TM AIHA Flashcards
Purpose of performing a warm autoadsorption (W.A.R.M.)
- Removes warm autoantibodies
- To ID any clinically significant alloantibodies in patient’s serum
T or F: autoadsorption using WARM/ ZZAP can be used for autoAb that have specificity to Kell, MNS and Duffy antigens
FALSE; WARM/ ZZAP destroys Kell, MNS, and Duffy antigens on patient’s cells
- autoAb that have specificity to these antigens will not be removed by treated cells
Why is the Donath-Landsteiner antibody called “biphasic?”
anti-P binds to RBCs at cold temperatures and causes complement-mediated hemolysis after warming to body temperature
Purpose of performing a cold autoadsorption
- Removes cold autoantibodies
- Cold autoAb (IgM) interfere with ABO Rh typing, Ab Scr, XM, and DATs
- To ID any clinically significant alloantibodies in patient’s serum
Discuss PCH: antibody specificity, immunoglobulin class, and ability to bind complement
Paroxysmal (sudden onset) Cold Hemoglobinuria (Hb in urine through IVH)
- Antibody specificity = anti-P
- IgG that reacts in the cold!
- binds complement right to C9 = IVH
What is another name for anti-P ?
Donath-Landsteiner antibody
Discuss PCH: typical clinical symptoms
intermittent hemolysis with exposure to cold = anemia, fatigue, etc.
Discuss PCH: lab findings
- same as CHD but NO SPHEROCYTOSIS
Anemia:
- decreased Hb
- decreased haptoglobin
- increased LDH
- increased bilirubin (slow)
- increased nBRCs
Does PCH involve IVH or EVH ?
IVH; anti-P binds complement right to C9
Purpose of Donath-Landsteiner Test
to identify autoanti-P in individuals suspect of PCH
why can’t we use EDTA to test for PCH ? What sample type is used ?
always SERUM !
EDTA = false negative as it would get rid of Ca 2+ and Mg 2+ which complement needs
why do we add normal serum in the Donath-Landsteiner test?
To supply complement
- in vivo, patient may have used up all of the complement
How is drug-related AIHA different from delayed hemolytic transfusion reactions ?
- Drug-related AIHA is an acute hemolytic reaction
- Delayed hemolytic is usually due to secondary exposure of an RBC antigen
three main types of AIHA
- WAIHA = 70%
- cold autoimmune hemolytic anemia
- cold hemagglutinin disease (CHD) = 16%
- paroxysmal cold hemoglobinuria = 1-2% - drug-related hemolytic anemia = 12%
instances when DAT is positive
- patient alloantibodies bind donor cells
- maternal Abs bind fetal cells
- passive antibodies (blood products/IVIg)
- autoantibodies
- antibodies/complement due to drugs
What does a DAT positive mean ?
In vivo binding of immunoglobulins, complement components, or both
if a DAT is positive, what follow-up testing is needed ?
- elution
- Ab ID
Describe warm autoimmune hemolytic anemia
- often in elderly patients
- primary idiopathic
- secondary
> white cell malignancies (CLL, lymphoma, MDS)
> autoimmune diseases (Lupus, rheumatoid arthritis)
> viral infections (children or adults)
Hematology results of WAIHA (CBC/ peripheral smear/ serological)
CBC:
- hemoglobin and hematocrit decreased
Peripheral smear:
- nRBC
- polychromasia
- spherocytosis
- HJ bodies (seen in asplenic individuals)
Serological indicators of EVH:
- increased bilirubin
- increase LDH
- deceased haptoglobin
- high RDW
T or F: autoadsorptions cannot be performed if the patient has been transfused in the past three months
TRUE; alloantibodies can be adsorbed/removed by donor cells
cold autoantibodies general characteristics
- IgM
- thermal range = 4°C (<15°C; sometimes RT; up to 32°C)
- binds complement
Compare harmless vs pathological autoanti-I characteristics
Harmless:
- titre <64
- max. thermal range = RT
- rxn not readily enhanced by albumin
- polyclonal
Pathological:
- titre >1000
- max. thermal range = 30°C
- rxn enhanced by albumin
- monoclonal (one B cell going out of control => making this autoAb)
CHD physiological and hematological symptoms
Physiological:
- tingling upon cold exposure = auto anti-I attaches at 30°C = decreased blood flow = lack of O2
- when warmed up = IgM pops off BUT complement stays and works more efficiently
Hematological:
- NO SPHEROCYTOSIS
- increased nBRCs
- anemia
Describe a CHD investigation
- ID autoAb
- cold autoadsorption
- panel
- AC = pos (at RT)
= cord cells = neg
- titration = >1000 titre - DAT
- polyspecific = pos
- IgG = neg
- C3 = pos
Describe a cold agglutinin titration
- pre-warm plasma
- serial dilution
- test with adult O cells, patient cells, and cord cells at various temps (37°C, RT, 4°C)
- determine titre at 4°C
- use strength of adult vs cord cells to determine identity (anti-I vs anti-i)
Often a cold agglutinin screen is performed before doing a ______. if the patient plasma does not react with O adult cells at 4 degrees when diluted at _____, there is no need for _______ _______
Often a cold agglutinin screen is performed before doing a TITRATION. If the patient plasma does not react with O adult cells at 4 degrees when diluted at 1/40 (harmless), there is no need for SERIAL DILUTIONS.
How to find compatible blood after CHD investigation
- prewarm XM samples
- use autoadsorbed patient plasma
- ensure monospecific anti-IgG used (don’t want to pick up complement binding)
- only EDTA
- transfuse using blood warmer if necessary
Discuss methyldopa HA: clinical symptoms and lab results
Symptoms: anemia
Lab results:
- PANREACTING Ab
- DAT IgG = pos
- Increased LDH, bilirubin, RDW
- Decreased haptoglobin, hemoglobin
NOTE: serologically indistinguishable from WAIHA
Describe how Drug-adsorption (penicillin) affects testing
- penicillin binds to RBCs
- drug/RBC complex stimulates immune response
- IgG antibodies attaches to penicillin on RBCs = mono-IgG DAT = pos
Lab results for drug adsorption of penicillin
- DAT = IgG pos; neg for C3d
- AbScr = negative bc screen cells do not have penicillin
- Eluate = neg
What is referred to as the “innocent bystander” reaction ?
- when patient makes IgM antibodies to quinidine (a drug)
- immune/ drug complex attaches to RBCs = complement activation = IVH
Immune complex lab results
- DAT = pos (for complement only; IgM against quinidine)
- Ab Scr = neg
- Eluate = NOT done; even if we did = still neg
Cases when complement is only positive for DAT
- Cold AIHA
- Immune complex (quinidine)
Cause of membrane modification AIHA
- Cephalosporins ADSORB to RBC
- Modifies RBC membranes (more sticky)
- NON-SPECIFIC BINDING of complement, IgG, IgM, IgA
Lab results for membrane modification AIHA (cephalosporins)
DAT = pos (IgG and complement; non-specific sticking)
Ab Scr = neg
Eluate = neg
- bc drug Ab are not represented on screen cells
