Download - Autoimmune hemolytic anaemia
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IMMUNE HEMOLYTIC
ANEMIA
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IMMUNE HEMOLYTIC ANEMIAGeneral Principles
All require antigen-antibody reactions
Types of reactions dependent on:Availability of complement
Environmental Temperature Functional status of reticuloendothelial system
Manifestations Intravascular hemolysis
Extravascular hemolysis
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IMMUNE HEMOLYTIC ANEMIAGeneral Principles - 2
Antibodies combine with RBC, & either1. Activate complement cascade, &/or2. Opsonize RBC for immune system
If 1, if all of complement cascade isfixed to red cell, intravascular cell lysisoccurs
If 2, &/or if complement is onlypartially fixed, macrophages recognizeFc receptor of Ig &/or C3b ofcomplement & phagocytize RBC,causing extravascular RBC destruction
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IMMUNE HEMOLYTIC ANEMIACoombs Test - Direct
Looks for immunoglobulin &/or complementof surface of red blood cell (normally neither
found on RBC surface) Coombs reagent - combination of anti-human
immunoglobulin & anti-human complement
Mixed with patients red cells; ifimmunoglobulin or complement are onsurface, Coombs reagent will link cellstogether and cause agglutination of RBCs
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IMMUNE HEMOLYTIC ANEMIACoombs Test - Indirect
Looks for anti-red blood cell antibodies in
the patients serum, using a panel of redcells with known surface antigens
Combine patients serum with cells from apanel of RBCswith known antigens
Add Coombsreagent to this mixture
If anti-RBC antigens are in serum,agglutination occurs
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HEMOLYTIC ANEMIA - IMMUNE
Autoimmune Hemolysis
Warm autoimmune hemolysis
Cold autoimmune hemolysisAlloimmune Hemolysis
Hemolytic Transfusion Reaction
Hemolytic Disease of the Newborn Drug-Related Hemolysis
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Autoimmune hemolytic anemia (AHA)
Autoimmune hemolytic anemia (AHA) is
characterized by shortened red bloodcell (RBC) survival and the presence ofautoantibodies directed against
autologous RBCs.
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AUTOIMMUNE HEMOLYSIS
Due to formation of autoantibodies thatattack patientsown RBCs
Type characterized by ability ofautoantibodies to fix complement & siteof RBC destruction
Often associated with eitherlymphoproliferative disease or collagenvascular disease
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Autoimmune Hemolytic Anemia
Classified by thermal reactivity Warm react near 37 oC, Cold at 0-4 oC
Serologic evidenceis positive DAT (directCoombs test) with IgG or C3d present
Indirect Coombs test and specificity (serum /eluate)
Diagnostic Criteria- serologic evidence and laboratory or clinical
hemolysis
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AIHA Classification
Warm autoimmune hemolytic anemia Idiopathic, Secondary
(Lymphoproliferative disorders, autoimmune diseases)
Cold autoimmune hemolytic anemia Cold agglutinin syndrome
(Idiopathic, Secondary- mycoplasma, infectious mono, LPD)
Paroxysmal cold hemoglobinuria
(Idiopathic, Secondary- measles, mumps, syphilis)
Drug-induced IHA (Autoimmune, Drug adsorption, Neoantigen)
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AUTOIMMUNE HEMOLYSISWarm Type
Usually IgG antibodies
Fix complement only to level of C3,if at all
Immunoglobulin binding occurs at all temps Fc receptors/C3b recognized by
macrophages;
Hemolysis primarily extravascular
70% associated with other illnesses
Responsive to steroids/splenectomy
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Diagnosis
2Anaemia.
2Spherocytes on peripheral blood film.
2Reticulocytes are increased.
2Neutrophilia common.
2 RBC coated with IgG, complement or both (detect
using DAT).
2Autoantibody often pan-reacting but specificity in
1015% (Rh,
mainly anti-e, anti-D or anti-c).
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Diagnosis
LDH increased.
2Serum haptoglobin decreased.
2Exclude underlying lymphoma (BM,blood and marrow cell markers).
2Autoimmune profileto exclude SLE or
other connective tissue disorder.
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AUTOIMMUNE HEMOLYSISCold Type
Most commonly IgM mediated
Antibodies bind best at 30 or lower
Fix entire complement cascade
Leads to formation of membrane attackcomplex, which leads to RBC lysis invasculature
90% associated with other illnesses
Poorly responsive to steroids, splenectomy;responsive to plasmapheresis
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Diagnosis
2Anaemia.
2Reticulocytes are increased.
2Neutrophilia common.
2Positive DATC3 only. 2 Autoantibodies IgG or IgM
Monoclonal in NHL.
Polyclonal in infection-related CHAD. 2IgM antibodies react best at 4C (thermal
amplitude 432C).
2Specificity
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Diagnosis
Anti-I (Mycoplasma). Anti-i (infectious mononucleosis)causes little
haemolysis in adults
since RBCs have little anti-i (cf. newborn i >> I).
2LDH increased.
2Serum haptoglobin decreased.
2Exclude under ly ing lym phoma (BM, blood and marrow cell
markers).
2Autoimmune profile to exclude SLE or other
connective tissue disorder.
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DRUG-INDUCED HEMOLYSISImmune Complex Mechanism
Drug & antibody bind in the plasma
Immune complexes either
Sit on red blood cell
Antigen-antibody complex recognized by REsystem
Red cells lysed as innocent bystander ofdestruction of immune complex
REQUIRES DRUG IN SYSTEM
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DRUG-INDUCED HEMOLYSISHaptenic Mechanism
Drug binds to & reacts with red cell
surface proteinsAntibodies recognize altered protein,
drug, as foreign
Antibodies bind to altered protein &initiate process leading to hemolysis
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DRUG-INDUCED HEMOLYSISTrue Autoantibody Formation
Certain drugs appear to causeantibodies that react with antigensnormally found on RBC surface, and doso even in the absence of the drug
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Drug-Induced Autoimmune Hemolytic Anemia
Prototype
Drugs
Clinical
Findings
Detection of
Drug-Induced
Antibody
Proposed
Mechanism
Stibophen AcuteIntravascular
Hemolysis
Serum +Drug + Red
Cells
Neoantigen
Penicillins/
Cephalosporin
Subacute
Extravascular
Hemolysis
Serum + Drug-
Coated Red
Cells
Drug Adsorption
-methyldopa Warm antibody
autoimmune
hemolytic
anemia
Serum + Normal
Red Cells
Autoimmune
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Drug-Induced Positive Antiglobulin Tests
Mechanism DAT Serum and Eluate
Neoantigen
-Drug +RBC complex
C3 (sometimes IgG also) Serum reacts with rbcsonly in the presence of
drug; eluate non-reactive
Drug Adsorption (DA)
-Drug binds to RBC
IgG (sometimes C3 also) React with drug-coated
RBCs but not untreated
RBCs- Ab to drug
Autoantibodies
-WAIHA
IgG (rarely C3 also)
11-36% of pts
React with normal RBCs in
absence of drug
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Treatment AIHA
WAIHA CAD PCH Drug-IHA
Folate
Corticosteroids20% complete
response
Folate
Avoid coldTreat secondary cause
Folate
Avoid cold
Treat if hemolysis
present
Splenectomy
60-75% response rate
Chlorambucil
Cytoxan,
-Interferon
Treat infection Folate
Stop drugs
Cytotoxic drugs-Cytoxan, Rituxan Plasmapheresis ? Plasmapheresis Corticosteroids-severecases
Transfuseleast
incompatible
Transfuse-I+, blood
warmer
Transfuse- P+, blood
warmer
Transfuse
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ALLOIMUNE HEMOLYSIS
Hemolytic Transfusion Reaction Caused by recognition of foreign antigens on
transfused blood cells
Several types Immediate Intravascular Hemolysis (Minutes) - Due topreformed antibodies; life-threatening
Slow extravascular hemolysis (Days) - Usually due torepeat exposure to a foreign antigen to which there
was a previous exposure; usually only mild symptoms Delayed sensitization - (Weeks) - Usually due to 1st
exposure to foreign antigen; asymptomatic
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Manifestations of Delayed Hemolytic
Transfusion Reactions
Clinical
Fevers
Chills
Symptoms of anemia
Jaundice
Oliguria or anuria (uncommon)
Generalized Bleeding (Rare)
Laboratory
Unexplained anemia (or decrease in hemoglobin)
Positive direct antiglobulin test Hemoglobinemia
Hemoglobinuria (Uncommon)
Hemosiderinuria
Decreased haptoglobin
Responsible antibody in post-transfusion RBC eluate
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ALLOIMMUNE HEMOLYSISHemolytic Disease of the Newborn
Due to incompatibility between mothernegative for an antigen & fetus/fatherpositive for that antigen. Rh incompatibility,
ABO incompatibility most common causes Usually occurs with 2nd or later pregnancies
Requires maternal IgG antibodies vs. RBC
antigens in fetus
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HYDROPS FETALIS
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ALLOIMMUNE HEMOLYSISHemolytic Disease of the Newborn - #2
Can cause severe anemia in fetus, witherythroblastosis and heart failure
Hyperbilirubinemia can lead to severe brain
damage (kernicterus) if not promptly treated
HDN due to Rh incompatibility can be almosttotally prevented by administration of anti-Rh
D to Rh negative mothers after eachpregnancy
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