Haemolysis Flashcards
haemolysis
red cell destruction
shortened red cell survival
why are red cells susceptible to damage
no nucleus, mitochondria etc
rely on biconcave shape so any problem with shape they are gonna struggle
cant generate new proteins once in circulation
compensated haemolysis
increased red cell destruction compensated by increased red cell production
haemolytic anaemia
increased rate of rred cell destruction exceeding bone marrow capacity for red cell production
consequences of haemolysis
Erythroid hyperplasia
Reticulocytosis
Excess red cell breakdown products eg billirubin
clinical features differ by aetiology and site of red cell breakdown
can you directly measure red cell survival
no it relies on detecting the consequences of haemolysis and then investigating the cause
bone marrow response to haemolysis
reticulocytosis
erythroid hyperplasia
are reticulocytes nucleated cells
no
what is erythroid hyperplasia
increase in red cell precursors- erythyroids in bone marrow
most commonly used stain for reticulocytes
methylene blue as it stains the residual rna making them appear dark blue granular cells
diagnosis of haemolysis criteria
Evidence of increase red cell production
AND
Evidence of increased red cell breakdown products
products of red cell destruction
bilirubin
what happens if red cell destruction is outside the macrophage
free hb circulates and needs removed
can clog the kidneys and emerge in urine - haemoglobunuria
binds to albumin - methaemalbuminaemia
binds to haptoglobin and removed
how do classify where haemolysis is occuring
Pathophysiological approach – by site in the red cell where the problem is occurring
A practical approach by site in the body where the haemolysis is occurring
Extravascular (ie in the macrophage as normal)
Intravascular (ie in the circulation – not normal so generates a short differential list)
extravascular red cell destruction
breakdown outside blood vessels particularly in spleen, bone marrow and liver
more common
macrophages eat up aged or damaged cells
what does extravascular haemolysis release
protoporphyrin which can then be broken down into bilirubin
normal products but in excess
intravascular red cell destruction
red cells destroyed in circulation spilling their contents immediately
not normal
reactions occuring in intravascular haemolysis
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia (Hb mopped up by albumin)
Haemoglobinuria: pink urine, turns black on standing
Haemosiderinuria (iron taken up by tubular cells and converted to haemosiderin the cells are later shed into urine)
intravascular causes
ABO incompatible blood transfusion
Mechanical RBC trauma (March haemoglobinuria,
DIC, HUS/TTP, valve disease)
G6PD deficiency if severe
Rarer still PNH,PCH, severe malaria, toxins
eg clostridia, some snake venoms
extravascular causes
essentially all other causes of haemolysis
investigations to confirm haemolytic state
FBC (+ BLOOD FILM) identify causes
Reticulocyte count (raised)
Serum unconjugated bilirubin (raised)
Serum haptoglobins (bind free Hb so will be low as consumed in haemolysis)
Urinary urobilinogen (raised)
Lactate dehydrogenase (raised) – non specific
alloimmune haemolysis
make an antibody to someone elses red cells that have been given to you or an antibody is given to you that attacks your cells
direct coombs test/ direct antiglobulin test use
lab test used to detect antibodies or complement proteins that are bound to the surface of red blood cells
uses of dat
haemolytic anaemia, autoimmune disorders and haemolytic disease of new born
igm assoc haemolysis
involved in cold agglutination disease
igm antibodies bind to red blood cells at lower temps <30
cause clumping of red blood cells
abnormal situations resulting in premature destruction
toxins - chlosridia
snake venoms
rupture of infected red cells by malaria parasites
hereditary spherocytosis
most common cause of hemolytic anaemia
caused by mutations in genes that code for proteins involved in the red blood cell membrane
These defects lead to the formation of abnormally shaped red blood cells (spherocytes) that are less flexible and more prone to breaking when passing through the spleen.
Symptoms include anemia, jaundice, and splenomegaly.
what is a spherocyte
abnormally shaped red blood cell that is spherical in shape rather than the typical biconcave disk shape.
causes of spherocytes
Hereditary Spherocytosis
Warm (IgG) haemolytic anaemia
Delayed transfusion reaction
Haemolytic disease of the newborn
Zieve’s Syndrome
Drug induced haemolysis
Fresh water drowning (but by a hypotonic effect)
g6pd deficiency
geentic disorder affecting red blooc cells leading to haemolysis
x linked- male problem usually
what does g69pd enzyme play a role in
protecting red blood cells from oxidative stress
what is sickle cell disease
abnormal haemoglobin structure
caused by a point mutatoin in beta chain
result in shortened red cell production
warm igg assoc haemolysis
igg antibodies bind to red blood cells at normal body temp leading to their premature destrcution
pathophysiology of igg automminune hemolytic anemia
igg autoantibodies coat rbcs
recognised by macrpohages in the spleen by fc receptors
extravascular hemolysis occurs
partially phagocytosed leading to formation of spherocytes
