BB - Immune RBC Destruction Flashcards

1
Q

Autoantibodies give positive test results for these 2 tests…

A

DAT

Auto control

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2
Q

What happens to the following levels during hemolysis: retic count, unconjugated bilirubin, LDH, haptoglobin

A

Increase: retic count, bilirubin

Decrease: LDH, haptoglobin

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3
Q

Define compensated vs uncompensated anemia

A

Compensated = bone marrow keeps up with RBC destruction

  • increase retic count
  • mild decrease in hemoglobin/hematocrit

Uncompensated = bone marrow cannot keep up with RBC destruction

  • macrocytosis and spherocytes
  • retic >3%
  • increase bilirubin and LDH
  • marked decrease in haptoglobin
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4
Q

AIHA - 3 types of antibodies

A

Cold reactive

Warm reactive

Drug induced

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5
Q

All AIHA antibodies are DAT ___. Requires this test…

A

Positive

Elution

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6
Q

Cold reactive autoantibodies - what class of immunoglobulins? Can they trigger complement?

A

IgM

Yes - in-vitro
-use polyspecific AHG to detect

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7
Q

When cold autoantibodies are present, what can we do to eliminate or minimize their detection (3)?

A

Use monoclonal reagents

  • IgM activate complement in vitro
  • monoclonal AHG detects IgG only

Wash cells at 37C

Cold adsorption

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8
Q

Although cold autoantibodies are not clinically significant, they can interfere with the detection and identification of…

A

Alloantibodies

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9
Q

Cold autoantibodies can cause false ___ reactions with ABO reagents

A

Positive

  • ABO antibodies also IgM
  • causes spontaneous agglutination
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10
Q

Although pre-warming reagents can help disperse the cold agglutinins, pre-warming also cause…

A

Missing clinically significant antibodies after pre-warming

-IgG reagent not effective when pre-warmed

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11
Q

Most cold autoantibodies have specificity to…

A

anti-I or anti-i

-i in babies, converts to I at 2 years of age

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12
Q

Anti-H cold autos react strongest against these ABO blood types. React weakest against these ABO blood types

A

O and A2 = most H antigens

A1 and A1B = fewest H antigens

-anti-H more common as allos than autos

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13
Q

Idiopathic cold AIHA is also called… Antibody specificity is…

A

Cold hemagglutinin disease

  • don’t know why it happens
  • in older people

Anti-I
-anti-i less common

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14
Q

Common feature of cold hemagglutinin disease is ___ of hands, feet, ears and nose and ___ in the urine upon exposure to the cold

A

Acrocyanosis

Hemoglobinuria

-caused by hemolytic anemia

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15
Q

PCH commonly occurs in… Cause by this specific antibody in this class…

A

Children with viral infection

Biphasic anti-P IgG

  • most other cold autos are anti-I
  • Donath-Landsteiner test to detect IgG
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16
Q

PCH - when does hemoglobinuria occur?

A

Upon exposure to cold

  • intravascular hemolysis (IgG)
  • hemoglobinuria
17
Q

PCH vs PNH - underlying cause of each?

A

PCH = IgG antibody

PNH = protein

18
Q

WAIHA - what class of antibodies?

A

IgG (1 and 3 subclasses)

  • IgG3 most destructive
  • severe anemia, acute hemolysis
  • similar to Rh system; broad “Rh-like” specificity
19
Q

DAT positive indicates an ___antibody whereas DAT negative indicates an ___antibody

A

Autoantibody

Alloantibody

20
Q

WAIHA usually affects this antigen system… but not this…

A

Rh

  • Rh typing a problem
  • Rh antibodies are IgGs, same with WAIHA

ABO

21
Q

When we have both warm autoantibodies and alloantibodies, how can we detect the alloantibodies?

A

Do a warm autoadsorption (aka autologous autoadsorption)

  • incubate patient’s serum and RBCs at 37C
  • warm autos bind to antigens, allos remain in the serum
  • use ZZAP to improve auto uptake
22
Q

Warm vs cold AIHA - Ig class? Complement activation?

A

Warm = IgG, may bind complement

Cold = IgM, binds complement

23
Q

Warm vs cold AIHA - site of hemolysis

A

Warm = extravascular, no cell lysis

Cold = extravascular and intravascular, cell lysis

24
Q

When a hemolytic patient is DAT positive and no other findings are presented, we should look at (2)…

A

Patient history

Drug history

25
Q

4 mechanisms for drug-induced hemolysis

A

Immune complex

Drug adsorption

Membrane modification

Autoantibody formation

26
Q

How do drug-induced immune complexes form and how do they cause hemolysis?

A
  • drugs combine with plasma proteins to form immunogens
  • IgM or IgG recognition to immunogen, forming drug-antibody complex (antigen-antibody)
  • complement cascade activate intravascular hemolysis
27
Q

Drug adsorption mechanism

A

Drugs bind to proteins, such as proteins on RBC membrane

28
Q

New 2nd and 3rd gen drugs from this class cause DAT positive reactions and severe hemolytic anemia. It is this category of drug-induced hemolytic anemia

A

Cephalosporin

Drug adsorption

29
Q

Drug induced membrane modification results in the nonspecific (non-immunologic) uptake of (2). The eluate test result is…

A

Antibodies and complement

  • not via antigen-antibody reactions
  • non-immunologic protein adsorption

Negative

30
Q

How do drugs like alpha-methyldopa (Aldomet), L-dopa, mefenamic acid, procainamide and diclofenac cause hemolysis? The eluate test result is…

A

Induce production of autoantibodies that recognize RBC antigens
-indistinguishable from WAIHA

Positive

31
Q

All 4 categories of drug-induced hemolytic anemias result in a positive ___ test

A

DAT

32
Q

Is the eluate positive or negative for the 4 categories of drug-induced hemolytic anemias?

A

Negative = immune complex, drug adsorption, membrane modification

Positive = methyldopa-induced (autoantibodies)

33
Q

If we are having issues with cold autoantibodies interfering at the AHG phase, we can use this reagent…

A

Monospecific AHG - detects IgG only

-polyspecific binds to both IgG and C3, the latter caused by cold agglutinins

34
Q

Mycoplasma pneumoniae and infectious mononucleosis can cause this secondary illness

A

Cold hemagglutinin disease

-patient should live in warmer climate

35
Q

Should a recently transfused patient’s sample be tested via warm autoadsorption to remove autoantibodies?

A

No, use allogeneic cells instead

-removes autoantibodies while leaving alloantibodies in the adsorbed serum