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Transfusion science
Blood group
A blood group is an inherited character of the red cell surface detected by a specific
alloantibody
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Most blood groups are organised into blood group systems, each system
represents a single gene or a cluster of two or more closely linked homologous genes
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Most blood group antigens are proteins or
glycoproteins, with the blood group specificity determined primarily by the amino acid
sequence
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These antigens are
not produced directly by the genes controlling their polymorphisms, but by genes encoding
transferase enzymes that catalyze the final biosynthetic stage of an oligosaccharide chain
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The O allele produces neither A nor B
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the product of the A allele is a glycosyltransferase
that catalyzes the transfer of N-acetylgalactosamine (GalNAc) from a nucleotide donor
substrate UDP-GalNAc, to the fucosylated galactose (Gal) residue of the H antigen, the
acceptor substrate
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GalNAc and Gal are the immunodominant
sugars of A and B antigens, respectively
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The ABO gene on chromosome 9 consists of 7 exons
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A and B
alleles are inherited in a co-dominant manner, the O allele by recessive inheritance
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It is synthesised by an alpha
1,2-fucosyltransferase, which catalyses the transfer of fucose from its donor substrate to the
terminal Gal residue of its acceptor substrate
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Two genes produce alpha 1,2-fucosyltransferase; FUT1 responsible
for H on red cells, FUT2 for H in other tissues and in secretions
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Individuals with inactivating mutations in FUT2 lack H, A, and
B from body secretions
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Bombay blood group individuals can only receive
transfusions of Bombay blood group blood
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Newborns develop ABO antibodies through exposure
to the environment
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The antigens of the Rh blood group system are encoded by two genes, RHD and RHCE,
which produce D and CcEe antigens, respectively
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13-p34
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The most significant Rh antigen clinically is D
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The D negative phenotype (Rh negative) is associated with the absence of the
whole D protein from the red cell membrane
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Partial D antigens lack some or most of the D epitopes
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Individuals with partial D
phenotypes must be transfused with D negative blood
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D variants result from amino acid
substitutions in the D protein occurring either as a result of one of more missense mutations
in RHD or from one of more exons of RHD being exchanged for the equivalent exons of
RHCE in a process called gene conversion
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Anti-D can cause severe immediate or delayed
haemolytic transfusion reactions (HTRs) and D positive blood must never be transfused to a
patient with anti-D
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Anti-c may also cause severe HDFN
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Individuals who are Rh
positive can be transfused with Rh positive and Rh negative blood, whereas Rh negative
blood types can only be transfused with Rh negative blood
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Laboratory techniques
Agglutination occurs when antibodies on coated cells form cross-linkages between cells
resulting in visible clumping
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In the laboratory agglutination indicates a
reaction between antibodies in the patient plasma and antigens in the test reagent
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Column agglutination (gel) systems are used to assess agglutination
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Positive
reactions (antibody/antigen interactions) are distinguished by agglutinates near or near the
top of the gel column and negative reactions appear as buttons of red cells at the bottom
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Pre blood donation criteria include; between 17-66 years of age, weigh over 50 kg, Hb >
125g/L for females, and Hb > 135g/L for males
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Whole donor blood is then screened to detect certain viral and bacterial antigens and
antibodies
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Each component has a specific clinical benefit
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Packed red blood cell donations are screened for the presence of hepatitis B surface
antigen, hepatitis C virus antigen, antibody to hepatitis C virus, antibodies to HIV-1 and
HIV-2, syphilis antibody, and human T-cell leukaemia virus antibody
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Packed red blood cell
transfusions are used to raise the oxygen carrying capacity of blood when it is
symptomatically reduced due to red blood cell loss or due to reduced erythropoiesis, for
example in haemoglobinopathies, leukemia, and anaemia of chronic disease
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Platelet donations can be stored for seven days
at 20-24 degrees celsius, there is a risk of bacterial contamination due to storage
temperature
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The D alloimmunization
rate following D positive platelet transfusion to a D negative recipient is low
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Fresh frozen plasma is obtained from whole blood donation from male donors and frozen to
maintain activity of labile coagulation factors
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Platelet transfusions are used in the prevention and
treatment of bleeding due to thrombocytopenia or platelet function defects
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Cryoprecipitate is the supernatant obtained from
centrifuged plasma, and consists of concentrated factor VIII:C, vWF, fibrinogen, factor XIII,
and fibronectin
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Cryoprecipitate is used in the treatment of
fibrinogen deficiency, dysfibrinogenemia, during invasive procedures, in trauma cases, and
in the treatment of disseminated intravascular coagulation
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Anti-D antibody is responsible for most cases of severe HDFN although anti-c, anti-E, and
anti-K are found in occasional cases
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An Rh negative mother
pregnant by an Rh positive father is in danger of developing a response to the Rh antigen
that the fetus may have inherited from the father and rejecting the Rh positive fetus
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During her first pregnancy with an Rh positive
fetus, and Rh negative women are usually not exposed to enough fetal red blood cells to
activate her Rh negative specific B cells
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These fetal red blood cells stimulate Rh specific B cells to mount an
immune response, resulting in the production of Rh specific plasma cells and memory B cells
in the mother
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Importantly, since IgM antibodies do not pass do not pass through the
placenta, IgM anti-Rh antigens are no threat to the fetus
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Severe
HDFN results in intrauterine death from hydrops fetalis
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If the unconjugated bilirubin is not controlled and reaches levels
exceeding 250 umol/L, bile pigment deposition in the basal ganglia may lead to kernicteruscentral nervous system damage
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Mild HDFN presents as mild anaemia with or without jaundice
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HDFN caused by Rh
incompatibility in a second or later pregnancy can be prevented by administration antibodies
against the Rh antigen to the mother at around 28 weeks of her first pregnancy and within 24
to 48 hours after the first delivery
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These antibodies bind to any fetal red blood cells that may have
entered the mother’s circulation and facilitate their clearance before B-cell activation and
ensuing memory cells predictions cab take place
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A haemolytic transfusion reaction (HTR) is the occurrence of lysis or accelerated clearance
of red cells in a recipient of a blood transfusion caused by immunological incompatibility
between the blood donor and the recipient
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;laboratory investigations suspected
acute haemolytic transfusion reaction; full blood count to provide baseline parameters and to
test for red cell agglutination; plasma/urinary haemoglobin to assess intravascular
haemolysis; test haptoglobin, bilirubin, lactate dehydrogenase (LDH) levels to assess
intravascular and extravascular haemolysis; blood grouping to confirm donro ABO group;
direct antiglobulin test which is positive in AHTR unless all incompatible cells are destroyed;
compatibility testing, an indirect antiglobulin test antibody screen and indirect antiglobulin
test crossmatch using the pre- and post transfusion red cells may aid identification of
antibody or confirm specificites identified in serum in cases of non-ABO incompatibility, red
cell phenotype should be performed on recipient pretransfusion sample and unit in cases of

non-ABO incompatibility, to confirm absence i patient and presence in unit of corresponding
antigen; urea, creatinine and electrolytes to assess baseline renal function; coagulation
screen to test for disseminated coagulation; and blood cultures from the patient and
implicated packs in the event of septic reaction caused by bacterial contamination of unit
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Investigation of suspected DHTRs include; examination of
the blood film which is likely to show spherocytosis; evidence if haemolysis- namely
hyperbilirubinemia, elevated LDH, reduced serum haptoglobin, haemoglobinaemia,
haemoglobinuria, and hemosiderinuria, positive direct antiglobulin test within a few days of
transfusion until incompatible cells are eliminated; and detection of antibody
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Haemovigilance is a set of surveillance procedures covering the
entire transfusion chain (from donation of blood and its components to the follow-up of
recipients of transfusions), intended to collect and assess information on unexpected or
undesirable effects resulting from the donation of blood and the therapeutic use of labile
blood products, and to prevent the occurrence or recurrence of such incidents
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serious hazards of
transfusions (SHOT) is the UK independent, professionally led haemovigilance scheme
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where risks and problems are identified, SHOT
produces recommendations to improve patient safety
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The blood safety and quality regulations govern
operation of blood establishments (establishments which collect, process and test human
blood and blood products) and hospitals blood banks (hospital units which store, distribute
and perform compatibility tests on blood and blood components for use in hospitals)/ the
regulations include traceability requirements and notification of adverse reactions and
events
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Human
errors which can lead to HTR include; blood sample drawn from the wrong patient, patirne
details recorded incorrectly on the sample or request form, the incorrect unit is collected from
the blood refrigerator, or incorrectly performed formal checks when administering blood
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