Anemia Summary

Definition

  • Men: Hb < 130 g/L
  • Women: Hb < 120 g/L
  • Pregnancy: Hb < 110 g/L
  • Children (12-14): Hb < 120 g/L

Classification by MCV

  • Microcytic: MCV < 80 fL
  • Normocytic: MCV 80-96 fL
  • Macrocytic: MCV > 96 fL

Clinical Features

  • Dyspnea, fatigue, weakness
  • Headache, dizziness, palpitations
  • Pallor (Hb < 90 g/L)
  • Cardiac signs (Hb < 80 g/L)

Key Investigations

  • FBC with indices
  • Blood film
  • Iron studies
  • B12/folate levels
  • Reticulocyte count

Iron Deficiency

  • Most common cause worldwide
  • ↓ Ferritin, ↑ TIBC
  • GI loss in men/postmenopausal women
  • Menstrual loss in premenopausal women

Megaloblastic Anemia

  • B12/folate deficiency
  • Neurological symptoms (B12)
  • Oval macrocytes on film
  • Pernicious anemia (common B12 cause)

Hemolytic Anemia

  • Shortened RBC lifespan
  • ↑ Reticulocytes, ↑ bilirubin
  • Jaundice, splenomegaly
  • ↓ Haptoglobin

Anemia

Comprehensive guide to classification, pathophysiology, diagnosis, and management

Definition

Anemia is defined as a haemoglobin (Hb) level two standard deviations below the normal for age and sex.

Diagnostic Thresholds

Population Hemoglobin Threshold
Men aged over 15 years Hb < 130 g/L
Non-pregnant women aged over 15 years Hb < 120 g/L
Children aged 12–14 years Hb < 120 g/L
Pregnant women Hb < 110 g/L throughout pregnancy
Postpartum Hb < 100 g/L

Pathophysiology

Hemoglobin Mass vs Plasma Volume

  • Actual reduction in total circulating hemoglobin mass
  • Increase in plasma volume (e.g., pregnancy) causing dilutional anemia
  • Reduction in plasma volume may mask anemia

Acute Blood Loss

  • Anemia not immediately apparent after acute major blood loss
  • Takes up to a day for plasma volume replacement
  • Initial clinical features due to reduced blood volume

Physiological Adaptation

  • Increase in red cell 2,3-diphosphoglycerate (2,3-DPG)
  • Shifts oxygen dissociation curve to the right
  • Enhanced O₂ delivery to tissues
  • Increase in stroke volume and heart rate

Clinical Features

Symptoms

  • Dyspnea
  • Fatigue
  • Headache
  • Dizziness
  • Weakness
  • Palpitations
  • Tinnitus
  • Cognitive changes
  • Worsening of angina, congestive heart failure or intermittent claudication

Signs

  • Pallor of mucous membranes or nail beds (if Hb < 90 g/L)
  • Tachycardia, murmurs, cardiac enlargement (Hb < 80 g/L)
  • Heart failure may occur if severe (Hb < 80 g/L)

Note: Symptoms are more marked in acute onset anemia and in older patients with impaired cardiovascular reserve.

Classification by MCV

Microcytic Anemia (MCV < 80 fL)

  • Iron deficiency
  • Thalassaemia
  • Sideroblastic anemia
  • Anemia of chronic disease (some cases)
  • Lead poisoning

Normocytic Anemia (MCV 80-96 fL)

  • Most hemolytic anemias
  • Anemia of chronic disease (most cases)
  • Mixed cases

Macrocytic Anemia (MCV > 96 fL)

  • Megaloblastic:
    • Vitamin B12 deficiency
    • Folate deficiency
  • Non-megaloblastic:
    • Alcohol
    • Drugs (antimetabolites)
    • Myelodysplasia, aplastic anemia
    • Liver disease
    • Hypothyroidism
    • Smoking

Iron Deficiency Anemia

Iron deficiency anemia is the most common cause of microcytic anemia and of any anemia worldwide.

Causes

Inadequate Intake

  • Dietary iron deficiency (uncommon in UK)
  • Growing children
  • Elderly with iron-poor diets

Excessive Requirements

  • Pregnancy, menstruation, lactation
  • Rapid growth in children
  • Exfoliative skin disease

Malabsorption

  • Drugs (tetracyclines, quinolones, antacids, PPIs)
  • Partial/total gastrectomy
  • Coeliac disease, IBD, H. pylori infection

Excessive Loss

  • GI blood loss (most common in men/postmenopausal women)
  • Menstrual blood loss (most common in premenopausal women)
  • Parasitic infections (hookworm, schistosomiasis)

Clinical Features

General Anemia Features

  • Fatigue, weakness, dyspnea
  • Pallor, tachycardia

Specific Iron Deficiency Features

  • Koilonychia (spoon-shaped nails)
  • Angular cheilitis
  • Atrophic glossitis
  • Pica (unusual dietary cravings)
  • Dry skin and hair
  • Alopecia

Laboratory Findings

Parameter Finding
Blood film Hypochromic microcytic RBCs, anisocytosis, poikilocytosis, pencil cells
Serum ferritin ↓ (less than 15 μg/L confirms deficiency)
Serum iron ↓
Transferrin ↑
Transferrin saturation ↓
TIBC ↑

Megaloblastic Anemia

Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production, most often due to vitamin B12 or folate deficiency.

Causes of Vitamin B12 Deficiency

Pernicious Anemia

Most common cause of severe B12 deficiency - autoimmune process affecting gastric mucosa

Other Causes

  • Drugs (colchicine, metformin, nitrous oxide, PPIs)
  • Gastric surgery
  • Intestinal malabsorption
  • Nutritional (vegan diet)

Causes of Folate Deficiency

Increased Requirements

  • Pregnancy and lactation
  • Malignancy
  • Hemolytic anemias
  • Inflammatory diseases

Other Causes

  • Drugs (alcohol, anticonvulsants, methotrexate)
  • Malabsorption
  • Nutritional deficiency

Clinical Features

General & Specific Features

  • General anemia symptoms
  • Lemon yellow tinge (pallor + jaundice)
  • Atrophic glossitis
  • Angular cheilitis
  • Neural tube defects in pregnancy

B12-Specific Neurological

  • Paraesthesia
  • Ataxia
  • Symmetrical neuropathy (legs > arms)
  • Memory impairment
  • Poor motor coordination

Laboratory Features

Finding Description
Blood film Oval macrocytes, hypersegmented neutrophils, circulating megaloblasts
B12/folate levels Low
MCV Increased (>96 fL)

Hemolytic Anemia

Hemolytic anemias are caused by a shortened red cell lifespan. Red cell destruction may be increased several-fold before anemia becomes apparent due to erythropoietic hyperplasia.

Causes

Hereditary

  • Red cell membrane disorders
  • Red cell metabolism disorders
  • Hemoglobin synthesis disorders

Acquired

  • Autoimmune (warm/cold antibody)
  • Alloimmune
  • Red cell fragmentation syndromes
  • Infections, drugs, chemicals

Clinical Features

General Features

  • Anemia
  • Jaundice (unconjugated bilirubin)
  • Pigment gallstones
  • Splenomegaly

Specific Features

  • Ankle ulcers
  • Bone expansion in children
  • Aplastic crisis (parvovirus)
  • Megaloblastic anemia (folate deficiency)

Laboratory Features

Parameter Finding
Reticulocyte count ↑
Blood film Polychromasia, altered RBC shape
Bilirubin ↑ Indirect (unconjugated)
Haptoglobin ↓ or absent
LDH ↑
Urine urobilinogen ↑

Anemia of Chronic Disease

Common normochromic or mildly hypochromic anemia occurring in patients with inflammatory and malignant diseases.

Causes

Chronic Infections

  • Osteomyelitis, endocarditis, TB
  • Chronic abscesses, bronchiectasis
  • HIV/AIDS, malaria

Chronic Inflammatory Disorders

  • Rheumatoid arthritis, SLE
  • Inflammatory bowel disease
  • Polymyalgia rheumatica

Malignancy & Other

  • Metastatic cancer, lymphoma
  • Congestive heart failure

Pathophysiology

Hepcidin, released by the liver in response to inflammatory cytokines, reduces iron absorption and iron release by macrophages into plasma. Cytokines also interact directly with marrow cells to reduce erythropoiesis and iron utilization.

Laboratory Features

Parameter Finding
Hemoglobin Moderate anemia (>90 g/L)
MCV Normocytic or mildly microcytic
Serum iron ↓
TIBC ↓
Transferrin saturation ↓
Ferritin Normal or ↑
ESR/CRP ↑