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MLSCI 370 > AIHA > Flashcards

AIHA Flashcards

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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

Describe how to perform a warm autoadsorption

A
  1. AutoAb removed from patients cells using W.A.R.M. (warm autoantibody removal medium) or ZZAP = DAT neg
  2. Wash and incubate DAT neg cells at 37ºC to allow warm autoAb to bind
    • alloAb will remain in plasma
  3. Sample is spun = supernatant is removed and step 2 is repeated “X” times depending on titre of autoAb
  4. Autoadsorbed (clean) plasma can now be tested against screen & panel cells to ID alloAb
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3
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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4
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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5
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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6
Q

Describe how to perform a cold autoadsorption

A
  1. AutoAb are removed from patient cells = DAT neg
    a). prewarm and wash 3-6 times w/ warm saline
    b). ZZAP removes IgM autoAb
  2. Incubate DAT neg cells at 4º C with patient plasma
  3. Sample is spun = supernatant is removed and step 2 is repeated “X” times depending on titre of autoAb
  4. Autoadsorbed (clean) plasma can now be tested against screen & panel cells to ID alloAb
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7
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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8
Q

What is another name for anti-P ?

A

Donath-Landsteiner Antibody

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9
Q

PCH etiology

A

often 2ry to MMRV; often seen in children

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10
Q

Discuss PCH: typical clinical symptoms

A

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

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11
Q

Discuss PCH: lab findings

A
  • same as CHD =
  • NO SPHEROCYTOSIS
  • increased nBRCs
  • anemia
  • decreased Hb
  • decreased haptoglobin
  • increased LDH
  • increased bilirubin (slow)
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12
Q

Does PCH involve IVH or EVH ?

A

IVH; anti-P binds complement right to C9

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13
Q

Describe how to do the Donath-Landsteiner Test and its purpose

A

Purpose: to identify autoanti-P in PCH

  • keep collected blood warm, and allow to clot (37C)
  • incubate tests with P(+) RBCs at 4C:
    a). patient serum = POS hemolysis
    b). normal serum = NEG
  • warm to 37C
  • spin and read for hemolysis

hemolysis = anti-P present
no hemolysis = anti-P not present

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14
Q

why can’t we use EDTA to test for PCH ?

A

always SERUM !

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

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15
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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16
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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17
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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18
Q

Discuss drug-related AIHA: follow-up investigation

A

WIP

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19
Q

Causes of autoimmunity

A
  • malfunctioning T cells
  • cross-reactivity
  • molecular mimicry
  • alteration of self-antigens
  • secondary to disease
  • inherited tendency
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20
Q

Primary idiopathic autoimmunity

A
  • Ab against own RBCs
  • unknown cause
  • 60 y/o +
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21
Q

autoimmunity secondary to disease

A
  • viral or bacteriogenic disease
  • often 2° to CLL
  • WBC problems (ex: B cell lymphoma = can make Ab that’s not quite right, if malignant = makes a whole lot)
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22
Q

three main types of AIHA

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A
  • WAIHA = 70%
  • cold autoimmune hemolytic anemia
    > cold hemagglutinin disease (CHD) = 16%
    > paroxysmal cold hemoglobinuria = 1-2%
  • drug-related hemolytic anemia = 12%
23
Q

instances when DAT is positive

Study These Flashcards
A
  • patient alloantibodies bind donor cells
  • maternal Abs bind fetal cells
  • passive antibodies (blood products/IVIg)
  • autoantibodies
  • antibodies/complement due to drugs
24
Q

What does a DAT positive mean ?

Study These Flashcards
A

In vivo binding of immunoglobulins, complement components, or both

25
if a DAT is positive, what follow-up testing is needed ?
elution > Ab ID
26
Describe warm autoimmune hemolytic anemia
- often in elderly patients - primary idiopathic - secondary > white cell malignancies (CLL, lymphoma, MDS) > autoimmune diseases (Lupus, rheumatoid arthritis) > viral infections (children or adults)
27
clinical symptoms of WAIHA
- pallor - weakness - shortness of breath - dizziness - jaundice (EVH) - fever - splenomegaly
28
Hematology results of WAIHA (CBC/ peripheral smear/ serological)
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
29
T or F: autoadsorptions cannot be performed if the patient has been transfused in the past three months
TRUE; alloantibodies can be adsorbed/removed by donor cells
30
cold autoantibodies general characteristics
- IgM - thermal range = 4°C (<15C; sometimes RT; up to 32C) - binds complement
31
Compare harmless vs pathological autoanti-I characteristics
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)
32
Causes of cold AIHA
1. Primary idiopathic = common in older people 2. Secondary to disease: > Mycoplasma pneumonia = anti-I > Erythromycin use > EBV = anti-i
33
CHD physiological and hematological symptoms
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
34
treatment for CHD and PCH
- avoid the cold - wait for secondary infection to clear
35
Define acrocyanosis
bluish discoloration of the extremities due to decreased amount of oxygen delivered
36
Describe a CHD investigation
1. ID autoAb - panel - AC = pos (at RT) = cord cells = neg - titration = >1000 titre 1. DAT - polyspecific = pos - IgG = neg - C3 = pos
37
Describe a cold agglutinin titration
- 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)
38
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 _______ _______
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.
39
How to find compatible blood after CHD investigation
- 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
40
Characteristics of Drug-induced HA
- ONLY monospecific DAT IgG = pos - rarely leads to hemolysis - more often seen as interference
41
When are blood products used as drugs?
- RhIg given to Rh pos patients with ITP - IVIg therapy > monitor Hb > drop in Hb (<100g/L); perform DAT, Bili, LD ITP = immune thrombocytopenia; platelet clotting disorder
42
Describe methyldopa HA
- positive DAT anemia autoAb produced serologically indistinguishable from WAIHA > panreacting > specificity substance sensitizing cells treatment = take them off drug
43
Cause of methyldopa HA
- due to methyldopa; antihypertensive drug used in pregnancy - autoantibody produced is related to dose and time
44
Discuss methyldopa HA: clinical symptoms and lab results
Symptoms: anemia Lab results: - PANREACTING; serologically indistinguishable from WAIHA - DAT = pos - Increased LDH, bilirubin, RDW - Decreased haptoglobin, hemoglobin
45
Treatment for methyldopa HA
take them off drug
46
Describe how Drug-adsorption (penicillin) affects testing
- penicillin binds to RBCs - drug/RBC complex stimulates immune response - IgG antibodies attaches to penicillin on RBCs = mono-IgG DAT = pos
47
What causes Drug-adsorption on RBCs ?
- massive IV doses of penicillin
48
Lab results for drug adsorption
- DAT = pos; due to IgG; neg for C3d - AbScr = negative bc screen cells do not have penicillin - Eluate = neg
49
What is referred to as the "innocent bystander" reaction ?
- when patient makes antibodies to quinidine (a drug) - immune/ drug complex attaches to RBCs = complement activation = IVH
50
Describe how quinidine causes AIHA
- "immune complex" - patient makes drug Ab (IgM) - Ab-Ag complex binds; RBC activates complement - RBC destroyed by complement - IVH
51
Immune complex lab results
DAT = pos (for complement only; IgM) Ab Scr = neg Eluate = NOT done; even if we did = still neg
52
Cases when complement is only positive for DAT
- Cold AIHA - Drug-induced (penicillin) - Immune complex (quinidine)
53
Cause of membrane modification AIHA
- Cephalosporins ADSORB to RBC - Modifies RBC membranes (more sticky) - NON-SPECIFIC BINDING of complement, IgG, IgM, IgA
54
Lab results for membrane modification AIHA (cephalosporins)
DAT = pos (IgG and complement) Ab Scr = neg Eluate = neg - bc drug Ab are not represented on screen cells

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