Pathology of Blood Groups Flashcards

1
Q

RBC antigens are most commonly ______, _____ or ________ in nature.
How are they attached to the RBC membrane?

A

carbohydrate, protein or glycoprotein

The can span the RBC membrane and extend into the interior of the cell or can be confined to the surface of the cell.

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2
Q

How are blood group antigens grouped into blood group systems?

A

Based on the genes that encode them

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3
Q

What are the six most clinically significant blood groups in humans?

A
  1. ABO
  2. Rh- C, c, D, E, e
  3. Duffy (Fya and Fyb)
  4. Kidd (Jka and Jkb)
  5. Kell ( K, k)
  6. MNSs (antibodies to M and N are less important than S and s)
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4
Q

How are blood groups inherited?

A

Mendelian inheritence

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5
Q

What are the three reasons why we need to know the major RBC blood groups?

A
  1. They are immunogenic
  2. Ab against them cause clinical hemolysis
  3. antigens have variable prevalence within different populations so when a person is getting transfused or is pregnant, there is a reasonable chance of being exposed to a foreign antigen
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6
Q

What makes ABO, Rh, Duffy, Kidd, Kell, and MNSs different from the 250-ish of other RBC antigens?

A

They are high prevalence so there is specific worry about the reaction to them in transfusion.
Low prevalence antigens will cause the recipient of the blood transfusion make Ab against them, but there is a really low chance of another interaction with that low prevalence antigen so it will most likely not cause a reaction.

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7
Q

What is serologic testing?

A

When the blood bank uses Ab to RBC to look for the presence of antigens on the surface of the persons RBC OR uses RBCs to look for the presence of Ab.

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8
Q

Which are the carbohydrate blood group antigens? and where can they be found?

A
  1. ABO, Lewis I and P

2. They are found on RBC, endothelial cells, epithelial cells

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9
Q

What is the difference between an alloantibody and an autoantibody?

A

Alloantibody- Ab produced in response to stimulation by a foreign substance or cell (transfusions, pregnancies)
Autoantibodies- Ab formed due to loss of regulation that attack the patient’s own cells

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10
Q

What percent of patients in select transfused populations will synthesize one or more RBC antibodies to antigens on the transfused blood?
What percent will become immunized?

What accounts for differences in immunization rates?
Who is least likely to make Ab against transfused blood?

A

36% will make antibodies and 1% will be immunized.
The difference in immunization rates depends on the underlying disease in the transfused patient (immunosuppressed patients or those receiving large amounts of blood in trauma will be less likely to make Ab.

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11
Q

The highest alloimmunization rates are found in what patients?

A
  1. Sickle cell disease patients
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12
Q

What is the most immunogenic antigen? (most likely to cause the recipient to make Ab against it)

A

D antigen in the Rh system.

K in Kell is also likely to cause Ab formation

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13
Q

In pregnancy where does antigenic stimulation come from?

When does this typically occur?

A

Fetal blood antigens somehow cross the placenta and the mother forms RBC antibodies against these antigens.
This most frequently occurs when the placenta pulls away from the endometrium at birth and the blood supplies mix.

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14
Q

What are naturally occurring alloantibodies?
Why do they occur?
What are the naturally occurring alloantibodies?

A

when RBC alloantibodies form without known exposure to foreign red cells.
Thought to be because of exposure to substances in the environment that mimic RBC antigens.

ABO blood group system is the best example of naturally occurring autoantibodies. People have anti-A or anti-B or both from a young age without transfusion exposure.
M and N are also examples

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15
Q

Which RBC antigens generally occur only following exposure to antigen positive blood (pregnancy, transfusion, IV drug use, transplant)?

A
Kell
Kidd
Rh
Duffy
S and s
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16
Q

What type of antibody are most RBC alloantibodies? What are the exceptions?

A
Most are IgG except ABO blood group. 
Anti-A and Anti-B tend to be IgM class antibodies (except in O-type people. Anti-A and B are IgG then)
17
Q

Why does the fact that anti-A and anti-B are IgM make blood type matching crucial?

A
  1. IgM can bind complement, damage the RBCs as they circulate and cause intravascular hemolysis. Acute hemolytic transfusion reactions can cause death.
  2. Complement will set off coagulation and bradykinin cascades. Cascades amplify effects of vasodilation, DIC, hemolysis
18
Q

When do RBC antibodies formed after transfusion become detectable in routine lab tests?

A

2-20 weeks with the mean being 6-12 wks after exposure.
By the time the antibodies are at a detectable level, most of the transfused RBC are gone from circulation (RBC circulate 7-10 days)

19
Q

What makes alloantibodies in type O people different from A, B or AB?

A

The alloantibodies are IgG so they can cross the placenta

20
Q

Describe the hemolysis that occurs from most IgG RBC antibodies.
What IgG antibody differs from this process?

A

It is delayed onset causing RBC destruction extravascularly hours or days following the transfusion.
The result is anemia occasionally with fever or discomfort.

Kidd IgG can bind complement causing immediate intravascular hemolysis that is more serious in nature

21
Q

Why is incompatible blood occasionally inadvertently administered during transfusion?

A

The immune system maintains the ability to make Ab against foreign RBC antigens despite long periods without stimulation.
The Ab level can drop to an undetectable level in the patients serum.
Upon re-exposure to RBC antigens there is a rise in Ab production within 3 to 10 days leading to hemolysis of the transfused RBCs. (anamnestic sensitization)

22
Q

If there is anamnestic sensitization, how will the patient react to the transfusion?
What lab tests will allow the blood bank to deem the sample “incompatible”?

A

3-10 days after the transfusion, the patient will have remade antibodies against a particular RBC antigen.
They will present with mild symptoms due to the delayed extravascular hemolysis (fever, malaise, mild anemia–drop in Hb, Hct)
When the patient is cross-matched for future donations, the levels of antibody are detectable again and the sample will be deemed incompatible.

23
Q

What RBC blood groups are most commonly involved in delayed hemolytic transfusion reactions?

A

Rh (CcEeD)

Kidd (Jka and Jkb)

24
Q

What is erythroblastosis fetalis?

The condition develops in what way?

A

Hemolytic disease of the newborn where maternal antibodies destroy fetal/newborn RBCs.
1, the fetus has RBCs that the mother lacks
2. the mother had previously made antibodies to the fetal RBCs antigen
3. IgG class crosses the placenta and enters fetal circulation
4. Ab destroys fetal RBCs

25
Q

Hemolytic disease of the newborn can be variable. When would antigen expression be most dangerous? What could it cause?

A

If the antigen is expressed early in gestation and the antibody was pre-existing at the time the fetus was conceived, it can cause hydrops fetalis.
The fetus will be swollen and can die in utero.

26
Q

What laboratory test would be positive for hemolytic disease of the newborn?

A

DAT - direct antiglobulin test.

In this test, labeled antibodies recognize Ab bound to cells/ its antigen

27
Q

Why does ABO blood group mismatch between mother and fetus rarely cause problems?

Generally only group _____ mothers have infants with ABO hemolytic disease because ________.

A

A and B antigens are poorly developed in the first year of life so even though the mother has antibodies against the antigens she lacks, it will cause very mild (if any) hemolysis. (especially because IgM don’t cross the placenta)

Generally only group O mothers have infants with ABO hemolytic disease because that is the only ABO type with IgG

28
Q

A woman has significant IgG antibodies detected during her pregnancy. What do you do to see if there is hemolytic disease of the newborn?

A

Amniocentesis to check the optical density of the amniotic fluid.

Cordocentesis (at more high tech centers) can use ultrasound to allow direct cannulation of the umbilical cord so fetal blood can be sampled and Hct determined

29
Q

If hemolytic disease of the fetus is determined, what do you do to treat during the pregnancy?
What can you do at birth?

A

Intrauterine transfusion- infuse blood into the abdominal cavity of the fetus where it can slowly be absorbed into circulation via lymphatics

(High tech centers transfuse into the umbilical cord)

At birth, there is a large volume “exchange” transfusion where you remove the babies RBCs that have the antigen being targeted and replace with - RBC. Also, the baby’s plasma that has the mothers antibodies is removed and replaced with Ab free plasma

30
Q

If there is mild hemolytic disease, how is the baby treated at birth?

A
  1. simple transfusion

2. UV light exposure (“bili lights”)

31
Q

How often is a patients blood retested if they are transfused or pregnant?

A

Every 72 hours to make sure they have not developed new antibodies.

32
Q

What is “type and screen”?
When is it ordered?
What 3 things are tested?

A

If the need for transfusion is not certain, type and screen is ordered for the patient with an EDTA (purple top tube)

  1. ABO typing
  2. RhD type
  3. antibody screen for unexpected RBC antibodies via indirect antiglobulin test
33
Q

What is a “type and cross”?
When is it ordered?
What is tested?

A

If the need for transfusion is CERTAIN, the type and cross is ordered.

  1. ABO
  2. RhD
  3. antibodies for unexpected RBC antibodies
  4. Crossmatching of donor RBC unit and patient plasma. If clumping occurs, it means the patient plasma has Ab against an antigen on the RBC
34
Q

In what four common settings would you order a DAT?

A
  1. work-up for a transfusion reaction
  2. newborn with jaundice (suspected hemolytic disease of the newborn)
  3. suspected autoimmune hemolytic anemia
  4. anemia of unknown cause
35
Q

If the DAT is positive, what would be the next test done?

A

Red cell elution.
Positive DAT means the antibody is bound to the RBC.
RBC elution sees what the specificity is of the antibody by removing it from the red cell and testing it on a panel of reagent cells with known antigens

36
Q

In what three settings would you order an IAT?

A
  1. type and screen or type and cross
  2. pregnancy screening
  3. work-up for autoimmune hemolysis