haemolysis

Question 1

haemolysis

Answer 1

premature red cell destruction - shortened red cell survival

Question 2

why are red cells particularly susceptible to damage? (haemolysis)

Answer 2

1. they need to have a biconcave shape to transit circulation successfully
2. they have limited metabilic reserve + rely exclusively on glucose metabolism for energy
3. cant generate new protein once in circular - no nucleus

Question 3

compensated vs decompensated haemolysis

Answer 3

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

Question 4

physiological consequences of haemolysis

Answer 4

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

Question 5

bone marrow response to haemolysis

Answer 5

reticulocytosis - bluer + bigger on stain, polychromasia

erythroid hyperplasia

Question 6

classification of haemolysis

Answer 6

by site
- intravascular
- extravascular

by cause
- hereditary - membrane, metabolism, haemoglobinopathis
- acquired - immune vs nonimmune causes

Question 7

causes of hereditary haemolytic anaemias

Answer 7

membrane -> hereditary spherocytosis

metabolism -> G6PD deficiency

haemoglobinopathies -> sickle cell, thalassaemia

Question 8

acquired immune causes of haemolytic anaemia

Answer 8

(Coombs positive)

autoimmune -> warm/cold antibody type

alloimmune -> transfusion reaction, haemolytic disease of newborn

drug -> methyldopa, penicillin

Question 9

acquired NON-immune causes of haemolytic anaemia

Answer 9

(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

Question 10

approach to investigation haemolysis

Answer 10

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

Question 11

blood film features that would suggest cause of haemolysis

Answer 11

membrane damage - spherocytes

mechanical damage - red cell fragments

oxidative damage - heinz bodies (G6PD, alpha thalassaemia)

sickle cells

Question 12

when to suspect haemolysis

Answer 12

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

Question 13

intravascular haemolysis causes

Answer 13

mismatch blood transfusion
G6PD deficiency (technically slightly extravascualr too)

red cell frags - heart valves, TTP, DIC, HUS
paroxysmal nocturnal haemoglobinuria
cold autoimmune haemolytic anaemia

Question 14

extravascular haemolysis causes

Answer 14

haemoglobinopathies - sickle cell, thalassaemia
hereditary spherocytosis
haemolytic disease of newborn
warm autoimmune haemolytic anaemia

Question 15

extravascular haemolysis

Answer 15

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

Question 16

intravascular haemolysis

Answer 16

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

Question 17

is there iron deficiency in extravascular / intravascular haemolysis respectively?

Answer 17

extra - no

intra - will, will be excreted out

Question 18

what is the usual pathway for energy production for RBC?

Answer 18

anaerobic glycolysis

Question 19

folic acid supplementation in rapid haemolysis?

Answer 19

yes !!

Question 20

autoimmune haemolysis

Answer 20

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

Question 21

warm autoimmune haemolysis

Answer 21

IgG
antibody (usually IgG) causes haemolysis best at body temp + haemolysis tends to occur in EXTRAVASCULAR sites -> the spleen

Question 22

causes of warm autoimmune haemolysis

Answer 22

idiopathic - commonest
autoimmune disrders (SLE)
lymphoproliferative disorders - lymphoma, CLL
drugs - penicillins, methyldopa
infections

Question 23

management of warm autoimmune haemolysis

Answer 23

treatment of underlying disorder

steroids (+/- rituximab)

Question 24

cold autoimmune haemolysis

Answer 24

IgM causes haemolysis best at 4degreesC

haemolysis is mediated by COMPLEMENT + is more commonly INTRAVASCULAR

features - raynauds, acrocyanosis
patients respond less well to steroids

Question 25

causes of cold autoimmune haemolysis

Answer 25

idiopathic infections - EBV, mycoplasma lymphoproliferative disorders - lymphoma

Question 26

general features of haemolytics anaemia

Answer 26

anaemia, reticulocytosis low haptoglobin raised LDH + indirect bilirubin blood film features - heinz bodies, spherocytes, fragments, reticulocytes

Question 27

alloimmune haemolysis

Answer 27

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

Question 28

abnormal red cell matabolism causing haemolysis

Answer 28

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

Question 29

pathophysio of intravascular haemolysis

Answer 29

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

Question 30

G6PD defieciency

Answer 30

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

Question 31

drugs causing haemolysis (in assoc with G6PD def)

Answer 31

anti-malarials - primaquine ciprofloxacin sulph- group drugs - sulfasalazine, sulfonylureas

Question 32

presentation of G6PD deficiency

Answer 32

neonatal jaundice intravascular haemolysis gall stones splenomegaly **heinz bodies on blood film bite + blister cells may also be seen

Question 33

G6PD investigations

Answer 33

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

Question 34

G6PD def vs hereditary spherocytosis

Answer 34

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