What are the differential diagnoses for severe microcytic hypochromic anemia in an 80‑year‑old bedridden woman with recent dyspnea, tachypnea, bilateral lung crackles, systolic murmur, history of pulmonary embolism treated with apixaban, prior ischemic stroke, hypothyroidism on levothyroxine, iron‑folate supplementation, tarry stools, elevated C‑reactive protein, chronic kidney disease, and mild thrombocytopenia?

Differential Diagnosis

In this bedridden octogenarian with severe microcytic hypochromic anemia (hemoglobin 1.7 g/dL), tarry stools, and anticoagulation therapy, the primary diagnosis is gastrointestinal bleeding causing iron-deficiency anemia, with urgent upper and lower endoscopy required to identify the bleeding source—most likely peptic ulcer disease, angiodysplasia, or malignancy. 1, 2

Primary Diagnosis: Iron-Deficiency Anemia from GI Blood Loss

Laboratory Confirmation

• Ferritin 20 ng/mL confirms depleted iron stores (threshold <30 µg/L indicates low body iron), though this level may be falsely elevated by the elevated CRP (3.56 mg/dL), making true iron deficiency even more severe. 2, 1
• Severe microcytosis (MCV 75 fL) with hypochromia (MCH 23.8 pg) and hemoglobin 1.7 g/dL represents life-threatening iron-deficiency anemia requiring immediate transfusion and investigation. 2, 3
• The combination of tarry stools, apixaban therapy, and severe anemia in an elderly patient makes occult GI bleeding the most common etiology, accounting for the majority of iron-deficiency cases in this demographic. 2, 1

Critical Source Identification Required

• Upper endoscopy with duodenal biopsies must be performed urgently to identify peptic ulcer disease, gastric cancer, NSAID-induced gastropathy, or angiodysplasia—all common in elderly patients on anticoagulation. 2, 1
• Colonoscopy is essential because colonic carcinoma, adenomatous polyps, and angiodysplasia are high-yield findings in patients over 80 years with iron-deficiency anemia. 2, 1
• Duodenal biopsies during upper endoscopy screen for celiac disease, which accounts for 2-3% of iron-deficiency anemia cases and can present with isolated anemia. 2, 1
• Apixaban 110 mg twice daily markedly increases bleeding risk from any mucosal lesion, but the drug should not be discontinued for endoscopy unless active hemorrhage occurs, as cardiovascular risk outweighs procedural bleeding risk. 2

Secondary Considerations

Anemia of Chronic Disease (Contributing Factor)

• Elevated CRP (3.56 mg/dL) with borderline-low ferritin (20 ng/mL) suggests coexisting anemia of chronic disease, though the severe microcytosis and extremely low hemoglobin favor predominant iron deficiency. 2, 1
• In inflammatory states, ferritin up to 100 µg/L may still indicate iron deficiency; transferrin saturation would help confirm (TSAT <16-20% supports iron deficiency), but this test was not performed. 2, 1
• Chronic kidney disease (creatinine 1.7 mg/dL, urea 135 mg/dL) contributes to anemia through erythropoietin deficiency and functional iron deficiency, though it does not explain the severe microcytosis. 1

Cardiac Decompensation (Consequence, Not Cause)

• BNP 804.30 pg/mL, bilateral crepitations, and tachypnea indicate high-output heart failure secondary to severe anemia (hemoglobin 1.7 g/dL), not primary cardiac disease. 1
• The systolic murmur throughout the precordium represents a flow murmur from the hyperdynamic circulation required to compensate for critically low oxygen-carrying capacity. 1
• Troponin I elevation (34 pg/mL, normalizing on repeat) reflects demand ischemia from severe anemia rather than acute coronary syndrome. 1

Hemolysis (Excluded)

• Negative direct Coombs test, normal bilirubin (0.7 mg/dL), and microcytic indices exclude hemolytic anemia as a primary cause. 4
• The absence of schistocytes on blood smear and normal urinalysis rule out microangiopathic hemolysis or intravascular hemolysis. 4

Thalassemia Trait (Unlikely)

• Severe anemia (hemoglobin 1.7 g/dL) excludes thalassemia trait, which causes mild microcytosis with near-normal hemoglobin and does not produce symptomatic anemia. 2, 5
• Hemoglobin electrophoresis would be indicated only if iron studies were normal, which they are not in this case. 2, 5

Rare Genetic Disorders (Not Applicable)

• Iron-refractory iron deficiency anemia (IRIDA) and congenital sideroblastic anemia present in childhood or young adulthood, not in the ninth decade of life. 6, 2
• The patient's age (late 80s) and acute presentation make acquired causes (GI bleeding) far more likely than inherited disorders of iron metabolism. 6, 2

Critical Diagnostic Pitfalls to Avoid

• Do not attribute tarry stools solely to oral iron supplementation—this is a dangerous assumption that delays diagnosis of life-threatening GI bleeding, especially in anticoagulated elderly patients. 2, 1
• Do not delay endoscopy to "optimize" the patient with iron therapy alone—the bleeding source must be identified and treated to prevent recurrent hemorrhage and death. 2, 1
• Do not assume ferritin 20 ng/mL excludes severe iron deficiency in the presence of inflammation—the elevated CRP means true iron stores are likely even lower than measured. 2, 1
• Do not overlook combined deficiencies—check vitamin B12 and folate, as iron deficiency can coexist with megaloblastic anemia, though the severe microcytosis here makes this less likely. 2, 1
• Do not discontinue apixaban for endoscopy unless active bleeding is ongoing—the cardiovascular risk (prior stroke, pulmonary embolism) outweighs procedural bleeding risk. 2

Immediate Management Priorities

• Urgent packed red blood cell transfusion to hemoglobin >7 g/dL (target 7-9 g/dL in elderly with cardiac symptoms) before endoscopy. 1
• Upper endoscopy with duodenal biopsies and colonoscopy within 24-48 hours after stabilization to identify and treat the bleeding source. 2, 1
• Intravenous iron (iron sucrose or ferric carboxymaltose) after endoscopy if malabsorption is identified or oral iron fails, with expected hemoglobin rise ≥2 g/dL within 4 weeks. 2, 1
• Hematology consultation is premature—gastroenterology should lead the initial workup to locate the bleeding source. 2