Autoimmune disorders Flashcards
What is the positive predictive value of a positive DAT? How does the presence of hemolysis affect this?
If hemolysis labs are positive, PPV is 83%. If negative, 1.4%.
What conditions can cause a positive DAT?
Hemolytic transfusion reactions, HDFN, AIHA, DIHA…
What can cause nonspecific DAT positivity?
Passive antibodies (IVIG), protein adsorption, complement adsorption and activation.
How can DAT due to mistransfusion be distinguished from other causes?
Look for mixed-field reactivity
What methods can be used to elute antibodies from a positive DAT?
Acid elution (preferred) Heat/freeze-thaw (for ABO only).
How should DAT eluates compare to plasma reactivity in WAIHA?
Antibodies usually end up on the DAT first; if the plasma screen is panreactive, expect the DAT and eluates to be strongly reactive.
How can warm autoantibodies be enhanced or subtracted?
Enhance: Use PEG(?), enzymes, gel
Subtract: Use LISS
When warm autoantibodies have antigen specificities, what are they generally targeted towards
Usually Rh antigens»_space; LW, Kell, Kidd, Duffy, Diego
What conditions cause cold agglutinin disease?
Mycoplasma infection (acute), lymphomas (chronic)
What options exist to subtract cold agglutinins on lab testing?
Pre-warm, use 0.01M DTT, or use RESt… carefully
What antibodies will RESt remove?
Cold agglutinins, but also D, E, Vel
What antibodies will HPC remove?
HLA, all carbohydrate antigens (ABO, I, P, Le)
What is the specificity of cold agglutinins?
Usually auto-anti-I. Rarely anti-i, anti-i+, or anti-Pr
What is mixed AIHA?
WAIHA but with cold agglutinins acting at 30C. Could be due to WAIHA+CAD or a high thermal amplitude cold agglutinin. Note IgG and C3 should both be reactive on DAT.
Paroxysmal cold hemoglobinuria
Transient response to infxn (formerly syphilis) where a cold-reactive and complement binding IgG (anti-P) causes hemolysis. Presents with DAT+ with anti-C3 or anti-IgG.
How can PCH be treated? In who is it worse?
Worse in children (higher thermal amplitude). Could transfuse P-negative blood, if you can find it.
What are the three mechanisms of drug induced hemolytic anemia?
Antibody may be targeted against drug, combined neoepitope, or just red cell membranes.
What drugs tend to cause DIHA in a drug-independent fashion?
Fludarabine, methyldopa
What drugs tend to cause DIHA in a drug-dependent fashion?
Beta-lactams, quinine, platinum drugs…
What is the behavior of a drug-dependent DIHA?
Once immunized, only a small amount of drug will precipitate hemolysis, which can be brisk and intravascular. Testing requires presence of drug.
What antibodies are hardest to elute from DAT+ cells?
IgMs
What options remain to identify a suspected AIHA when DAT is negative?
Consider IgM-mediated AIHA. Can try flow, ADCC assays, chemiluminescence or monocyte monolayer assays.
Are primary or secondary AIHAs more common? Warm, cold, or mixed?
Secondary is more common! Warm > Cold > Mixed & Drug
What is the mechanism of red cell clearance in warm AIHA?
IgG1/3 coating, limited complement activation in the form of C3b deposition which accelerates removal by macrophages.
What are secondary causes of warm AIHA?
B-cell neoplasms (note: the neoplastic lineage is NOT which produces the antibodies)
Ovarian dermoids
Kaposi’s sarcoma? HIV? Babesia microti?
How sensitive must a DAT be to detect AIHA?
Should be able to detect at 100-500 molecules per RBC of IgG and 400-1100 molecules of C3D.
When are cold antibodies clinically significant?
Generally only when the titer is >64 (but usually actually in 1000s) and acting ad broad thermal amplitude.
What are secondary causes of cold AIHA?
B-cell neoplasms (including LPL/WM)
Mycoplasma infection
Epstein-Barr virus infection
How does AIHA due to IgA usually present?
Cold-like pattern with acrocyanosis but without significant hemolysis.
DIHA: Hapten model
Drug binds strongly to membrane, reaction only occurs in presence of drug. IgG, not C3.
DIHA: Complex model
Drug binds loosely to antibody in circulation. IgM > IgG.
DIHA: Drug-independent models
Drug induces antibody production in non-immunologic fashion, or alters membrane to cause non-immunologic protein adsorption.
