DAT/WAA/AIHA Flashcards
What is an important factor to keep in mind for serological workups of WAA and AIHA
the reaction strength. Typically the Strength is going to be higher in a WAA or AIHA than with an HTR
Causes of WAIHA
Idiopathic, lymphoma SLE, AIDS, Carcinoma
Most commom warm auto specificities
Rh type, most common e- specificity
Autologous adsorption
Cannot do if patient has been recently transfused. Must prepare red cells but ZZAP, Ficin, Papain, 2-ME or DTT. Pull antibodies off the surface of the red cell so that more antibodies can be adsorbed out of the system
W.A.R.M.
Warm antibody removal media- this is a trademark brand
Stroma
White fluffy membranes
Autoadsorption considerations
Has patient been transfused? How much blood do you have, how sick is the patient, may not be able to perform enough adsorptions without high quantity of red cells
Allogenic adsorptions 3 red cell choices
- R1R1; Jka- 2. R2R2 Jkb- S- 3. rr K- s-
DDA
drug dependent antibody
WAIHA vs. DDA
WAIHA eluate strongly positive, persists in serum. DDA Eluate is negative or weak and disappears from serum within days if drug is discontinued
Management of WAIHA
steroids, rituximab, immunosuppressive drugs (cytoxan) IVIG, plasmapheresis, cyclosporin
Acute Cold- Hemagllutinin Disease
lyphoproliferative disorders, Mycoplasma pneumonia infection, infectious mono
Chronic Cold hemagglutinin disease
More severe symptoms elderly during cold weather, hemolysis mild-medium
Serology of Cold-hemagglutinin disease
Serology DAT show complement only increased Ttiter >1000. antibody binds at 30 degree, intravascular hemolysis
Autoanti-i disease association
infectious mono
Autoanti-I disease association
Mycoplasma pneumonia
Cold Agglutinin Disease clinical manifestations
Mild Chronic anemia, occasional juandice, usually self limiting if associated with mono or mycoplasma pneumoniae
Management of CAD
Avoid the cold, other treatments are of little help
Drug induced immune hemolytic anemia
DAT usually fairly strong reacts with both IgG and complement C3. most eluate are negative , many are positive with Peg or Ficin at IAT
drug adsorption DIIHA (hapten dependant) Type 1
penicillin/penicillin derivative and cephalosporins. Drug bind covalently to membrane proteins and stimulate hapten-dependent antibodies. Antibody reacts with normal rbs pretreated with drug
Immune complex DIIHA (Type 3, drug dependent antibody)
Quinidine, quinine, NSAIDS, through an unknown mechanism drug induces antibodies that bind to RBC only when drug is present in soluble form , antibody reacts with rbcs when soluble drug is present. Complex of drug, rbc and antibody all three come in contact
drug induced auto-antibody Type II
alpha methydopa (helpful in pregnancy), procainamide, through an unknown mechanism drug induces autoantibodies specific for RBC membrane proteins. Antibody reacts with normal RBCs in the absence of the drug
Nonimmunologic protein adsorption NIPA membrane modification
cephalosporins, tazobactum, clavunate, drug coats RBCs and causes them to get “sticky” DAT weakly positive, this is rarely associated with DIIHA
For the test: Things to Remember!!
- Always look for medication history in a question- don’t assume it’s the answer 2. look at strength of reactivity of the DAT 3. Correlate DAT reactivity with patients clinical info 4.
Drugs related to drug adsorption/hapten
penicillin, penicillin derivatives, cephalosporins
Drugs related to immune complex DIIHA
quinidine, quinine, NSAIDS
Drugs related to drug induced autoantibody
Alpha methyldopa (b.p. in pregnant women) procainamide
Drugs related to Nonimmunologic protein adsorption membrane modificatin (NIPA)
cephalosporins, not typically presented as DIIHA
PCH DAT results
C3d will be positive and IgG will be negative- even though caused by a biphasic IgG, it causes complement and then dissociates and warmer temperatures leaving complement bound
Important drug related questions in light of positive DAT
is patient on any drugs, are they on Anti-lymphocyte or anti-thymocyte globulin
CAS
cold agglutinin syndrome- cold reactive IgM auto agglutinin binds to RBCs in peripheral circulation. IgM binds complement as RBCs return to warmer parts of circuclation. Complement remains bound by IgM dissociates
Drug related positive DAT results
Non-antibody-mediated binding of immunoglobulin to RBCs in patients with hypergammaglobulinemia- associated with positive DAT results. High dose IV gamma globuilin, ALG, ATG and hypergammaglobulinemia
why doesn’t the DAT require an incubation phase like the IAT
because the antibody-antigen interaction took place in vivo (at 37 degrees)
What level of IgG and C3d can a DAT detect?
100-500 IgG molecules per RBC and 400-1100 molecules of C3d per RBC
what level of IgG can an IAT detect
must be between 100-200 IgG or C3 moleucles on cell to obtain a positive reaction