Haemolysis Flashcards
what is haemolysis
premature red cell destruction
i.e. shortened red cell survival
why are red cells susceptible to damage
- need a biconcave shape to transit in the circulation
- limited metabolic reserve and rely on glucose metabolism for energy (no mitochondria)
- can’t generate new proteins once in the circulation (no nucleus)
what is compensated haemolysis
increased red cell destruction compensated by increased red cell production
i.e. Hb maintained
what is decompensated haemolysis know as
haemolytic anaemia
what is haemolytic anaemia
increased rate of red cell destruction exceeding bone marrow capacity for red cell production
i.e. Hb falls
consequences of haemolysis
erythroid hyperplasia (increased bone marrow red cell production) excess red cell breakdown products e.g. bilirubin
what is the bone marrow response to haemolysis
reticulocytosis
erythroid hyperplasia- see higher number of RBC precursors in the bone marrow
what stain is used to just see reticulocytes on a blood film
supravital stain
what is seen on blood film in reticulocytosis
polychomasia (blue staining ribosomal RNA)
how can haemolytic anaemia be classified
extravascular
- RBC destroyed by liver and spleen
Intravascular
- RBC destroyed within the circulation
what form of haemolytic anaemia is more common
extravascular
features of extravascular haemolysis
splenomegaly +/- hepatomegaly
release of protoporphyrin
effects of protoporphyrin release
Unconjugated bilrubinaemia – jaundice + gall stones
Urobiliogenuria
what does it mean if bilirubin is unconjugated
pre-hepatic cause
pathophysiology of intravascular haemolysis
red cells are destroyed in the circulation spilling their contents
- haemoglobinaemia (free Hb in circulation)
- Methaemalbuminaemia
- Haemoglobinuria (pink Turing, turns black on standing)
- Haemosiderinuria
ABNORMAL product
big difference between symptoms of extra and intra vascular haemolysis
intravascular causes ABNORMAL products- may be life threatening
cause of intravascular haemolysis
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (blackwater fever)
Paroxsysmal nocturnal haemoglobinuria (PNH)
Paroxsysmal cold haemoglobinuria (PCH)
investigations of haemolytic anaemia
FBC + Blood film reticulocyte count serum unconjugated bilirubin serum hapatoglobins urinary urobilinogen
what is seen on blood film if there has been membrane damage
spherocytes
what is seen on blood film if there has been mechanical damage
red cell fragments
what is seen on blood film if there has been oxidative damage
Heinz bodies
what is another way to classify haemolytic anaemia
site of red cell defect
what are the 4 types of haemolytic anaemia by site of red cell defect
- premature destruction of normal red cells (immune or mechanical)
- abnormal cell membrane
- abnormal red cell metabolism
- abnormal Hb
causes of acquired haemolysis
immune:
autoimmune
alloimmune
(premature destruction of normal red cells)
subtypes of autoimmune haemolysis
warm (IgG)
cold (IgM)
What antibody is involved in warm autoimmune haemolysis
IgG
what antibody is involved in cold autoimmune haemolysis
IgM
causes of warm autoimmune haemolysis
Idiopathic (most common) autoimmune disorders (SLE) lymphoproliferative disorders (CLL) drugs (penicillin) infections
causes of cold autoimmune haemolysis
idiopathic
infections (EBV, Mycoplasma)
Lymphoproliferative disorders
test for autoimmune haemolytic anaemia
direct Coomb’s test
two forms of alloimmune haemolysis
immune response (antibody produced)
passive transfer of antibody
what can cause an immune response leading to alloimmune haemolysis
Haemolytic transfusion reaction:
IgM : immediate (intravascular)
IgG: delayed (extravascular)
what can cause a passive transfer of antibody leading to haemolysis
haemolytic disease of the new born
causes of mechanical red cell destruction
disseminated intravascular coagulation haemolytic uraemia syndrome (e.g. caused by E.Coli O157) TTP leaking heart valve malaria
what is seen in a blood film if there has been mechanical red cell destruction
red cell fragmentation
what is seen in a blood film if there has been burns related haemolysis
microspherocytes- small spherocytes predominate and RBCs are smaller and more globular than normal
causes of acquired RBC membrane defects (rare)
Liver disease – Zieve’s syndrome
Vitamin E deficiency
Paroxysmal nocturnal haemoglobinuria
what is Zieve’s syndrome
Haemolysis, alcoholic liver disease, hyperlipidaemia
causes of congenital RBC membrane defect
hereditary spherocytosis
genetic causes of abnormal red cell metabolism
failure to cope with oxidant stress (G6PD deficiency is most common)
failure to generate ATP: metabolic process fail
what can cause stress to metabolic pathways in normal cells
dapsone or salazopyrin
what does dapsone cause
bite cells a.ka. irregularly contracted cell
what genetic disease can cause haemolytic anaemia by making abnormal haemoglobin
sickle cell disease
what are pappenheimer bodies
what condition are they seen in
abnormal granules of iron found inside red blood cells
beta thalassaemia major
what type of haemolysis is seen in hereditary spherocytosis
chronic extravascular haemolysis
what does the defect in hereditary spherocytosis affect
RBC membrane flexibility
what type of haemolysis is seen in malaria
intravascular haemolysis
what is seen on blood film of HbH (severe alpha thalassaemia)
inclusion bodies- golf ball appearance
what are Heinz bodies
red cell inclusions made of denatured Hb that is normally removed by the spleen
what condition are Heinz bodies seen in
G6PD deficiency
splenomegaly, intermittent mild jaundice + gall stones
most likely diagnosis?
hereditary spherocytosis
Long standing splenomegaly, no spherocytes on blood film
most likely diagnosis?
Hb Koln disease
Child with anaemia, intermittent jaundice when unwell, asian ethnicity
most likely diagnosis?
HbH
alpha thalassaemia
illness precipitates oxidative stress– haemolysis + jaundice
what test detects methaemalbumin
schumm’s test
