What are the guidelines for evaluating and managing anaemia?

Guidelines for Evaluating and Managing Anemia

The evaluation of anemia should begin with hemoglobin measurement, with anemia defined as hemoglobin <135 g/L in adult males and <120 g/L in adult females, followed by a systematic workup to determine the underlying cause before initiating appropriate treatment. 1, 2

Initial Evaluation

Diagnosis of Anemia

• Definition thresholds:

  • Males ≥18 years: Hemoglobin <135 g/L
  • Females ≥18 years: Hemoglobin <120 g/L 1

• Special populations where standard definitions may not apply:

  • Pregnancy or menstruating women
  • Individuals living at high altitude
  • Smokers
  • Men aged ≥70 years
  • Non-Caucasian race
  • Chronic lung disease
  • Hemoglobinopathy 1

Laboratory Assessment

1. Complete Blood Count (CBC):

   • Hemoglobin measurement is preferred over hematocrit as it's more reproducible across laboratories 1
   • Mean Corpuscular Volume (MCV) for classification:
     • Microcytic (low MCV): Suggests iron deficiency, thalassemia, or anemia of chronic disease
     • Normocytic (normal MCV): Suggests anemia of chronic disease, renal disease, or early deficiency
     • Macrocytic (high MCV): Suggests vitamin B12/folate deficiency or medication effects 1

2. Reticulocyte count:

   • Evaluates bone marrow response to anemia
   • Low count suggests defective red cell production
   • High count suggests hemolysis or blood loss 1

3. Iron studies:

   • Serum ferritin: Assesses tissue iron stores
   • Transferrin saturation: Evaluates iron available for erythropoiesis
   • In non-dialysis CKD patients, ferritin <25 ng/ml in males and <11 ng/ml in females indicates insufficient iron stores 1
   • Transferrin saturation may be more reliable than ferritin in CKD patients as it's less affected by inflammation 1, 2

4. Additional tests:

   • Vitamin B12 and folate levels to rule out nutritional deficiencies 2
   • If abnormalities in multiple cell lines (white cells, red cells, platelets), hematology consultation is warranted 1

Management Approach

Iron Deficiency Management

1. Oral iron supplementation:

   • First-line therapy for iron deficiency 2
   • Continue for 2-3 months after hemoglobin normalizes to replenish iron stores 2
   • In patients with gastrointestinal symptoms or inadequate response, consider IV iron 2

2. Evaluation for blood loss:

   • In non-dialysis CKD patients with iron deficiency without known causes, evaluate for gastrointestinal bleeding 1
   • Referral to gastroenterology may be indicated to rule out GI malignancy 1

Erythropoiesis-Stimulating Agents (ESAs)

1. Indications:

   • Consider ESAs if hemoglobin falls below 10 g/dL despite iron repletion 2, 3
   • Primarily indicated for anemia due to:
     • Chronic kidney disease
     • Zidovudine therapy in HIV infection
     • Myelosuppressive chemotherapy (with at least 2 months of planned chemotherapy)
     • Reduction of allogeneic blood transfusions in elective surgery 3

2. Dosing:

   • CKD patients: Initial dose 50-100 Units/kg three times weekly 3
   • Cancer patients on chemotherapy: 40,000 Units weekly or 150 Units/kg three times weekly 3

3. Safety considerations:

   • Target hemoglobin should not exceed 12 g/dL due to increased risk of stroke and thromboembolic events 2, 3
   • Use the lowest effective dose to reduce need for transfusions 3
   • Monitor blood pressure with each dose 2

Monitoring Recommendations

1. Hemoglobin monitoring:

   • In CKD patients: At least yearly, more frequently in diabetics 1
   • During ESA treatment: Every 2-4 weeks initially, then monthly once stable 2
   • For hemodialysis patients: Measure predialysis hemoglobin before midweek session 1

2. Iron status monitoring:

   • Every 3 months during treatment 2
   • Adjust iron supplementation based on ferritin and transferrin saturation levels 1

3. Other monitoring:

   • Renal function: Regularly, with adjustment of anemia management as needed 2
   • Blood pressure: With each dose of erythropoietin 2

Special Considerations

Chronic Kidney Disease

• Anemia prevalence increases as kidney function declines 1
• Anemia in CKD is associated with higher mortality and faster progression to end-stage renal disease 1
• Transferrin saturation is more reliable than ferritin for assessing iron status due to less influence from inflammation 1

Preoperative Setting

• Evaluate hemoglobin approximately 28 days before elective surgery to allow time for correction 1
• Target preoperative hemoglobin within normal WHO range 1
• For surgical patients, ESA dosing options include 300 Units/kg daily for 15 days or 600 Units/kg weekly 3
• Deep venous thrombosis prophylaxis is recommended due to increased thrombotic risk 3

Cancer-Related Anemia

• ESAs are only indicated for anemia from myelosuppressive chemotherapy, not for patients receiving hormonal agents, biologics, or radiotherapy alone 3
• ESAs should not be used when the anticipated outcome of chemotherapy is cure 3
• Discontinue ESAs following completion of chemotherapy course 3

Pitfalls and Caveats

1. Ferritin interpretation:

   • Ferritin is an acute-phase reactant and may be elevated in inflammatory states regardless of iron stores 1
   • Traditional thresholds (12 mg/L) may not identify iron deficiency in patients with inflammation 1
   • Ferritin >100 mg/L generally confirms presence of stored iron in non-CKD patients 1

2. ESA risks:

   • Targeting hemoglobin >11 g/dL increases risk of death, myocardial infarction, and stroke 3
   • In cancer patients, ESAs may increase risk of tumor progression or recurrence 3

3. Comprehensive evaluation:

   • Never assume anemia is solely due to one cause (e.g., CKD) without thorough evaluation 2
   • Always evaluate for nutritional deficiencies, chronic inflammation, and other causes 1, 2

4. Timing of measurements:

   • For hemodialysis patients, use predialysis hemoglobin levels as postdialysis levels vary with fluid removal 1
   • Preferably measure before midweek dialysis session due to significant variations between 2-day and 3-day intervals 1