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Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in...

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Hemolytic Anemia by Areej T.Kadhum
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Page 1: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

Hemolytic Anemiaby

Areej T.Kadhum

Page 2: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 3: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 4: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 5: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 6: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 7: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 8: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

• 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

Page 9: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 10: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 11: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 12: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 13: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

Transfusion reaction-Alloimmune

Page 14: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 15: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.
Page 16: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 17: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

Associated & leading causes-AIHA

• SLE – due to immune dysregulation• Non-Hodgkins lymphomas• Hodgkins disease• Myeloma• HIV• Hepatitis C• Mumps , Mycoplasma infections• Idiopathic

Page 18: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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.

Page 19: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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

Page 20: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

(+) Coombs test inImmune mediated HA

Page 21: Hemolytic Anemia by Areej T.Kadhum. Haemolysis Normal life span of a RBC is 120 days (80-90 days in a full term infant). Senescent RBC is detected & cleared.

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