What are the typical presentation, differential diagnosis (DDX), diagnostic investigations (INVX), management (MX), and complications of anemia?

Anemia: Typical Presentation, Differential Diagnosis, Investigation, Management, and Complications

Anemia is defined as hemoglobin levels <12.0 g/dL in women and <13.0 g/dL in men, and requires prompt evaluation and management to prevent significant morbidity and mortality. 1

Typical Presentation (Signs and Symptoms)

Common Symptoms

• Fatigue and weakness
• Dyspnea on exertion
• Lightheadedness or dizziness
• Pallor (most frequent physical finding)
• Tachycardia
• Poor exercise tolerance

Severe Anemia Symptoms

• Shortness of breath at rest
• Tachycardia and diaphoresis
• Poor capillary refilling
• Chest pain (in patients with cardiovascular disease)

Specific Symptoms Based on Type

• Iron deficiency: Pica, koilonychia (spoon nails), glossitis
• B12 deficiency: Peripheral neuropathy, ataxia, paresthesias, loss of proprioception, cognitive changes 2
• Hemolytic anemia: Jaundice, dark urine

Differential Diagnosis

Based on MCV and Reticulocyte Count

1. Microcytic Anemia (MCV <80 fL)

   • With normal/low reticulocytes:
     • Iron deficiency anemia
     • Anemia of chronic disease
     • Lead poisoning (rare)
     • Hereditary microcytic anemia (rare)
   • With elevated reticulocytes:
     • Hemoglobinopathies (thalassemia)

2. Normocytic Anemia (MCV 80-100 fL)

   • With normal/low reticulocytes:
     • Acute hemorrhage
     • Renal anemia
     • Anemia of chronic disease (cancer, infection)
     • Aplastic anemia
     • Primary bone marrow diseases
     • Bone marrow infiltration by cancer
   • With elevated reticulocytes:
     • Hemolytic anemia

3. Macrocytic Anemia (MCV >100 fL)

   • With normal/low reticulocytes:
     • Vitamin B12 deficiency
     • Folate deficiency
     • Myelodysplastic syndrome
     • Medication-induced (hydroxyurea, methotrexate, azathioprine)
     • Hypothyroidism
     • Alcoholism
   • With elevated reticulocytes:
     • Hemolytic anemia
     • Myelodysplastic syndrome with hemolysis 1

Investigations (INVX)

Initial Workup

1. Complete Blood Count (CBC)

   • Hemoglobin and hematocrit
   • Red cell indices (MCV, MCH, MCHC)
   • Red cell distribution width (RDW)
   • Reticulocyte count
   • White blood cell count and differential
   • Platelet count

2. Peripheral Blood Smear

   • Morphology of red cells
   • Presence of schistocytes, spherocytes, or other abnormal forms

3. Iron Studies

   • Serum ferritin
   • Transferrin saturation (TSAT)
   • Total iron binding capacity (TIBC)
   • Serum iron

4. Inflammatory Markers

   • C-reactive protein (CRP)
   • Erythrocyte sedimentation rate (ESR) 1, 3

Additional Tests Based on Initial Results

1. For Microcytic Anemia:

   • Hemoglobin electrophoresis (for thalassemia)
   • Lead levels (if suspected)

2. For Macrocytic Anemia:

   • Vitamin B12 and folate levels
   • Thyroid function tests
   • Liver function tests

3. For Suspected Hemolysis:

   • Lactate dehydrogenase (LDH)
   • Haptoglobin
   • Direct antiglobulin test (Coombs test)
   • Bilirubin (direct and indirect)

4. For Suspected Bleeding:

   • Fecal occult blood test
   • Endoscopy (upper and lower GI)
   • Gynecological evaluation in women 1, 3

Management (MX)

General Principles

1. Treat the underlying cause
2. Correct the anemia
3. Prevent recurrence

Specific Management Based on Type

1. Iron Deficiency Anemia:

   • Oral iron therapy: 3-6 mg/kg of elemental iron per day
   • Continue therapy for 3 months after correction of anemia to replenish stores
   • Target ferritin level of at least 100 ng/mL
   • Intravenous iron if oral iron is not tolerated, poor response to oral therapy, malabsorption, or rapid correction needed 1, 3, 4

2. B12 Deficiency:

   • Intramuscular vitamin B12 injections
   • Oral supplementation if not due to malabsorption 2

3. Folate Deficiency:

   • Oral folate supplementation

4. Anemia of Chronic Disease:

   • Treat underlying inflammatory condition
   • Consider erythropoiesis-stimulating agents in selected cases 1, 3

5. Acute Blood Loss:

   • Red blood cell transfusion when hemoglobin is below 7 g/dL or if symptomatic
   • Follow transfusions with iron supplementation 1, 3

Complications

1. Cardiovascular Complications:

   • High-output heart failure
   • Myocardial ischemia in patients with coronary artery disease
   • Arrhythmias

2. Neurological Complications:

   • Cognitive impairment
   • In B12 deficiency: irreversible neurological damage if untreated
   • Syncope and falls

3. Growth and Development Issues:

   • Neurodevelopmental and cognitive deficits in children (especially with iron deficiency)
   • Growth retardation in children

4. Immune System Dysfunction:

   • Increased susceptibility to infections

5. Pregnancy Complications:

   • Preterm delivery
   • Low birth weight
   • Increased maternal and perinatal mortality 3, 4

Special Considerations

Elderly Patients

• Anemia in elderly is defined as Hb <12 g/dL in both sexes
• Often multifactorial and associated with increased morbidity and mortality
• One-third have nutritional deficiency, one-third have anemia of chronic disease, and one-third have unexplained anemia 5

Pregnant Women

• Higher iron requirements (30-60 mg/day)
• May need 60-120 mg/day for anemia 3

Post-bariatric Surgery Patients

• Require regular monitoring for multiple nutritional deficiencies 3

Cancer Patients

• Consider IV iron for those with TSAT <20% 1, 3

Pitfalls to Avoid

• Assuming iron deficiency is the only cause of microcytic anemia
• Failing to investigate the cause of iron deficiency, especially in men and postmenopausal women
• Overlooking combined deficiencies (e.g., iron and B12)
• Treating with iron without confirming iron deficiency
• Stopping iron therapy too soon (before replenishing stores)
• Missing malignancy as a cause of anemia, particularly in older adults 1, 3