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Haematology > Haemolysis > Flashcards

Haemolysis Flashcards

1
Q

Haemolysis definition

A

Premature destruction or ‘lysis’ of circulating red blood cells i.e. shortened RBC survival

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2
Q

Why are RBCs so susceptible to damage?

A
  • Need to be biconcave (can’t have damaged membrane)
  • Limited metabolic reserve (no mitochondria)
  • Can’t replace/repair damage e.g. proteins (no nucleus)
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3
Q

Compensated haemolysis vs decompensated haemolysis (haemolytic anaemia) definition

A

Compensated haemolysis
- Increased RBC destruction
- matched by increased RBC production
=> Hb maintained

Decompensated haemolysis
- Increased rate of red cell destruction
- exceeds bone marrow capacity for RBC production
=> Hb Falls (anaemia)

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4
Q

(Bone marrow) consequences of haemolysis

A
  • Erythroid hyperplasia (note: not specific to haemolysis)
  • Reticulocytosis (note: not specific to haemolysis)
  • Excess RBC breakdown => Increased bilirubin (SPECIFIC!)
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5
Q

What two components characterise haemolysis?

A
  • Increased RBC production (reticulocytosis) AND
  • Increased RBC breakdown (bilirubinaemia (extravascular) or haemoglobinaemia (intravascular))
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6
Q

Extravascular haemolysis (spleen/macrophages) consequences

A
  • Unconjugated bilirubinaemia (jaundice) (other LFTs ok)
  • Urobilinogenuria (dark urine)
  • Splenomegaly +/- hepatomegaly (work hypertrophy)
  • Gallstones (if chronic)
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7
Q

Intravascular haemolysis (outside macrophages) consequences

A
  • Haemogolbinaemia (free Hb in cicrulation)
  • Haemoglobinuria (Hb removal in kidneys) (pink -> dark urine)
  • metHaemalbuminaemia (Hb binding to albumin in blood)
  • Haemosiderinuria (iron taken up by kidney tubular cells and converted to haemosiderin that is then removed)
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8
Q

Intravascular vs extravascular haemolysis aetiology

A

Intravascular
- Mechanical RBC trauma e.g valvular disease, severe burns…
- Incompatible ABO blood transfusion
- Severe G6PD deficiency
- Some snake venoms, malaria, toxins etc (rarer)

Extravascular
- all other causes of haemolysis

Mixed
- Haemolysis is commonly a mix of both

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9
Q

Summarise the investigations used to confirm (extravascular) haemolysis

A

Test for increased production of RBCs
- Reticulocyte count (raised)

Test for destruction of RBCs
- FBC (anaemia if decompensated)

Test for products of RBCs destruction
- Lactate Dehydrogenase (raised - non specific)
- Serum haptoglobins (binds free Hb => will be low)
- Serum unconjugated bilirubin (raised)
- Urinary urobilinogen (raised)

Test for cause
- Blood film (to confirm if cause e.g. membrane damage)

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10
Q

Haemolysis can be classified by:
- Location of RBC destruction
- Reason for RBC destruction
- Compensatory mechanisms of the body
…Describe these.

A

Location of RBC destruction
- Extravascular (reticuloenothelial system e.g. spleen) (normal response but in excess)
- Intravascular (blood circulation) (abnormal response)

Reason for RBC destruction
- No abnormality of RBC
- Abnormality of RBC membrane
- Abnormality of RBC metabolism
- Abnormality of haemoglobin structure

Compensatory mechanisms
- Compensated (production matches destruction)
- Decompensated (anaemia) (too much destruction)

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11
Q

What is the reticuloendothelial system

A

The group of macrophages that breakdown and remove RBCs. The RE system is present in many main organs like the liver, bone marrow, adrenals, but is mainly present in the spleen.

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12
Q

What would a spherocyte on blood film suggest

A

RBC membrane damage

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13
Q

How would Haemolysis caused by DIC or Valvular disease present on blood film?

A

RBC fragments

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14
Q

What would Heinz bodies and keratocytes on a blood film suggest is the cause of haemolysis?

A

Oxidative damage

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15
Q

List some causes of haemolysis/ haemolytic anaemia
(autoimmune, alloimmune, mechanical, membrane, metabolic, Hb structure)

A
  • Autoimmune haemolytic anaemia - WAHA, CAD
  • Alloimmune haemolytic anaemia - blood transfusion incompatibility, HDN
  • Mechanical haemolytic anaemia - valvular disease, MAHA, severe burns, march haemaglobinuria
  • Membrane damage - Hereditary spherocytosis, zieve’s disease, paroxysmal nocturnal haemoglobinuria
  • Metabolic damage - G6PD deficiency
  • Hb structure defect - Sickle cell
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16
Q

What is the difference between autoimmune and alloimmune haemolysis

A

Autoimmune haemolysis - You make an antibody to your own RBCs

Alloimmune haemolysis - You are given an antibody or RBC that is incompatible with your own RBCs/antibodies
(i.e. incompatible transfusion or haemolytic disease of newborn)

17
Q

Autoimmune haemolytic anaemia can be classified into:
- Warm Autoimmune Haemolytic Anaemia (WAHA) &
- Cold Agglutinin Disease (CAD)
Describe the differences between these (IgG or IgM, Intravascular or extravascular, temperature?), state which is more common and list some causes of each

A

Warm Autoimmune Haemolytic Anaemia (WAHA)
- Most common
- IgG mediated (& so usually extravascular)
- Occurs at body temperature
- SLE, CLL, penicillin, infections, idiopathic etc

Cold Agglutinin Disease
- IgM mediated (& so usually intravascular)
- Occurs in cold conditions
- Infections like EBV & mycoplasma, idiopathic etc

18
Q

What is the name of the test used to identify autoantibodies on RBCs

A

Direct Coombs Test aka Direct Antiglobulin Test

19
Q

Describe the mechanisms of Haemolytic Disease of the Newborn:
- Autoimmune or Alloimmune?
- IgG or IgM
- Extravascular or intravascular

A

Mum’s IgG antibody against the RhD antigen transfer to the baby causing alloimmune, intravascular haemolysis in the newborn.

20
Q

How would you work out whether a haemolytic transfusion reaction is due to ABO or RhD antigen i.e. what are the differences between the two?

A

ABO
- Immediate reaction
- Intravascular, IgM

RhD
- Delayed reaction
- Extravascular IgG

21
Q

Intravascular haemolysis can be caused by mechanical destruction of RBCs. List 4 main causes for this

A
  • Damaged heart valves
  • Severe burns (damaging microcirculation)
  • Microangiopathic haemolysis (due to e.g. DIC or TTP)
  • March haemoglobinuria (transient hemoglobinuria after strenuous exercise)
22
Q

Haemolysis can occur as a result of RBC membrane damage. Name 3 causes of this

A

CONGENITAL
- Hereditary spherocytosis (usually an autosomal dominant mutation affecting membrane proteins)

ACQUIRED
- Zieve’s syndrome (due to alcoholism & liver disease)
- Paroxysmal nocturnal haemoglobinuria (acquired mutation that affects membrane protein binding)

23
Q

What is a spherocyte? List some causes of spherocytes

A

Removal of RBC membrane to minimum thickness required to enclose Hb. Can be genetic, autoimmune, mechanical.

  • Hereditary spherocytosis (genetic)
  • Zeive’s syndrome
  • WAHA (autoimmune)
  • Delayed (RhD) transfusion reaction, HDN (autoimmune)
  • Severe burns (mechanical)
  • Microangiopathic haemolysis (mechanical)
24
Q

Why does G6PD deficiency lead to haemolysis

A
  • G6PD deficiency limits the hexose monophosphate shunt
  • Limited glutathione (GSH) formation
  • Unable to prevent oxidative damage (Fe2+ -> Fe3+)
  • Haemolysis is therefore triggered with oxidative stress e.g. infections, certain foods, drugs
25
Q

Sickle cell disease can cause haemolytic anaemia, why?

A

Abnormal beta chain & heamoglobin
Abnormal polymerisation of HB in certain situations
Shortened RBC survival => haemolytic anaemia

Haematology (22 decks)

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