What are the potential causes of microcytic iron deficiency anemia in an adult female presenting with severe anemia?

Causes of Iron Deficiency Anemia in Adult Female with Severe Microcytic Anemia (Hb 73 g/L)

In an adult female with severe microcytic anemia (hemoglobin 73 g/L), the most likely causes are menstrual blood loss if premenopausal, or gastrointestinal blood loss requiring urgent investigation if postmenopausal, with approximately one-third of such patients having underlying GI pathology including malignancy. 1

Primary Causes by Menopausal Status

Premenopausal Women

• Menstrual blood loss is the most common cause of iron deficiency anemia in premenopausal women, with menometrorrhagia (excessive, prolonged, irregular uterine bleeding) capable of producing profound anemia. 1, 2
• Even with menstruation as the presumed cause, gastrointestinal sources must still be excluded if the degree of anemia is disproportionate to menstrual history or if GI symptoms are present. 1

Postmenopausal Women

• Gastrointestinal blood loss is the most common cause in postmenopausal women, with approximately one-third having underlying pathological abnormalities, most commonly in the GI tract. 1
• GI malignancies (colonic and gastric carcinoma) are of prime concern and can present asymptomatically with iron deficiency anemia alone. 1

Common Gastrointestinal Causes (All Women)

Occult GI Blood Loss

• NSAID use is a common cause of occult gastrointestinal bleeding leading to iron deficiency. 1, 3
• Colonic cancer and polyps are critical diagnoses requiring exclusion. 1
• Angiodysplasia represents a significant source of chronic blood loss. 1
• Gastric cancer must be considered in the differential. 1

Malabsorption

• Celiac disease is found in 3-5% of cases of iron deficiency anemia and should be routinely screened for serologically. 1
• Previous gastrectomy (partial or total) and gastric atrophy impair iron absorption. 1
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) can cause both blood loss and malabsorption. 1

Less Common but Important Causes

• Poor dietary intake is an uncommon sole cause in developed countries but may contribute. 1
• Hookworm infection should be considered based on geographic origin and exposure history. 1
• Small bowel pathology including lymphoma, leiomyoma, and other tumors may present with iron deficiency. 1

Differential Diagnosis Considerations

While iron deficiency is most likely given the microcytic picture, other causes of microcytosis must be excluded:

• Thalassemia trait should be considered if the patient has appropriate ethnic background, with hemoglobin electrophoresis showing elevated HbA2 >3.5% in beta-thalassemia. 4, 5, 6
• Anemia of chronic disease can present with microcytosis and is characterized by elevated ferritin with low serum iron and transferrin saturation. 3, 7, 6
• Sideroblastic anemia presents with elevated ferritin and transferrin saturation, requiring bone marrow examination showing ring sideroblasts. 3, 5

Critical Diagnostic Approach

Confirm iron deficiency first with serum ferritin <15 μg/L (diagnostic) or <30 μg/L (indicating low stores), though ferritin up to 100 μg/L may still indicate iron deficiency in the presence of inflammation. 4, 3, 6

Red cell distribution width (RDW) >14.0% with low MCV strongly indicates iron deficiency anemia, whereas RDW ≤14.0% suggests thalassemia minor. 4, 3

Mandatory Investigation Algorithm

Given the severity of anemia (Hb 73 g/L):

1. Detailed menstrual history including duration, frequency, and volume of bleeding. 1
2. Urinalysis or urine microscopy to exclude urinary blood loss. 1
3. Celiac disease screening with tissue transglutaminase antibodies. 1
4. Bidirectional endoscopy (gastroscopy and colonoscopy) is the standard diagnostic approach for men and postmenopausal women, and should be considered in premenopausal women with severe anemia or GI symptoms. 1
5. Small bowel evaluation with wireless capsule endoscopy if upper and lower endoscopy are unrevealing in recurrent or refractory cases. 1

Critical Pitfalls to Avoid

• Do not assume menstruation alone explains severe anemia without excluding concurrent GI pathology, especially if anemia is disproportionate to menstrual history. 1
• Do not overlook malignancy risk: unexplained iron deficiency anemia in at-risk individuals is an accepted indication for fast-track secondary care referral. 1
• Do not assume all microcytic anemia is iron deficiency: thalassemia and anemia of chronic disease must be differentiated to avoid unnecessary or harmful iron therapy. 4, 3
• Do not miss combined deficiencies: iron deficiency can coexist with B12 or folate deficiency, which may be recognized by elevated RDW. 1, 4