15 Blood Banking and Transfusion Disorders

ABO Blood Group Antigens

Definition of ABO blood group antigens
They are glycoproteins attached to the RBC surface.
ABO Blood Group Antigens
Definition of ABO blood group antigens
They are glycoproteins attached to the RBC surface.
Definition of ABO blood group antigens
They are glycoproteins attached to the RBC surface.
Blood group O characteristics
Blood group antibodies are natural antibodies that are synthesized in Peyer's
patches. A and B antigens that are normally present in food are trapped by
specialized epithelial cells called cells that o!erlie Peyer's patches. cells ha!e
close pro"imity to B lymphocytes lying #ithin the epithelium. cells transport the A
and B antigens to these lymphocytes$ resulting in the de!elopment of natural
antibodies against the antigens. %atural antibodies de!elop against antigens that
are not present on the RBC$ #hich e"plains #hy blood group O patients ha!e
antibodies against both A and B antigens.
&. ost common blood group
o No blood group antigens are present on the RBC membrane.
'. %atural antibodies (isohemagglutinins) in serum
a. Anti*A*+g$ anti*B*+g
b. ost people ha!e anti*AB*+g, antibodies.
'. +ncreased incidence of duodenal ulcers
Blood group A characteristics
&. Anti*B*+g antibodies
'. +ncreased incidence of gastric carcinoma
Blood group B
characteristics
Anti*A*+g antibodies
Blood group
AB
characteristics
&. -east common blood group
2. No natural antibodies
%e#borns
&. Do not ha!e natural antibodies at birth
'. +g, antibodies are of maternal origin.
o +g, antibodies cross the placenta.
.lderly people
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.lderly patients may not ha!e a hemolytic transfusion reaction if they are transfused
#ith the #rong blood group because they fre2uently lose their natural antibodies.
3re2uently lose their natural antibodies
Paternity issues in ne#borns
&. Blood group AB parents cannot ha!e an O child.
'. Blood group O parents cannot ha!e an AB$ A$ or B child.
4. Blood group A and B parents can ha!e O children if both ha!e AO and BO phenotypes.
Determining the ABO group
&. 3or#ard type
a. +dentifies the blood group antigen
Patient RBCs are added to test tubes that contain either anti*A or anti*B test
serum.
b. ."ample*blood group A RBCs
Agglutination reaction #ith anti*A test serum but not #ith anti*B test serum
'. Bac5 type
a. +dentifies the natural antibodies
Patient serum is added to test tubes containing either A or B test RBCs.
b. ."ample*blood group A serum
Patient anti*B*+g antibodies agglutinate B test RBCs but not A test RBCs.
Rh and Non-Rh Antigen Systems
Rh antigen system
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&. +t has three ad6oining gene loci.
a. -ocus coding for D antigen (no d antigen)
b. -ocus coding for C and c antigen
c. -ocus coding for . and e antigen
'. Autosomal codominant inheritance
a. One of the sets of three Rh antigens from each parent is transmitted to each child.
i. ."ample*child #ith CDe from the father and cde from the mother
%ote that the child lac5s . antigen.
ii. Absence of D antigen on a chromosome is designated d e!en though the antigen
does not e"ist.
b. Possible Rh antigen profiles
i. DD$ Dd$ or dd
ii. CC$ Cc$ or cc
iii. ..$ .e$ or ee
4. An indi!idual #ho is Rh positi!e is D antigen positi!e.
a. Appro"imately 708 of the population has D antigen.
b. +ndi!iduals lac5ing D antigen are considered Rh negati!e.
9. Rh phenotype of an indi!idual
a. RBCs are reacted #ith test antisera against each of the Rh antigens.
b. ."ample*Rh phenotype that is positi!e for C$ c$ D$ and . antigens but negati!e for e
antigen (phenotype is CcD.)
Rh antigen system
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&. +t has three ad6oining gene loci.
a. -ocus coding for D antigen (no d antigen)
b. -ocus coding for C and c antigen
c. -ocus coding for . and e antigen
'. Autosomal codominant inheritance
a. One of the sets of three Rh antigens from each parent is transmitted to each child.
i. ."ample*child #ith CDe from the father and cde from the mother
%ote that the child lac5s . antigen.
ii. Absence of D antigen on a chromosome is designated d e!en though the antigen
does not e"ist.
b. Possible Rh antigen profiles
i. DD$ Dd$ or dd
ii. CC$ Cc$ or cc
iii. ..$ .e$ or ee
4. An indi!idual #ho is Rh positi!e is D antigen positi!e.
a. Appro"imately 708 of the population has D antigen.
b. +ndi!iduals lac5ing D antigen are considered Rh negati!e.
9. Rh phenotype of an indi!idual
a. RBCs are reacted #ith test antisera against each of the Rh antigens.
b. ."ample*Rh phenotype that is positi!e for C$ c$ D$ and . antigens but negati!e for e
antigen (phenotype is CcD.)
Alloimmunization
&. Production of an antibody against a foreign antigen not present on an indi!idual's RBCs
a. Patient e"posure to Rh antigen he is lac5ing (e.g.$ D antigen)
b. Patient e"posure to non*Rh antigen she is lac5ing (e.g.$ :ell antigen)
c. These antibodies are called atypical antibodies.
The indi!idual is considered sensitized if atypical antibodies are present.
'. ;ignificance of atypical antibodies
a. ay produce a hemolytic transfusion reaction (<TR)
ii Occurs #hen blood containing the foreign antigen is infused into an indi!idual
iii ."ample*indi!idual #ith anti*:ell antibodies is e"posed to :ell antigen positi!e
RBCs.
iiii +g, antibodies are more li5ely to produce an <TR than +g antibodies.
+g, antibodies react best in #arm temperatures$ but +g antibodies react
best in cold temperatures.
b. Transfusion re2uirements in an indi!idual #ith atypical antibodies
ii +ndi!idual must recei!e blood that is negati!e for the foreign antigen.
iii ."ample*indi!idual #ith anti*:ell antibodies must recei!e :ell antigen negati!e
blood.
Clinically important non*Rh antigens
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&. Duffy (3y) antigens
a. 3y antigens are the binding site for infestation of RBCs by Plasmodium vivax.
b. a6ority of blac5 Americans lac5 the 3y antigen.
Offers protection against contracting P. vivax malaria
'. + and i antigen systems
a. +g antibodies (cold agglutinins) may de!elop against + or i antigen.
b. +ncreased ris5 for de!eloping a cold autoimmune hemolytic anemia
ii Anti*i hemolytic anemia may occur in infectious mononucleosis.
iii Anti*+ hemolytic anemia may occur in Mycoplasma pneumoniae infections.
Blood Transfusion Therapy
Blood donors
There is a ris5 for transmitting infection #hen transfusing blood because there is an
incubation period before specific antibodies are de!eloped against the pathogen.
The ris5 for de!eloping an infection per unit of blood for different pathogens is as
follo#s= &=44>> for hepatitis C? &='>>$>>> for hepatitis B? and$ &='$>>>$>>> for <+@.
The most common infectious agent transmitted by blood transfusion is
cytomegalo!irus (C@)$ #hich is present in donor lymphocytes.
&. Autologous transfusion
a. Process of collection$ storage$ and reinfusion of the indi!idual's o#n blood
b. ;afest form of transfusion
'. Tests performed on donor blood
a. ,roup (ABO) and type (Rh)
b. Antibody screen (indirect Coombs' test)
Detects atypical antibodies (e.g.$ anti*D$ anti*:ell)
c. ;creening tests for infectious disease
."amples*syphilis$ hepatitis B and C$ <+@*& and '$ <T-@*&
Blood donors
There is a ris5 for transmitting infection #hen transfusing blood because there is an
incubation period before specific antibodies are de!eloped against the pathogen.
The ris5 for de!eloping an infection per unit of blood for different pathogens is as
follo#s= &=44>> for hepatitis C? &='>>$>>> for hepatitis B? and$ &='$>>>$>>> for <+@.
The most common infectious agent transmitted by blood transfusion is
cytomegalo!irus (C@)$ #hich is present in donor lymphocytes.
&. Autologous transfusion
a. Process of collection$ storage$ and reinfusion of the indi!idual's o#n blood
b. ;afest form of transfusion
'. Tests performed on donor blood
a. ,roup (ABO) and type (Rh)
b. Antibody screen (indirect Coombs' test)
Detects atypical antibodies (e.g.$ anti*D$ anti*:ell)
c. ;creening tests for infectious disease
."amples*syphilis$ hepatitis B and C$ <+@*& and '$ <T-@*&
Patient crossmatch
Patients #ith a negati!e antibody screen should ha!e a compatible crossmatch.
<o#e!er$ a compatible crossmatch does not guarantee that the recipient #ill not
de!elop atypical antibodies$ a transfusion reaction$ or an infection.
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Before blood is transfused into ne#borns or patients #ith T*cell deficiencies$ it must
be irradiated to 5ill donor lymphocytes. This pre!ents the patient from de!eloping a
graft*!ersus*host reaction or a C@ infection.
&. Components of a standard crossmatch
a. ABO group and Rh type
b. Antibody screen for atypical antibodies
c. Direct Coombs' test to identify atypical +g, antibodies on patient RBCs
d. a6or crossmatch
'. a6or crossmatch
a. Purpose of a ma6or crossmatch
Detect atypical antibodies that are directed against foreign antigens on donor
RBCs
b. Patient serum is mi"ed #ith a sample of RBCs from a donor unit.
ii .ach unit of donor blood must ha!e a separate crossmatch.
iii -ac5 of RBC agglutination or hemolysis indicates a compatible crossmatch.
'. Bse of blood group O pac5ed RBCs for transfusion
a. Can be transfused into any patient$ regardless of the blood group
ii Blood group O RBCs lac5 A and B antigens.
iii Blood group O indi!iduals are considered uni!ersal donors.
b. Blood group O indi!iduals can recei!e only O blood.
Anti*A*+g and anti*B*+g #ill hemolyze transfused A$ B$ or AB RBCs.
ii Blood group AB indi!iduals can be transfused #ith blood from any blood group.
a. They lac5 natural antibodies.
b. They are considered uni!ersal recipients.
Blood component therapy
Tale 15-1! Blood "omponents
"omponent Dis#ussion
Pac5ed RBCs Purpose= increase O' transport to tissues
Pac5ed RBCs ha!e less !olume and a higher <ct than #hole blood
.ach unit of pac5ed RBCs should raise the <b by & gCd- and the <ct by 48? lac5 of an increment
implies a hemolytic transfusion reaction or blood loss in the patient
Yersinia enterocolitica, a pathogen that thri!es on iron$ is the most common contaminant of stored
blood
Platelets Purpose= stop medically significant bleeding related to thrombocytopenia or 2ualitati!e platelet
defects (e.g.$ aspirin)
Platelets ha!e <-A antigens and ABO antigens on their surface? ho#e!er$ they lac5 Rh antigens
.ach unit of platelets should raise the platelet count by 0>>>*&>$>>> cellsCD-
3resh frozen
plasma
Purpose= treatment of multiple coagulation deficiencies (e.g.$ D+C? cirrhosis) or treatment of #arfarin
o!er*anticoagulation if bleeding is life*threatening
Cryoprecipitate Purpose= treatment of coagulation factor deficiencies in!ol!ing fibrinogen and factor @+++ (e.g.$ D+C)
Cryoprecipitate contains fibrinogen$ factor @+++$ and factor E+++
Desmopressin acetate is used instead of cryoprecipitate in treating mild hemophilia A and !on
Fillebrand disease
D+C$ disseminated intra!ascular coagulation? <ct$ hematocrit? <b$ hemoglobin.
Transfusion reactions
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+ndi!iduals #ho are deficient in +gA and #ho ha!e antibodies directed against +gA
from pre!ious e"posure to a blood product may de!elop a se!ere anaphylactic
reaction. +gA deficient indi!iduals must recei!e blood or blood products that lac5 +gA.
Anti*<-A antibodies de!elop #hen indi!iduals are e"posed to foreign <-A antigens
(e.g.$ pre!ious blood transfusion or organ transplant). Fomen commonly ha!e these
reactions o#ing to pregnancy$ #hen there is an increased ris5 for e"posure to fetal
blood during deli!ery or after a spontaneous abortion.
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+ndi!iduals #ho ha!e been infused #ith blood in the past may ha!e been e"posed to
a foreign blood group antigen and de!eloped atypical antibodies that are no longer
circulating? therefore$ the pretransfusion antibody screen is negati!e. <o#e!er$
memory B cells are present and ree"posure to the foreign antigen causes them to
produce antibodies$ resulting in an e"tra!ascular hemolytic anemia. This reaction
may occur #ithin hours to 4 to &> days after the transfusion.
&. Allergic reactions
a. ost common transfusion reaction
b. Type + +g.*mediated hypersensiti!ity reaction against proteins in the donor blood
c. Clinical findings
i. Brticaria #ith pruritus
ii. 3e!er$ tachycardia$ #heezing
iii. Potential for anaphylactic shoc5
i!. ild cases are treated #ith antihistamines.
'. 3ebrile reaction
a. Pathogenesis
i. Recipient has anti*human leu5ocyte antigen (<-A) antibodies directed against
foreign <-A antigens on donor leu5ocytes.
There are no <-A antigens on RBCs.
ii. Type ++ hypersensiti!ity reaction
b. Clinical findings
i. 3e!er$ chills$ headache$ and flushing
ii. Treated #ith antipyretics
4. Acute hemolytic transfusion reaction (<TR)
a. ay be intra!ascular or e"tra!ascular hemolytic reactions
b. +ntra!ascular hemolysis
i. ABO blood group incompatibility
ii. ."ample*group B patient recei!es group A donor blood.
Anti A*+g attaches to A positi!e donor RBCs producing intra!ascular
hemolysis.
iii. Type ++ hypersensiti!ity reaction
c. ."tra!ascular hemolysis
i. An atypical antibody reacts #ith a foreign antigen on donor RBCs.
acrophage phagocytosis and destruction of donor RBCs coated by the
atypical antibody
ii. Gaundice commonly occurs.
Bncon6ugated bilirubin is the end product of macrophage degradation of
<b.
iii. Type ++ hypersensiti!ity reaction
d. Clinical findings
i. 3e!er$ bac5 pain$ hypotension
ii. Disseminated intra!ascular coagulation$ oliguria (renal failure)
e. -aboratory findings
i. Positi!e direct Coombs' test
+g, antibody andCor C4b is coating donor RBCs.
ii. Positi!e indirect Coombs' test
Atypical antibody is present in serum.
iii. No significant increase in <b o!er pretransfusion le!els.
i!. <emoglobinuria (sign of intra!ascular hemolysis)
!. Gaundice (sign of e"tra!ascular hemolysis)
$emolyti# disease of the ne%orn &$DN'
<D% results from the transplacental passage of maternal +g, antibodies (e.g.$ anti*D antibodies$
anti*AB antibodies in O mothers) resulting in an e"tra!ascular hemolytic anemia in the fetus.
ABO <D%
&. .pidemiology
a. ost common <D%
Present in '>8 to '08 of all pregnancies
b. others are blood group O and the fetus is either blood group A or B.
'. Pathogenesis
a. Blood group O indi!iduals ha!e anti*AB*+g, antibodies.
ii +g, antibodies cross the placenta and attach to fetal A or B RBCs.
iii 3etal splenic macrophages phagocytose RBCs$ causing anemia.
iiii Bncon6ugated bilirubin from e"tra!ascular hemolysis is disposed of in the
mother's li!er.
b. ay affect the firstborn or any future pregnancy if ABO incompatibility e"ists
'. Clinical and laboratory findings
a. Gaundice de!elops #ithin the first '9 hours after birth.
ii ABO <D% is the most common cause of 6aundice in this period.
%e#born li!er cannot handle the e"cess bilirubin load.
iii Ris5 for 5ernicterus is !ery small (see belo#).
b. Anemia
ii ild normocytic anemia or no anemia at all
iii ."change transfusions are rarely indicated.
c. Positi!e direct Coombs' test on fetal cord blood RBCs
Due to anti*AB*+g, antibodies coating fetal A or B RBCs
b. ;pherocytes are present in the cord blood peripheral smear.
Due to macrophage remo!al of a portion of the RBC membrane
Rh <D%
;pecial tests are performed on the mother's blood that detect fetal RBCs in her
blood. The amount of fetal blood is 2uantified so that the appropriate amount of anti*
D globulin is gi!en to the mother. Anti*D globulin mas5s the antigenic sites on the
fetal RBCs or destroys the fetal RBCs so that the mother does not host an antibody
response against the D antigen. +f the patient de!elops anti*D antibodies$ there is no
indication for gi!ing the globulin either during or after deli!ery$ because its main
purpose is to pre!ent sensitization.
:ernicterus refers to deposition of free (not bound to albumin) lipid*soluble
uncon6ugated bilirubin in the basal ganglia o#ing to an incompletely formed blood*
brain barrier. Bilirubin damages neurons in the brain$ causing se!ere dysfunction.
ABO incompatibility protects the mother from de!eloping Rh sensitization. 3or
e"ample$ in a mother #ho is O negati!e and carrying a fetus #ho is A positi!e$ any A
positi!e fetal RBCs entering her circulation #ill be destroyed by maternal anti*A*+g
antibodies$ thereby pre!enting sensitization.
&. Pathogenesis
a. other is Rh (D antigen) negati!e and the fetus is Rh positi!e.
b. other is e"posed to fetal Rh positi!e blood (fetomaternal bleed).
Occurs during the last trimester or during childbirth itself
c. Cytotrophoblast is absent during the last trimester.
+ncreases the ris5 for a fetomaternal bleed
d. other de!elops anti*D*+g, antibodies #hen e"posed to fetal Rh positi!e cells.
3irst Rh incompatible pregnancy does not affect the firstborn.
e. ;ubse2uent Rh incompatible pregnancies result in e"tra!ascular hemolytic anemia in the
fetus.
ii Anti*D*+g, antibodies cross the placenta and attach to fetal Rh positi!e RBCs.
iii 3etal splenic macrophages phagocytose RBCs$ causing se!ere anemia.
3etus may de!elop high*output cardiac failure leading to hydrops fetalis
and death.
<ydrops fetalis is a combined left* and right*sided heart failure #ith
ascites and edema.
."tramedullary hematopoiesis is present in the li!er and spleen.
Bncon6ugated bilirubin is con6ugated in the mother's li!er.
'. Pre!ention of Rh <D% in Rh negati!e mothers #ithout anti*D
a. Recei!e anti*D globulin (Rh immune globulin) during the '7th #ee5 of pregnancy
b. Anti*D globulin does not cross the placenta.
c. Anti*D globulin protects the mother from sensitization to fetal Rh positi!e cells that may
enter her circulation during the last trimester.
d. Anti*D globulin lasts 4 months in the mother's blood.
e. Additional anti*D globulin is gi!en to the mother after deli!ery if the baby is Rh positi!e.
4. Clinical and laboratory findings
a. Degree of anemia is more se!ere than #ith ABO <D%.
b. Gaundice de!elops shortly after birth.
ii -e!el of uncon6ugated bilirubin is much higher than #ith ABO <D%.
ost of the uncon6ugated bilirubin is not bound by albumin and circulates
free in the blood.
iii +ncreased ris5 for 5ernicterus
The free$ unbound lipid soluble uncon6ugated bilirubin poses the greatest
ris5 for bilirubin entry into the brain .
c. Positi!e direct and indirect Coombs' tests on fetal cord blood
d. ;pherocytes are not present in cord blood.
acrophages phagocytose the entire RBC.
b. ."change transfusions are re2uired.
ii %e#born's blood is remo!ed and replaced #ith fresh blood.
iii Transfusion corrects anemia and remo!es antibodies and uncon6ugated bilirubin.
Bse of blue fluorescent light
&. Bsed as a treatment of 6aundice in the ne#born
'. Bncon6ugated bilirubin in the s5in absorbs light energy from blue fluorescent light.
4. Photoisomerization con!erts uncon6ugated bilirubin to a nonto"ic #ater*soluble dipyrrole (called
lumirubin).
o -umirubin is e"creted in bile or urine.