Approach to Hemolytic Anemia

CLASSIFICATION OF HEMOLYTIC ANEMIAS

Intra Corpuscular DefectsExtra Corpuscular Factors
Hereditary• Hemoglobinopathies
• Enzymopathies
• Membrane-cytoskeletal defects
• Familial hemolytic uremic syndrome
Acquired• Paroxysmal nocturnal hemoglobinuria• Mechanical destruction (microangiopathic)
• Toxic agents
• Drugs
• Infectious
• Autoimmune

classification of haemolytic disorders

Inherited hemolytic disorders

  1. Defects in the structure of the red cell membrane:

    • Hereditary spherocytosis
    • Hereditary elliptocytosis
    • Hereditary stomatocytosis
  2. Defects of erythrocyte metabolism:

    • G6PD deficiency
    • Pyruvate kinase deficiency
    • Other enzyme disorders
  3. Qualitative haemoglobin disorders:

    • Stable variants, such as sickle cell disease
    • Unstable variants
  4. Quantitative haemoglobin disorders:

    • Impaired globin chain synthesis
    • Thalassaemias

Hemolytic Anemia Diagnosis

Two main principles:

  1. Confirm hemolysis
  2. Determine the etiology

The Key To The Etiology Of Hemolytic Anemia

  • The history
  • The peripheral blood film

How to diagnose hemolytic anemia

  • New onset pallor or anemia
  • Jaundice
  • Splenomegaly
  • Gall stones - Calciumbilirubinate stones
  • Dark colored urine (hemoglobinuria)
  • Leg ulcers (poor circulation and microinfarcts, healing is delayed and infection becomes established).

Patient History

  • Acute or chronic
  • Medication/Drug precipitants
  • G6PD
  • AIHA
  • Family history
  • Concomitant medical illnesses
  • Clinical presentation

GENERAL FEATURES OF HEMOLYTIC DISORDERS

  • General Examination: Jaundice, Pallor, Bossing Of Skull
  • Physical Findings: Enlarged Spleen
  • Hemoglobin: From Normal To Severely Reduced
  • MCV: Usually Increased
  • Reticulocytes: Increased
  • Bilirubin: Increased [mostly Unconjugated]
  • LDH: Increased
  • Haptoglobulin: Reduced To Absent

Laboratory Diagnosis of Hemolytic Anemia:

Evidence for Red cell Destruction

  • i) PERIPHERAL BLOOD SMEAR → - Burr Cell - Tear drop cell (Intravascular Hemolysis) - Fragmented cell Spherocytes - Spherocytes → H. spherocytosis - Malaria → Malaria parasite - Sickle cells → Sickle cell anemia
  • ii) Plasma haptoglobin & Plasma hemopexin → ↓
  • iii) Plasma Hb ↑
  • iv) Serum LDH & Serum Carboxy Hb → ↑
  • v) Indirect bilirubin & urobilinogin → ↑
  • vi) Red cell survival → ↓ Using Chromium 52

Evidence of Red cell Generation:

  1. Peripheral blood smear
    • Polychromasia
    • Nucleated red cells
  2. Reticulocyte count → ↑

Laboratory Evaluation of Hemolysis

Laboratory Evaluation of HemolysisExtravascularIntravascular
HEMATOLOGIC
Routine blood filmPolychromatophiliaPolychromatophilia
Reticulocyte count
Bone marrow examinationErythroid hyperplasiaErythroid hyperplasia
PLASMA OR SERUM
BilirubinUnconjugated ↑Unconjugated
Haptoglobin↓, AbsentAbsent
Plasma hemoglobinN/↑↑↑
Lactate dehydrogenase↑ (Variable)↑↑ (Variable)
URINE
Bilirubin++
Hemosiderin0+
Hemoglobin0+ → severe cases