How do you diagnose and manage iron deficiency anemia?

Diagnosis and Management of Iron Deficiency Anemia

Diagnostic Criteria

Diagnose iron deficiency anemia using a ferritin cutoff of <45 ng/mL, as this threshold provides superior diagnostic accuracy compared to lower cutoffs. 1

• Serum ferritin is the most powerful single test for iron deficiency, though additional testing may be needed in patients with inflammation or chronic kidney disease where ferritin can be falsely elevated 1
• Define anemia using your laboratory's lower limit of normal hemoglobin, and investigate any level of anemia when iron deficiency is present 1
• Red cell indices (microcytosis and hypochromia) provide sensitive indicators of iron deficiency in the absence of chronic disease or hemoglobinopathy 1
• Consider hemoglobin electrophoresis in patients of appropriate ethnic background with microcytosis to avoid unnecessary GI investigation for thalassemia 1

Investigation Algorithm

All Patients: Initial Workup

Screen all patients with iron deficiency anemia for celiac disease using tissue transglutaminase (tTG) antibody with IgA level, as celiac disease is found in 3-5% of cases 2

• Take a focused history on NSAID/aspirin use, dietary iron intake, family history of bleeding disorders or telangiectasia, and GI bleeding symptoms 2
• Perform urinalysis to exclude urinary tract bleeding as a rare cause 2
• Stop NSAIDs and aspirin where clinically appropriate, as these are common causes of iron deficiency anemia 1

Postmenopausal Women and All Men

Perform bidirectional endoscopy (both upper endoscopy and colonoscopy) as first-line investigation, as GI malignancy is the primary concern and dual pathology occurs in 10-15% of patients 1, 2

• Upper endoscopy reveals a cause in 30-50% of patients 2
• Obtain small bowel biopsies during gastroscopy even if mucosa appears normal, as 2-3% have celiac disease despite normal-appearing mucosa 2
• Perform colonoscopy even if upper endoscopy reveals a lesion, as dual pathology is common and only advanced gastric cancer or confirmed celiac disease should deter lower GI investigation 1
• Colonoscopy is superior to CT colonography or barium enema for detecting angiodysplasia and allowing tissue biopsy 1

Premenopausal Women

Screen for celiac disease in all premenopausal women, but base decisions about upper and lower GI investigations on clinical judgment rather than routine bidirectional endoscopy 1

• The AGA suggests bidirectional endoscopy over iron replacement alone, though this is a conditional recommendation 1
• Consider endoscopy more strongly in women over age 50, those with marked anemia, significant family history of colorectal cancer, or inadequate response to iron therapy 1

Additional Testing Based on Initial Results

If Celiac Serology is Positive

• Confirm with small bowel biopsy 1
• Still consider lower GI investigation in patients >50 years, with marked anemia, or significant family history of colorectal cancer 1

If Celiac Serology is Negative

• Small bowel biopsies are not needed unless other features (such as diarrhea) suggest celiac disease 1
• The negative likelihood ratio for tTG antibody is 0.06, making post-test probability only 0.3% 1

If H. pylori is Suspected

Test non-invasively for H. pylori and treat if positive, particularly in patients with recurrent iron deficiency anemia and normal endoscopy results 1

Further Investigation for Persistent or Recurrent Anemia

Pursue small bowel evaluation only if there is inadequate response to iron therapy, recurrent iron deficiency anemia, transfusion-dependent anemia, or symptoms suggesting small bowel disease 1, 2

• Capsule endoscopy is the preferred test for small bowel examination, as it is highly sensitive for mucosal lesions 2
• Consider CT or MRI enterography if capsule endoscopy is not suitable 2

Treatment Principles

Initiate oral iron supplementation immediately to correct anemia and replenish body stores, without waiting for investigation results unless colonoscopy is imminent 1, 2

• Use parenteral iron when oral preparations are not tolerated 1
• Reserve blood transfusions for patients with or at risk of cardiovascular instability 1
• Do not assume dietary deficiency as the sole cause or stop investigation after finding minor upper GI lesions, as full evaluation is still required 2

Critical Pitfalls to Avoid

• Never rely on fecal occult blood testing in the investigation of iron deficiency anemia, as it provides no diagnostic benefit 1
• Do not defer investigation based on symptoms, as they rarely correlate with endoscopic findings 2
• Do not stop investigation after finding a minor upper GI lesion without completing lower GI evaluation 2
• Investigate more urgently when hemoglobin is <12 g/dL in men or <10 g/dL in postmenopausal women, as lower levels suggest more serious disease 1