Haemalytic anaemia Flashcards
normal red cell life span
120 days
definition of haemolysis
shortened red cell survival
can be:
* intravascular - within circulation
* extravascular - removal/destruction by reticuloendothelial system (spleen)
inherited/acquired
causes of extravascular haemolysis
autoimmune
alloimmune
hereditary spherocytosis
causes of intravascular haemolysis
malaria - most common globally (plasmodium falcipium) - in severe forms depicted as black water fever, acute haeloysis -> haemoglobinuria -> anaemia
G6PD deficiency
mismatched Ab transfusion
cold Ab haemolytic syndromes (IgM)
drugs (dapsin)
MAHA damage to endothelium and to red cells as they travel through eg HUS, TTP
paroxysmal nocturnal haemoglobinuria - acquired genetic defect in synthesis of GPIanka - mechanism by which cells attach protein to surface
what can hereditory haemolytic anaemias be a defect of
membrane - cytoskeletal proteins, cation permeability
red cell metabolism - require anaerobic glyocysis to make ATP
Hb (most common) - thalassaemia, sickle cell syndrome, unstable Hb varient
inheritence of hereditory spherocytosis
autosomal dominant
consequences of haemolysis
- anaemia - but bone marrow can compensate sometimes
- erythropid hyperplasia with increased red cell production and circulating reticulocytes
- increased folate demand
- susceptibility to effect parvovirus B19
- propensity to gallstones (increased bilirubin)
- increased risk of iron overload (increased intestinal absorption)/osteoporosis
why does haemolysis -> risk from parvovirus b19
parvovirus infect developing erythroid cells in the bone marrow -> arrest maturation
in normal = little impact on Hb
if Hb survival shortened -> parvovirus fall in Hb level
self limiting problem - infection cleared by immune system
might need transfusion
immunity is lifelong
cell count in parvovirus
expect bone marrow production switched off -> drop in reticulocyte
aplastic crisis due to parvovirus
low/absent reticulocyte
marrow in a person with parvovirus infection
erythroid precursers
arrested at early stage of maturation
they all look similar - no differentiation
liver biopsy in pyruvate kinase deficiency - defect in glycolysis
increased iron in the parenchyma of liver and guppfer cells
what increases the risk of gallstones in haemolytic anaemia
coinheritance of gilberts disease (where BR conjugation impaired) -> moe unconjugated BR
-> more propensity to get gall stones
pathogenesis of gilberts
genetic polymorphism - change in promoter of UGT 1A1 gene -
instead of normal 6TA repeat in TATA box - get extra dinucleotide on each allele -> TA7/TA7 ->
reduction of trasncription of UGT 1A1 -> reduction expression of protein in liver -> less efficient BR conjugation
clinical features of haemolytic disorders
pallor - anaemia
jaundice
splenomegaly - when spleen playing role in destruction of RBC (extravascular haemolysis) or extramedullary haemopoiesis
pigmenturia - abnormal colour to urine, haemoglobinuria
FHx- inhertited
blood lab features of haemolytic anaemia
- anaemia (not always)
- high reticulocyte - except when parvovirus
- polychromasia - cells take eosinophilic and basophilic dye - blue/pruple colour - correspond to reticulocyte
biochemical features of haemolytic anaemia
- hyperbilirubinaemia
- increased LDH - enzyme in the RBC is released into blood stream in intravascular haemolysis
- reduced/absent haptoglobins - in intravascular haemolysis, they bind to Hb - binding capacity is overloaded
- haemoglobinuria
- haemosiderinuria - stain for iron - Pearl stain - detect iron excreted from tubular cells - implies intravascular haemolysis
structure of RBC membrane
lipid bilayer - rests on cytoskeletal scaffold made of spectrin
proteins link lipid bilayer to spectrin including:
* band 3 - major anion transporter
* Ankyrin-1
* 4.2
* GPI
pathophysiology of paroxysmal nocturnal haemoglobinuria
GPI lacking in paroxysmal nocturnal haemoglobinuria - produced by biosynthesis, highly coinserved mech
for attachment of biomolecules to cell surface including complement regulatory proteins,
protect RBC from damage from complement
**so w/o GPI - red cells are destroyed by complement -> intravascular haemolysis **
where is the defect in hereditary spherocytosis
vertical interaction in membrane between protiens that link bilayer and cytoskeleton
* band 3
* protein 4.2
* ankyrin
* B-spectrin
where is the defect in hereditary elliptocytosis
Horizontal interaction
* a spectrin
* b spectrin
* protein 4.1
blood film with hereditary spherocytosis
lack central pallor
smaller
more densly stained
MCHC increased - hyperchromic cells
polychromatic cells - young red cell population
blood film for carrier hereditary elliptocytosis
elliptical/oval appearance
no polychromasia
normal blood count
hereditary pyropoikilocytosis film
homozygous state for hereditary elliptocytosis (heterozygotes barely clinically effected, homozygotes get severe haemolytic anaemia in new born)
fragmentation of red cells
vesiculation of membrane of red cells
poikilocytosis
clinical features of G6PD deficiency
Steady state asx
neonatal jaundice (world wide most common cause of kernicterus)
acute haemolysis - triggered by oxidants/infection/drugs/fava beans
chronic haemolytic anaemia - rare
blood film from G6PD def
contracted cells
nucleated RBC
bite cells
Hb retracted to one side of cell - hemighosts
only seen in acute haemolytic episode
In steady state - the blood film is unremarkable
blood film for G6PD when stain with methyl violet
peripheal inclusions - Heinz bodies - denatured Hb - characteristic if oxidative haemolysis
seen transiently because heinz bodies removed by splene
film for pyruvate kinase deficiency
defect in glycoytic pathway
echinocytes - red cell projections. as they shrink - cells look like spherocytes
number of echinocytes increase post-splenectomy.
film in pyrimidine 5’-nucleotidase deficiency
pyrimidine nucleotides are toxic to RBC - but cell need to salvage purine nucleotides
deficiency of this enzyme -> basophilic stippling in red cells
Hb stability test
heat stability and isopropanol precipitation tests positive
