1.07 Haemolysis

Question 1

What reaction is catalysed by heme oxygenase?

What other molecules are needed?

Answer 1

The breakdown of haem to biliverdin
O2 and NADPH are needed
(produced include Fe2+, CO, H2O, NADP+)

Question 2

What reaction is catalysed by biliverdin reductase?

Answer 2

The breakdown of biliverdin to bilirubin

Question 3

Haemolysis

Answer 3

premature red cell destruction- shortened red ell survival

Question 4

compensated haemolysis

Answer 4

increased red cell destruction compensated by increased red cell production
=Hb maintained

Question 5

Haemolytic anaemia

Answer 5

decompensated haemolysis
increased red cell destruction greater than bone marrow capacity for red cell production
hb falls

Question 6

how is haemolysis and red cell survival detected?

Answer 6

assessing increased red cell production

detecting breakdown products

Question 7

what is the normal bone marrow response to haemolysis?

Answer 7

reticulocytosis

erythroid hyperplasia

Question 8

T/F: polychromasia is diagnositc of haemolysis?

Answer 8

False
polychromasia represents reticulocytes with ribosomal RNA
This could be due to a response to bleeding, iron therapy in iron deficiency, or haemolysis

Question 9

what does new methylene blue stain for?

Answer 9

reticulocytes

this is a supravital stain for ribosomal RNA

Question 10

how are reticulocytes automatically counted?

Answer 10

ribosomal RNA labelled with fluorochrome and those are counted

Question 11

extravascular haemolysis

Answer 11

rbc taken up by reticuloendothelial system- spleen and liver +

Question 12

intravascular haemolysis

Answer 12

red cells destroyed in circulation

Question 13

What are the s/s of extravascular red cell destruction?

Answer 13

hyperplasia at site of destruction ( spleen +/- liver)
release of normal products in excess: protoporphyrin
-unconjugated bilirubinaemia–> jaundice, gallstones
-urobilinogenuria

Question 14

What are the abnormal products found in intravascular haemolysis?

Answer 14

haemoglobinaemia
methaemalbuminaemia
haemoglobinuria- pink urine that turns black
haemosiderinuria

Question 15

T/F: Intravascular haemolysis may be life threatening?

Answer 15

True

Question 16

Intra or extravascular:

ABO incompatability

Answer 16

Intravascular

Question 17

Intra or extravascular:

Glucose-6 phosphatase deficiency

Answer 17

intravascular

Question 18

Intra or extravascular:

severe falciparum malaria- blackwater fever

Answer 18

intravascular

Question 19

Intra or extravascular:

paroxysmal noctural haematuria

Answer 19

Intravascular

Question 20

what is haptoglobin?

Answer 20

protein in the blood that binds free haemoglobin
can help differentiate extravascular from intravascular haemolysis (if decreased, intravascular, unless excessive extravascular)
-not terribly discriminative

Question 21

What tests confirm haemolytic state?

Answer 21

FBC
blood film 
retic count
serum unconjugated bilirubin
serum hpatoglobins
urinary urobilinogen

Question 22

spherocytes on blood film

Answer 22

membrane damage

Question 23

red cell fragments on blood film

Answer 23

mechanical damage

Question 24

heinz bodies on blood film

Answer 24

oxidative damage

Question 25

HbS on blood film

Answer 25

sickle cells

Question 26

Warm autoantibody

Answer 26

IgG - idiopathic - autoimmune- SLE - lymphoproliferative- CLL - drugs- penicillins, etc. - infection

Question 27

Cold autoantibody

Answer 27

IgM - idiopathic - infections-EBV, mycoplasma - lymphoproliferative

Question 28

What antibody is coated on RBC for detection on Direct Coombs Test?

Answer 28

IgG + complement on RBC mouse anti-human IgG is added agglutination indicates there is antibody and complement bound to the patient's own red cells.

Question 29

immediate haemolytic transfusion reaction

Answer 29

IgM (ImMediate) | intravascular (couldn't wait to make it to spleen/liver)

Question 30

Delayed haemolytic transfusion reaction

Answer 30

IgG (lonGer after) | Extravascular (was able to make it to spleen/liver)

Question 31

Passive transfer of antibody in haemolytic disease of newborn - RhD - ABO incompat - Anti-Kell, Duffy, etc. is alloimmune or autoimmune?

Answer 31

Alloimmune haemolysis

Question 32

causes of mechanical red cell destruction

Answer 32

``` DIC HUS- E Coli 0157 TTP leaking heart valve infections eg. malaria ```

Question 33

microspherocytes

Answer 33

burns related haemolysis

Question 34

causes of acquired haemolysis - membrane defects

Answer 34

liver disease vitamin E deficiency paroxysmal nocturnal haemoglobinuria

Question 35

Liver disease- Zieve's syndrom

Answer 35

an acute metabolic condition that can occur during withdrawal from prolonged alcohol abuse ``` haemolysis alcoholic liver disease hyperlipidaemia anaemia polychromatic macrocyets irregularly contracted cells ```

Question 36

how is paroxysmal nocturnal haemoglobinruia detected?

Answer 36

blood film ham's test- acid lysis bone marrow rare cause of haemolysis

Question 37

why do RBC need G6P?

Answer 37

to make antioxidant and ATP | and reduce glucose to lactate

Question 38

What drugs may sufficiency stress rbc and cause abnormal rbc metabolism?

Answer 38

dapsone | salazopyrin

Question 39

dapsone therapy

Answer 39

keratocyte | irregularly contracted cell

Question 40

haemoglobin S- sickle cell disease

Answer 40

abnormal haemoglobin polymerisation | shortened red cell survival

Question 41

beta thalassaemia major clinical s/s blood film bone marrow

Answer 41

s/s: bony deformities film: hypo/micro targets, nucleated RBCs, pappenheimer bodies, alpha chain ppts marrow: erythroid hyperplasia

Question 42

what is the inheritance pattern of hereditary spherocytosis?

Answer 42

autosomal dominant

Question 43

what is the gene mutation in hereditary spherocytosis, the most common hereditary haemolytic anaemia?

Answer 43

spectrin gene

Question 44

Hb-Koln

Answer 44

unstable Hb variant | chronic haemolysis

Question 45

What is the number of abnormal Hb-a genes are required for HbH- alpha thalassaemia?

Answer 45

3 genes | if 4- Barts disease= hydrops fetalis, if 2 or 1 then normal Hb

Question 46

What is seen on the blood film of HbH disease?

Answer 46

alpha thalassaemia is seen as: -HbH B4 containing golf balls reticulocytes B4 is toxic and ppts when there is oxidative stress eg. dapsone

Question 47

What are heinz bodies?

Answer 47

red cell inclusions denated HB these cells normally removed by spleen causes: G6PD unstable Hb eg. HbH- alpha thalassaemia