What is the treatment algorithm for anemia?

Treatment Algorithm for Anemia

The treatment approach for anemia depends critically on identifying the underlying cause, with iron deficiency anemia being the most common and requiring systematic evaluation followed by oral iron supplementation as first-line therapy, escalating to intravenous iron when oral therapy fails or is contraindicated.

Initial Diagnostic Workup

Laboratory Assessment

• Obtain complete blood count (CBC) with hemoglobin, hematocrit, and red cell indices (MCV, RDW) 1
• Measure serum ferritin, iron, transferrin saturation (TSAT), and iron binding capacity to assess iron status 1
• Add vitamin B12, folate, thyroid function tests, creatinine, and C-reactive protein (CRP) when evaluating anemia 1

Defining Anemia

• Women: Hemoglobin <12 g/dL 1
• Men: Hemoglobin <13 g/dL 1
• Pregnancy-specific thresholds vary by trimester 1

Iron Deficiency Anemia Management

Diagnostic Criteria for Iron Deficiency

• Ferritin <15 ng/mL in general population 1
• Ferritin <100 ng/mL with TSAT <20% suggests iron deficiency 1
• In inflammatory conditions (elevated CRP), ferritin up to 100 μg/L may still reflect iron deficiency 1
• Consider reticulocyte hemoglobin concentration (CHr) or soluble transferrin receptor (sTfR) when ferritin is inconclusive 1

First-Line Treatment: Oral Iron

Prescribe ferrous sulfate 200 mg twice daily (not three times daily) as the standard regimen 1. This represents a shift from older recommendations, as recent evidence shows lower doses are equally effective with better tolerability 2, 3.

Alternative Oral Dosing Strategies

• For asymptomatic patients: 100 mg ferrous fumarate once daily is sufficient 3
• For severe anemia or symptomatic patients: 200 mg daily 3
• If gastrointestinal side effects occur: switch to alternate-day dosing, which maintains efficacy while reducing hepcidin elevation 1, 2
• Alternative formulations (ferrous fumarate, ferrous gluconate, iron protein succinylate) may improve tolerability 1, 4

Enhancing Oral Iron Absorption

• Consider adding ascorbic acid 250-500 mg twice daily with iron, though data on effectiveness in IDA treatment are limited 1
• Avoid H2-blockers and proton pump inhibitors, which impair absorption 1

Duration of Oral Therapy

• Continue oral iron for 3 months after hemoglobin normalizes to replenish iron stores 1

Assessing Response to Oral Iron

After 4 weeks of compliant oral iron therapy, expect hemoglobin increase of ≥1 g/dL or hematocrit increase of ≥3% 1.

If No Response After 4 Weeks

• Verify compliance with supplementation regimen 1
• Exclude acute illness 1
• Perform additional testing: MCV, RDW, serum ferritin 1
• In patients of African, Mediterranean, or Southeast Asian ancestry, consider thalassemia minor or sickle cell trait 1
• Trial intravenous iron, as only 21% of oral iron non-responders respond to extended oral therapy versus 65% responding to IV iron 1

Second-Line Treatment: Intravenous Iron

Intravenous iron is indicated when: 1, 5

• Oral iron is not tolerated due to gastrointestinal side effects
• Oral iron is ineffective despite compliance
• Rapid hemoglobin correction is required
• Malabsorption is present (inflammatory bowel disease, celiac disease, post-bariatric surgery)
• Ongoing blood loss exceeds intestinal iron absorption capacity
• Chronic kidney disease with dialysis
• Congestive heart failure (oral iron poorly absorbed due to gut edema)

IV Iron Formulations 1

• Iron sucrose (Venofer): 200 mg over 10 minutes, maximum single dose
• Ferric carboxymaltose (Ferinject): 1000 mg over 15 minutes, maximum single dose
• Iron dextran (Cosmofer): 20 mg/kg over 6 hours, can replenish stores in single infusion but carries 0.6-0.7% risk of serious reactions

IV Iron Dosing Strategy

• Calculate total iron deficit based on hemoglobin deficit and need to replenish stores 1
• Administer doses every 3-7 days until total dose given 1
• Monitor serum ferritin; keep <500 ng/mL to avoid iron overload toxicity, especially in children 1
• Always administer in medical facilities with resuscitation capabilities available 6

Special Consideration: Iron-Refractory Iron Deficiency Anemia (IRIDA)

In patients with microcytic anemia, low TSAT, normal/low ferritin who partially respond to IV iron but not oral iron, measure serum hepcidin and consider TMPRSS6 mutation analysis 1.

Population-Specific Algorithms

Pregnant Women 1

1. Start 30 mg/day oral iron at first prenatal visit for primary prevention
2. Screen for anemia at first prenatal visit using pregnancy-specific thresholds
3. If anemic, treat with 60-120 mg/day oral iron
4. If Hb <9.0 g/dL or Hct <27%, refer to physician for further evaluation
5. After 4 weeks, if no response (Hb increase <1 g/dL), perform additional testing
6. When Hb normalizes for gestational stage, reduce to 30 mg/day maintenance

Premenopausal Women 1

• Menstrual loss, menorrhagia, pregnancy, and breastfeeding are common causes 1
• Treat with standard oral iron regimen
• Consider gynecological evaluation if menorrhagia suspected

Postmenopausal Women and Men 1

• No routine screening recommended 1
• Any iron deficiency detected must be fully evaluated for underlying cause, particularly gastrointestinal malignancy 1
• These populations usually do not need iron supplements unless pathology identified 1

Chronic Kidney Disease 1

• For CKD non-dialysis patients with Hb <10 g/dL, individualize ESA therapy decision based on rate of Hb fall, iron therapy response, transfusion risk, and symptoms 1
• Prescribe iron when TSAT ≤30% and ferritin ≤500 ng/mL 1
• Balance benefits of avoiding transfusions against risks of ESA therapy 1

Congestive Heart Failure 1

• Define iron deficiency as: ferritin <100 ng/mL OR ferritin 100-300 ng/mL with TSAT <20% 1
• Avoid oral iron due to poor absorption from gut edema and frequent side effects 1
• Use intravenous iron as preferred treatment 1

Inflammatory Bowel Disease 1

• Ferritin up to 100 μg/L may reflect iron deficiency in presence of inflammation 1
• Oral iron should contain ≤100 mg elemental iron daily 1
• IV iron indicated for moderate-to-severe IDA (Hb <100 g/L) or oral intolerance 1
• Monitor for recurrent iron deficiency every 3 months for at least 1 year after correction 1

Post-Gastrointestinal Surgery 1

• IDA common after gastric/small bowel resection or bypass, including bariatric surgery 1
• Do not automatically attribute IDA to previous surgery; exclude other causes, particularly malignancy 1
• Prevalence increases over first 10 postoperative years without supplementation 1

Investigation for Underlying Cause

When to Investigate

All adults with confirmed iron deficiency anemia require investigation to identify the source of blood loss or malabsorption 1.

Gastrointestinal Evaluation 1

1. Upper GI endoscopy (OGD) with duodenal biopsies to exclude celiac disease
2. Colonoscopy (preferred) or CT colonography
3. If both negative and IDA persists/recurs: test for Helicobacter pylori by non-invasive testing and eradicate if present 1
4. Consider video capsule endoscopy or CT enterography for small bowel evaluation only if transfusion-dependent or visible blood loss 1

Tests to Avoid

• Faecal occult blood testing has no benefit—it is insensitive and non-specific 1
• Routine liver function, renal function, and clotting studies are not diagnostic unless history suggests systemic disease 1

Follow-Up Monitoring

After Correction of Anemia 1

• Monitor hemoglobin and red cell indices every 3 months for 1 year
• Repeat monitoring after an additional year
• Give additional oral iron if hemoglobin or MCV falls below normal
• Further investigation only necessary if hemoglobin and MCV cannot be maintained

Vitamin B12 Deficiency Anemia

For pernicious anemia, parenteral vitamin B12 is required for life; oral forms are not dependable 7.

Treatment Regimen 7

1. 100 mcg daily IM or deep subcutaneous for 6-7 days
2. If clinical improvement and reticulocyte response: same dose on alternate days for 7 doses
3. Then every 3-4 days for 2-3 weeks
4. Maintenance: 100 mcg monthly for life
5. Administer folic acid concomitantly if needed

Critical Care Anemia 1

In critically ill patients, use restrictive transfusion threshold of Hb <70 g/L for most patients, including those with ARDS and septic shock 1.

• Available evidence does not support routine use of iron therapy or erythropoietin in critically ill patients 1
• Hemoglobin drops by mean 0.52 g/L per day in ICU 1

Common Pitfalls to Avoid

• Do not prescribe ferrous sulfate three times daily—twice daily is equally effective with better tolerability 1, 3
• Do not continue investigating if hemoglobin and MCV normalize and remain stable on follow-up 1
• Do not use intravenous route for vitamin B12—almost all will be lost in urine 7
• Do not assume post-surgical patients' anemia is solely due to surgery without excluding malignancy 1
• Do not overlook iron deficiency in heart failure patients—it requires IV iron, not oral 1
• Do not ignore the possibility of IRIDA in patients with persistent microcytic anemia despite treatment 1