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 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 also known 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
what are consequences of haemolysis
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)
what is the bone marrow response to haemolysis
1 - reticulocytosis
2 - erythroid hyperplasia [see a higher number of precursors of RBC in the bone marrow]
what special stain can be used to just see reticulocytes on a blood film
supravital stain
how can haemolytic anaemia be classified
extravascular
- RBC destroyed by spleen and liver
intravascular
- RBC destroyed within the circulation
what form of haemolytic anaemia is more common
extravascular
what are features of extravascular haemolytic anaemia
splenomegaly +/- hepatomegaly
Release of protoporphyrin
what does release of protoporphyrin cause
Unconjugated bilrubinaemia
> Jaundice and Gall stones
Urobilinogenuria
Normal products
what does it mean if bilirubin is unconjugated
pre hepatic cause
what is the pathophysiology of intravascular haemolysis
Red cells are destroyed in the circulation spilling their contents.
- Haemoglobinaemia (free Hb in circulation)
- Methaemalbuminaemia
- Haemoglobinuria: pink urine, turns black on letting the urine stand
- Haemosiderinuria
what is the big difference in symptoms between extra and intra vascular haemolysis
intravascular cause ABNORMAL products
- may be life threatening
what are causes of intravascular haemolysis
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria
(Blackwater Fever)
PNH,PCH
what Ix are done first in haemolytic anaemia
FBC (+ BLOOD FILM) Reticulocyte count Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
what Ix are done second in haemolytic anaemia
Blood Film: Membrane damage (spherocytes) Mechanical damage (red cell fragments) Oxidative damage (Heinz bodies) Others e.g.. HbS (sickle cells)
what is another way to classify haemolytic anaemia
by site of red cell defect
what are the 4 types of haemolytic anaemia by site
- Premature destruction of normal red cells (immune or mechanical)
- Abnormal cell membrane
- Abnormal red cell metabolism
- Abnormal haemoglobin
what are acquired immune haemolysis
autoimmune haemolysis
alloimmune haemolysis
what are the subtypes of autoimmune haemolysis
warm (IgG)
cold (IgM)
what are the cause of warm autoimmune haemolysis
idiopathic
autoimmune disorders (SLE)
Lymphoproliferative disorders (CLL)
Drugs (penicillins, etc) Infections
what is the test for autoimmune haemolytic anaemia
direct Coombs test
what are the two possible forms of alloimmune haemolysis
immune response (antibody produced)
passive transfer of antibody
what can cause an immune response leading to haemolysis
Haemolytic transfusion reaction
- Immediate (IgM) predominantly intravascular
- Delayed (IgG) predominantly extravascular
what can cause an passive transfer of antibody leading to haemolysis
Haemolytic disease of the newborn
what are causes of mechanical red cell destruction
DIC HUS TTP leaking heart valve infections e.g. malaria
what seen in a blood film would be suggestive of a mechanical red cell destruction
red cell fragmentation
what is seen in burns related haemolysis
Microspherocytes
- small spherocytes predominate and red blood cells are smaller and more globular than normal
what are 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, hyperlilidaemia
what are causes of congenital RBC membrane defects
Hereditary Spherocytosis
what are genetic causes of abnormal red cell metabolism
failure to cope with oxidant stress (G6PD deficiency - most common form)
failure to generate ATP: metabolic processes fail
what can cause stress to the metabolic pathways in normal cells
dapsone or salazopyrin
what does dapsone cause
bite cells a.k.a irregularly contracted cell
what genetic disease can cause haemolytic anaemia by making abnormal haemoglobin
Sickle cell disease
what are pappenheimer bodies and what 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 affect in hereditary spherocytosis
the RBC membrane flexibility
what type of haemolysis is seen in Falciparum malaria
intravascular haemolysis
what is seen on a blood film of HbH
inclusion bodies
- golf ball appearance
what are Heinz bodies
Red cell inclusions comprised of denatured Hb normally removed by spleen (eg seen in G6PD deficiency)
