February 13th – A Day to Address a Global Public Health Challenge
Anaemia is not a single disease but a marker of underlying dysfunction—a red flag indicating that the body’s oxygen-carrying capacity is compromised. It affects billions worldwide, with the World Health Organization estimating that 42.7% of children under 5 and 34.9% of women of reproductive age in the Eastern Mediterranean Region alone are affected. This article provides a detailed medical overview of anaemia, with a special focus on drug-induced anaemia—a critical concern from a pharmacovigilance standpoint—and its comprehensive management.
What is Anaemia?
Anaemia is a condition characterized by a reduction in the number of red blood cells or the haemoglobin concentration below the normal range for age, sex, and physiological status. Haemoglobin is the iron-rich protein in red blood cells that binds to oxygen in the lungs and releases it into tissues throughout the body. When haemoglobin levels drop, tissues become starved of oxygen, leading to the classic symptoms of fatigue, weakness, and shortness of breath.
Normal Haemoglobin Ranges (Approximate):
- Adult males: 13.5–17.5 g/dL
- Adult females: 12.0–15.5 g/dL
- Children: Varies by age
- Pregnant women: Lower thresholds due to physiological plasma volume expansion
What Causes Anaemia?
The causes of anaemia are diverse and can be categorized into three main mechanisms: blood loss, decreased red blood cell production, and increased red blood cell destruction (haemolysis) .
| Mechanism | Causes |
|---|---|
| Blood Loss | Heavy menstruation, gastrointestinal bleeding (ulcers, haemorrhoids, cancer), trauma, postpartum haemorrhage, surgical procedures, frequent blood donations |
| Decreased Production | Nutrient deficiencies (iron, folate, vitamin B12, vitamin A), chronic diseases (chronic kidney disease, cancer, rheumatoid arthritis, inflammatory bowel disease), bone marrow disorders (aplastic anaemia, myelodysplasia), infections (HIV, tuberculosis), medications (see below) |
| Increased Destruction (Haemolysis) | Inherited red blood cell disorders (sickle cell disease, thalassaemia, glucose-6-phosphate dehydrogenase deficiency), autoimmune haemolytic anaemia, infections (malaria), medications (see below) |
Specific Causes Highlighted in Public Health Data:
- Inherited red blood cell disorders: Common in the Eastern Mediterranean Region, including sickle cell disease and thalassaemia.
- Nutrient deficiencies: Iron, vitamin A, folate, vitamin B12, and riboflavin deficiency are widespread, often due to poor dietary intake or malabsorption.
- Chronic diseases: Many chronic conditions cause inflammation, leading to anaemia of chronic disease (also called anaemia of inflammation).
- Heavy menstruation and pregnancy-related issues: Consistent heavy menstrual losses, maternal blood volume expansion during pregnancy, and blood loss during/after childbirth are major contributors.
- Infections: HIV and parasitic infections (e.g., hookworm, malaria) directly cause blood loss or bone marrow suppression.
Drug-Induced Anaemia: A Pharmacovigilance Perspective
From a pharmacovigilance standpoint, drug-induced anaemia is a significant and often under-recognized adverse drug reaction (ADR). It can occur through various mechanisms, and early detection is crucial to prevent morbidity and mortality.
Mechanisms of Drug-Induced Anaemia
| Mechanism | Description | Examples of Causative Drugs |
|---|---|---|
| Bone Marrow Suppression (Myelosuppression) | Drugs directly suppress the bone marrow’s ability to produce red blood cells, as well as white blood cells and platelets. This is often dose-dependent and predictable. | Chemotherapy agents (e.g., cisplatin, carboplatin, doxorubicin), immunosuppressants (azathioprine, mycophenolate), chloramphenicol, linezolid (with prolonged use) |
| Haemolysis (Immune-Mediated) | Drugs act as haptens, binding to red blood cell membranes and triggering an immune response. Antibodies attack the drug-RBC complex, leading to red blood cell destruction. | Penicillins, cephalosporins, methyldopa, levodopa, quinidine, NSAIDs (e.g., diclofenac), rifampicin |
| Haemolysis (G6PD Deficiency-Related) | In individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, certain drugs cause oxidative stress, leading to acute haemolytic anaemia. This is a classic pharmacogenomic ADR. | Antimalarials (primaquine, chloroquine), sulfonamides (sulfamethoxazole-trimethoprim), dapsone, nitrofurantoin, aspirin (high doses), methylene blue |
| Megaloblastic Anaemia | Drugs interfere with folate or vitamin B12 absorption or metabolism, leading to impaired DNA synthesis and abnormal red blood cell maturation. | Methotrexate, phenytoin, sulfasalazine, trimethoprim, oral contraceptives (rare), metformin (long-term use impairs B12 absorption) |
| Blood Loss (Drug-Induced Bleeding) | Drugs increase the risk of gastrointestinal bleeding or other haemorrhage, leading to chronic blood loss anaemia. | NSAIDs (aspirin, ibuprofen, naproxen), anticoagulants (warfarin, heparin, DOACs like apixaban and rivaroxaban), antiplatelets (clopidogrel), corticosteroids |
| Red Cell Aplasia (Pure Red Cell Aplasia) | Drugs selectively suppress red blood cell precursors in the bone marrow, leading to severe anaemia with normal white blood cell and platelet counts. A rare but serious ADR. | Recombinant erythropoietin (antibody-mediated), azathioprine, isoniazid, phenytoin, valproic acid |
| Microangiopathic Haemolytic Anaemia (MAHA) | Drugs cause damage to the endothelium of small blood vessels, leading to red blood cell fragmentation and destruction. | Chemotherapy (gemcitabine, mitomycin C), calcineurin inhibitors (cyclosporine, tacrolimus), quinine, ticlopidine |
Pharmacovigilance: Detection and Reporting of Drug-Induced Anaemia
Healthcare professionals play a critical role in identifying and reporting suspected drug-induced anaemia. Key considerations include:
- Temporal Association: Does the anaemia develop after starting the drug, and does it improve upon withdrawal (dechallenge)?
- Exclusion of Other Causes: Have other common causes (nutritional deficiencies, blood loss, chronic disease) been ruled out?
- Laboratory Clues:
- Haemolytic anaemia: Elevated bilirubin, lactate dehydrogenase (LDH), reticulocyte count; decreased haptoglobin; positive direct antiglobulin test (Coombs test) in immune-mediated cases.
- Megaloblastic anaemia: Macrocytosis (high MCV), low serum B12 or folate levels.
- Bone marrow suppression: Pancytopenia (low RBCs, WBCs, and platelets) with a hypocellular bone marrow on biopsy.
- Reporting: All suspected serious adverse reactions, including drug-induced anaemia requiring hospitalization or blood transfusion, should be reported to national pharmacovigilance centres (e.g., Medsafe in New Zealand, FDA in the USA, or local regulatory authorities).
Common Symptoms of Anaemia
Symptoms vary depending on the severity and speed of onset. Mild anaemia may be asymptomatic, while severe anaemia can be life-threatening.
Common Symptoms (Mild to Moderate Anaemia)
- Tiredness and fatigue
- Dizziness or feeling light-headed
- Cold hands and feet
- Headache
- Shortness of breath, especially upon exertion
- Pale skin
- Irritability
Severe Anaemia Symptoms (Requiring Urgent Medical Attention)
- Pale mucus membranes (inside the mouth, nose, conjunctiva)
- Pale skin, including under the fingernails
- Rapid breathing and heart rate (tachypnoea and tachycardia)
- Dizziness when standing up (orthostatic hypotension)
- Chest pain, angina, or heart failure (in severe cases)
- Syncope (fainting)
Special Populations: Children and Pregnancy
- Children under 5: Anaemia can cause poor cognitive and motor development, with irreversible effects on brain development and learning. It affects school performance, leading to decreased motor activity, social interaction, and attention to tasks.
- Pregnant women: Anaemia increases the risk of maternal mortality, postpartum haemorrhage, preterm birth, and low birth weight. It also reduces the mother’s energy and ability to care for her newborn.
Management of Anaemia: A Multifaceted Approach
Management depends entirely on the underlying cause. A “one-size-fits-all” approach is ineffective and potentially harmful.
1. Nutritional Anaemia (Iron, Folate, B12 Deficiency)
| Deficiency | Dietary Sources | Supplementation | Monitoring |
|---|---|---|---|
| Iron Deficiency | Iron-rich foods: Legumes (beans, lentils, chickpeas), meat (red meat, poultry, fish), eggs, nuts and seeds, dark leafy greens (spinach, kale). Enhancers: Vitamin C (citrus fruits, tomatoes, bell peppers) increases iron absorption. Inhibitors: Tea, coffee, calcium supplements, and whole grains (phytates) decrease absorption—avoid consuming with iron-rich meals. | Oral iron (ferrous sulphate, ferrous gluconate) is first-line. Dose: 60–200 mg elemental iron daily. IV iron (ferric carboxymaltose, iron sucrose) for severe cases, malabsorption, or intolerance. | Hb should rise by 1–2 g/dL within 3–4 weeks. Continue supplementation for 3–6 months after Hb normalizes to replenish stores. |
| Folate Deficiency | Leafy green vegetables, legumes, fortified grains, citrus fruits, liver. | Oral folic acid (1–5 mg daily). In pregnancy, 400–800 mcg daily for prevention. | Monitor Hb and folate levels. |
| Vitamin B12 Deficiency | Meat, fish, eggs, dairy products, fortified foods. | Oral B12 (1000–2000 mcg daily) for mild deficiency or maintenance. Intramuscular B12 (hydroxocobalamin or cyanocobalamin) for severe deficiency, malabsorption (pernicious anaemia), or neurological symptoms. | Monitor Hb, B12 levels, and neurological symptoms. |
2. Anaemia of Chronic Disease
- Treatment: Focus on managing the underlying chronic disease (e.g., optimal control of inflammatory arthritis, cancer treatment, management of chronic kidney disease).
- Erythropoiesis-Stimulating Agents (ESAs): Used selectively in chronic kidney disease or cancer patients on chemotherapy. Pharmacovigilance note: ESAs carry Boxed Warnings for increased risk of thrombosis, tumour progression, and cardiovascular events when used off-label or at high doses.
- Iron Supplementation: May be beneficial even if ferritin is normal or high, as iron is often “trapped” in macrophages in anaemia of chronic disease. IV iron is sometimes used.
3. Drug-Induced Anaemia: Management Steps
| Step | Action |
|---|---|
| 1. Identification | Recognize the potential culprit drug. Review the patient’s medication list, including over-the-counter drugs and supplements. |
| 2. Discontinuation (Dechallenge) | If safe and feasible, stop the suspected drug. Monitor for improvement in Hb and symptoms. This is both diagnostic and therapeutic. |
| 3. Supportive Care | Blood transfusion for severe, symptomatic anaemia (e.g., Hb <7 g/dL or higher in patients with cardiac disease). |
| 4. Specific Treatment | – Immune-mediated haemolysis: Corticosteroids (prednisone 1 mg/kg/day) or other immunosuppressants if severe. IVIG or rituximab in refractory cases. – G6PD deficiency-related haemolysis: Discontinue offending drug, provide supportive care, and avoid future triggers. – Megaloblastic anaemia: Supplement with folate or B12 as indicated. – Bone marrow suppression: May require growth factors (G-CSF for neutrophils, ESAs for RBCs) or discontinuation of myelosuppressive therapy. |
| 5. Reporting | Report the adverse reaction to the national pharmacovigilance centre (e.g., Medsafe, FDA, MHRA). This contributes to global drug safety knowledge. |
| 6. Prevention | Avoid re-exposure to the causative drug. For G6PD deficiency, provide a list of drugs to avoid. For patients requiring long-term therapy with a known risk (e.g., methotrexate), ensure adequate folic acid supplementation and regular blood monitoring. |
4. Anaemia Due to Blood Loss
- Acute blood loss: Stabilize the patient, identify and control the source of bleeding, and transfuse as needed.
- Chronic blood loss: Identify the source (e.g., colonoscopy for GI bleeding, gynaecological evaluation for menorrhagia). Treat the underlying cause (e.g., surgery for fibroids, proton pump inhibitors for peptic ulcers). Replace iron stores.
5. Inherited Red Blood Cell Disorders
- Thalassaemia: May require chronic transfusions, iron chelation therapy (to prevent iron overload from transfusions), folic acid supplementation, and, in severe cases, bone marrow transplantation.
- Sickle cell disease: Hydroxyurea to reduce crises, pain management, folic acid supplementation, infection prevention (vaccinations, penicillin prophylaxis), and transfusions for complications.
- G6PD deficiency: Avoidance of triggers (certain drugs, fava beans), supportive care during haemolytic crises.
Prevention: A Public Health Priority
Prevention strategies are essential, especially in high-burden regions.
| Strategy | Details |
|---|---|
| Dietary Diversity | Encourage consumption of iron-rich foods, vitamin C-rich foods to enhance absorption, and foods rich in folate and B12. |
| Supplementation Programs | Intermittent iron and folic acid supplementation for menstruating women. Daily iron and folic acid for pregnant women (as per WHO guidelines). |
| Food Fortification | Fortification of staple foods (flour, rice, salt) with iron, folic acid, and other micronutrients. |
| Infection Control | Get vaccinated against preventable infections (e.g., hepatitis B, HPV) that can contribute to chronic disease or cancer. Treat parasitic infections (deworming programs). |
| Management of Chronic Diseases | Optimize control of conditions like obesity, diabetes, and inflammatory diseases that can lead to anaemia of chronic disease. |
| Menstrual Health | Treat heavy menstruation (hormonal therapies, tranexamic acid, or surgical options). |
| Birth Spacing | Wait at least 24 months between pregnancies to allow maternal nutrient stores to replenish. |
| Genetic Counselling | For couples at risk of inherited red blood cell disorders (thalassaemia, sickle cell disease). |
| Medication Safety | Avoid unnecessary medications. When prescribing drugs known to cause anaemia, ensure baseline blood counts and regular monitoring. Educate patients on symptoms to report. |
The Risk-Benefit Calculus in Drug-Induced Anaemia
From a pharmacovigilance and clinical perspective, the decision to use a drug known to cause anaemia requires a careful risk-benefit analysis.
Example: Methotrexate for Rheumatoid Arthritis
- Benefit: Methotrexate is a highly effective disease-modifying antirheumatic drug (DMARD) that improves symptoms, prevents joint damage, and maintains quality of life in rheumatoid arthritis patients.
- Risk: Methotrexate can cause megaloblastic anaemia due to folate antagonism. It may also cause bone marrow suppression, leading to pancytopenia in some cases.
- Analysis: The risk of anaemia is manageable. By co-prescribing folic acid (typically 5 mg weekly, taken 24–48 hours after methotrexate), the risk of megaloblastic anaemia is significantly reduced. Regular monitoring of full blood counts (every 1–3 months) allows for early detection of bone marrow suppression. Therefore, the risk-benefit ratio is favorable—the drug’s benefits outweigh the manageable risks, provided that standard precautions are followed.
- Pharmacovigilance Message: The goal is not to avoid effective drugs but to use them safely, with monitoring, and with patient education. When anaemia occurs, it should be reported, investigated, and managed promptly.
Example: Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia (PCP) Prophylaxis in HIV
- Benefit: This combination drug is highly effective at preventing a life-threatening opportunistic infection in immunocompromised patients.
- Risk: It can cause folate deficiency megaloblastic anaemia and, in G6PD-deficient individuals, acute haemolytic anaemia.
- Analysis: The life-saving benefit of PCP prophylaxis generally outweighs the haematological risks. Management includes screening for G6PD deficiency in at-risk populations before prescribing, using lower doses for prophylaxis, and monitoring blood counts. If anaemia develops, alternatives (e.g., dapsone, atovaquone) can be considered.
Special Considerations from Regional Data
The statistics from the Eastern Mediterranean Region highlight the need for targeted interventions:
- Children under 5 (42.7% prevalence): This is a critical window for brain development. Prevention through maternal nutrition, exclusive breastfeeding for 6 months, timely introduction of iron-rich complementary foods, and deworming programs is essential.
- Women of reproductive age (34.9% prevalence): Adolescent girls and women need access to iron supplementation, menstrual health education, and family planning services to allow for optimal birth spacing.
- Pregnant women (36.8% prevalence): Antenatal care must include routine haemoglobin testing, iron and folic acid supplementation, and management of complications like postpartum haemorrhage.
Conclusion: A Call to Action for Pharmacovigilance and Public Health
Anaemia is a multi-faceted condition with causes ranging from nutritional deficiencies and inherited disorders to chronic diseases and drug-induced adverse reactions. On this World Anaemia Awareness Day, the message is clear:
- For Healthcare Professionals: Maintain a high index of suspicion for drug-induced anaemia. Take a thorough medication history, monitor blood counts when prescribing high-risk drugs, and report suspected adverse reactions to pharmacovigilance centres. Your report could be the signal that prevents harm in thousands of future patients.
- For Patients: Be aware of the symptoms of anaemia. If you experience unusual fatigue, dizziness, or shortness of breath—especially after starting a new medication—consult your healthcare provider. Do not stop prescribed medications without medical advice, but do speak up.
- For Public Health: Invest in prevention—nutrition programs, infection control, genetic counselling, and education. Address the social determinants of health that make anaemia a disease of poverty and inequality.
Through vigilance, education, and evidence-based management, we can reduce the burden of anaemia worldwide and ensure that every individual—from the youngest child to the oldest adult—has the healthy red blood cells they need to live a full and productive life.
References
- BMJ Best Practice. Assessment of anaemia [Internet]. London: BMJ Publishing Group; 2026 [cited 2026 Feb 14]. Available from: https://bestpractice.bmj.com/topics/en-gb/93
- World Health Organization (WHO). Anaemia [Fact Sheet]. In: Global Health Observatory (GHO) data [Internet]. Geneva: World Health Organization; [cited 2026 Feb 14]. Available from: https://www.who.int/health-topics/anaemia
- Pharmacy Times. The Blood Detective: Tackling Medication-Induced Hematological Disorders [Internet]. Cranbury, NJ: Pharmacy Times; 2024 Feb 14 [cited 2026 Feb 14];6(2). Available from: https://www.pharmacytimes.com/view/the-blood-detective-tackling-medication-induced-hematological-disorders
- UF Health. Drug-Induced Immune Hemolytic Anemia [Internet]. Gainesville (FL): University of Florida Health; 2025 Oct 14 [cited 2026 Feb 14]. Available from: https://ufhealth.org/conditions-and-treatments/drug-induced-immune-hemolytic-anemia
- NIH National Library of Medicine. Paediatric anaemia prevalence trends in the Eastern Mediterranean Region: a 20-year analysis by income level [Internet]. Bethesda (MD): National Institutes of Health; 2025 May 5 [cited 2026 Feb 14];15:04160. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12050902/
- Archives of Medical Science. A silent crisis: two decades of anaemia trends among women in the Eastern Mediterranean Region (2000–2019) [Internet]. Poznan: Termedia Publishing; 2025 Apr 20 [cited 2026 Feb 14]. Available from: https://www.archivesofmedicalscience.com/A-silent-crisis-two-decades-of-anaemia-trends-among-women-in-the-Eastern-Mediterranean,203989,0,2.html
- Our World in Data. Share of women of reproductive age who have anemia [Internet]. Oxford: Global Change Data Lab; 2026 Jan 29 [cited 2026 Feb 14]. Available from: https://ourworldindata.org/grapher/prevalence-of-anemia-in-women-of-reproductive-age-aged-15-29
- Brayfield A, editor. Martindale: The Complete Drug Reference. 39th ed. London: Pharmaceutical Press; 2017.
- U.S. Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) [Internet]. Silver Spring (MD): U.S. Food and Drug Administration; [cited 2026 Feb 14]. Available from: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard
- Medsafe New Zealand. Clinical Trials Safety Reporting Guidelines [Internet]. Wellington: New Zealand Medicines and Medical Devices Safety Authority; [cited 2026 Feb 14]. Available from: https://www.medsafe.govt.nz/
