What is the appropriate work‑up and initial management for a patient presenting with severe anemia (hemoglobin less than 8 g/dL or symptomatic)?

Work-Up for Severe Anemia (Hemoglobin <8 g/dL)

Immediate Assessment and Stabilization

For severe anemia (Hb <8 g/dL), immediately assess hemodynamic stability and symptoms (chest pain, shortness of breath at rest, dizziness, tachycardia, hypotension) to determine transfusion urgency, while simultaneously initiating diagnostic workup. 1, 2

Transfusion Decision

• Transfuse symptomatic patients presenting with weakness, fatigue, dyspnea, chest pain, dizziness, or cardiovascular compromise regardless of exact hemoglobin level 1, 3
• Transfuse asymptomatic patients with Hb <8 g/dL if they have active coronary syndrome, recent cardiac surgery, or significant cardiovascular disease 1, 2
• Use single-unit transfusion strategy targeting Hb 7-8 g/dL, as each unit raises Hb approximately 1 g/dL 1, 2, 3
• Avoid transfusing to Hb >10 g/dL, which increases mortality risk 3-fold (OR: 3.34) 2

Essential Initial Laboratory Work-Up

First-Tier Tests (Obtain Immediately)

• Complete blood count with differential and reticulocyte count to distinguish regenerative (>100 × 10⁹/L suggests hemolysis or acute blood loss) from non-regenerative anemia 1, 4, 5
• Mean corpuscular volume (MCV) to categorize as microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 1, 4
• Peripheral blood smear to identify hemolysis, schistocytes, or morphologic abnormalities 4, 5
• Iron studies including serum ferritin and transferrin saturation (TSAT): ferritin <100 μg/L and TSAT <20% indicate iron deficiency 1, 4
• Comprehensive metabolic panel including creatinine and estimated GFR to assess for chronic kidney disease 4, 3
• Vitamin B12 and folate levels to exclude nutritional deficiencies 1, 4

Second-Tier Tests Based on Initial Results

If reticulocyte count is elevated (>100 × 10⁹/L):

• Direct Coombs test to evaluate for immune-mediated hemolytic anemia 1, 5
• Lactate dehydrogenase, indirect bilirubin, and haptoglobin to confirm hemolysis 5

If MCV is elevated (>100 fL):

• TSH and free T4 to exclude hypothyroidism 1
• Methylmalonic acid if B12 level is borderline (150-400 pmol/L), as levels >271 nmol/L confirm B12 deficiency 1

If iron deficiency is confirmed or suspected:

• Fecal occult blood testing and assessment for gastrointestinal blood loss, particularly in older adults where endoscopy is warranted to exclude malignancy 4, 6
• Urinalysis to assess for hematuria 4

If anemia is normocytic with low reticulocytes:

• C-reactive protein to identify anemia of chronic disease/inflammation 4
• Consider bone marrow biopsy if multiple cell lines are affected (cytopenias), if anemia is unexplained after complete workup, or if steroid-refractory 1, 4

Etiology-Specific Management

Iron Deficiency Anemia

• Initiate oral iron supplementation (lower-dose formulations have fewer adverse effects) with normalization expected by 8 weeks 4, 6
• Parenteral iron infusion reserved for patients who fail or cannot tolerate oral therapy 6

Anemia of Chronic Disease/Inflammation

• Address underlying inflammatory condition as primary treatment 4
• Consider iron supplementation even with elevated ferritin if TSAT is low (functional iron deficiency) 4
• Erythropoiesis-stimulating agents (ESAs) are NOT routinely indicated outside specific contexts (chronic kidney disease, chemotherapy-related anemia) due to risks of thromboembolism, hypertension, and seizures 4, 3

Hemolytic Anemia

• If Coombs-positive, initiate corticosteroids (0.5-1.0 mg/kg/day methylprednisolone) once infection excluded 1
• Consider plasmapheresis for severe refractory cases 1

Vitamin Deficiencies

• Folate supplementation 1 mg daily if serum folate <10 nmol/L 1, 3
• Vitamin B12 replacement if serum B12 <150 pmol/L 1

Monitoring Strategy

• Recheck hemoglobin at 2-4 week intervals after initiating treatment 3
• Monitor for symptom resolution including improvement in fatigue, dyspnea, and functional capacity 2, 3
• Weekly monitoring during corticosteroid taper if treating immune-mediated hemolytic anemia 3

Hematology Referral Indications

Refer urgently to hematology if:

• Multiple cell line abnormalities (cytopenias) are present 4
• Unexplained anemia persists after complete workup 4
• Hemolytic anemia is steroid-refractory 1
• Bone marrow biopsy is being considered 1

Common Pitfalls to Avoid

• Do not empirically treat with nutritional supplements without identifying specific deficiencies, as this obscures diagnosis 7
• Do not use liberal transfusion strategies targeting Hb >10 g/dL, which worsen outcomes 2
• Do not overlook gastrointestinal malignancy in older adults with iron deficiency anemia—endoscopy is mandatory 6
• Do not initiate ESAs before ensuring adequate iron stores and excluding correctable causes 4, 3