Haemolysis

Question 1

what is haemolysis

Answer 1

Premature red cell destruction

i.e. shortened red cell survival

Question 2

why are red cells susceptible to damage

Answer 2

1. need a biconcave shape to transit the circulation
2. limited metabolic reserve and rely on glucose metabolism for energy (no mitochondria)
3. Can’t generate new proteins once in the circulation (no nucleus)

Question 3

what is compensated haemolysis

Answer 3

Increased red cell destruction compensated by increased red cell production
i.e. Hb Maintained

Question 4

what is decompensated haemolysis also known as

Answer 4

Haemolytic anaemia

Question 5

what is haemolytic anaemia

Answer 5

Increased rate of red cell destruction exceeding bone marrow capacity for red cell production
i.e. Hb Falls

Question 6

what are consequences of haemolysis

Answer 6

Erythroid hyperplasia (increased bone marrow red cell production)

Excess red cell breakdown products eg billirubin (clinical features differ by aetiology and site of red cell breakdown)

Question 7

what is the bone marrow response to haemolysis

Answer 7

1 - reticulocytosis

2 - erythroid hyperplasia [see a higher number of precursors of RBC in the bone marrow]

Question 8

what special stain can be used to just see reticulocytes on a blood film

Answer 8

supravital stain

Question 9

how can haemolytic anaemia be classified

Answer 9

extravascular
- RBC destroyed by spleen and liver

intravascular
- RBC destroyed within the circulation

Question 10

what form of haemolytic anaemia is more common

Answer 10

extravascular

Question 11

what are features of extravascular haemolytic anaemia

Answer 11

splenomegaly +/- hepatomegaly

Release of protoporphyrin

Question 12

what does release of protoporphyrin cause

Answer 12

Unconjugated bilrubinaemia
> Jaundice and Gall stones

Urobilinogenuria

Normal products

Question 13

what does it mean if bilirubin is unconjugated

Answer 13

pre hepatic cause

Question 14

what is the pathophysiology of intravascular haemolysis

Answer 14

Red cells are destroyed in the circulation spilling their contents.

1. Haemoglobinaemia (free Hb in circulation)
2. Methaemalbuminaemia
3. Haemoglobinuria: pink urine, turns black on letting the urine stand
4. Haemosiderinuria

Question 15

what is the big difference in symptoms between extra and intra vascular haemolysis

Answer 15

intravascular cause ABNORMAL products

- may be life threatening

Question 16

what are causes of intravascular haemolysis

Answer 16

ABO incompatible blood transfusion

G6PD deficiency

Severe falciparum malaria
(Blackwater Fever)

PNH,PCH

Question 17

what Ix are done first in haemolytic anaemia

Answer 17

FBC (+ BLOOD FILM)
Reticulocyte count
Serum unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen

Question 18

what Ix are done second in haemolytic anaemia

Answer 18

Blood Film: 
Membrane damage (spherocytes)
Mechanical damage (red cell fragments)
 Oxidative damage (Heinz bodies)
 Others e.g.. HbS (sickle cells)

Question 19

what is another way to classify haemolytic anaemia

Answer 19

by site of red cell defect

Question 20

what are the 4 types of haemolytic anaemia by site

Answer 20

1. Premature destruction of normal red cells (immune or mechanical)
2. Abnormal cell membrane
3. Abnormal red cell metabolism
4. Abnormal haemoglobin

Question 21

what are acquired immune haemolysis

Answer 21

autoimmune haemolysis

alloimmune haemolysis

Question 22

what are the subtypes of autoimmune haemolysis

Answer 22

warm (IgG)

cold (IgM)

Question 23

what are the cause of warm autoimmune haemolysis

Answer 23

idiopathic
autoimmune disorders (SLE)
Lymphoproliferative disorders (CLL)
Drugs (penicillins, etc) Infections

Question 24

what is the test for autoimmune haemolytic anaemia

Answer 24

direct Coombs test

Question 25

what are the two possible forms of alloimmune haemolysis

Answer 25

immune response (antibody produced) passive transfer of antibody

Question 26

what can cause an immune response leading to haemolysis

Answer 26

Haemolytic transfusion reaction - Immediate (IgM) predominantly intravascular - Delayed (IgG) predominantly extravascular

Question 27

what can cause an passive transfer of antibody leading to haemolysis

Answer 27

Haemolytic disease of the newborn

Question 28

what are causes of mechanical red cell destruction

Answer 28

``` DIC HUS TTP leaking heart valve infections e.g. malaria ```

Question 29

what seen in a blood film would be suggestive of a mechanical red cell destruction

Answer 29

red cell fragmentation

Question 30

what is seen in burns related haemolysis

Answer 30

Microspherocytes | - small spherocytes predominate and red blood cells are smaller and more globular than normal

Question 31

what are causes of acquired RBC membrane defects (rare)

Answer 31

``` Liver Disease (Zieve’s Syndrome) Vitamin E deficiency Paroxysmal Nocturnal Haemoglobinuria ```

Question 32

what is Zieve's syndrome

Answer 32

Haemolysis, Alcoholic liver disease, hyperlilidaemia

Question 33

what are causes of congenital RBC membrane defects

Answer 33

Hereditary Spherocytosis

Question 34

what are genetic causes of abnormal red cell metabolism

Answer 34

failure to cope with oxidant stress (G6PD deficiency - most common form) failure to generate ATP: metabolic processes fail

Question 35

what can cause stress to the metabolic pathways in normal cells

Answer 35

dapsone or salazopyrin

Question 36

what does dapsone cause

Answer 36

bite cells a.k.a irregularly contracted cell

Question 37

what genetic disease can cause haemolytic anaemia by making abnormal haemoglobin

Answer 37

Sickle cell disease

Question 38

what are pappenheimer bodies and what are they seen in

Answer 38

abnormal granules of iron found inside red blood cells beta thalassaemia major

Question 39

what type of haemolysis is seen in hereditary spherocytosis

Answer 39

Chronic extravascular haemolysis.

Question 40

what does the defect affect in hereditary spherocytosis

Answer 40

the RBC membrane flexibility

Question 41

what type of haemolysis is seen in Falciparum malaria

Answer 41

intravascular haemolysis

Question 42

what is seen on a blood film of HbH

Answer 42

inclusion bodies | - golf ball appearance

Question 43

what are Heinz bodies

Answer 43

Red cell inclusions comprised of denatured Hb normally removed by spleen (eg seen in G6PD deficiency)