Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Scribd Logo
Upload

Welcome to Scribd!

  • 7 views

    Hereditary Haemolytic Anaemia - Handout-By DR - Chandima Kulathilake-26th Batch

    Uploaded by

    chanakacb1

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd

    Hereditary Haemolytic Anaemia - Handout-By DR - Chandima Kulathilake-26th Batch

    Uploaded by

    chanakacb1
    7 views7 pages

    Original Title

    Hereditary haemolytic anaemia -Handout-By Dr.Chandima Kulathilake-26th batch

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    7 views7 pages

    Hereditary Haemolytic Anaemia - Handout-By DR - Chandima Kulathilake-26th Batch

    Uploaded by

    chanakacb1

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 7

    Haemolytic anaemia

     Classified as hereditary and acquired.

    Hereditary Haemolytic Anaemias


    Due to intrinsic or intracorpuscular red cell defects.
    1). Red cell membrane defects
    - Hereditary Spherocytosis
    - Hereditary Elliptocytosis
    2). Red cell enzymes defects (defects in metabolism)
    - Glucose 6 Phosphate dehydrogenase deficiency (G6PD deficiency)
    - Pyruvate kinase deficiency

    3). Abnormal haemoglobin (haemoglobinopathies)


    - Thalassaemia
    - Sickle cell disease
    - Haemoglobin C,E,D
    - Unstable haemoglobin

     Red cell membrane defects


    (1)Hereditary Spherocytosis (HS)
    HS is the commonest hereditary haemolytic anaemia among North Europeans.
    This is usually caused by defects in the structural proteins involved in the vertical interactions
    between membrane skeleton and lipid bilayer of the red cell membrane.
    The most common membrane abnormality is a reduction in spectrin content.
    Pathogenesis

    Loss of membrane (due to release of parts of the lipid bilayer that are not supported by the
    protein skeleton) as they circulate through the spleen & rest of the RE system.

    Produce spherocytes (loss of surface area relative to volume)

    Ultimately, Spherocytes are unable to pass through the splenic microcirculation

    Premature destruction of RBC

    Inheritance
    The inheritance is autosomal dominant with variable expression (patients have different levels of
    clinical presentations).
    Rarely, inherited as autosomal recessive.
    **Family studies are important in confirmation.

    Clinical features
    There is a wide spectrum of severity. Usually,severity tends to be similar among members of the
    same family, but exceptions are seen.
    Some patients can be asymptomatic.
    Patients can present with anaemia and icterus at any age from infancy to old age.
    Patients lead a near normal life with the mild to moderate chronic haemolytic process.
    Jaundice and anaemia get aggravated by infection or exercise which cause increase in the
    haemolytic process.
    Neonatal jaundice is also one of the presentations
    Splenomegaly is seen in most patients.
    Complications
    1.Pigment gallstones
    2. Aplastic crisis – usually precipitated by Parvo virus infection.May cause sudden increase
    in the severity of anaemia.

    Laboratary findings
     Usual biochemical investigations of EVH are positive

     Haematological
    Anaemia is usual but not invariable
    Reticulocytosis (usually 5-20%)
    Blood film – Spherocytes (densely staining with smaller diameters than that of normal red cells)
    MCHC ( increased )

    Blood film- spherocytes

     Other special laboratory tests to confirm the diagnosis


    1.Osmotic fragility – increased.*Not a specific test. Positive in any spherocytic condition
    2.Acidified Glycerol Lysis Test (AGLT50)-positive
    3.*Cryohaemolysis test-Specific test. Confirms the diagnosis.
    4.*Direct antiglobulin test(DAT) /Coombs test- Normal.
    5.Red cell membrane studies –not freely available in SL

    Management
    1.The principle form of treatment is Splenectomy but NOT performed unless clinically indicated.
    Eg. Anaemia requiring frequent transfusions, gallstones
    2. Regular folic acid supplements are given to prevent folate deficiency.
    3.When haemolysis is precipitated/aggravated by infection and exercise patients may need blood
    transfusion at times.
    Differential diagnosis of spherocytes
     ABO Haemolytic disease of the new born
     Autoimmune haemolytic anaemia
     Clostridium welchii infection
     Burns
     Haemolytic transfusion reactions

    (2)Hereditary Elliptocytosis
    This is also due to defect in structural proteins.(ankyrin or spectrin)
    Usually a milder disorder with no haemolysis in most patients. This is usually discovered by
    chance on a blood film.
    Severe disease in homozygous state(hereditary pyropoikilocytosis)

     Red cell enzymes defects


    (1)Glucose-6-phosphate dehydrogenase (G6PD) deficiency

    This is a disorder with a sex-linked(X chromosome) inheritance, affecting males, and carried by
    females.
    Usually this is seen in Africa, Mediterranean and Middle East.
    Pathogenesis

    The G6PD enzyme is needed to produce nicotinamide adenine dinucleotide phosphate


    (NADPH). NADPH is a required cofactor to maintain glutathione in its reduced form(GSH)in
    the red cell.
    Reduced glutathione protects the RBC from oxidant stress.
    People deficient in glucose-6-phosphatase dehydrogenase (G6PD) will undergo rapid hemolysis
    under oxidative stresses.

    Agents which may cause haemolytic anaemia in G6PD deficiency


     Infections /acute illnesses
     Drugs
    Antimalarials-primaquine,chloroquine,Fansidar
    Sulphonamides-Dapsone,co-trimoxazole
    Other antibacterial agents-nitrofurans
    chloramphenicol
    Analgesics- aspirin
    Clinical features

    Usually asymptomatic and blood counts are normal. They present with acute haemolytic
    anaemia in response to oxidant stress by infection or drugs
    Patients present with massive intravascular haemolysis with haemoglobinuria.
    Other presentations are,
     Neonatal jaundice
     Rarely congenital non-spherocytic haemolytic anaemia (a chronic haemolytic process)
    occurs

    Laboratory findings
    During acute episode,
     Haematological
    1.Anaemia
    2.Reticulocytosis
    3.Blood film
    contracted and fragmented cells, bite and blister cells.
    Blister cell

    bite cell (when oxidized, denatured Hb is


    removed by the spleen)

    4.Features of intravascular haemolysis


    - Low / absent serum haptoglobins
    - Methhaemoglobinaemia
    - Haemoglobinaemia
    - Haemoglobinuria

    5. Specific test
    *Heinz bodies ( oxidized, denatured haemoglobin )are seen in the reticulocyte preparation.
    (Heinz body preparation). Only test that can be used to diagnose the condition in a acute crisis.

    During acute episode, increased reticulocytes which have near normal enzyme levels will
    give a false normal value to G6PD enzyme assay.

    After the acute phase,


    1. Brewer’s test ( methaemoglobin reduction test)- for screening
    ( If done during acute phase increased reticulocytes will produce a false negative result)
    2. Enzyme assay - on red cells
    when reticulocyte count is normal

    Treatment
    Stop the offending drug.
    Treat the infection
    Supportive Rx until haemolysis settles spontaneously
    -Maintain a high urine output
    -Consider blood transfusion in severe anaemia

    (2)Pyruvate Kinase deficiency

    Autosomal recessive
    Reduced ATP formation
    Anaemia ,jaundice
    BP- prickle cells Dr Chandima Kulathilake
    Diagnosed by enzyme assay
    Splenectomy in pts with frequent transfusions Senior Lecturer/Consultant
    Haematologist

    Dept of Pathology,FMS,USJ

    You might also like