highlighted in the guidelines 1.
• Consider checking copper and zinc levels, as deficiencies can contribute to anemia, as suggested by the clinical practice guidelines for the use of video capsule endoscopy 1.

Prioritization of Investigations

• The British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults provide a framework for prioritizing investigations, with a focus on ruling out underlying pathology and identifying potential causes of anemia 1.
• The guidelines recommend a step-wise approach to investigation, with consideration of iron studies, evaluation for hemolysis, and assessment for rare causes, as well as the use of imaging studies such as CT enterography or MR enterography to detect small bowel lesions 1.

From the Research

Additional Anemia Investigations

Given the patient's long-standing history of chronic anemia and extensive GI consults, the following additional investigations should be considered:

• Celiac disease screening:
  • Tissue anti-transglutaminase and anti-endomysial antibodies testing 2, 3, 4, 5
  • Digestive endoscopy and intestinal biopsy if antibody testing is positive 2, 4, 5
• Evaluation for anemia of chronic disease:
  • Serum levels of erythropoietin, prohepcidin, and interferon-gamma 6
  • Body iron status and soluble transferrin receptor levels 6
• Assessment for other potential causes of anemia:
  • Inflammatory bowel disease (IBD) screening 2, 3
  • Lymphoma screening, especially enteropathy-type T-cell lymphoma (ETL) and B-cell lymphoma of the gut 3

Rationale for Additional Investigations

The patient's symptoms and history suggest a possible underlying condition such as celiac disease, which can cause anemia due to malabsorption of iron, folic acid, and/or vitamin B12 2, 3, 4, 5. Anemia of chronic disease is also a potential cause, as it can occur in patients with celiac disease due to intestinal inflammatory changes 6. Evaluating the patient for these conditions can help identify the underlying cause of their anemia and guide appropriate treatment.