Makindo Medical Notes

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Thrombotic Thrombocytopenic purpura (TTP) |Haemolytic Uraemic syndrome (HUS) |Thrombocytopenia |Disseminated Intravascular Coagulation (DIC)

About

• Haemolytic Anaemia: A condition in which red blood cells (RBCs) are destroyed faster than they can be replaced.
• While all red cells are eventually hemolyzed (normal half-life is approximately 120 days), the critical issue in haemolytic anaemia is a significant shortening of the red cell half-life.
• When red cell destruction exceeds the bone marrow's capacity to produce new cells, anemia develops.

Causes

• Membrane Defects: Hereditary spherocytosis, Hereditary elliptocytosis
• Metabolic Defects: G6PDH deficiency, Pyruvate kinase deficiency
• Haemoglobinopathies: Sickle cell anaemia (HbSS), Thalassaemia
• Drugs: Examples include Penicillin and Quinine
• Immune: Transfusion reactions, Hemolytic disease of the newborn
• Others:
  • Microangiopathic haemolytic anaemia (e.g., TTP, HUS, DIC, PET)
  • Mechanical damage from metal heart valves
  • Infections such as malaria
  • Paroxysmal nocturnal haemoglobinuria (PNH)

Causes: Congenital and Acquired

Clinical Features

• Pallor, fatigue, and dyspnoea (shortness of breath)
• Bleeding tendencies, easy bruising, and rashes
• Lymphadenopathy (enlarged lymph nodes)
• Hepatosplenomegaly (enlargement of the liver and spleen)
• Leg ulcers and jaundice

Comparison of Intravascular vs. Extravascular Haemolysis

Intravascular Haemolysis

• RBCs are destroyed directly within the circulation.
• Free haemoglobin binds to albumin, forming methaemalbumin (detectable by Schumm's test).
• Laboratory findings include very low haptoglobin, raised LDH, and increased unconjugated bilirubin; haemoglobin and its degradation products may be found in urine as haemosiderin.
• Common causes include PNH, G6PDH deficiency, mechanical damage from prosthetic heart valves, microangiopathic processes (e.g., HUS, TTP, DIC), and cold autoimmune haemolytic anaemia.

Extravascular Haemolysis

• Old or damaged RBCs are removed by macrophages, primarily in the spleen, liver, and bone marrow.
• Leads to elevated levels of unconjugated bilirubin and increased reticulocyte count, with normal haptoglobin since hemoglobin is degraded intracellularly.
• Common causes include hereditary spherocytosis, sickle cell anaemia, thalassaemia, warm autoimmune haemolytic anaemia, haemolytic disease of the newborn, and other haemoglobinopathies.

Investigations

• Hemoglobin (Hb): Reduced levels indicate anemia.
• Blood Film: May show reticulocytosis, polychromasia, spherocytes, anisopoikilocytosis, stomatocytosis, sickle cells (in HbSS), Heinz bodies (in G6PD deficiency), schistocytes, helmet cells, and echinocytes.
• Serum Unconjugated Bilirubin: Raised in hemolytic conditions.
• Urinary Urobilinogen: Increased due to excess bilirubin breakdown.
• Urinary Hemoglobinuria: Increased in intravascular hemolysis.
• Direct Coombs (DAT) Test: Positive in immune-mediated hemolysis; negative in mechanical and non-immune causes.
• Reticulocyte Count: Elevated as the bone marrow compensates for RBC loss.
• Urinary Haemosiderin: Indicates chronic intravascular hemolysis (e.g., in PNH).
• Schumm’s Test: Detects methaemalbumin, supporting a diagnosis of intravascular hemolysis.
• Serum Haptoglobin: Low or absent in intravascular hemolysis due to binding of free hemoglobin.
• LDH: Elevated with increased RBC breakdown.
• Enzyme Assays: Reduced red cell G6PD or pyruvate kinase levels in respective deficiency states.
• Hemoglobin Analysis: Useful for detecting hemoglobinopathies such as sickle cell disease.
• Antibody Testing: Warm antibodies (IgG) or cold antibodies (IgM) can be identified via DAT in autoimmune hemolysis.
• ADAMTS13 Assay: May be indicated if microangiopathic hemolytic anemia (MAHA) is suspected.