HAEMOLYSIS Flashcards
what is haemolysis
premature red cell destruction
ie shortened red cell survival
why are red cells particularly susceptible to damage
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
can’t generate new proteins once in the circulation
what is compensated haemolysis
increased red cell production is able to maintain Hb concentration despite increased red cell destruction
what is decompensated haemolysis
increased rate of red cell destruction exceeds bone marrow capacity for red cell production causing Hb to fall
what are some consequences of haemolysis
erythroid hyperplasia (increased bone marrow red cell production) excess red cell breakdown products (eg bilirubin)
how is haemolysis detected clinically
evidence of increased red cell production
evidence of increased breakdown products
what is the bone marrow response to haemolysis
reticulocytosis
erythroid hyperplasia
in which situations, other than haemolysis, might reticulocyte count be increased
bleeding
response to iron therapy in iron deficiency
what is the difference between extravascular and intravascular haemolysis
extravascular occurs in the reticuloendothelial system (spleen and liver)
intravascular occurs within the circulation
which type of haemolysis is more common
extravascular
which sign, palpable on examination, might suggest extravascular haemolysis
hyperplasia at the site of destruction
splenomegaly +/- hepatomegaly
what are signs of excess breakdown products in extravascular haemolysis
unconjugated bilirubinaemia - jaundice - gall stones urobilinogenuria - dark urine
extravascular haemolysis causes an excess of normal/abnormal breakdown products
normal breakdown products
what are signs of intravascular haemolysis
haemoglobinaemia (free Hb in circulation)
methaemalbuminaemia (oxidised Hb bound to albumin)
haemoglobinuria (pink urine, turns black on standing)
haemosiderinuria (brown urine)
intravascular haemolysis causes an excess of normal/abnormal breakdown products
abnormal breakdown products
what are causes of intravascular haemolyiss
ABO incompatible blood transfusion
G6PD deficiency
severe falciparum malaria
PNH/PCH
how to confirm haemolytic state (Ix)
FBC + blood film reticulocyte count serum unconjugated bilirubin serum haptoglobin urinary urobilinogen
what is the function of haptoglobin
bind free Hb in the plasma
what does a low Haptoglobin level indicate
haemolysis
how can a blood film help identify the cause of haemolysis
spherocytes suggest membrane damage
red cell fragments suggest mechanical damage
Heinz bodies suggest oxidative damage
what is a coombs’ test used for
to detect the presence of antibodies in the plasma in suspected autoimmune haemolysis
what are the possible sites of red cell defect leading to haemolysis
premature destruction of normal red cells (immune or mechanical)
abnormal cell membrane
abnormal red cell metabolism
abnormal Hb
what is the difference between warm and cold autoimmune haemolysis
warm = IgG cold = IgM
what are possible causes of autoimmune haemolysis
idiopathic autoimmune disorders (SLE) lymphoproliferative disorders drugs infections (EBV, malaria)
what are causes of alloimmune haemolysis
haemolytic transfusion reaction
passive transfer of antibodies eg pregnancy
what is the difference between immediate and delayed haemolytic transfusion reaction
immediate = IgM and is predominantly intravascular delayed = IgG and is predominantly extravascular
what can cause mechanical red cell destruction
DIC HUS (Ecoli 0157) TTP leaking heat valve infections eg malaria
how do DIC and HUS cause mechanical damage to red cells
create turbulent flow
what is microangiopathic haemolytic anaemia
red cell fragmentation as a result of mechanical (extrinsic) damage
how do severe burn result in haemolysis
red cells are sheared as they pass though the damaged capillaries
in what situation do microspherocytes occur
severe-burns related haemolysis
what is Zieve’s syndrome associated with
haemolysis
alcoholic liver disease
hyperlipidaema
what types of haemolysis are caused by membrane defects
liver disease (Zieve's syndrome) vitamine E deficiency PNH
what is the pathophysiology of hereditary spherocytosis
red cell membrane abnormalities cause reduced membrane deformability
increased transit time through spleen as unable to move through small blood vessels
prolonged exposure to oxidant environment in spleen causes extravascular red cell destruction
what is G6PD needed for
G6PD is needed to regenerate NADPH, which in turn regenerate glutathione
glutathione is needed as a reducing agent to prevent oxidative damage
what does deficiency of G6PD result in
inability to reduce oxidative agents therefore resulting in damage to the cell
which Hb abnormality can cause haemolysis
sickle cells disease (HbS)
why do bony deformities occur in beta thal major
marrow cavity expansion due to chronic erythroid hyperplasia
