Autoimmune hemolytic anaemia

8/12/2019 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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Autoimmune hemolytic anaemia