Pathology of Blood Groups Flashcards
RBC antigens are most commonly ______, _____ or ________ in nature.
How are they attached to the RBC membrane?
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.
How are blood group antigens grouped into blood group systems?
Based on the genes that encode them
What are the six most clinically significant blood groups in humans?
- ABO
- Rh- C, c, D, E, e
- Duffy (Fya and Fyb)
- Kidd (Jka and Jkb)
- Kell ( K, k)
- MNSs (antibodies to M and N are less important than S and s)
How are blood groups inherited?
Mendelian inheritence
What are the three reasons why we need to know the major RBC blood groups?
- They are immunogenic
- Ab against them cause clinical hemolysis
- 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
What makes ABO, Rh, Duffy, Kidd, Kell, and MNSs different from the 250-ish of other RBC antigens?
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.
What is serologic testing?
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.
Which are the carbohydrate blood group antigens? and where can they be found?
- ABO, Lewis I and P
2. They are found on RBC, endothelial cells, epithelial cells
What is the difference between an alloantibody and an autoantibody?
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
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?
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.
The highest alloimmunization rates are found in what patients?
- Sickle cell disease patients
What is the most immunogenic antigen? (most likely to cause the recipient to make Ab against it)
D antigen in the Rh system.
K in Kell is also likely to cause Ab formation
In pregnancy where does antigenic stimulation come from?
When does this typically occur?
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.
What are naturally occurring alloantibodies?
Why do they occur?
What are the naturally occurring alloantibodies?
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
Which RBC antigens generally occur only following exposure to antigen positive blood (pregnancy, transfusion, IV drug use, transplant)?
Kell Kidd Rh Duffy S and s
What type of antibody are most RBC alloantibodies? What are the exceptions?
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)
Why does the fact that anti-A and anti-B are IgM make blood type matching crucial?
- IgM can bind complement, damage the RBCs as they circulate and cause intravascular hemolysis. Acute hemolytic transfusion reactions can cause death.
- Complement will set off coagulation and bradykinin cascades. Cascades amplify effects of vasodilation, DIC, hemolysis
When do RBC antibodies formed after transfusion become detectable in routine lab tests?
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)
What makes alloantibodies in type O people different from A, B or AB?
The alloantibodies are IgG so they can cross the placenta
Describe the hemolysis that occurs from most IgG RBC antibodies.
What IgG antibody differs from this process?
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
Why is incompatible blood occasionally inadvertently administered during transfusion?
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)
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”?
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.
What RBC blood groups are most commonly involved in delayed hemolytic transfusion reactions?
Rh (CcEeD)
Kidd (Jka and Jkb)
What is erythroblastosis fetalis?
The condition develops in what way?
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
