Auto Immune Hemolytic Anemias Flashcards
Clinical findings of AIHA?
- Positive DAT
- Hemolysis
- ABO discrepancy maybe
- Schistocytes
- Reticulocytes
- Bilirubin
- LDH
- Hemoglobinemia
- Hemoglobinuria
List AIHA diseases?
- Cold agglutinin syndrome
- PCH
- Warm AIHA
- Drug-dependent
Differentiating IHA questions to ask
- thermal amplitude
- benign vs pathologic
- Ig class
- complement fixation
- titer
- underlying disease
Complement binding capacity of warm and cold antibodies
- Warm: may bind
- Cold: binds complement
Warm antibody DAT results
IgG+
C3+ or -
Cold antibody DAT results
IgG-
C3+
Warm antibody hemolysis site
Extravascular
Cold antibody hemolysis site
Intravascular or extravascular
Warm antibody specificity
Frequently Rh
Cold antibody specificity
Frequently I or P
Warm auto-Ab clinical presentation
Exhausted
Anemic
Cold auto-Ab clinical presentation
Purpling of extremities
Describe benign cold-reactive Ab
- Low titer
- Enhanced with albumin and enzyme
- IgM
- Anti-I or anti-IH or anti-i
Describe pathologic cold-reactive Ab
- Not common
- High titer > 1000
- Enhanced with albumin and enzyme
- IgM
- Anti-I or anti-P or anti-M
List benign cold agglutinins
- anti-I
- anti-i
- anti-IH
What does anti-I react with?
Adult RBCs, NOT cord cells
What does anti-i react with?
Cord cells, NOT adult RBCs
What does anti-IH react with?
Does NOT react with A1, B, or AB RBCs
How to handle cold agglutinins
Prewarm immediate spin crossmatch and reverse type
List pathologic cold agglutinins
- anti-I
- Wide thermal range igM
- Donath-Landsteiner anti-P
How to handle pathologic cold agglutinins
May have to perform 60 min settling technique to obtain negative results for reverse or screen
How to test for Donath-Landsteiner anti-P?
- 0°C for 90 min patient serum
- 37°C for 90 min patient serum
- 0°C for 30 min
- 37°C for 60 min
The most annoying about warm auto-Ab
They prevent serological ID of allo-antibodies because everything is reactive
How to remove warm auto-Ab
- Autoadsorption is best
- Alloadsorption (ref lab)
- Phenotype/molecular
- Reduce enhancement to just saline and cells
- Transfuse incompatible cells (bad idea)
What’s the most annoying thing about drug-induced Ab?
They look like warm auto-Ab
How to tell if you have hemolysis
Tea-like plasma color (dark)
Mechanism of drug-adsorption
- Drugs attach to RBC membrane
- Anti-drug Ab causes RBC destruction (intravasc/extravasc hemolysis)
- IgG, no complement (but RBC blown up)
Which drugs feature drug-adsorption? List in highest to lowest severity
Highest
Cefotetan
Streptomycin
Penicillin
Lowest
Drug-adsorption Ab detection in DAT
IgG+
C3-
Drug-adsorption Ab detection in eluate
Neg
Mechanism of immune complex drug Ab
- Patient forms an antibody to a drug, and the Ab-drug complex absorbs onto RBC membrane
- Complement activated that cause RBC destruction - “innocent bystander”
- Complement, no IgG
- Intravascular hemolysis only
Which drugs feature immune complex formation?
- Quinidine
- Phenacetin
Drug immune complex formation detection in DAT
IgG+/-
C3+
Drug immune complex formation detection in eluate
Negative
Mechanism of membrane modification Ab
- Drug modifies RBC membrane so that IgG/IgM/IgA can attach
- Non-immune process
- No hemolysis
- Rare/not fully researched
Drugs involved in membrane modification Ab
Cephalosporin
Membrane modification Ab detection in DAT
IgG+
C3+
Membrane modification Ab detection in eluate
Negative
Mechanism of drug-independent Ab
- Mechanism unknown
- Auto-Ab forms after 6 months of taking the drug and resolves gradually once stopped
- Hemolysis mimics WAIHA
Which drugs feature drug-independent Ab?
Alpha-methyldopa “Aldomet”
Drug-independent detection in DAT
IgG+
C3+/-
Drug-independent detection in eluate
Positive with all cells
Mechanism of chemo drug Ab
The drug is an antibody that attaches to CD38 as its method of chemotherapy
Drugs that feature chemo drug Ab
- Darzalex (multiple myeloma patients)
- -umab
Chemo drug Ab detection in DAT
Weak positive DAT poly-AHG and IgG
Chemo drug Ab detection in eluate
Positive with all cells and auto (Ab ID also has same results)
How to remove chemo drug antigen (CD38 I think) to make the Ab ID negative?
DTT
Transfusion/treatment recs for cold Ab
- skip immediate spin testing
- run slowly thru blood warmer
- keep warm
Transfusion/treatment recs for warm Ab
- do not trust serological presentation
- transfuse only to support cardio function
- transfuse “least incompatible” blood slowly (in vivo crossmatch)
- plasma exchange to remove Ab
- steroids or IVIG to reduce immune response
- splenectomy
Transfusion/treatment recs for drug-induced Ab
- transfusion recommended in most cases
- plasma exchange may also help
- stop taking drug
What does IgM wide thermal range look like serologically?
