Acquired Hemolytic Anemias (2)

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    ACQUIRED HEMOLYTIC ANEMIASACQUIRED HEMOLYTIC ANEMIAS

    BY

    Dr.Ammar

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    Acquired haemolytic anaemiasAcquired haemolytic anaemias

    Divided into two main categories

    depending on the mechanism by which

    the premature destruction of red bloodcells is produced.

    Immune haemolytic anaemias

    Non-immune haemolytic

    anaemias

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    IMMUNE HEMOLYTIC ANEMIAIMMUNE HEMOLYTIC ANEMIA

    Antibody-mediated haemolysis is an

    important cause of acquired haemolytic

    anaemia. Antibodies may be:

    autoantibodies

    alloantibodies.

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    IMMUNE HEMOLYTIC ANEMIAIMMUNE HEMOLYTIC ANEMIAGENERAL PRINCIPLESGENERAL PRINCIPLES

    All require antigen-antibody reactions

    Types of reactions dependent on:

    Class of Antibody

    Number & Spacing of antigenic sites on cell

    Availability of complement

    Environmental Temperature

    Functional status of reticuloendothelial system

    Manifestations Intravascular hemolysis

    Extravascular hemolysis

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    Classification of hemolytic anemias

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    Autoimmune Hemolytic AnemiasAutoimmune Hemolytic Anemias

    These are caused by antibody production

    by the body against its own red cells.

    Warm and cold types according towhether the antibody reacts more strongly

    with red cells at 37C or 4C.

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    Warmautoimmune haemolyticanaemiasWarmautoimmune haemolyticanaemias

    The red cells are coated with immunoglobulin(Ig)

    (IgG) alone or with complement

    They are taken up by RE macrophages which

    have receptors for the Ig Fc fragment.

    Part of the coated membrane is lost so the cell

    becomes progressively more spherical to

    maintain the same volume and is prematurelydestroyed in the spleen.

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    Clinical featuresClinical features

    Any age

    Either sex

    presents as a haemolytic anaemia of varying severity

    The spleen is often enlarged.

    It may occur alone or in association with other diseases

    May arise in some patients as a result of methyldopatherapy

    When associated with idiopathic thrombocytopenicpurpura (ITP)it is known as Evans' syndrome

    When secondary to systemic lupus erythematosus thecells typically are coated with immunoglobulin andcomplement.

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    Lab findingsLab findings

    Positive DAT

    Normocytic normochromic anemia

    Increased reticulocytosis Spherocytosis

    Presence of autoantibodies in serum

    Leukocyte counts are normal Platelet count normal or slightly decreased

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    Coombs test(direct):Coombs test(direct):

    Looks for immunoglobulin &/or complement of

    surface of red blood cell (normally neither found

    on RBC surface)

    Coombs reagent - combination of anti-humanimmunoglobulin & anti-human complement

    Mixed with patients red cells; if immunoglobulin

    or complement are on surface, Coombs reagentwill link cells together and cause agglutination of

    RBCs

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    Coombs test (indirect):Coombs test (indirect):

    Looks for anti-red blood cell antibodies in the patientsserum, using a panel of red cells with known surfaceantigens

    Combine patients serum with cells from a panel ofRBCs with known antigens

    Add Coombs reagent to this mixture

    If anti-RBC antigens are in serum, agglutination occurs

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    TreatmentTreatment

    1. Remove the underlying cause (e.g.methyldopa)

    2. .Corticosteroids.(Prednisolone)

    3. Splenectomy

    4. Immunosupression(Azothioprim,Cyclophosphomide)

    5. Monoclonal antibodies.Rituximab(anti-CD20).Campath-IH(anti-CD52)

    6. Folic acid

    7. Blood transfusion

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    Cold autoimmune hemolytic anemiasCold autoimmune hemolytic anemias

    Monoclonal

    idiopathic cold haemagglutinin syndrome

    lymphoproliferative disordersPolyclonal

    e.g. infectious mononucleosis

    Mycoplasmapneumonia

    attaches to red cells mainly in the peripheral

    circulation where the blood temperature is cooled

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    The antibody is usually IgM

    Binds to red cells best at 4C.

    IgM antibodies are highly efficient at fixingcomplement

    Intravascular and extravascular

    haemolysis can occur.

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    Clinical featuresClinical features

    Chronic haemolytic anaemia aggravatedby the cold

    Intravascular haemolysis.

    Mild jaundice

    Splenomegaly

    Acrocyanosis (pllrplish skin discoloration)

    at the tip of the nose, ears, fingers andtoes caused by the agglutination of redcells in small vessels.

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    Lab findingsLab findings

    DAT positive with polyspecific AHG

    Negative with anti-IgG

    Positive with anti-C3 Cold agglutinin titre >1000 at 4oc

    Normocytic normochromic anemia

    Reticulocytosis Spherocytosis

    Agglutinated RBCs

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    Cold autoimmune hemolytic anemia

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    TreatmentTreatment

    keeping the patient warm

    treating the underlying cause,

    Alkylating agents such as chlorambucil ishelpful in the chronic varieties.

    Both anti-CD20(rituximab) and anti-CD52

    (Campath-lH) havebeen used. .

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    Proxysmal cold hemoglobinuriaProxysmal cold hemoglobinuria

    Acute intravascular hemolysis after exposure to

    the cold.

    It is caused by the Donath-Landsteiner

    antibody, an IgG antibody with specificity for theP blood group antigens which binds to red cells

    in cold but cause lysis in warm conditions.

    viral infections,syphilis are predesposing factors.

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    Alloimmune Hemolytic anemiaAlloimmune Hemolytic anemia

    Hemolytic anemia of newborn

    Hemolytic transfusion reaction

    Allograft asoociated

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    Hemolytic transfusion ReactionHemolytic transfusion Reaction

    Caused by recognition of foreign antigens ontransfused blood cells

    Several types

    Immediate Intravascular Hemolysis (Minutes)

    - Due to preformed antibodies; life-threatening Slow extravascular hemolysis (Days) -

    Usually due to repeat exposure to a foreignantigen to which there was a previous

    exposure; usually only mild symptoms Delayed sensitization - (Weeks) - Usually due

    to first exposure to foreign antigen;asymptomatic

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    PrePre--transfusion tests:transfusion tests:

    ABO & Rh Type of both donor & recipient

    Antibody Screen of Donor & Recipient,including indirect Coombs

    Major cross-match by same procedure(recipient serum & donor red cells)

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    Hemolytic anemia of the newborn:Hemolytic anemia of the newborn:

    Due to incompatibility between mother negative for anantigen & fetus/father positive for that antigen.

    Usually occurs with 2nd or later pregnancies.Requiresmaternal IgG antibodies vs. RBC antigens in fetus

    Can cause severe anemia in fetus, with erythroblastosisand heart failure

    Hyperbilirubinemia can lead to severe brain damage

    (kernicterus) if not promptly treated

    HDN due to Rh incompatibility can be almost totallyprevented by administration of anti-Rh D to Rh negativemothers after each pregnancy

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    Drug induced hemolyticDrug induced hemolytic

    anemias:anemias:1. Antibody directed against drug-red cellmembrane complex.e.g penicillin

    2. Deposition of complement via drugprotein(antigen)-antibody complex on the

    RBC e.g quinidine, rifampicin.

    3. True autoimmune hemolytic anemia e.g

    methyl dopa, pencillin(high doses).

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    II) NonII) Non--ImmuneHemolytic anemiasImmuneHemolytic anemias

    Due to mechanisms or agents other thanantibodies +/or complement e.g:

    Mechanical (traumatic)(fragmentaion)

    Toxins

    Infections

    Splenomegaly

    Burn(physical)

    Renal and liver failure

    chemical

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    MechanicalMechanical

    (traumatic,Fragmentation)(traumatic,Fragmentation)

    Due to direct trauma(stress)to the RBCcausing fragmentation and intra-vascularhemolysis.

    Peripheral blood smears : schistocytes Cause:

    1.Physical damage to RBC by abnormalsurfaces;

    Prosthetic valves

    Patches

    Valvular diseasee.g stenosis

    2.AV malformations

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