week 1- immunohematology Flashcards

1
Q

• What is immunohematology?

A

o Specialized branch of medical science
o concepts and clinical techniques related to modern transfusion therapy
o determine blood group and type, so blood and organs are safely transfused and transplants
o prevent materno=-fetal transplacental rxns (HDN, hemolytic dz of the newborn)

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2
Q

• what is the sig hx of blood transfusions?

A

o William harvery described circulation of blood in 1616
o 1665, Lower, dog-dog transfusion -> feasibility demonstrated
o 1667, Denis, animal-human -> banned experimentation
o 1818, Blundell, human-human -> techniques, rational indications
o 1800s, Various, frequent severe reactions -> search for blood substitute (saline)

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3
Q

• What dis Denis do in 1667?

A

o Transfuse blood from docile lamb to man accused by wife of running thru streets of Paris naked w other women, in attempt to rid “wild” blood
o As soon as blood entered veins, felt heat, HR inc, sweaty face
o Upset stomach, kidney pain, felt like choking
o After sleeping all night, really black urine (Hb, bilirubin, blood)

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4
Q

• What are the main sxs of acute hemolytic reaction?

A
o	Systemic: fever, chills
o	Heart: inc HR
o	Vascular: hypotension, uncontrollable bleeding
o	Transfused vein: heat sensation
o	Chest: constricting pain
o	Lumbar: pain
o	Urinary: Hb, bilirubin
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5
Q

• Who first described the ABO blood groups? Significance?

A

o Karl Landsteiner in 1901
o Until then, all blood assumed to be the same
o Often tragic consequences of blood transfusions not previously understood

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6
Q

• What are the Ag’s and Ab’s found in each blood type?

A

o A: a-B, A Ag
o B: a-A, B Ag
o AB: no Ab’s, A and B Ag’s
o O: a-A and a-B, no Ag’s

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7
Q

• Where are the A-B Ag’s found? What other Ag is there? What other phenotype?

A

o Expressed on proteins or lipid bi-layer pf RBCs
o Also H-Ag= foundation on which both A and B are created
o H-Ag: RBC-glu-gal-NAG-gal-fru (A-B attached to oligosaccharide off RBC)
o Bombay phenotype: no H-Ag, need transfusion from other H-def, 1/10000 in India, 1/million in Europe

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8
Q

• What is the clinical significance of blood group Ab’s?

A

o Abs to system destroy RBC in vivo
o Cause HDN
o Are common

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9
Q

• What are the AIHAs?

A

o Warm

o Cold: cold hemaglutinin dz, paroxysmal cold Hb-uria

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10
Q

• What are other types of immune hemolytic anemias?

A

o Alloimmune: Hemolytic dz of newborn (HDN), Hemolytic transfusion rxns
o Drug induced

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11
Q

• A transfusion is a tissue graft. What are the types? Blood?

A

o Also Abs against chemicals, drugs
o Autograft: animal has auto-Abs to its own blood
o Allograft: allo-Abs, against another individual of its own species
o Xenograft: heterologous Abs, against another species
o ABO Abs are allo-Abs; but also heterologous bc formed in response to exposure to gut and environmental bacteria, reacting w allo-Ags

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12
Q

• What was the first blood group system to be identified? Applications?

A

o ABO, most significant for transfusion practice
o Only system that reciprocal Abs are consistently and predictably present in sera of ppl who have no exposure to RBCs
o One of the first human characteristics proven to be inherited
o Used by lawyers in paternity suits, police in forensic science, anthropologists

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13
Q

• What are the ABO Abs?

A

o Occur naturally, aka natural isohemaglutinins, against A and B Ags
o Complete Abs=IgM class (u heavy chain) (st IgG, y HC)
o IgM large enough to produce visible agglutination of RBCs
o Formed w/o prior sensitization to non-self RBCs
o Form by encountering similar antigenic determinants found on micro-organisms (not present at birth)

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14
Q

• What are the relative amounts a-A and a-B in blood?

A

o Both decrease with age, highest at 10yrs
o a-A: much higher, in B and O
o a-B: about half, in A and O

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15
Q

• what is the difference bw sensitization and agglutination?

A

o S: Abs attach to a single RBC

o A: Abs attach to multiple RBCs, forming a clump of Ag-RBCs

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16
Q

• What is the mechaniom of immune hemolysis?

A

o C1,4,3 attach to sensitized RBCs

o C5,6,7,8 attach to those, signaling intravascular hemolysis

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17
Q

• How does complement activation occur in hemolysis (up to C1s)?

A

o 6 C1q subunits, 2 bind Fc of Ab to activate C’
o 1) Pentameric IgM bind Ags on cell surface, adopt “staple” form; C1q binds IgM
o OR 2) IgG bind Ags, C1q binds at least 2 IgG
o BOTH: binding of 2 C1q subunits to Ig activates C1r, cleaves and activates serine protease C1s
o IgM only requires 1 molecule, so may be better at fixing C’ and causing hemolysis

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18
Q

• What is the final course of C’ activation?

A

o C5b + C6 + C7 = complex, binds surface, basis to form membrane attack complex, binds to C8 + C9
o MAC=pore (causes lysis); C8 damages membrane, C9 polymerizes to form pore

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19
Q

• What is the fate of intravascular Hb after incompatible transfusion? Ssx?

A

o Hb Peaks in plasma at 6 hrs, after all Hpt used up
o Hpt drops to zero in first 2 hrs (bc binds all Hb, takes to liver)
o Urine Hb and serum also peak ~6 hrs, but lower levels
o All falls back to zero by 24 hrs
o Red/brown urine sign of EXTRAVASCULAR RBC destruction
o Jaundice also important sign of hemolysis

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20
Q

• How is ABO blood type testing done?

A

o Forward grouping: pt RBC added to reagent a-A and a-B antisera
o Reverse grouping: pt serum added to reagent A and B cells
o Crossmatching: last step before transfusion. Mix donor RBC w recipient plasma and test for rxn

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21
Q

• What are the levels of agglutination of RBCs?

A

o Graded on a scale of 1-4
o Negative reaction, no clumps
o +2: dispersed clumps
o +4: strongly positive, all RBCs in a single clump, can’t “de-glutinate”

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22
Q

• What happens if each blood type is added to a-A serum?

A

o A: agglutinates
o B: no rxn
o AB: agglutinates
o O: no rxn

23
Q

• What happens if each blood type is added to a-B serum?

A

o A: no rxn
o B: agglutinates
o AB: agglutinates
o O: no rxn

24
Q

• Method? Blood type? Reagent a-A binds pt RBCs, but not a-B:

A

o Forward grouping

o Type A

25
Q

• Method? Blood type? Pt antibodies bind B cells, not A cells:

A

o Reverse grouping

o Type A

26
Q

• What are the ABO blood compatibilities for receiving?

A

o A: from A or O
o B: from A or O
o AB: from A, B, AB, or O
o O: only from O

27
Q

• What are the ABO blood compatibilities for donating?

A

o O: to O, A, B, AB
o A: to A, AB
o B: to B, AB
o AB: to AB only

28
Q

• How are ABO blood groups genetic? What are the types?

A

o Make a punnett square of Mom and Dad types (AB x AO, etc)
o Each A, B, or O Ag is one allele from each parent
o We have two alleles
o A=AA, AO
o B=BB, BO
o AB=AB
o O=OO

29
Q

• What are the most common blood types? Least?

A
o	Worldwide, O; >50% in Africans, Native Americans, Australian Aborigines
o	O+ very common in US
o	English: A and O
o	SE Asian and Indians: O and B
o	Least: AB
30
Q

• What were the major developments in immunohematology?

A

o 1901, Landsteiner, ABO groups, explained transfusion rxns
o 1907, ottenberg, donor-recipient match, compatibility testing
o 1910, Moss; Agglutination parallels hemolysis, Testing practical and sensitive
o 1939 Levine and Stetson; discover Rh, immunization by pregnancy, Explained HDN
o 1940; Landsteiner & Weiner; Rh polymorphism, Improved safety
o 1945 Coombs, Mourant & Race; Anti-Human Globulin, Demonstrate IgG Abs

31
Q

• How was the Rh factor discovered?

A

o 1940 Landsteiner and Weiner discovered Ab that agglutinated ~85% of ABO compatible blood
o Hypothesized it was same Ab causing HDN (discovered by Levine and Stetson)
o Abs produced by injecting blood from Rhesus monkeys into guinea pigs and rabbits
o Hence “Rh factor”

32
Q

• What is hemolytic dz of the newborn, HDN?

A

o Aka: erythroblastosis fetalis
o Occurs secondary to transplacental transfer of maternal Abs:
o 1) ABO incompatibility: uncommon
o 2) Rh incompatibility: more common
o Occurs w Rh- mother, Rh+ father, firstborn OK, subsequent babies affected after mother sensitized

33
Q

• How does woman become sensitized to Rh+ blood?

A

o First pregnancy: Rh- mom with RH+ fetus
o Cells from Rh+ fetus enter woman’s bloodstream, usu during birth
o Becomes senstitied, makes Abs (anti-D)
o Next Rh+ pregnancy: maternal Abs attack fetal RBCs

34
Q

• How does immunization work for HDN?

A

o Inject mother w “RhoGam” (Rh immune globulin= anti-D)
o anti-D destroys Rh+ fetal RBCs before mother can mount an immune response
o Must do before birth of first Rh+ child

35
Q

• What is the Fisher-Race theory of Rh factors?

A

o Each Rh gene: multiallelic, 3 sets of 2 alleles: D d, C c, E e
o Rh genes: C, c, D, E, e…but no “d” (a-d has never been identified)
o Rh+ means D-Ag positive= DD or D”d” (weak D)
o Rh- means D Ag negative
o D is the most antigenic of this group. A-D is strong IgG

36
Q

• What is the significance of Rh in blood transfusions?

A

o Ppl receiving an Ag they don’t have MAY form Abs
o Serum of Rh- person doesn’t have anti-D unless had previous exposure to D Ag
o Unlike ABO Abs, the only way a-D is formed is through placental sensitization or transfusion

37
Q

• What happens to D”d” ppl?

A

o It’s a weak subgroup of D Ag
o Person appears to be Rh- (D-) w a-D typing sera, so need more testing
o a-D coats weak D cells w/o agglutination
o 2-3% of “Rh-“ are actually D”d”
o All seemingly Rh- pts should be screened for D”d” variant, aka “weak D”
o Screening for weak D = add a-Ig (indirect a-Ig test)

38
Q

• What is the charge on RBCs?

A

o Negative, they repel each other

39
Q

• How is Direct coombs (direct antiglobulin test, DAT) used to detect RBC Abs introduced into pt’s circulation?

A

o Used in cases of blood transfusion rxns and HDN
o RBCs coated w Abs in vivo, but no visible agglutination
o Pt RBCs mixed w AHG (anti-human globulin, a-Ig)
o If RBCs were actually coated by Abs in vivo, AHG will bind, giving visible agglutination
o If neg, nothing binds to RBCs, no agglutination

40
Q

• What are applications of DAT?

A

o Detects in vivo sensitization by Ab or complement

o AIAH, hemolytic transfusion rxn, HDN, Drug/RBC Abs, passive immunization

41
Q

• What is the Indirect Coombs test used for?

A

o For acquired blood group Abs
o Detect IgG againsts RBC Ags. Rxns occur invitro
o Abs result of prior exposure to foreign Ag
o Usu no agglutination in vivo
o Known Ags are added to pt blood to see if they have certain Abs
o AHG added to cause visible agglutination (if Abs present)

42
Q

• What is mechanisms of extravascular immune hemolysis?

A

o Abs bind RBCs (sensitized), complement binds
o M0s eat w or w/o C’
o M0s detect with Fcy

43
Q

• What are the features of blood group IgM Abs?

A
o	Cold reacting
o	Naturally occurring
o	Complete
o	Fix Complement to C’9
o	Intravascular hemolysis
44
Q

• What are features of IgG Abs?

A
o	Warm reacting
o	Immune
o	Incomplete
o	Opsonizing
o	Extravascular hemolysis
45
Q

• What is pre-transfusion testing? Crossmatch?

A

o ABO, Rh, Ab screen (AST or indirect coombs)
o C: D and R should be same ABO and Rh
o D RBCs mixed with Pt serum, look for agglutination or hemolysis
o If either occurs, they are incompatible
o If R has Abs, must determine before transfusion
o D is screened to make sure LACK Ags

46
Q

• What are the 5 most common blood groups assoc w transfusion rxns?

A
o	ABO
o	R(Rh+ 85%)
o	Kell (K k) (k 91%)
o	Duffy, Fya, Fyb, Fy (FyaFyb 46%)
o	Kidd, Jk, JKa, Jkb, Jkab (50%)
47
Q

• What are the universal donors and recipients?

A

o Donor: O negative, reserved for emergency situations w massive blood loss
o R- AB positive

48
Q

• What is the blood type distribution in the US?

A
o	O+: 37%
o	A+: 35
o	B+: 8
o	O-: 6
o	A-: 6
o	AB: 3
o	B-: 1
o	AB-: 0.6
49
Q

• Blood type? aA no rxn, aB + rxn, A cells + rxn, B cells no rxn:

50
Q

• Blood type? No rxn aA or aB, + rxn both A and B cells:

51
Q

• Blood type? + rxn both aA and aB, no rxn A or B cells:

52
Q

• How is Rh typing done?

A

o Can only add aD to pt blood to see if Rh+
o Ppl don’t naturally have aD Abs if they are Rh-
o So can only do forward typing
o Positive= agglutination

53
Q

• Rh type? Adding aD causes agglutination: