hemolysis Flashcards
what is hemolysis?
premature red cell destruction
why are red cells particularly susceptible to damage? (3)
biconcave shape
limited metabolic reserve - no mitochondria
no nucleus (no new proteins)
what metabolism do red cells depend on?
glucose metabolism
what is compensated hemolysis?
increased red cell destruction compensated by increased red cell production - Hb maintained
what is most commonly seen?
haemolytic anaemia
what is hemolytic anaemia?
increased rate of red cell destruction exceeding bone marrow capacity for red cell production - Hb falls
what are the consequences of hemolysis? (2)
erythroid hyperplasia
excess red cell breakdown products eg. bilirubin
bone marrow response to haemolysis?
reticulocytosis
erythroid hyperplasia
what stains reticulocyte ribosomal RNA?
new methylene blue
what is extravascular hemolytic anaemia?
taken up by reticuloendothelial system (spleen and liver predominantly)
what is intravascular hemolytic anaemia?
red cells destroyed within the circulation
what is the common form of hemolytic anaemia?
extravascular
chronic extravascular hemolytic anaemia may present with?
splenomegaly +/- hepatomegaly
what type of. products are released in extravascular red cell destruction?
normal products in excess
what products are released in extravascular red cell destruction?
unconjugated bilirubinaemia
urobilinogenuria
what is the presentation of unconjugated bilirubinaemia?
jaundice and gall stones
what is intravascular red cell destruction?
red cells are destroyed in the circulation spilling their contents
what products are released in intravascular red cell destruction?
haemoglobinaemia
methaemalbuniaemia
haemolgobinuria
haemosiderinuria
what happens to hemoglobinuria?
pink urine turns black on oxidation
what type of products are released in intravascular red cell destruction?
abnormal products
which type of haemolysis is life threatening?
intravascular
what conditions cause intravascular hemolysis? (4)
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (Blackwater Fever)
Rarer still PNH,PCH
what is the most common red cell enzyme deficiency?
G6PD deficiency
what conditions cause extravascular hemolysis?
essentially all other causes of hemolysis
what investigations confirm hemolytic state? (5)
FBC (+ BLOOD FILM) Reticulocyte count Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
what excludes someone haemolysing?
FBC and blood film
what do you see on the blood film if red cell membranes are damaged?
spherocytes
what do you see on the blood film if there is oxidative damage?
Heinz bodies
what do you see on the blood film If there is mechanical damage?
red cell fragments
what is a specialist investigation for hemolysis?
direct coombs’ test and others
what is the most common cause of premature destruction of normal red cells?
autoimmune, or mechanical
valve disease
autoimmune hemolysis?
antibodies developed to own red cell
what is alloimmune hemolysis?
antibodies developed to foreign red cells
what are warm autoantibodies?
IgG
what are cold autoantibodies?
IgM
what is the commonest cause of warm autoimmune hemolysis?
idiopathic
what are other warm autoimmune hemolysis?
Idiopathic (commonest) Autoimmune disorders (SLE) Lymphoproliferative disorders (CLL) Drugs (penicillins, etc) - high doses given IM Infections
what are causes of cold autoimmune hemolysis?
idiopathic
infections (EBV, mycoplasma)
Lymphoproliferative
what is the commonest form of autoimmune hemolysis?
warm (IgG) hemolysis
what is the purpose of direct coombs’ test?
identifies antibody (and complement) bound to own red cells
alloimmune hemolysis can be?
immune response (antibodies produced) passive transfer of antibody
what is an example of alloimmune immune response hemolysis?
hemolyticc transfusion reaction
how can you differentially if the HTR is predominantly intravascular or extravascular?
Immediate IgM - intravascular
delayed IgG - extravascular
what are examples of passive transfer of antibody in alloimmune hamemolysiss?
hemolytic disease of the newborn
what are causes of acquired haemolysis - mechanical red cell destruction?
Disseminated intravascular coagulation Haemolytic uraemic syndrome (eg E. coli O157) TTP Leaking heart valve Infections e.g. Malaria
what are examples of membrane defects?
Liver Disease (Zieve’s Syndrome) Vitamin E deficiency Paroxysmal Nocturnal Haemoglobinuria
what is a genetic cause of red cell membrane abnormalities?
hereditary spherocytosis
people with normal levels of G6PD are also under
oxidative stress then they are on dapsone therapy
what is an example of abnormal hemoglobin?
sickle cell disease
what is affected in sickle cell disease>
physical properties of haemoglobin (abnormal polymerisation) resulting in shortened red cell survival
where is the mutation in sickle cell disease?
caused by a point mutation in beta globin chain
why isn’t the presence of spherocytes diagnostic in hereditary spherocytosis?
it can be seen in severe burns
immune hemolytic anaemias
