TM AIHA Flashcards

1
Q

Purpose of performing a warm autoadsorption (W.A.R.M.)

A
  • Removes warm autoantibodies
  • To ID any clinically significant alloantibodies in patient’s serum
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2
Q

T or F: autoadsorption using WARM/ ZZAP can be used for autoAb that have specificity to Kell, MNS and Duffy antigens

A

FALSE; WARM/ ZZAP destroys Kell, MNS, and Duffy antigens on patient’s cells
- autoAb that have specificity to these antigens will not be removed by treated cells

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3
Q

Why is the Donath-Landsteiner antibody called “biphasic?”

A

anti-P binds to RBCs at cold temperatures and causes complement-mediated hemolysis after warming to body temperature

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4
Q

Purpose of performing a cold autoadsorption

A
  • Removes cold autoantibodies
  • Cold autoAb (IgM) interfere with ABO Rh typing, Ab Scr, XM, and DATs
  • To ID any clinically significant alloantibodies in patient’s serum
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5
Q

Discuss PCH: antibody specificity, immunoglobulin class, and ability to bind complement

A

Paroxysmal (sudden onset) Cold Hemoglobinuria (Hb in urine through IVH)

  • Antibody specificity = anti-P
  • IgG that reacts in the cold!
  • binds complement right to C9 = IVH
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6
Q

What is another name for anti-P ?

A

What is another name for anti-P ?

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7
Q

Discuss PCH: typical clinical symptoms

A

intermittent hemolysis with exposure to cold = anemia, fatigue, etc.

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8
Q

Discuss PCH: lab findings

A
  • same as CHD but
  • NO SPHEROCYTOSIS
  • increased nBRCs
  • anemia
  • decreased Hb
  • decreased haptoglobin
  • increased LDH
  • increased bilirubin (slow)
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9
Q

Does PCH involve IVH or EVH ?

A

IVH; anti-P binds complement right to C9

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10
Q

Purpose of Donath-Landsteiner Test

A

to identify autoanti-P in individuals suspect of PCH

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11
Q

why can’t we use EDTA to test for PCH ? What sample type is used ?

A

always SERUM !

EDTA = false negative as it would get rid of Ca 2+ and Mg 2+ which complement needs

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12
Q

why do we add normal serum in the Donath-Landsteiner test?

A

To supply complement
- in vivo, patient may have used up all of the complement

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13
Q

Compare/ contrast drug-related autoantibodies vs warm autoantibodies

A

— both are active at body temp
— methyldopa HA and WAIHA are serologically similar
Drug-related autoAb:
- IVH
- Penicillin = IgG Ab = DAT IgG pos
- Quinidine = DAT C3 pos
- Methyldopa = IgG Ab = DAT IgG+C3 pos

WAIHA:
- EVH
- IgG
- DAT IgG pos +/- C3

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14
Q

How is drug-related AIHA different from delayed hemolytic transfusion reactions ?

A
  • Drug-related AIHA is an acute hemolytic reaction
  • Delayed hemolytic is usually due to secondary exposure of an RBC antigen
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15
Q

three main types of AIHA

A
  • WAIHA = 70%
    -cold autoimmune hemolytic anemia
    > cold hemagglutinin disease (CHD) = 16%
    > paroxysmal cold hemoglobinuria = 1-2%
  • drug-related hemolytic anemia = 12%
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16
Q

instances when DAT is positive

A
  • patient alloantibodies bind donor cells
  • maternal Abs bind fetal cells
  • passive antibodies (blood products/IVIg)
  • autoantibodies
  • antibodies/complement due to drugs
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17
Q

What does a DAT positive mean ?

A

In vivo binding of immunoglobulins, complement components, or both

18
Q

if a DAT is positive, what follow-up testing is needed ?

A
  • elution
  • Ab ID
19
Q

Describe warm autoimmune hemolytic anemia

A
  • often in elderly patients
  • primary idiopathic
  • secondary
    > white cell malignancies (CLL, lymphoma, MDS)
    > autoimmune diseases (Lupus, rheumatoid arthritis)
    > viral infections (children or adults)
20
Q

Hematology results of WAIHA (CBC/ peripheral smear/ serological)

A

CBC:
- hemoglobin and hematocrit decreased

Peripheral smear:
- nRBC
- polychromasia
- spherocytosis
- HJ bodies (seen in asplenic individuals)

Serological indicators of EVH:
- increased bilirubin
- increase LDH
- deceased haptoglobin
- high RDW

21
Q

T or F: autoadsorptions cannot be performed if the patient has been transfused in the past three months

A

TRUE; alloantibodies can be adsorbed/removed by donor cells

22
Q

cold autoantibodies general characteristics

A
  • IgM
  • thermal range = 4°C (<15°C; sometimes RT; up to 32°C)
  • binds complement
23
Q

Compare harmless vs pathological autoanti-I characteristics

A

Harmless:
- titre <64
- max. thermal range = RT
- rxn not readily enhanced by albumin
- polyclonal

Pathological:
- titre >1000
- max. thermal range = 30°C
- rxn enhanced by albumin
- monoclonal (one B cell going out of control => making this autoAb)

24
Q

CHD physiological and hematological symptoms

A

Physiological:
- tingling upon cold exposure = auto anti-I attaches at 30°C = decreased blood flow = lack of O2
- when warmed up = IgM pops off BUT complement stays and works more efficiently

Hematological:
- NO SPHEROCYTOSIS
- increased nBRCs
- anemia

25
Q

Describe a CHD investigation

A
  1. ID autoAb
    - panel
    - AC = pos (at RT)
    = cord cells = neg
    - titration = >1000 titre
  2. DAT
    - polyspecific = pos
    - IgG = neg
    - C3 = pos
26
Q

Describe a cold agglutinin titration

A
  • pre-warm plasma
  • serial dilution
  • test with adult O cells, patient cells, and cord cells at various temps (37°C, RT, 4°C)
  • determine titre at 4°C
  • use strength of adult vs cord cells to determine identity (anti-I vs anti-i)
27
Q

Often a cold agglutinin screen is performed before doing a ______. if the patient plasma does not react with O adult cells at 4 degrees when diluted at _____, there is no need for _______ _______

A

Often a cold agglutinin screen is performed before doing a TITRATION. if the patient plasma does not react with O adult cells at 4 degrees when diluted at 1/40 (harmless), there is no need for SERIAL DILUTIONS.

28
Q

How to find compatible blood after CHD investigation

A
  • prewarm XM samples
  • use autoadsorbed patient plasma
  • ensure monospecific anti-IgG used (don’t want to pick up complement binding)
  • only EDTA
  • transfuse using blood warmer if necessary
29
Q

Characteristics of Drug-induced HA

A
  • ONLY monospecific DAT IgG = pos
  • rarely leads to hemolysis
  • more often seen as interference
30
Q

Describe methyldopa HA

A
  • positive DAT
    anemia
    autoAb produced
    serologically indistinguishable from WAIHA
    > panreacting
    > specificity
    substance sensitizing cells
    treatment = take them off drug
31
Q

Cause of methyldopa HA

A
  • due to methyldopa; antihypertensive drug used in pregnancy
  • autoantibody produced is related to dose and time
32
Q

Discuss methyldopa HA: clinical symptoms and lab results

A

Symptoms: anemia

Lab results:
- PANREACTING; serologically indistinguishable from WAIHA
- DAT = pos
- Increased LDH, bilirubin, RDW
- Decreased haptoglobin, hemoglobin

33
Q

Describe how Drug-adsorption (penicillin) affects testing

A
  • penicillin binds to RBCs
  • drug/RBC complex stimulates immune response
  • IgG antibodies attaches to penicillin on RBCs = mono-IgG DAT = pos
34
Q

What causes Drug-adsorption on RBCs ?

A

massive IV doses of penicillin

35
Q

Lab results for drug adsorption

A
  • DAT = pos; due to IgG; neg for C3d
  • AbScr = negative bc screen cells do not have penicillin
  • Eluate = neg
36
Q

What is referred to as the “innocent bystander” reaction ?

A
  • when patient makes antibodies to quinidine (a drug)
  • immune/ drug complex attaches to RBCs = complement activation = IVH
37
Q

Describe how quinidine causes AIHA

A
  • “immune complex”
  • patient makes drug Ab (IgM)
  • Ab-Ag complex binds; RBC activates complement
  • RBC destroyed by complement
  • IVH
38
Q

Immune complex lab results

A
  • DAT = pos (for complement only; IgM)
  • Ab Scr = neg
  • Eluate = NOT done; even if we did = still neg
39
Q

Cases when complement is only positive for DAT

A
  • Cold AIHA
  • Drug-induced (penicillin)
  • Immune complex (quinidine)
40
Q

Cause of membrane modification AIHA

A
  • Cephalosporins ADSORB to RBC
  • Modifies RBC membranes (more sticky)
  • NON-SPECIFIC BINDING of complement, IgG, IgM, IgA
41
Q

Lab results for membrane modification AIHA (cephalosporins)

A

DAT = pos (IgG and complement)
Ab Scr = neg
Eluate = neg

  • bc drug Ab are not represented on screen cells