Immune Hemolytic Anemias Flashcards
immune hemolytic anemia
shortening of RBC survival due to antibodies coating the red cells
anemia of increased destruction
Immune Hemolytic Anemias requiring transfusion support (3 categories)
- Alloimmune hemolytic anemia
- Autoimmune hemolytic anemia
- Drug-induced hemolytic anemia
Lab indicators of immune hemolysis
positive DAT increased retics increased LDH-intravascular hemolysis increased indirect bilirubin decreased hemoglobin & hematocrit decreased haptoglobin spherocytes -extravascular
Intravascular hemolysis
increased bilirubin
hemoglobinuria, hemoglobinemia
positive DAT
schistocytes
Extravascular hemolysis
increased bilirubin
no hemoglobinuria, no hemoglobinemia
positive DAT
spherocytes
Extravascular targeting of Coated RBCs
A. reticular endothelial system (RES) can ‘pluck’ IgG-coated RBCs & create spherocytes
B. RES can engulf & phagocytize RBCs IgG-coated RBCs in the spleen
C. RES can remove IgG & Complement coated RBCs in the liver
Direct Antiglobulin Test
detect IgG &/or complement attached to the red cell surface
up to 90 molecules of IgG may be present normally
threshold for positive DAT
100-500 molecules of IgG
400-1100 molecules of C3d
reasons for positive DAT besides the obvious
0.3-1.0% of hospitalized pts will have a positive DAT w/o clinical hemolysis
IVIG!!!
recent transfusion
drug associated w/ immune hemolytic anemias
organ transplant
septicemia-bc of constant complement activation
DAT tips for accuracy
RBCs must be washed thoroughly = false negative
RBCs must be tested immediately after washing to avoid false negatives
used EDTA sample to avoid false positive
Additional testing when autoantibodies are present
- elution when DAT IgG is positive
2. absorption: remove warm/cold autoantibody
Autoantibodies general
must resolve cold autos in order to ABO type
must resolve warm autos in order to screen for alloantibodies
serologic findings DO NOT always imply hemolytic anemias
clinical significance varies
how to predict if autoantibodies are clinically significant
thermal range - high range cold autos & warm autos
ability of antibody to fix complement
titer of antibody bound to RBCs
underlying disease
Cold Autoagglutinin Disease
hemolytic anemia associated w/ autoantibodies reacting in the cold
18% of all AIHAs
acute & chronic
Acute CAD
usually fairly mild anemia
anti-I: can happen in mycoplasma pneumonia & other bacterial infections
anti-i: CMV, infectious mononucleosis etc
usually do not require any transfusion support
chronic CAD
most serious clinically
more common in the elderly, lymphoma, chronoic lymphocytic leukemia
most severe cases in younger individuals w/ no known underlying cause
CAD clinical features
anemia jaundice acrocyanosis Raynaud's phenomenon therapy: avoid cold
CAD manifestation/mechanism
- IgM antibody binds to RBC in lower temps of peripheral circulation causing complement to attach to RBCs
- as RBCs move to warmer areas, IgM dissociates but complement remains
- intravascular hemolysis
CAD serologic testing
can interfere with serologic testing- wash cells
usually can skip this step for antibody screen/panel/crossmatch
prewarming techniques
typical reactivity seen with CAD
4C= 3-4+ 15-18C= 1-2+ 20-24C = 0-1+ 37C = 0 IgG = 0
CAD lab results
positive DAT - anti-C3d
reticulocytosis
agglutination in peripheral smear- have to warm up sample before testing
Anti-I: pathologic
greater thermal amplitude >30C
titer >1000 @ 4C (always titer at 4C)
other cold autoantibodies
anti-H & anti-IH: present in only A1 & A1B individuals at low levels
clinically insignificant unless in a BOMBAY phenotype
anti-M
anti-M cold autoantibody
not uncommon in children less than 1 year old
Paroxysmal Cold Hemoglobinuria (PCH)
uncommon; occurs in children after viral illnesses
biphasic hemolysin (anti-P): binds at low temps & causes hemolysis @ 37C
DONATH-LANDSTEINER TEST
PCH treatment
normally self-limiting after virus passes
anti-P negative blood is rare-> transfuse w/ ABO compatible blood w/ blood warmer
treat w/ steroids
Warm autoimmune hemolytic anemia
majority of AIHA
most detected are not clinically significant (no hemolysis)
important because they can mask an underlying alloantibody & will make crossmatches incompatible
WAIHA serologic reactions
IS - 0 37C - 0 AHG - 2-4+ polyspecific DAT - 2-4+ IgG DAT - 2-4+ C3b/d DAT- 0-2+
most common warm autoantibody
anti-e
work around warm autoantibodies
perform an autoadsorption- cannot have had a transfusion recently
mixed-type autoimmune hemolytic anemia
features similar to both warm & cold
DAT - both IgG & C3d/b
Drug Induced Immune Hemolytic anemia
rare; first seen in penicillin & methyldopa
>100 drugs could cause IHA &/or positive DAT
DIIHA mechanisms (4)
- penicillin-type (drug adsorption)
- immune complex
- membrane modification
- drug-independent
Penicillin type DIIHA
penicillin or its metabolites are adsorbed onto the RBCs
antibodies attach to the drug causing a positive DAT (IgG) & may increase RBC destruction
hemolysis is extravascular
elute should be tested w/ RBCs sensitized w/ penicillin
immune complex DIIHA
after patient receives a drug, an antibody to the drug forms
drug-antibody complex absorbs to the RBCs
complement is activated
intravascular hemolysis w/ hemoglobinemia & hemoglobinuria
classic drugs that cause immune complex DIIHA
quinine
quinidine
non-immunologic protein adsorption (Membrane modification)
drugs that MODIFY THE CELL MEMBRANE of RBCs by making the membrane ‘sticky’
positive DAT may demonstrate IgG, IgM, IgA, C3
rarely associated with RBC destruction
eluates are non-reactive bc there is no drug antibody present
unique feature of drug-independent DIIHA
the drug does NOT have to be present to have a positive DAT
methyldopa
anti-hypertensive drug; interferes with suppressor T cell function, leading to the production of autoantibodies
Drug Independent features DIIHA
positive DAT - IgG; after 3-6 months of discontinuing the drug
eluate is reactive against all panel cells!
looks exactly like a warm autoantibody
hemolysis RARELY occurs
