10. AIHA Flashcards

1
Q

the first clue to an autoAb

A

DAT+ with plasma Abs reactive with ALL cells tested

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

important to obtain patient’s … (3) in autoAb investigation

A
  1. diagnosis
  2. transfusion hx
  3. medications
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

clinical s/s that point to AIHA (6)

A
  1. Normocytic or macrocytic anemia
  2. Reticulocytosis
  3. ↓ haptoglobin
  4. ↑ lactate dehydrogenase
  5. ↑ bilirubin
  6. DAT+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

cold AIHA often associated with… (4)

A
  • Pneumonia (Mycoplasma pneumoniae)
  • Anemia
  • Lymphoma
  • Viral infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

DAT+ specificity

trxn

A

IgG with specific Ab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

DAT+ specificity

WAIHA

A

IgG and/or C3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

DAT+ specificity

CAIHA

A

C3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

DAT+ specificity

drug interaction

A

IgG
serum may be nonreactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

DAT+ specificity

Clot tube stored at 4°

A

C3
no serum Ab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

DAT+ specificity

HDFN

A

IgG
ABO or alloAb from mom

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

CAIHA phase of rxn

A

IS
strong reactions may carry over to AHG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

may cause an ABO discrepancy

A

cold autoAb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

IgM found in normal healthy individuals against I or H antigens

A

benign cold auto Ab

anti-I more common

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

benign cold auto titers

A

<64 at 4°

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

benign cold max temp

A

RT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

benigns autos are NR with…

A

I= (cord and adult i) cells at RT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

anti-H most common in —– type people

A

A1 type

least amount of H antigen present

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

occasional clinical manifestation of high-titer anti-HI benign cold autos

A

group O cells will have decreased red cell survival after transfusion

O cells have the most H antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

3 pathologic cold autoAb conditions

A
  • CAIHA
  • Cold Agglutinin Syndrome (CAS)
  • Paroxysmal Cold Hemoglobinuria (PCH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

characterized by agglutination, at room temp, of red cells in an EDTA specimen

A

CAS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

CAS etiology

A

underlying disorder
infection (eg, Mycoplasma pneumoniae or Epstein-Barr virus)
autoimmune disorder
lymphoid malignancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

CAS type of anemia

A

extravascular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

investigation of CAS is difficult because agglutinins are active at refrigerator temp

how do we cirumvent?

A

The blood tubes need to be prewarmed and samples must be transported at 37C.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

CAS resolution

A

usually self-limiting when underlying condition is resolved

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

—- anti-H is CS (Bombay)

A

allo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

CAS
DAT
eluate
titer
specificity

A

C3 only
eluate NR
>1000 at 4°
anti-I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

treatment for severe CAS cases targets…

A

C1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

PCH population

A

children
acute transient condition secondary to infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

biphasic hemolysin
definition

A

PCH IgG
binding to RBCs occurs at low temps, but hemolysis does not occur until C3-coated cells are warmed to 37°

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

affects the extremities

A

PCH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

diagnostic test for PCH

A

Donath-Landsteiner test

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

PCH
DAT
eluate
IAT
specificity

A

DAT+ with C3 only
eluate NR
IAT=
anti-P

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

PCH sx

A

anemia, frequently marked
hemoglobinurea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

resolve ABO discrepancy once cold autoAb is IDd

A

prewarm technique

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

steps of prewarm technique

A
  1. incubate plasma and reagent cells at 37° for 15 min
  2. two drops plasma added to reagent cells
  3. incubate for 30 mins w/o potentiator
  4. if AHG, warm saline must be used for wash
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

methods to eliminate cold autoAb after ID

A

sulfhydryl reagents (DTT and 2-ME) denature IgM pentamer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

rarely used to resolve cold autoAb

A

adsorption at 4°

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

transfusions for benign cold autoAb pts

A

XM compatible by prewarm
and/or
use of IgG AHG reagent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

transfusions for CAS pts

A

transfusion should not be withheld due to serologic incompatibility

transfuse smallest volume possible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

transfusions for PCH pts

A

randomly selected units of blood
if pt does not response adequately, use P= units

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

WAIHA lab findings (6)

A
  • ↓ H&H
  • ↑ MCV
  • ↓ haptoglobin
  • ↑ bilirubin
  • ↑LDH
  • reticulocytes, spherocytes, nRBCs, fragmented RBCs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

polychromasia

A

symptom of WAIHA
bluish tint to RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

WAIHA etiology

A

secondary to disease state (Hodgkins; CLL; SLE; viral infection; immune deficiencies; GI autoimmune disease)
idiopathic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

hallmark of WAIHA

A

DAT+
mostly IgG and C3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

WAIHA with —- + are more hemolytic and harder to tx

A

C3d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

WAIHA pts may have a +/= ——, because…

A

ABS
at low titer, all autoAb is adsorbed
DAT+ before ABS+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

warm autoAb is detectable in plasma after…

A

titer rises and it spills into plasma from saturated RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

panagglutinin in AHG

A

warm autoAb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

main problem warm autoAb poses to BB

A

panagglutinins “cover” underlying alloAb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

overview of BB investiation into warm autoAb (8)

A
  • pt hx check (dx may establish link between serological findings and primary disease)
  • TS
  • ABID
  • DAT
  • elution
  • techniques to remove Ab
  • Ag type
  • XM
51
Q

ABO grouping usually not affected by…

A

warm autoAb

if ABO is affected, it’s with VERY strong DAT+

52
Q

cannot interpret ABO if…

A

autocontrol is +

53
Q

DAT+ may cause false pos Rh results when…

A

anti-D reagent has a high protein content
contains molecular additives
“slide and modified tube anti-D”

most BBs use a low protein anti-D

54
Q

using a slide and modified tube anti-D requires…

A

Rh control with every test

contains all additives, but no anti-D

55
Q

most BBs use ——— anti-D for Rh typing

A

monoclonal blend

IgG and IgM, from multiple clones for partial Ds

56
Q

monoclonal blend anti-D only requires control if…

A

pt is AB+

control is by manufacturer, or 6% albumin

57
Q

weak-D testing is invalid when DAT+ because…

A

weak-D control is +

58
Q

why must specimens for DAT be collected in EDTA tubes?

A

EDTA binds Ca2+
C3 requires calcium
C3 would otherwise bind normal cold agglutinins in the fridge

59
Q

2 causes of rare AIHA with DAT=

A
  • low levels of IgG
  • IgM or IgA cause
60
Q

next step after DAT+ with IgG+

A

eluate

61
Q

eluates should always be performed if…

A

pt transfused in last 3 weeks

alloAb may ONLY be present on transfused cells in first 3 weeks

62
Q

eluate pattern with WAIHA, DIIHA, and HTR

A

WAIHA —panagglutination
DIIHA —strong DAT, but no ABID rxns
HTR —specific alloantibody pattern

63
Q

if a warm autoAb has a specificity at ABID stage…

A

run a selected cell panel for autoAb

64
Q

How do we know that the Ab identified at ABID is an allo or auto Ab?

A

Ag typing
If pt =, it’s an allo
If pt +, it’s an auto

65
Q

cannot Ag type on patients…

A

transfused in last 3 months

66
Q

blood for patients with specific autoAbs

A

evaluated for need for Ag= blood on a case by case basis

67
Q

technique of choice if patient has panagglutinin, assuming…

A

autoadsorption
not transfused w/i last 3 months

68
Q

purpose of autoadsorption

A

remove autoAb to reveal underlying alloAb

69
Q

autoadsorption procedure

A
  1. mix equal volumes cells and plasma, incubate at 37° (may use enzymes, PEG, ZZAP)
  2. mix autoadsorbed plasma with additional aliquots of pt cells until all autoAb removed
  3. test adsorped plasma for alloAb

usually takes the same number of repititions as the rxn strength

70
Q

ficin and papain are good for autoadsorption when…

A

strength is W+ or 1+

71
Q

ZZAP

A

DTT + papain
elutes IgG from cells, opening up more space for adsorption

72
Q

volume PEG in autoadsorption

A

same as volume of patient plasma

73
Q

drawbacks of autoadsorption (4)

A
  • cannot be performed on patient transfused in last 3 months
  • residual saline from RBC washes dilutes weak Ab
  • ZZAP destroys Kell (anti-K not removed from plasma)
  • requires large volume of RBCs, and patients are usually anemic
74
Q

indications for allogeneic adsorption

A
  • pt transfused in last 3 months
  • pt cells in short supply
75
Q

principle of allogeneic adsorption

A

donor or reagent RBCs of known phenotypes are used to remove autoantibody and selective alloantibodies

76
Q

allogeneic adsorption procedure

A
  1. select 3 donor cells of known phenotypes
  2. wash them
  3. mix with patient plasma in equal volumes, adsorb at 37°
  4. each adsorped plasma is added to more aliquots of cells until all autoAb reactivity is gone
  5. underlying alloAb remains in at least one of the plasmas

use same enhancement techniques as with autoadsorption

77
Q

antibody against —— are difficult to find using allogeneic adsorption

A

high freqs
ex) anti-U

78
Q

drawbacks of allogeneic adsorption (3)

A
  • hard to find high freqs
  • saline from washings dilutes weak alloAb
  • differential cells difficult to find

cells may be available from reference lab

79
Q

problem with Ag typing in patients with warm autoAb

A

IgG coating cells may interfere with Ag typing

80
Q

false positives occur during Ag typing when…

resolution

A

pt has DAT+

elution to remove IgG from cells prior to Ag type
delay Ag type until time when pt becomes DAT=

81
Q

cannot use —— to render cells DAT= for Ag typing

appropriate methods (3)

A

acid elution—denatures RBC antigens
- EGA
- gentle heat elution
- chloroquine disphosphate treatment

82
Q

how to remove IgM (cold auto) from cells for Ag typing

A

warm saline washes
sulfhydryl reagents

83
Q

WAIHA general tx

A
  • corticosteroids (prednisone)
  • immunosuppressive drugs
  • splenectomy (rare)
84
Q

transfusions should be avoided for ——- because… (4)

A

WAIHA patients
- compatible blood usually not available
- transfused blood will not survive
- transfusions stimulate alloAb production
- transfusions may actaully increase anemia over time (↓ signal for erythropoiesis)

85
Q

transfusion criteria for WAIHA pts (4)

A
  • Ag= for corresponding alloAb
  • compatible blood if autoAb has a simple specificity (ie. anti-e)
  • units compatible with adsorbed plasma (incompatible with neat plasma)
  • phenotypically matched RBCs (very hard to find)
86
Q

mixed type AIHA
prevalence

A

IgM and IgG present
7-10% cases

87
Q

severe hemolysis, very low H&H, responds well to steroid tx

A

mixed type AIHA

88
Q

ABS/panel reactive at IS and AHG

A

mixed type AIHA

89
Q

mixed type AIHA associated with…

A

SLE
CLL

90
Q

DIIHA

A

hemolytic anemia occuring when drugs induce formation of Ab against drug or RBC antigens

91
Q

tx for DIIHA

A

d/c drug

92
Q

3 categories of DIIHA

A
  • WAIHA-like DIIHA —Ab to RBC membrane components
  • Drug adsorption DIIHA —Ab to drug bound to RBC
  • Immune complex DIIHA —Ab to part drug and part RBC membrane
93
Q

drugs act as ——, inducing an immune response by binding to RBC

A

haptens

94
Q

HTN drug for pregnant women causing DIIHA

A

methyldopa

95
Q

drug adsorption DIIHA causes —– hemolysis

A

extravascular

96
Q

drug adsorption
DAT
ABS
eluate

A

DAT strongly + due to IgG, rarely C3
ABS=
eluate NR

requires RBCs to react

97
Q

drug adsorption DIIHA lab confirmation procedure

A
  1. incubate O cells with drug
  2. wash
  3. test pt plasma or eluate with drug-coated RBCs
  4. observe for agglutintion or hemolysis

rarely done; usually only in reference lab

98
Q

immune complex DIIHA causes —— hemolysis

A

severe intravascular

99
Q

DIIHA with hemoglobinuria/emia

A

immune complex

100
Q

immune complex
DAT
eluate
ABS

A

DAT+ due to C3, rarely to IgG
eluate NR
ABS=

reactivity only in presence of drug

101
Q

immune complex DIIHA lab confirmation procedure

A
  1. mix pt serum + normal serum + drug
  2. mix control — pt serum + normal serum + saline
  3. test O RBCs with mixtures
  4. observe for agglutination
102
Q

purpose of normal plasma included in mixtures for immune complex DIIHA workup

A

provides complement

103
Q

drug that demonstrates multiple DIIHA mechanisms

A

cefotetan

104
Q

drug-dependent

A

DIIHA where drug must be present in test system to detect

105
Q

nonimmunological protein adsorption

A

drugs may cause DAT+ by altering RBC membrane so plasma proteins bind nonspecifically

all proteins —Ig, complement, albumins etc

106
Q

multiple myeloma drug that can cause DAT+
why?
how to resolve?

A

darzalex (daratumumab)
anti-CD38, which is present on RBCs (but more so on myeloma cells)

DTT destroys CD38 on RBCs

107
Q

you probably have autoAb if… (3)

A
  • DAT+
  • autocontrol +
  • rxns with all cells showing similar strength
108
Q

you probably have alloAb if… (4)

A
  • DAT +/=
  • autocontrol +/= (recent transfusion)
  • prior immunization
  • variation in rxn strength
109
Q

you may have multiple specificities if… (3)

A
  • all cells reactive
  • variation in rxn strength
  • variation in phase
110
Q

you may have a trxn sample if… (3)

A
  • DAT+ mf
  • eluate exhibits Ab with specificity
  • previous specimen with ABS=
111
Q

frequencies of WAIHA, CAS, and PCH

A

70-80%
18%
<2%

112
Q

peak age for WAIHA, CAS, PCH, and benign

A

60s
60s
children
adults

113
Q

primary Ig class for WAIHA, CAS, PCH, and benign

A

IgG
IgM
IgG
IgM

114
Q

Ab specificities for WAIHA, CAS, PCH, and benign

A

Rh, Kell
Ii
P1
Ii, H

115
Q

disease associations for WAIHA, CAS, PCH, and benign

A

malignancy, autoimmune, HIV
epstein-barr, M. pneumo, lymphoproliferative
viral infection, syphilis
none

116
Q

tx for WAIHA, CAS, PCH, and benign

A

block spleen, steroids, drugs, surgery
tx sx
supportive
none

117
Q

drug-dependent DIIHA

A

immune complex
drug-adsorption

118
Q

drug-independent DIIHA

A

autoantibody formation

119
Q

drugs causing immune complex DIIHA

A

piperacillin
ceftriaxone

120
Q

drugs causing drug-adsorption DIIHA

A

penicillin
1st gen ceph (Keflex, Keflin)

121
Q

drug causing nonimmune protein adsorption

A

Keflin

122
Q

drugs causing autoAb formation

A

methyldopa
2nd and 3rd gen ceph
fludarabine

123
Q

requirements for 3 cells used to allogeneically adsorb

A
  • at least one must be negative for all CS Ags, so the alloAb is left in at least one plasma
  • R1R1, R2R2, and rr