haemolysis Flashcards
haemolysis
premature red cell destruction - shortened red cell survival
why are red cells particularly susceptible to damage? (haemolysis)
- they need to have a biconcave shape to transit circulation successfully
- they have limited metabilic reserve + rely exclusively on glucose metabolism for energy
- cant generate new protein once in circular - no nucleus
compensated vs decompensated haemolysis
compensated = increased red cell destruction compensated by increased red cell production (Hb maintained)
decompensated = increased rate of red cell destruction exceeding bone marrow capacity for red cell production - Hb falls
physiological consequences of haemolysis
erythroid hyperplasia - increased bone marrow red cell production
excess red cell breakdown product - eg bilirubin
–> clinical feature differ by aetiology + site of red cell breakdown
bone marrow response to haemolysis
reticulocytosis - bluer + bigger on stain, polychromasia
erythroid hyperplasia
classification of haemolysis
by site
- intravascular
- extravascular
by cause
- hereditary - membrane, metabolism, haemoglobinopathis
- acquired - immune vs nonimmune causes
causes of hereditary haemolytic anaemias
membrane -> hereditary spherocytosis
metabolism -> G6PD deficiency
haemoglobinopathies -> sickle cell, thalassaemia
acquired immune causes of haemolytic anaemia
(Coombs positive)
autoimmune -> warm/cold antibody type
alloimmune -> transfusion reaction, haemolytic disease of newborn
drug -> methyldopa, penicillin
acquired NON-immune causes of haemolytic anaemia
(Coombs NEGATIVE)
microangiopathic haemolytic anaemia - TTP, HUS(ecoli), DIC, malignancy, preeclampsia
prosthetic heart valves
paroxysmal nocturnal haemoglobinuria
infections - malaria
drug - dapsone
Zieve syndrome - assoc with heavy alcohol, resolves with abstinence
approach to investigation haemolysis
confirm haemolytic state
- FBC, reticulocyte count
- serum unconjugated bilirubin
- serum haptoglobins
- urinary urobilinogen
identify cause
- Hx + exam - FH, organomegaly
- blood film
specialist features - Coombs test
blood film features that would suggest cause of haemolysis
membrane damage - spherocytes
mechanical damage - red cell fragments
oxidative damage - heinz bodies (G6PD, alpha thalassaemia)
sickle cells
when to suspect haemolysis
anaemia with polychromasia -> either acute blood loss or haemolysis
spherocytes
haemosiderin/haemoglobin in urinne - urine dipstick may test pos for but urine microscopy negative for red cells in intravascualr haemolysis
intravascular haemolysis causes
mismatch blood transfusion
G6PD deficiency (technically slightly extravascualr too)
red cell frags - heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia
extravascular haemolysis causes
haemoglobinopathies - sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia
extravascular haemolysis
taken up by reticuloendothelial system (spleen + liver predominantly)
commoner
hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)
release of protoporphyrin
- unconjugated bilirubinaemia - jaundice, gallstones
- urobilinogenuria
normal products in excess
intravascular haemolysis
red cells destroyed within the circulation spilling their contents
- haemoglobinaemia/uria - pink urine, turns black on standing
abnormal products in excess
intravascualt haemolysis may be life threatening
is there iron deficiency in extravascular / intravascular haemolysis respectively?
extra - no
intra - will, will be excreted out
what is the usual pathway for energy production for RBC?
anaerobic glycolysis
folic acid supplementation in rapid haemolysis?
yes !!
autoimmune haemolysis
can be divided into “warm” or cold types according to which temperature the antibodies best cause haemolysis
most commonly idiopathic but may be secondary to a ymphoproliferative disorder, infection or drug
warm autoimmune haemolysis
IgG
antibody (usually IgG) causes haemolysis best at body temp + haemolysis tends to occur in EXTRAVASCULAR sites -> the spleen
causes of warm autoimmune haemolysis
idiopathic - commonest
autoimmune disrders (SLE)
lymphoproliferative disorders - lymphoma, CLL
drugs - penicillins, methyldopa
infections
management of warm autoimmune haemolysis
treatment of underlying disorder
steroids (+/- rituximab)
cold autoimmune haemolysis
IgM causes haemolysis best at 4degreesC
haemolysis is mediated by COMPLEMENT + is more commonly INTRAVASCULAR
features - raynauds, acrocyanosis
patients respond less well to steroids
causes of cold autoimmune haemolysis
idiopathic
infections - EBV, mycoplasma
lymphoproliferative disorders - lymphoma
general features of haemolytics anaemia
anaemia, reticulocytosis
low haptoglobin
raised LDH + indirect bilirubin
blood film features - heinz bodies, spherocytes, fragments, reticulocytes
alloimmune haemolysis
immune response, antibody produced
(Coombs positive)
haemolytic transfusion reaction
- immediate (IgM predominantly intravascualr
- delayed (IgG) predominantly extravascular
passive transfer of antibody
- haemolytic disease of newborn - RhD, aBO incompatibility, anti-Kell
abnormal red cell matabolism causing haemolysis
failure to cope with oxidant stress - G6PD deficiency
failure to generate ATP - metabolic processes fail
even metabolic pathways of normal cells if sufficiently stress by dapsone or salazopyrin can get oxidative damage
**Avoid dapsone therapy in G6PD deficiency
pathophysio of intravascular haemolysis
free haemoglobin is released which then binds to haptoglobin
- as haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm’s test)
free Hb is excreted in urine as haemoglobinuria, haemosiderinuria
G6PD defieciency
commonest red blood cell defect
more common in mediteranean + africa
X-linked recessive
many drugs can precipitate a crisis as well as infections + broad (fava) beans
drugs causing haemolysis (in assoc with G6PD def)
anti-malarials - primaquine
ciprofloxacin
sulph- group drugs - sulfasalazine, sulfonylureas
presentation of G6PD deficiency
neonatal jaundice
intravascular haemolysis
gall stones
splenomegaly
**heinz bodies on blood film
bite + blister cells may also be seen
G6PD investigations
using G6PD enzyme assay
- levels should be checked 3 months after an acute episode of haemolysis
- RBCs with most severely reduced G6PD activity will have haemolysed -> reduced G6PD activity -> not be measure in assay -> false neg results
G6PD def vs hereditary spherocytosis
SAME presentations - neonatal jaundice, gall stones, infection/drugs precipitate
G6PD
- male only - xlinked recess
- african/med
- heinz bodies
- Ix - enzyme activity of g6pd
hered sphero
- male + female - auto dominant
- northern europe
- spherocytes
- Ix = EMA binding
