Haemolysis: extravascular vs intravascular
- Mechanism
Red cells that die early are eaten by macrophages or burst inside vessels. Each route leaves its own signs in blood, urine and organs.
What it is
Haemolytic anaemias shorten red cell survival below the normal 120 days, raise erythropoietin and expand erythropoiesis, and leave haemoglobin breakdown products behind. Most haemolysis is extravascular: rigid or antibody-coated cells are removed by macrophages in the spleen and liver. Intravascular haemolysis occurs when cells are torn, lysed by complement or damaged by toxins or parasites, releasing haemoglobin into plasma and urine. Chronic haemolysis causes pigment gallstones and haemosiderin deposits.
Step by step
- A red cell becomes rigid, coated or abnormal, or is directly torn or lysed.
- Extravascular route: macrophages in the splenic cords engulf it and turn haem into bilirubin.
- Intravascular route: free haemoglobin binds haptoglobin; when haptoglobin runs out it is filtered in the kidney.
- Tubular cells store iron as haemosiderin and shed it in urine; free haemoglobin oxidizes to brown methaemoglobin.
- Bilirubin rises; the liver excretes more into bile, which may form pigment stones.
- Erythropoietin drives erythroid hyperplasia and reticulocytosis.
Extravascular vs intravascular haemolysis
| Feature | Extravascular | Intravascular |
|---|---|---|
| Where and examples | Spleen and liver macrophages: hereditary spherocytosis, warm antibodies, sickle cell disease, thalassaemia | Inside vessels: PNH, mismatched transfusion, G6PD crises, microangiopathy, valves, malaria, clostridial toxins |
| Signs | Splenomegaly, jaundice, gallstones; urine free of haemoglobin | Haemoglobinaemia, dark urine (haemoglobinuria), haemosiderinuria, possible kidney injury |
Clinical notes
- Aplastic crises (parvovirus B19) are dangerous in any chronic haemolytic anaemia because survival of red cells is short.
- Folate needs increase with brisk erythropoiesis.
In the lab
- Unconjugated bilirubin, LDH, haptoglobin, reticulocyte count and the smear.
- Direct antiglobulin (Coombs) test separates immune from non-immune haemolysis.
Test yourself
Think of the answer, then tap the question to see it.
Which finding indicates intravascular rather than extravascular haemolysis?
Haemoglobinuria and haemosiderinuria (with haemoglobinaemia and very low haptoglobin).
What kind of gallstones form in chronic haemolysis?
Pigment (bilirubinate) gallstones.
Why is bilirubin unconjugated in haemolysis?
Macrophages produce bilirubin faster than the liver can conjugate and excrete it.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Hemolytic anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Bilirubin blood test: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.