Download - Hemolytic Anemia by Areej T.Kadhum
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Hemolytic Anemiaby
Areej T.Kadhum
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Haemolysis • Normal life span of a RBC is 120 days (80-90 days in
a full term infant). Senescent RBC is detected & cleared by RE.
• Reduced/shortened life span = premature cell destruction + No marrow compensation Abnormal hemolysis
Hemolytic Anemia is a condition in which the blood has a low number of erythrocytes due to premature destruction of RBCs coupled with increased erythropoieses.
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Classification
• There are many types of hemolytic Anemia, classified according to the site of RBC destruction-Intravascular or Extravascular & cause of hemolysis.
• the causing factors can be Intrinsic (defect is within the cell) or Extrinsic ( external impact)
• Intrinsic factor is Inherited . Extrinsic is often acquired.
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Inherited (ntracorpuscular)
• Enzymopathies (Deficiency of G6PD , pyruvate kinase,hexokinase def.)
• Defects of red cell membrane: spherocytosis,elliptocytosis
acanthocytosis • Hemoglobinopathies,sickle
cell,hemoglobin E disease.• Infantile pyknocytosis
Acquired (extracorpuscular)
• Immune mediated: Alloimmune : Rh
incompatibility and ABO hemolytic disorders
• Oxidant drugs induced hemolysis (primaquine)
• Autoimmune:• Infections such as hep.
C ,HIV , Malaria,tuberculosis.• Burns• Microangiopathy• Transfusion reaction.
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Cytoskeleton of RBC• Note the Spectrin mesh
like pattern , main demonstrating protein on the membrane. Together with ankyrin maintain the normal bi concave shape of the cell, if any defect of spectrin - reduced density of membrane skeleton, (spheroid RBC ) recognized by RE as abnormal shaped and destoyed in the spleen
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Favism linked to hemolytic G6PD deficiency
Opss! Avoid fava beans in type II G6PD def.
Most common in Mediterranean countries, south Europe and Middle East
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Diagnosis of HASymptoms depend on degree & severity of hemolysis (the rate of destruction)Clinical features: general anemia symptoms (fatigue,dyspnea,palpitations, postural dizziness, cold extremities etc), In severe phases: lemon yellowish sclera & jaundice Lab. Findings: reticulocytosis , high MCV, elevated indirect bilirubin, elevated LDH, low haptoglobin, positive DAT (Coomb’s test) in AIHA, negative in non-immune mediated types.Acute intravascular hemolysis: fever, chills, low back pain, hemoglobinuria, & hemosiderinuria( usually seen 3-4 days after the onset of hemolytic conditions)Blood Smear: polychromatophilia (a sign of b.marrow stress), spherocytosis & autoagglutination
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• Intravascular hemolysis event:• Immediate drop in Haptoglobin; rises at 2
days• Hemoglobinemia detectable 6-12 hrs post
hemolytic phase• Hemoglobinuria detectable 12-24 hrs• Hemosiderinuria detectable 3-12 days• Methemalbumin detectable 1-12 days
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Drug-induced Hemolysis
• May occur by an immune mechanism or by challenging the RBC metabolic machinery
• Oxidant drugs causing hemolysis in G6PD deficiency: sulfa drugs,anti-pyretics, dapsone, primaquine, pyridium, doxorubicin
• Drugs causing immune-mediated hemolysis: penicillin, quinidine, methyldopa, streptomycin
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Drug Induced Hemolysis
• Formation of antibodies specific to the drugs: in high doses of PCN bind proteins on RBC membrane, patient forms Ab against PCN- RBC is destroyed.
• Induction of Abs to RBC membrane antigens:methyldopa induces autoAb to Rh Ag
• Selective binding of streptomycin to RBC membrane with formation of complement fixing antibody
• All have Coombs (DAT) positive for IgG
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Immune Complex Mechanism
• Drug and antibody bind in the plasma• This Immune complex will either–Activate complement in the plasma, or–Choose a RBC surface to occupy
• Antigen-antibody complex recognized by RE system
• RBC is destroyed as “innocent bystander” of destruction of immune complex.
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Compatibility check before graft & transfusion
• 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),performed if no clear result from the easier screening tests.
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Transfusion reaction-Alloimmune
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Alloimmune HemolysisHemolytic Disease of the Newborn
• Due to incompatibility between mother negative for an antigen & fetus + his father r positive for that antigen. Rh incompatibility, ABO incompatibility most common causes
• Usually occurs with 2nd or later pregnancies• Requires maternal IgG antibodies and RBC
antigens in fetus• can be prevented by administration of anti-Rh
to Rh negative mothers after each pregnancy
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Autoimmune HA
• Occurs due to formation of autoantibodies that attack patient’s own RBC’s
• Generally has 2 types: Warm & Cold each type is characterized by ability of autoantibodies to fix complement & site of RBC destruction
• Often is secondary ,associated with either lymphoproliferative disease ,collagen vascular disease ,&infections.
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Associated & leading causes-AIHA
• SLE – due to immune dysregulation• Non-Hodgkins lymphomas• Hodgkins disease• Myeloma• HIV• Hepatitis C• Mumps , Mycoplasma infections• Idiopathic
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Warm Type - AIHA• Mainly IgG antibodies• Fix complement to level of C1 & C3• Antibodies are warm n bind best at a temp of 37
C.• Fc receptors +/- C3b recognized by macrophages,• Hemolysis primarily extravascular• About 60% is associated with other disorders.• Respond to steroids(prednisone 2mg/day)
splenectomy in severe chronic cases.
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Cold Type-AIHA• IgM mediated, most commonly with
Mycoplasma infections• Antibodies can bind at 6º C or lower• Fix entire complement cascade• Typically only complement found on
cells(Macrophages have no Rcs to detect IgM coated cells , if complement is absent.
• Intravascular hemolysis (by hepatic cells)• 90% associated with other disorders.• Shows no response to steroids, splenectomy;
responsive to plasmapheresis
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(+) Coombs test inImmune mediated HA
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