Haemolysis

Question 1

what is haemolysis?

Answer 1

premature red cell destruction (shortened RBC survival)

Question 2

why are red cells particularly susceptible to damage?

Answer 2

they need to have a biconcave shape to transit the circulation successfully
they have limited metabolic reserve and rely exclusively on glucose metabolism for energy (no mitochondria)
cant 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 concentration is maintained

Question 4

what is haemolytic anaemia?

Answer 4

decompensated haemolysis
increased rate of red cell destruction exceeding bone marrow capacity for red cell production
i.e - Hb concentration falls

Question 5

2 main consequences of haemlysis?

Answer 5

erythroid hyperplasia (increased bone marrow red cell production)
excess red cell breakdown products e.g bilirubin

Question 6

how can red cell survival be measured?

Answer 6

not possible to directly measure
rely on detecting the consequences of haemolysis and then investigating the cause
- increased RBC production (look for signs of erythroid hyperplasia in blood)
- detection of breakdown products

Question 7

2 responses to haemolysis in bone marrow?

Answer 7

reticulocytosis

erythroid hyperplasia

Question 8

what are reticulocytes?

Answer 8

non-nucleated precursors of erythrocytes
don’t have the central pallor that mature RBCs have
not diagnostic of haemolysis, occur in response to bleeding, iron therapy in iron deficiency anaemia

Question 9

how is reticulocytosis measured?

Answer 9

automated reticulocyte counting

ribosomal RNA is labelled with a fluorochrome and fluorescent cells are counted

Question 10

how can haemolysis be classified?

Answer 10

extravascular vs intravascular

different mechanisms and breakdown products

Question 11

extravascular haemolysis?

Answer 11

RBCs taken up by reticuloendothelial system (spleen and liver predominantly)

Question 12

intravascular haemolysis?

Answer 12

RBCs destroyed within circulation

Question 13

which classification of haemolysis is more common?

Answer 13

extravascular

Question 14

features of extravascular haemolysis?

Answer 14

hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)
release of protoporphyrin causing unconjugated bilirubinaemia (results in jaundice and gall stones) and urobilinogenuria
normal products but in excess

Question 15

features of intravascular haemolysis?

Answer 15

RBCs destroyed within circulation and contents spilled out causing:
- haemoglobinaemia (free Hb in circulation)
- methaemalbuminaemia
haemoglobinuria (pink urine, turns black on standing)
- haemosiderinuria
abnormal poducts

Question 16

which classification of haemolysis can be life threatening?

Answer 16

intravascular

Question 17

causes of intravascular haemolysis?

Answer 17

ABO incompatible blood transfusion
G6PD deficiency
severe falciparum malaria (blackwater fever)
PNH,PCH (rare)

Question 18

causes of extravascular haemolysis?

Answer 18

basically every other cause of haemolysis

Question 19

investigations in haemolysis to confirm haemolytic state?

Answer 19

FBC + blood film
reticulocyte count
serum unconjugated bilirubin
serum haptoglobins
urinary urobilinogen

Question 20

investigations to identify cause of haemolysis?

Answer 20

history and examination (shows whether genetic/acquired)
blood film
specialist investigations (coombs test etc)

Question 21

what might be found on blood film?

Answer 21

membrane damage (spherocytes)
mechanical damage (red cell fragments)
oxidative damage (Heinz bodies)
others (e.g HbS - sickle cells)

Question 22

how else can haemolysis be classified?

Answer 22

by site of defect
- premature destruction of normal RBCs (immune/mechanical)
- abnormal cell membrane
- abnormal RBC metabolism
- abnormal Hb
(all can be congenital or acquired)

Question 23

causes of acquired immune haemolysis?

Answer 23

autoimmune haemolysis

alloimmune haemolysis

Question 24

causes of autoimmune haemolysis?

Answer 24

warm or cold autoantibody

• warm (IgG) = most common
• cold (IgM) = less common

Question 25

what is warm IgG autoantibody autoimmune haemolysis associated with?

Answer 25

``` idiopathic (most common) autoimmune disorders (SLE etc) lymphoproliferative disorders (CLL) drugs (penicillins etc) infections (cross reactive antibodies etc) ```

Question 26

what is cold (IgM) autoantibody autoimmune haemolysis associated with?

Answer 26

idiopathic infections (EBV, mycoplasma) lymphoproliferative disorders

Question 27

what does direct coombs test do?

Answer 27

``` identifies antibody (and complement) bound to own red cells identifies agglutination when antibodies and RBCs react ```

Question 28

causes of alloimmune haemolysis?

Answer 28

``` immune response (antibody produced) - e.g haemolytic transfusion reaction passive transfer of antibody - e.g haemolytic disease of newborn ```

Question 29

how does haemolytic transfusion reaction cause alloimmune haemolysis?

Answer 29

immediate (IgM) predominantly causes intravascular haemolysis delayed (IgG) predominantly causes extravascular haemolysis

Question 30

causes of acquired mechanical haemolysis?

Answer 30

``` disseminated intravascular coagulation haemolytic uraemic syndrome (e.g E.coli 0157) TTP leaking heart valve infections (e.g malaria) ```

Question 31

acquired causes of haemolysis due to abnormal cell membrane?

Answer 31

``` liver disease (sieve's syndrome) vitamin E deficiency paroxysmal nocturnal haemoglobinuria ```

Question 32

what is sieve's syndrome?

Answer 32

haemolysis alcoholic liver disease hyperlipidaemia causes anaemia, polychromatic macrocytes and irregularly contracted cells)

Question 33

congenital causes of haemolysis due to abnormal RBC membrane?

Answer 33

reduced membrane deformability increased transit time through spleen oxidant environment in spleen causes extravascular RBC destruction hereditary spherocytosis

Question 34

congenital causes of haemolysis due to abnormal RBC metabolism?

Answer 34

disturbance in enzyme pathways | e.g G6PD deficiency due to failure to cope with oxidative stress > failure to generate ATP > metabolic processes fail

Question 35

what can cause significant stress in metabolic pathways of normal cells enough to cause oxidative damage?

Answer 35

dapsone | salazopyrin

Question 36

congenital causes of haemolysis due to abnormal haemoglobin?

Answer 36

sickle cell disease (presence of haemoglobin S)

Question 37

what happens in sickle cell disease?

Answer 37

point mutation in beta globin chain | HbS affects physical properties of Hb (abnormal polymerisation) resulting in shortened RBC survival