Haemolytic Anaemia

Question 1

How can HA be classified?

Answer 1

• Acute vs chronic
• Intravascular (within blood vessels) vs extravascular (spleen/liver)
• Intracorpuscular (intrinsic - defect in RBC, cell lysis) vs extracorpuscular (extrinsic - outside RBC, cell lysis)
• Inherited (usually intrinsic defects) vs acquired (extrinsic)

Question 2

What is extravascular RBC destruction and the mechanism?

Answer 2

These are destructions of normal RBC. It destroys the reticuloendothelial system. The repeated circulation through the splenic vessels damages the RBC membrane.

Mechanism: after RBC lysis
1. Globin is broken down into amino acids
2. Amino acids are taken into the BM to make more red cells

1. Iron in RBC binds to transferrin
2. This is taken to the BM to make more red cells
3. Protoporphyrin is converted to biliverdin
4. Biliverdin –> bilirubin
5. bilirubin leaves the spleen as unconjugated but enters liver conjugated - more soluble
6. conjugated bilirubin goes to faeces - excreted as stercobilinogen
7. Or can be reabsorbed in intestines through kidneys but excreted as urobilinogen (urine)

Question 3

What is intravascular RBC destruction and the mechanism?

Answer 3

Associated with disease. RBC are destroyed within the vasculature within the blood vessels.

Mechanism: after RBC lysis
1. Hb is released directly from RBC
2. Hb binds to proteins within the bloodstream (albumin)
3. Becomes oxidised
4. Converted to methaealbumin
5. Hb/methaealbumin can be excreted from the kidneys in the form of haemoglobinuria/haemosiderinuria

Question 4

Clinical features: congenital HA

Answer 4

• Anaemia - mild/moderate
  Due to more destruction of RBC
• Jaundice
  Due to degradation of haem
  Bilirubin released into bloodstream
• Splenomegaly
  More RBC destruction = increased spleen size
• Cholelithiasis (gallstones)
  Bile pigments crystallised in gallbladder
• Leg ulcers
  Caused by release of haem
  Haem can inhibit NO promoting coagualtion
  Can cause thrombosis = ischemia + leg ulcers
• Skeletal abnormalities
  Frontal bossing
  Maxillary + dental abnormalities = thalassaemia major
  BM needs to make more TBC to compensate the haemolysis, and parts of the skeleton that are not normally associated with make RBC = changes in skeleton

Question 5

Blood film HA

Answer 5

Polychromatophilia
Basophilic stippling
Erythroblastosis
Schistocytes
Acanthocytes
Echinocytes

Question 6

Red cell indices HA

Answer 6

Reticulocytosis - increased reticulocytes
Macrocytosis - increased MCV

Question 7

What are the signs of intravascular haemolysis?

Answer 7

• Haemoglobinaemia - increased Hb
• Haemoglobinuria - taken to kidneys to excrete = increased Hb in urine
• Haemosiderinuria - Fe binding proteins in kidneys, stores of Fe, increased
• Decreased serum haptoglobin - binds to haem, becomes saturated, decrease in free serum haptoglobin, haem in urine
• Methemalbuminaemia - can be oxidised + bind to albumin

Question 8

What are the types of intrinsic HA

Answer 8

• Hb abnormalities
  Thalassaemia
  Sickle cell disease
• Abnormalities of red cell membrane
  Hereditary spherocytosis (HS)
  Hereditary elliptocytosis
• Defects of cell metabolism
  Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Question 9

What is hereditary spherocytosis?

Answer 9

It is autosomal dominant. It’s where there are mutations in the membrane cytoskeleton proteins (spectrin). Spectrin is a horizontal protein that spans along the horizontal axis of red cells. There’s also mutations in the transmembrane proteins (ankyrin). Ankyrin is a vertical protein that binds to extracellular carbohydrates to spectrin.

Question 10

What do the mutations of spectrin and ankyrin do to the cell membrane?

Answer 10

It reduces the membrane fluidity and deformability - rigid.
This does not allow anything to pass through the circulation. Causes deformity leading to splenic destruction.

Question 11

Clinical features of HS

Answer 11

Triad
- Pallor
- Jaundice
- Splenomegaly

Severity: mild/severe

Question 12

What is the osmotic fragility test?

Answer 12

A test to see if RBC breaks down.
RBC is exposed to saline solutions with increasing dilution. RBC burst in hypotonic solutions <0.9% NaCl. RBC shrink in hypertonic.
Quicker haemolysis = greater osmotic fragility

Question 13

How can you use the osmotic fragility test to detect HS?

Answer 13

Patients with HS will have red cells that have been lysed in hypertonic solutions

Question 14

What are the treatments of HS

Answer 14

• Splenonectomy - depends degree of anaemia
• Partial splenectomy - laparoscopic
• Cholecystectomy - pigmented gallstones
• Folate supplement - extreme cases
• Phototherapy - neonatal jaundice, UV light on babies, UV converts bilirubin to soluble pigment, excreted in urine
• Exchange transfusion - withdraw spherocytes + give normal RBC