BB - Immune RBC Destruction Flashcards
Autoantibodies give positive test results for these 2 tests…
DAT
Auto control
What happens to the following levels during hemolysis: retic count, unconjugated bilirubin, LDH, haptoglobin
Increase: retic count, bilirubin
Decrease: LDH, haptoglobin
Define compensated vs uncompensated anemia
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
AIHA - 3 types of antibodies
Cold reactive
Warm reactive
Drug induced
All AIHA antibodies are DAT ___. Requires this test…
Positive
Elution
Cold reactive autoantibodies - what class of immunoglobulins? Can they trigger complement?
IgM
Yes - in-vitro
-use polyspecific AHG to detect
When cold autoantibodies are present, what can we do to eliminate or minimize their detection (3)?
Use monoclonal reagents
- IgM activate complement in vitro
- monoclonal AHG detects IgG only
Wash cells at 37C
Cold adsorption
Although cold autoantibodies are not clinically significant, they can interfere with the detection and identification of…
Alloantibodies
Cold autoantibodies can cause false ___ reactions with ABO reagents
Positive
- ABO antibodies also IgM
- causes spontaneous agglutination
Although pre-warming reagents can help disperse the cold agglutinins, pre-warming also cause…
Missing clinically significant antibodies after pre-warming
-IgG reagent not effective when pre-warmed
Most cold autoantibodies have specificity to…
anti-I or anti-i
-i in babies, converts to I at 2 years of age
Anti-H cold autos react strongest against these ABO blood types. React weakest against these ABO blood types
O and A2 = most H antigens
A1 and A1B = fewest H antigens
-anti-H more common as allos than autos
Idiopathic cold AIHA is also called… Antibody specificity is…
Cold hemagglutinin disease
- don’t know why it happens
- in older people
Anti-I
-anti-i less common
Common feature of cold hemagglutinin disease is ___ of hands, feet, ears and nose and ___ in the urine upon exposure to the cold
Acrocyanosis
Hemoglobinuria
-caused by hemolytic anemia
PCH commonly occurs in… Cause by this specific antibody in this class…
Children with viral infection
Biphasic anti-P IgG
- most other cold autos are anti-I
- Donath-Landsteiner test to detect IgG
PCH - when does hemoglobinuria occur?
Upon exposure to cold
- intravascular hemolysis (IgG)
- hemoglobinuria
PCH vs PNH - underlying cause of each?
PCH = IgG antibody
PNH = protein
WAIHA - what class of antibodies?
IgG (1 and 3 subclasses)
- IgG3 most destructive
- severe anemia, acute hemolysis
- similar to Rh system; broad “Rh-like” specificity
DAT positive indicates an ___antibody whereas DAT negative indicates an ___antibody
Autoantibody
Alloantibody
WAIHA usually affects this antigen system… but not this…
Rh
- Rh typing a problem
- Rh antibodies are IgGs, same with WAIHA
ABO
When we have both warm autoantibodies and alloantibodies, how can we detect the alloantibodies?
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
Warm vs cold AIHA - Ig class? Complement activation?
Warm = IgG, may bind complement
Cold = IgM, binds complement
Warm vs cold AIHA - site of hemolysis
Warm = extravascular, no cell lysis
Cold = extravascular and intravascular, cell lysis
When a hemolytic patient is DAT positive and no other findings are presented, we should look at (2)…
Patient history
Drug history
4 mechanisms for drug-induced hemolysis
Immune complex
Drug adsorption
Membrane modification
Autoantibody formation
How do drug-induced immune complexes form and how do they cause hemolysis?
- 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
Drug adsorption mechanism
Drugs bind to proteins, such as proteins on RBC membrane
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
Cephalosporin
Drug adsorption
Drug induced membrane modification results in the nonspecific (non-immunologic) uptake of (2). The eluate test result is…
Antibodies and complement
- not via antigen-antibody reactions
- non-immunologic protein adsorption
Negative
How do drugs like alpha-methyldopa (Aldomet), L-dopa, mefenamic acid, procainamide and diclofenac cause hemolysis? The eluate test result is…
Induce production of autoantibodies that recognize RBC antigens
-indistinguishable from WAIHA
Positive
All 4 categories of drug-induced hemolytic anemias result in a positive ___ test
DAT
Is the eluate positive or negative for the 4 categories of drug-induced hemolytic anemias?
Negative = immune complex, drug adsorption, membrane modification
Positive = methyldopa-induced (autoantibodies)
If we are having issues with cold autoantibodies interfering at the AHG phase, we can use this reagent…
Monospecific AHG - detects IgG only
-polyspecific binds to both IgG and C3, the latter caused by cold agglutinins
Mycoplasma pneumoniae and infectious mononucleosis can cause this secondary illness
Cold hemagglutinin disease
-patient should live in warmer climate
Should a recently transfused patient’s sample be tested via warm autoadsorption to remove autoantibodies?
No, use allogeneic cells instead
-removes autoantibodies while leaving alloantibodies in the adsorbed serum
