AIHA Flashcards
theories of autoimmunity
- malfunctioning T cells
- cross-reactivity
- molecular mimicry
- alteration of self-antigens
- secondary to disease
- inherited tendency
primary idiopathic autoimmunity
- Ab against own RBCs
- unknown cause
- 60 y/o +
autoimmunity secondary to diseas
- viral or bacteriogenic disease
- often 2y to CLL
- WBC problems (ex: B cell lymphoma = can make Ab that’s not quite right, if malignant = makes a whole lot)
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
in vivo binding of immunoglobulins, complement components, or both
DAT positive
if a DAT is positive, what follow-up testing is needed
elution
Ab ID
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)
clinical symptoms of WAIHA
- pallor
- weakness
- shortness of breath
- dizziness
- jaundice (EVH)
- fever
- splenomegaly
hematology results of WAIHA
CBC - hemoglobin and hematocrit decreased - peripheral smear > nRBC > polychromasia > spherocytosis > HJ bodies (seen in asplenic individuals)
other indicators of EVH
- increase bilirubin
- increase LDH
- decease haptoglobin
- high RDW
T or F. autoadsorptions cannot be performed if the patient has been transfused in the past three months
T as alloantibodies might be removed by donor cells
cold autoantibodies general characteristics
- IgM
- thermal range = 4C (<15C; sometimes RT; up to 32C)
- binds complement
- specificities
harmless autoanti-I
- titre <64
- max thermal range (20-24C; most below)
- rxn not readily enhanced by albumin
- polyclonal
pathological autoanti-I
- titre >1000
- max. thermal range (30-32C)
- rxn enhanced by albumin
- monoclonal (one B cell going out of control => making this autoAb)
cold AIHA
- primary idiopathic = tend to see in older people
- secondary to disease
> Mycoplasma pneumonia = anti-I
> use erythromycin
> EBV = anti-i
CHD
cold hemagglutinin disease
- symptoms: tingle due to lack of O2 = go inside = warm up; IgM pops off BUT complement stays and works more efficiently
- when blood cools down to 30C = ears, nose, etc first things to go down => auto anti I attaches at 30C = decreased blood flow; O2 used up from those cells unable to move freely
=> binds complement - no spherocytosis
- increased polychomasia
- anemia symptoms (fatigue, etc.)
treatment for CHD
just avoid the cold
ACROCYANOSIS
bluish discoloration of the extremities due to decreased amount of oxygen delivered to the peripheral part
CHD investigation
identify autoAb
- panel
- auto control (at room temp = pos)
- cord cells (without autoanti-I = neg)
- titration (>1000)
DAT = pos
- polyspecific pos
- monospecific = only pos for C3
cold agglutinin titration
- pre-warmed patient plasma is serially diluted
- test with adult O cells, patient cells, and cord cells at various temps (37C, RT, 4C)
- determine titre at 4C
- use strength of adult vs cord cells to determine identity (anti-I vs anti-i)
finding compatible blood (follow-up CHD investigation
- prewarm
- use autoadsorbed plasma
- ensure monospecific anti-IgG used (don’t want to pick up complement binding)
- ensure EDTA sample used
- transfuse using blood warmer if necessary
PCH
paroxysmal (sudden onset) cold hemoglobinuria (Hb in urine through IVH)
- antibody specificity is anti-P
- AKA Donath-Landsteiner Ab
- IgG that reacts in the cold!
- binds complement right to C9
- hemolysis (IVH bc of C9)
PCH etiology
often 2ry to MMRV; often was found in children
symptoms of PCH
intermittent hemolysis with exposure to cold = anemia hemolysis, etc.
lab findings for PCH
similar to CHD
- decrease Hb, haptoglobin; increase LDH, bilirubin (takes a while to increase)
treatment for PCH
wait for underlying infection to clear; avoid cold
Donath-Landsteiner Test
- PCH
- collect blood, keep warm, and allow to clot (37C)
- incubate serum with P(+) RBCs and normal serum at 4C
- warm to 37C
- spin and read for hemolysis
hemolysis = anti-P present
no hemolysis = anti-P not present
why can’t we use EDTA to test for PCH?
- always serum! bc EDTA will cause a 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
- ensuring that there is enough complement source; bc in vivo, patient may have used up all of the complement
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 _______ _______
titration
1/40
serial dilutions
drug induced HA
- positive DAT could be caused by dug
- rarely leads to hemolysis
- more often seen as interference
- should be considered in DAT workup
when are blood products used as drugs?
- RhIg given to Rh pos patients with ITP
- IVIg therapy
> monitor Hb
> drop in Hb (<100g/L); perform DAT, Bili, LD
methyldopa HA
- antihypertensive drug used in pregnancy: Aldomet
- autoantibody related to dose and time
- positive DAT
- anemia
- autoAb produced
- serologically indistinguishable from WAIHA
> panreacting
> specificity - substance sensitizing cells
- treatment = take them off drug
drug adsorption (penicillin)
- IV (massive doses)
- drug binds to RBC
- drug/RBC complex stimulates immune response
- IgG Ab attaches to penicillin
lab results for drug adsorption
- DAT = pos; due to IgG; neg for C3d
- antibody screen = negative bc screen cells do not have penicillin
- Eluate = neg
immune complex “innocent bystander”
Quinidine = antimalarial drug
Quinidine AIHA
- patient maks drug Ab
- Ab-Ag complex binds; RBC activates complement
- RBC destroyed by complement
- IVH
immune complex lab results
- DAT = pos (for complement only)
- Ab scr = neg
- Eluate = NOT done; even if w did = still neg
if complement is only positive from DAT
either cold auto, drug-induced, or immune complex
membrane modification (cephalosporins) AIHA
- uses adsorption mechanism
- modifies RBC membrane (makes it sticky)
- nonspecific protein binding
> complement, IgG, IgM, IgA
lab results for membrane modification
- DAT = pos (due to IgG and complement)
- Abscr = neg
- eluate = neg
bc drug Abs not specific Abs
