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MCC > Wk 2 Transfusions > Flashcards

Wk 2 Transfusions Flashcards

1
Q

What happens in the T cell zone?

A

T cells activated by MCH-expressing dendritic cells that present antigens to T cells, allowing them to expand , become effector T cells and migrate to inflamed tissues. Or they become
folicular helper T cells that help B cell activation

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2
Q

What happens in the B cell zone/follicle?

A

Naive B cells are exposed to antigens (virus, soluble protein, etc) -> some undergo minimal proliferation to form short-lived plasma cells that make IgM. Others internalize the antigens and then present peptides from those antigens on MHC Class II, allowing them to interact w/ T follicular cells, which provide co-stim signals and cytokines -> formation of germinal center (clonal expansion, affinity maturation, isotype switching, formation of long-lived plasma cells and memory B cells for rapid response to 2nd exposure)

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3
Q

What kind of plasma cells can be formed with single T cell exposure to antigens?

A

short and long-lived plasma cells
-short-lived IgM response, long-lived IgG response

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4
Q

What happens when a person is exposed to antigens a second time?

A

Memory B cells activated -> formation of more long-lived plasma cells, mostly IgG, boosting Ig titers in serum

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5
Q

What happens when a person has persistent exposure to non-protein antigens (no T cell help)?

A

Continuous induction of short-lived plasma cells, which can -> long-lived IgM response and some IgG

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6
Q

What are 3 mechanisms that can lead to long-lived antibody responses?

A
  1. Single exposure to antigens w/ T cell help -> long-lived IgG response
  2. 2nd exposure to antigens -> memory B cells -> long-lived plasma cells and boost in serum Ig titers (mostly IgG)
  3. Persistent exposure to non-protein antigens (no T cell help) -> continuous induction of short-lived plasma cells -> long-lived IgM response, some IgG
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7
Q

What allows the antibody isotypes to bind to antigen?

A

The antibody variable region (AKA antigen-binding region)

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8
Q

What does the antibody constant region (Fc) do?

A

Helps antibodies to mediate their functions
-each is distinct

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9
Q

What are 3 functions of IgM?

A
  1. neutralization
  2. complement activation
  3. earliest produced
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10
Q

What are the 5 functions of IgG?

A
  1. neutralization
  2. complement activation
  3. opsonization
  4. activate ADCC (antibody-dependent cell-mediated cytotoxicity)
  5. most prevalent in serum
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11
Q

What are 2 functions of IgA?

A
  1. neutralization
  2. found on mucosal surfaces?
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12
Q

What is 1 function of IgE?

A
  1. specialized in activation of mast cells/eosinophils
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13
Q

What is 1 function of IgD?

A
  1. not secreted, but expressed on surface of naive B cells
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14
Q

What is valency?

A

How many antigen-binding sites an antibody has
-all Abs are bivalent (2 Ag-binding sites)

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15
Q

What is the valency of IgG compared to IgM?

A

IgG - 4 binding sites
IgM - 10 binding sites

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16
Q

What is avidity?

A

Strength of binding b/w antibody and antigen
-increases for repeated antigen motifs

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17
Q

How does avidity change w/ binding site number?

A

Increased binding sites -> increased avidity of interaction

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18
Q

Which Abs have greater affinity, IgG or IgM?

A

IgG

But, IgM are pentamers, which increases their valency and therefore overall binding avidity

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19
Q

What are 4 antibody-mediated mechanisms of destruction and their associated antibodies?

A
  1. opsonization (IgG)
  2. Complement activation (IgG, IgM)
  3. Allergic reaction (IgE)
  4. ADCC (IgG)
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20
Q

What is opsonization?

A

IgG antibodies specific for pathogen coat the pathogen (opsonize it) which is then recognized by phagocytes expressing the Fc gamma receptors (specific for Fc region of IgG)
-> enhances phagocytosis -> destruction in phagolysosome

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21
Q

What is opsonization?

A

Mechanism used by antibodies or the complement system
- use opsonins to tag foreign pathogens for elimination by phagocytes. Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other. The pathogen can then avoid destruction and continue to replicate inside the human body.

Opsonins are used to overcome the repellent force between the negative cell walls and promote uptake of the pathogen by the macrophage.

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22
Q

What can activate complement and what is it?

A

IgG and IgM
-protein cascade activated by antibodies bound to surface of pathogens -> either:
1. formation of MAC -> lysis of the bacteria
2. opsonization after complement fragments, which -> either:
a. phagocytosis
b. if the complement fragments are soluble, can -> vasodilation/inflammation

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23
Q

What antibody-mediated pathologies can occur following transfusion?

A
  1. opsonization
  2. complement activation
  3. allergic reactions
  4. ADCC
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24
Q

What is the allergic reaction?

A

-Mediated by IgE
-can be induced by an allergen like pollen or by foreign blood components
-> production of IgE on first exposure
-2nd exposure -> IgE molecules coat surface of mast cell binding to mast cell surface receptors, Fc epsilon
-> release of granules from mast cell, including histamines and leukotrienes, which mediate allergic response

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25
Q

What is ADCC?

A

=antibody-dependent cell-mediated cytotoxicty
-mediated by NK cells

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26
Q

How is ADCC mediated?

A

Mostly by NK cells, which express lots of Fc gamma receptors that can bind to the Fc region of IgG antibodies
Process example: IgG specific for viral GP binds to NK cell Fc gamma receptors. NK cell secretes cytolytic granules (granzyme B, perforin) -> kill & induce apoptosis of virally infected cell
-can occur w/ RBCs after transfusion

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27
Q

What are 2 cytolytic granules secreted by NK cells?

A

granzyme B
perforin

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28
Q

Why do antibodies attack cells rather than pathogens?

A
  1. autoimmunity due to formation of autoantibodies
  2. many antibodies are cross-reactive to commensal (microbiota) antigens (ex. ABO blood group antigens)
  3. Exposure to non-self antigens
  4. Exposure to foreign (non-self) MHC
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29
Q

What are 3 examples of non-self antigen exposures which can cause antibodies to attacks cells rather than pathogens?

A
  1. pregnancy (Rh antigens)
  2. prior transfusion (reaction to non-self blood products or antigens)
  3. prior transplant (major and minor histocompatibility antigens)
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30
Q

What are 2 types of non-self MHC exposures that can cause antibodies to attack cells rather than pathogens?

A
  1. non-self MHC-specific IgG antibodies (alloantibodies)
  2. hyperacute rejection (occurs w/in min-hrs)
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31
Q

What are two categories of antibody-mediated destruction of RBCs?

A
  1. intravascular hemolysis
  2. extravascular hemolysis
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32
Q

What are 2 characteristics of intravascular hemolysis?

A
  1. acute
  2. faster rate of hemolysis
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33
Q

What are 2 types of antibodies involved in intravascular hemolysis?

A
  1. anti-ABO antibodies (IgM)
  2. Allo-antibodies (IgG)
34
Q

What are 3 forms of destruction in intravascular hemolysis?

A
  1. complement-mediated RBC lysis
  2. complement-induced neutrophil recruitment
  3. neutrophil degranulation, thrombosis, vascular destruction
35
Q

What are 2 characteristics of extravascular hemolysis?

A
  1. persistent
  2. slower rate of hemolysis
36
Q

What are 2 types of antibodies involved in extravascular hemolysis?

A

IgM and IgG

37
Q

What are 3 forms of destruction in extravascular hemolysis?

A
  1. complement-mediated opsonization
  2. IgG-mediated opsonization (macrophages, granulocytes)
  3. IgG-mediated ADCC (NK cells)
38
Q

Describe cross-reactivity to commensal organisms with regard to the ABO blood groups -> intravascular hemolysis

A
39
Q

What is an example of extravascular hemolysis with a transfusion reaction?

A

Erythroblastosis fetalis (=hemolytic disease of the newborn)
-induced by exposure or Rh- mother to Rh+ fetal blood during birth or fetal RBCs that move across the placenta -> Rh-specific IgG
-a subsequent pregnancy (usually) -> IgG antibodies cross the placenta to fetus and induce extravascular hemolytic anemia

40
Q

Can transfusions induce an allergic response and anaphylaxis?

A

Yes, mediated by IgE antibodies -> degranulation of mast cells -> release histamines and leukotrienes.
-> symptoms like hives, edema, allergic rhinitis, conjunctivitis, bronchoconstriction, wheezing, vomiting, diarrhea
-at high concentrations -> dysregulated vasodulation -> BP drop, poor organ perfusion, eventual organ failure (shock)

41
Q

What are 4 categories of blood for transfusions?

A
  1. PRBCs
  2. Plt
  3. FFP
  4. Cryo
42
Q

What percentages of whole blood is plasma and erythrocytes?

A
43
Q

What is the erythrocyte portion of blood called?

A

Hematocrit ~45%

44
Q

What are the 2 major techniques in transfusions?

A
  1. Collect whole blood, separate plasma and RBC
  2. separate buffy coat to use WBC
45
Q

How do we collect platelets?

A

Apheresis
-separates blood into components
-suck out platelets from plasma

46
Q

What are PRBCs?

A

Packed/concentrated RBCs then stored in fridge for max of 42 days

47
Q

What is the Hb cutoff for transfusion?

A

Hgb <7 g/dL, then transfusion

48
Q

Max day allowance to keep platelets?

A

7 days, stored at room temp

49
Q

When do we transfuse for severe thrombocytopenia?

A

Plt count < 10k/uL

50
Q

Max shelf-life for FFP

A

1 year stored in freezer -20 degrees C
Transfuse for clotting factor deficiency (INR> 2.0)

51
Q

What is AHF?

A

Anti-hemophylic factor
-a precipitate forms in cold temps
-used for tranfusion for fibrinogen deficiency (<150 mg/dL)

52
Q

Where is the ABO locus?

A

Chromosome 9
-get one copy from mom, one from dad
-A allele and B allele - determine which sugar will bind ABO transferaase
O is a nonfunctional allele w/ stop codon - don’t make any transferase so don’t decorate RBC sugars

53
Q

What is the H antigen?

A

ABO transferase recognizes it and transfers particular sugar based on which allele the H antigen is on
-person w/ O allele only has H antigen. It does not get translated into the A or B antigen

54
Q

Where is ABO expressed?

A

On erythroids as well as many other cell types - thyroid, intestines, ovary, colon

55
Q

What happens to the erythroid precursor nucleus?

A

Macrophage in BM ingests it after the precursor spits in out

56
Q

What is the perinuclear Hopf?

A

White on staining, golgi body where ABO transferase interacts and determines ABO surface sugars

57
Q

Gut bacteria ABO

A

Bacteria in microbiota have surface sugars that look like AB surface sugars - will not generate antibodies against those that align with your blood type
-CHO antigens
-mostly create IgM
FILL IN MORE

58
Q

What is on every bag of blood?

A
59
Q

What is the Rh D antigen?

A

Rhesus antigen
~80-85% are (+)

60
Q

Where is Rh D expressed?

A

Almost completely on RBCs

61
Q

How is blood typing done?

A

Forward type - what’s on cells
Reverse type - what’s in plasma
Agglutination = 4+
No agglutination = 0

62
Q

How is Rh D Type determined?

A

Forward type only b/c D is a protein on RBCs
-mix reagent w/ erythrocyte sample
-grade 0-4
-most people are 4+

63
Q

What is a transfusion reaction?

A

dverse event in the recipient of a blood product caused by the
transfusion

64
Q

What are the 3 major groupings of transfusion reactions?

A
  1. Timing - acute vs delayed
  2. Hemolysis: hemolytic and non-hemolytic - detected by color change, which is very sensitive
  3. Severity: mild/moderate (no vital sign change/loss of airway) vs severe (vital sign change/compromise of airway)
65
Q

What to do if suspect transfusion reaction

A
  1. stop transfusion
  2. contact blood bank
  3. bedside clerical check
  4. send post-transfusion specimen for:
    visible hemolysis check
    DAT
    ABO confirmation
66
Q

What is DAT?

A

=Direct antiglobulin test
-detects antibodies attached to new/transfused RBCs

67
Q

Bad transfusions reactions to know

A
  1. Acute hemolytic transfusion reaction - IgM activation of complement
  2. Anaphylactic Transfusion Reaction
  3. Septic Reaction
  4. Transfusion Associated Circulatory Overload (TACO)
  5. Transfusion-Related Acute Lung Injury (TRALI)
68
Q

Symptoms of acute hemolytic transfusion reaction

A

Symptoms
pain at infusion site chills/rigors
back pain
sense of impending doom
Signs
Fever (Δ1°C) the first symptom in 80% hypotension
hemoglobinuria
oligouric AKI
DIC

69
Q

Less bad transfusion reactions to know

A
  1. Delayed Hemolytic Transfusion Reaction (DHTR)
  2. Allergic TRXN
  3. Febrile Non-hemolytic Transfusion reaction (FNHTR)
70
Q

Signs/symptoms of DHTR

A

Symptoms
generally none
Signs
drop in H/H
new DAT+ with hemolysis ↑ bilirubin
↑LDH
↓haptoglobin spherocytes

71
Q

Signs/symptoms of allergic TRXN

A

Symptoms
rash (urticarial)
pruritus
flushing
wheezing
angioedema
Signs
Urticaria (hives)
generally none
but non-life threatening hypotension, low grade blood oxygen desat possible

W/in 4 hrs of transfusion
Tx: benadryl, H2 blockers, steroids

72
Q

Signs/symptoms of anaphylactic transfusion rxn

A

Symptoms
allergic (urticaria/angioedema) dyspnea

Signs
hypotension/shock loss of consciousness

73
Q

What is the work-up and tx for anaphylactic transfusion reaction?

A

Work-up
IgA (severe deficiency < 0.05 mg/dL, 1:500 have sIgA deficiency of which 1:1,200 develop IgG anti-IgA) Haptoglobin (1:1000 Chinese, Hp(del) allele homozygotes)
Treatment
IM epinephrine (0.5mg) q5 minutes
IV fluids
maintain airway
wash PRBCs, plts, avoid FFP if possible or supply FFP from IgA deficient donors

74
Q

Signs/symptoms of FNHTR

A

Symptoms
chills rigors
Signs
fever (Δ1°C)

75
Q

Mechanism of FNHTR

A

donor leukocytes release cytokines (TNF-α, IL-1β, sCD40L) in the bag during storage or in response to recipient antibodies -> activation of cytokine receptors in recipient induces pyrogenic response

76
Q

Pathophys of septic rxn

A

Pathophysiology (1:10,000 Plts / 1:180,000 PRBCs; FFP/Cryo extremely rare)
organism on donor skin/donor blood present in the unit -> proliferates during storage
-> transfusion results endotoxin mediated response (gram -ve) or TLR response (gram +ve) in recipient

77
Q

What is the most common source of septic transfusion reaction

A

Occurs in platelets, not RBCs b/c stored at room temp

78
Q

What are the 2 classic presentations in septic rxns?

A

Timing
2 classic presentations
Ø gram +ve cocci in Plts (most common): typically, 8 - 24 hours after transfusion
Ø gram –ve rods in PRBCs:
rapid onset within 15 minutes

79
Q

What happens in TACO

A

Pathophysiology (1% of all transfusions)
Increase in intravascular volume induces cardiac dilatation beyond Frank-Starling maximum volume overload -> decreased LV output -> pulmonary edema -> respiratory distress
-heart gets overloaded, backs up fluid -> resp distress (tightness, orthopnia)
-assoc w/ older age (>70) & infants, CHF, renal dz

80
Q

What happens in TRALI

A

Pathophysiology (1:100,000 of all transfusions)
passive transfer of donor HLA/HNA antibodies mediates neutrophil trapping in the pulmonary vasculature -> degranulation -> lung injury -> pulmonary edema
-occurs w/ donations from indiv who had previous transfusion or women who had multiple pregnancies

MCC (44 decks)

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