Intro to blood group serology Flashcards
Genetic control of blood groups - the two types of determinants
Protein - gene codes for the antigenic determinant itself - Rh, Kell, Duffy, Kidd systems
Glycolipid - gene codes for production of enzymes that add or remove carbohydrates or lipids - ABO, lewis group systems
Functional aspects of blood group antigens
- Duffy blood group system and malaria - duffy antigen acts as entry point for malaria into RBC’s, in caucasians null phenotype rare, black african ethnics up to 40% have null phenotype (natural selection for resistance)
- The McLeod phenotype, Kx null phenotype associated with chronic granulomatous disease and acanthocytosis
what is the most likely reason for having different blood groups
genetic drift, can monitor patterns of migration, need migrants to donate blood so rare types in their population can be supported
Rh(D) types - ethnic differences
17% caucasians -ve
<1% Polynesians -ve
Kidd types - ethnic differences
<0.01% in caucasians
1% in Polynesians
MNS system - the U phenotype
only in black african ethnic background
The 3 types of antibodies
IgM IgG IgA
Naturally occurring antibodies
No exposure to foreign red cells but exposure to red cells containing A and B like antigens
Immune occurring antibodies
Exposure to foreign red cells e.g. Rh+, by transfusion or pregnancy
Naturally occurring red cell antibodies
Develop in the absence of exposure to the red cell antigen
Stimulated by cross reacting antigens derived from bacteria
Not present at birth but develop during the first year of life
Usually glycolipid
Significant IgM component to antibody but IgG may also be present
ABO and lewis antigens
Ability to activate compliment
Intravascular site of red cell destruction
Immune stimulated red cell antibodies
Usually glycoprotein
develop only following expose to specific antigen
produced following - transfusion, pregnancy, injection
normally IgG in nature
Extravascular sie of red cell destruction
ABO antigens distribution
widely distributed: blood cells, epic cells, body fluids
ABO phenotype determined by
glycosyltransferase enzymes, responsible for addition of CHO molecules to basic membrane structure
H antigen nessecary for ABO phenotype to be expressed
What is the terminal sugar for each ABO antigen?
A = N acetyl galactosamine B = D galactose O = Nil
ABO incompatible transfusion leads to?
Intravascular haemolysis, renal failure, DIC = disseminated intravascular coagulation
Universal recipient, donor and whether their rare or common?
Donor = O common Recipient = AB rare
Rh blood group system, summary
discovered in 1939, protein dominant, expression only on red blood cells, antibodies produced following immune stimulation, highly immunogenic particularly Rh(D) –> if you transfuse a D- individual with D+ red cells 80-90% will form anti D
What is anti D
an IgG antibody that is unable to bind complement, red cell destruction is extravascular
most common cause of haemolytic disease of new born
protocol for transfusion of Rh(D) cells
normally transfuse cells of same type as recipient
Never transfuse positive cells to negative woman of childbearing age
alleles producing the Rh antigen
3 genetically closely linked alleles C and c D and d E and e the 3 allelic agents usually behave as a single entity, a number of common alleles can thus be defined
Minor blood group systems
over 400 blood group systems have been defined
majority only of theoretical interest
Factors involved in the clinical importance of blood group systems
frequency of antigen in population
frequency of antibody production following transfusion of red cells containing antigen (immunogenicity)
Ability of antibody to destroy transfused red cells
Commercially sourced monoclonal antibodies
for antigen testing
high sensitivity and specificity
are IgM in nature
produce direct agglutination
Zeta potential
distance between red cells as they are negatively charged and so repel each other
IgG molecule too small to produce cross linking and hence a potentiator needed to produce agglutination e.g. antihuman globulin or enzymes such as albumin
Haemolytic disease of newborn
when material antibody crosses placenta, destruction of fatal red cells
Always involves an IgG antibody
most commonly caused by anti D, then Anti c then anti kill
Frequencies greatly reduced by introduction of immunoprophylaxis
antenatal prophylaxis
still birth with hyropsfetalis caused by Rh antibodies
Infant with kernicterus - mechanism
brain damage caused by jaundice
- born alive with maternal antibodies in babes plasma for several weeks, infant continues to produce D positive red cells which are destroyed by anti D, babe becomes jaundiced after birth, doesn’t happen in utero because bilirubin sucked out into maternal circulation, infant BBB not well developed, bilirubin cross into CNS neurological irritant and abnormalities e.g. cerebral palsy
Prevention of Rh(D) HDN
RhD Ig immunoglobulin given routinely after birth of an Rh(D)pos baby to an RhD neg mum
Kleehauer test used to detect women with larger fetomaternal bleeds
Anti D Ig given during pregnancy following potentially sensitising event
- Abortion
- termination
- Amniocentesis
Routine antenatal prophylaxis
Why is ABO haemolytic disease of newborn rare?
AB antigens weakly expressed in the foetus and newborn
Ab antigens widely distributed in placental tissue and absorb antibody before it reaches fetus
