Week 4- Red cell alloantibodies

Question 1

when are red cell allo-antibodies formed

Answer 1

after a potential sensitising event e.g. transfusion, pregnancy, transplant

Question 2

which antibodies are tested for in a transfusion hospital lab

Answer 2

only the most clinically significant antibodies i.e. those capable of causing transfusion
reactions and HDFN.

Question 3

what does antibodies do in acute haemolytic reaction

Answer 3

• activate complement pathway
• macrophage recognition of the red cell bound antibody

Question 4

what is the complement pathway

Answer 4

used to destroy any invading cells
e.g. bacteria, but red cell antibodies also initiate this pathway.

Question 5

what is intravascular haemolysis

Answer 5

the final steps of the complement cascade causes ‘channels’ to be formed through the cell membrane & results in haemolysis

Question 6

what are the clinical phases of acute haemolytic reaction

Answer 6

phase 1: haemolytic shock
Phase 2: Post shock, evidence of haemolysis
Phase 3: Oliguric
Phase 4: Diuretic

Question 7

how does acute haemolytic reaction occur

Answer 7

1. Lysis of red cells causes circulation of free haemoglobin and remnants of red cell
   membrane.
2. This combined with complement cascade results in activation of coagulation cascade.
3. Uncontrolled systemic coagulation results in disseminated intravascular coagulation (DIC):
4. DIC leads to many small thromboses being deposited in vessels in most organs.
5. As the clotting factors begin to be consumed, there is an increased risk of simultaneous
   haemorrhage especially whilst undergoing surgery.
6. Death can be due to multi organ failure if DIC is untreated.

Question 8

what is phase 1: haemolytic shock

Answer 8

Circulatory shock due to lack of red cells leads to:
* Hypotension (cytokine release leads to
vasodilation)
* Tachycardia (heart beats faster to maintain BP)
* Chills (vasoconstriction to maintain BP)
* Rapid and shallow breathing due to
sympathetic nervous system stimulation and acidosis
* Chest & lumbar pain (cytokine release constricts gut & lung smooth muscle)
* Release of inflammatory cytokines can cause a ‘sense of impending doom’ - a classic transfusion
reaction symptom

Question 9

what is Phase 2: Post shock, evidence
of haemolysis

Answer 9

• Haemoglobinuria
• Drop in Hb
• Raised bilirubin
• Jaundice
• Blood film shows
  agglutination, spherocytes, red
  cell fragments

Question 10

what is Phase 3: Oliguric

Answer 10

Free haemoglobin in the blood causes toxic acute tubular
necrosis. Leads to acute renal failure

Question 11

what is phase 4: diuretic

Answer 11

• Renal tubules remain scarred
• Spontaneous diuresis
• Inc loss of sodium, potassium, fluid
• Leads to electrolyte imbalance
• Slow recovery or permanent renal damage

Question 12

how often does ABO- incompatibility transfusion occur

Answer 12

around 1 in 180,000

Question 13

how is ABO- incompatibility transfusion caused

Answer 13

human error:
- when taking or labelling pre-transfusion blood samples
- collecting components from the blood bank or satellite refrigerator
- failing to perform a correct identity check of blood pack and patient at the bedside

Question 14

what is the chances of a patient being ABO incompatible if red cells are transfused incorrectly

Answer 14

around 30%

Question 15

how many cases does major morbidity occur in due to ABO- incompatible transfusion

Answer 15

up to 30% and 5-10% of episodes contribute to the death of the patient

Question 16

where are macrophages located

Answer 16

mainly in the spleen which monitor the circulating red cells for bound igG antibodies

Question 17

what is extravascular haemolysis

Answer 17

when macrophages:
- remove the whole red cell from circulation
- remove the part of the membrane with the bound antibody (creating spherocytes)

Question 18

when does extravascular haemolysis occur

Answer 18

more than 24 hours following transfusion

Question 19

what is extravascular haemolysis usually a result of

Answer 19

previous alloimmunisation and subsequent undetectable level of antibody in pre-transfusion screen.

Question 20

what is indirect antiglobulin test

Answer 20

1. serum with specific antibody mixed with reagent red cells. washed 3x after incubation to remove unbound globulin
2. anti-human globulin (AHG) added to promote angulation on centrifugation

Question 20

what does + refer to on antibody screening cells

Answer 20

presence of antigen

Question 21

what does 0 refer to on antibody screening cells

Answer 21

absence of antigen

Question 22

when should antibody specificity be assigned

Answer 22

when the plasma is reactive with at least two
examples of reagent red cells expressing the antigen and non‐ reactive with at least two examples of reagent red cells lacking the antigen.

Question 23

what is essential when one antibody specificity has been identified

Answer 23

that the presence or absence of additional clinically significant antibodies is established

Question 24

what does dosage refer to

Answer 24

the effect of seeing stronger reactions with
homozygous antigen expression compared to heterozygous expression.

Question 25

why is phenotypic a good practice when investing red cell antibodies

Answer 25

to confirm identification

Question 26

what should a patient be antigen negative for

Answer 26

the corresponding antibody

Question 27

how else can a phenotype guide identification

Answer 27

by excluding alloantibodies

Question 28

why should auto control be performed with each panel

Answer 28

to detect autoantibodies

Question 29

what is a persons phenotype

Answer 29

expression of antigens as determined by their genes

Question 30

when is genotyping used

Answer 30

• if a patient has recently been transfused- phenotype is unreliable
• if strong autoantibodies or drug therapy are interfering with results

Question 31

what does genotyping allow

Answer 31

for variant blood group genes to be detected

Question 32

what is genotyping recommended for

Answer 32

haemoglobinopathy patients who are transfusion dependant

Question 33

what does receiving blood with a significantly different phenotype increase the risk of

Answer 33

alloimmunisation

Question 34

what is Rh & Kell phenotype matched for

Answer 34

patients who are transfusion dependant

Question 35

what does the frequency of red cell antibodies depend on

Answer 35

• frequency of antigens in different ethnic populations
• frequency of antigens in donor populations

Question 36

what patients are known as responders

Answer 36

alloimmunised patients that represent a genetically distinct group with an increased susceptibility to RBC sensitisation

Question 37

what happens to proportion of donor blood as the number of antibodies goes up

Answer 37

proportion of donor blood available as compatible goes down

Question 38

what is the compatibility calculation

Answer 38

(Frequency of antigen negative for antibody 1 x Frequency of antigen negative for antibody 2)