Haemolysis Flashcards
why are red cells particularly susceptible to damage
- they need a biconcave shape to get round the circulation
- they have limited metabolic reserve and rely on glucose metabolism (no mitochondria)
- cant generate new proteins once in the circulation (no nucleus)
what is compensated haemolysis
when there is increased red cell destruction which is balanced out by increased production in the bone marrow
Hb is maintained
what is haemolytic anaemia (decompensated haemolysis)
increased rate of red cell destruction exceeding bone marrow capacity for red cell production
Hb falls
what are the consequences of haemolysis
erythroid hyperplasia
-increased bone marrow red cell production
excess red cell breakdown products eg. bilirubin
how do you measure haemolysis
cant measure is directly
need to measure the consequences eg. increased red cell production, and detection of breakdown products
-billirubin
what is the bone marrow’s response to hameolysis
Reticulocytosis
Erythroid hyperplasia
what are reticulocytes
red cells straight out fo the bone marrow
have no nucleus
larger than RBCs
automated reticulocyte counting is used
what are the two main types of haemolysis
extravascular
intravascular
what is extravascular haemolysis
most common
red cells taken up by reticuloendothelial system and destroyed in the spleen or liver
hyperplasia of the site of production occurs (splenomegaly +/- hepatomegaly)
release of protoporphyrin
-unconjugated bilrubinaemia (jaundice, gall stones)
-urobilinogenuria
normal products in excess
what is intravascular haemolysis
red cells destroyed within the circulation
causes:
haemoglobinaemia (free Hb in circulation)
methaemalbuminaemia (albumin in circulation)
haemoglobinuria (pink urine, turns black on standing)
haemosiderinuria (haemosiderein = iron containing protein in urine)
causes of intravascular haemolysis
- ABO incompatible blood transfusion
- G6PD deficiency
- severe falciparum malaria
- rare PNH(paroxysmal nocturnal haemoturia), PCH
causes of extravascular haemolysis
all other causes of haemolysis
investigations for haemolysis
1 confirm haemolytic state
FBC Reticulocyte count Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
- identify cause
history + examination
blood film
specialist investigations (eg. Coombs’ test)
how can you classify haemolysis by red cell defect
- premature destruction
- abnormal cell membrane
- abnormal red cell metabolism
- abnormal haemoglobin
can be congenital or acquired
what are the immune causes of haemolysis
autoimmune haemolysis
-antibodies to your own cells
alloimmune haemolysis
-antibodies to foreign red cells
what is warm (IgG) autoimmune haemolysis
IgG mediated
idiopathic autoimmune disorders lymphoproliferative disorders drugs (penicillins) infections
what is cold autoimmune haemolysis
IgM mediated
infections
lymphoproliferative disorders
what is direct combo’ test
identifies antibody bound to OWN red cells
causes of alloimmune haemolysis
Haemolytic transfusion reaction
- immediate IgM - intravascular
- delayer IgG - extravascular
Passive transfers of antibody
- haemolytic disease of the newborn
- Rh D
- ABO incompatibility
causes of acquired haemolysis
Disseminated intravascular coagulation
Haemolytic uraemia syndrome
TTP
Leaking heart valve
infections eg. malaria
what acquired membrane defects cause haemolysis
- severe liver disease (Zeeive’s syndrome)
- Vitamin E deficiency
- Proxsysmal nocturnal haemoglobinuria
what congenital membrane defects cause haemolysis
reduced membrane deformability
increased transit time through spleen
oxidant environment in spleen causes extravascular red cell destruction
hereditary spherocytosis
what red cell metabolism defects cause hameolysis
glucose-6-phosphodehydrogenase deficiency (preventing glycolysis and ATP production for the red cells) so less ATP produced and cant cope with oxidative stress
failure to generate ATP - metabolic processes fail
congenital causes of abnormal haemoglobin causing haemolysis
Sickle cell disease -HbS
