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Haemolytic Anaemia PowerPoint Presentation

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					HEMOLYTIC ANEMIA
EXTRACORPUSCULAR
     DEFECTS



         DR. SWAMY C.R.
Anemia resulting from an increase in the rate of red cell destruction.



       CAUSES:
       I.Immune
A.     A. Isoimmune
•      Hemolytic disease of the newborn
•      incompatible blood transfusion
•
B.     B. Autoimmune: lgG only; c’3 only; mixed lgG and C’3
       1.    Idiopathic
             a.Warm antibody
             b. Cold antibody
c.           c. Cold – warm (Donath – Landsteiner antibody)
SECONDARY:

  a. Infection, viral: Infectious mononucleosis
  (Epstein – Barr virus (EBVI), kcytomegalovius
  (CMV), hepatitis, herpes simplex, measles,
  varicella, influenza A, coxsackie B, human
  immunodeficiency virus (HIV), bacterial;
  streptococcal, typhoid fever, Escherichia coli
  sapticemia; Mycoplasma pneumoniae (atypical
  pneumonia).

  b.Drugs and chemicals: quinine, quinidine,
  phenacetin, p-aminosalicylic acid, Sodium
  cephalothin (Keflin), penicillin, tetracycline,
  rifampin,sulfonamides,chlorpromazine,pyramidon,
  dipyrone, insulin
 c.Hematologic disorders: leukemias, lymphomas,
  lymphoproliferative     syndrome,        idiopathic
  thrombocytopenic purpura (Evans        syndrome),
  paroxysmal     cold hemoglobinuria,    paroxysmal
  noctumal hemoglobinuria

 d.   Immunopathic disorders: Systemic lupus
  erythematosus, perirteritis nodosa, scleroderma,
  dermatomyositis, rheumatoid arthritis, ulcerative
  colitis,   agammaglobulinemia,  Wiskott   Aldrich
  syndrome, dysgammaglobinemai igA deficiency,
  thyroid disorders

 e.   Tumors : ovarian teratomate, dermods
     Nonimmune
A. Idiopathic
B. Secondary
 1. Infection, viral; infectious mononucleosis, viral
  hepatitis; bacterial; streptococcal, E.coli septicemia,
  clostridium perfringens, Bartonella bacilliformis;
  parasites; malaria, histoplasmosis.
 2. Drugs: phenylhydrazine, vitamin k, benzene,
  nitrobenzene       sulfones,     lead       phenacetin,
  acetinalimide
 3. Hematologic        disorders: leukemia, aplastic
  anemia, megaloblastic anemia, bypersplenism,
  pyknocytosis
 Microangiopathic hemolytic anemia: thrombotic
thrombocytopenic purpura, hemolytic uremic
syndrome, chronic relapsing schestocytstic
hemolytic anemia, burns, postcardiac surgery,
march hemoglobinuria.


 Miscellaneous: Wilson’s disease, erythropoietic
  porphyria, osteopetrosis, hypersplenism
 HEMOLYTIC DISEASE OF THE NEWBORN
 Immune hemolysis occurring in the fetus as a result of
  the transplacental passage of maternal antibody directed
  against a fetal red cell antigen that is not shared by the
  mother. The antibody is the product of the normal immune
  response to a foreign substance and is invariably of the
  lgG type, although hemolytic disease of the newborn
  caused by ABO incompatibility always has been more
  common than that caused by Rh incompatibility, ABO
  hemolytic disease is usually less severe and has not been
  associated with fetal and neonatal death or significant
  sequelae to the extent that Rh hemolytic disease has.
 The spectrum of pathologic conditions resulting from
  minimal anemia or hyperbilirubinemia to hydrops fetalis.
  ETIOLOGY AND PATHOGENESES
     Rh disease is most significant clinically because
   of its severity, although ABO hemolytic disease is
   about twice as common.
           The passage of fetal red cells across the
   placenta into the maternal circulation may result in
   the production of antibodies against fetal red cell
   antigens recognized by mother as “not self” .
           The introduction of a sensitive acid elution
   technique for identifying fetal cells by the
   demonstration of intracellular Hb F enabled the
   detection of 0.05 ml of fetal blood in the maternal
   circulation.
       The gestational are at which fetal maternal
transplacental leakage of red cells begins is uncertain, The
volume of fetal blood that at any one time enters the
maternal circulation during a normal pregnancy is small,
probably less than 0.1 ml.
  It is during delivery that larger boluses, greater than 0.2
      ml, enter the maternal circulation.

          It is these larger fetal maternal hemorrhages that
stimulate the production of antibody Immunology fetal maternal
bleeds may occur in spontaneous or induced abortions.
Entopic pregnancy, cesarean section and manual removal of
the placenta. The risk of sensitization is related to the volume
of the fetal maternal bleed ing.
     In general the larger the fetal – maternal hemorrhage, the
greater the incidence of demonstrable sensitization. Since
sensitization occurs most frequently during birth, the most
accurate indicator for sensitization is the demonstration of
maternal antibodies during the succeeding pregnancy, The
incidence of sensitization at the end of the second pregnancy is
about 17% in ABO compatible mothers.

 CLINICAL FEATURES
 § Jaundice – Noted with in the first 24 hrs after birth
    and in untreated infants reaches maximal levels
   § Immune hemolysis and anemia
   § Encephalopathy (kernicterus) – Caused by the
    effects of unconjugated bilirubin on the central
    nervous system.
   § Purpura associated with thrombocyutopenia
   § Hypoglycemia -is frequently noted in severally
    affected infants.
 INVESTIGATOINS
    Peripheral blood – Evidence for increased red
  cell destruction is the degree of anemia,
  reticulocytosis, and normoblasas, polychromasia and
  anisocytosis, intense leukocytosis may be seen in
  severely affected infants.
          Bone marrow – Erythroid hyperplasia is
  invariably present.
        Immunologic evaluation – The diagnosis is
  established if red cells from an Rh positive infant born
  to an Rh negative mother give a positive direct
  antiglobulin test.
       Serum bilirubin - Cord bilirubin levels are not
  high and levels in excess of 4 mg/dl are evidence of
  severe disease.

 THERAPY
 Prevention of Rh isosensitization            - Routine
    administration of Rh immune globulin to all
    unsensitized Rh-negative mothers who have given
    birth to an Rh-positive infant or who have had a
    spjontaneous or induced abortion.
   Administration of 300 micro grams of Rh immune
    globulin intramuscularly to all unsensitized Rh-
    negative women within 72 hours of the delivery of an
    Rh-positive infant. In cases in which Rh immune
    globulin has not been given within 72 hours, it should
    be administered late rather than withheld.
   After abortion – less than 12 weeks gestation, 50
    micro grams more than 12 weeks gestation, 100
    micro grams
   After amniocentesis – 50 micro grams (depending
    on amount of fetomaternal hemorrhage)
   After ruptured – ectopic pregnancy or manual
    version, 10 to 15 micro grams ml fetal blood.
 TREATEMENT OF THE AFFECTED INFANT
 v  Major objectives : 1). Prevention of intrauterine
    fetal death 2) prevention of bilirubin encepkjhalopathy
    in the live born infant.
   v      Prevention of intrauterine fetal death : The
    developing fetus s at risk from severe anemia, not
    from hyperbilirubinemia, since the placenta effectively
    clears this substance. Therapy of the severely
    affected fetus is directed therefore solely toward
    correcting the severe anemia.
   v     Prevention of bilirubin encephalopathy -
   Exchange transfusion : The volume of an exchange
    transfusion is usually calculated at two times the
    blood volume of the exchanged infant. Or about 160
    ml/kg.
   Phototherapy :

ABO HEMOLYTIC DISEASE OF THE NEWBORN
        A reported to Cause of about two thirds of the
cases of hemolytic disease of the newborn. It differs
from Rh hemolytic disease primarily in the degree of
severity. Severe hyperbilirubinemia is unusual and
hyudrops fetalis extremely rare. The pathophysiology of
ABO hemolytic disease is identical to that to Rh
disease. The antibody causing the immune destruction
is of the lgG class. Since igM anti – A or anti-B cannot
cross the placenta.
        ABO hemolytic disease is restricted almost to
tally to group A or B infants born to group O mothers.
        The reason for the lack of clinical disease are not
completely known. However, certain factors may affect
the interaction of anti –A with A cells in the fetus and
newborn.
2.     A weakly Positive direct antiglobulin test on cord
blood or newborn blood may be found.
3.     free anti – A or anti –B may be demonstrated in the
serum of the newborn.
4.     Confirmatory evidence is the presence of lgG anti
–A or and –B in the maternal serum.

     TREATMENT
            Therapy of severe ABO hemolytic disease is
     similar to that of Rh hemolytic disease. In the
     frequently occurring mild cases phototherapy or
     phenobarbital therapy can be given.
   WARM AUTOIMMUNE HEMOLYTIC ANEMIA
   Antibodies of the lgG class arWARe most
commonly responsible for AIHA in children. The
antigen to which the lgG antbody is directed is one of
the Rh erythrocyle antigens in more than 70% of
cases. The antibody usually has its maximal activity at
37%C, and resultant hemolysis is called warm
antibody-induced hemolytic anemial. Rarely, warm –
reacting lgM antibodies may be responsible.
 Clinical Features
 1. Severe, life-threatening condition
 2. Sudden onset of pallor, jaundice, dark urine
 3. Splenomegaly
 4. Laboratory findings.
 a. Hemoglobin level: may be very low
 b. Marked reticulocytosis is very common
 c. Smear: prominent spherocytes, polychromasia,
  macrocytes, autoagglutination
 d. Neutropenia and thrombocytopenia (occasionally)
 e. Increased osmotic fragility and autohemolysis
  proportional to sphero cytes
  •   a. Direct coombs test positive
  •  b. Hyperbilirubinemia

  • c.        Haptoglobin level is usually markedly
  decreased
  • d.          Hemoglobinuria, increased urinary
  urobilinogen
  •

MANAGEMENT
       Because this is a life-theatening condition, the
following parameters must be monitored carefully.
1.     Hemoglobin level (q4h)
2.     Reticulocyte count (daily)
3.     Splenic size (daily)
4.     Hemoglobinuria (daily)
 5.     Haptoglobin level (weekly)
 6.     Coombs test (weekly
        TREATMENT
1.      Blood transfusion
a.       If specific antibody is identified, compatible donor
may be selected.
b. Washed packed red cells should be used
c.      The volume of transfused blood should only be of
sufficient quantity to relieve any cardiopulmonary
embarrassment from the anemia.
2.      Corticosteriod therapy.
a.                 Hydrocortisone 8-40 mg/day IV in divided
doses (q8h) or prednisone 2-10 mg/day PO is
administered. dosage corticosteroid therapy should be
a.           High
maintained for several days. Threafter, corticosteroid
therapy in the form of prednisone should be slowly
tapered off over a 3 to 4 week period.
3.Plasmapheresis
has been successful in slowing the rate of hemosysis in
patients with severe IgG- induced immune hemolytic
anemia. Success is limited, possibly because more than
half of the IgG is extravascular and the plasma contains
only small amounts of the antibody ; most of the antibody
is on the red cell surface.

4.Intravenous gamma globulin (IVGG) in a dose of 5
gm/kg,

5.splenectomy: Indicated if the hemolytic process
continues to be brisk despite highdosage corticosteroid
therapy and intravenous gamma globulin for 3-4 weeks.
6.    Cytoxic Agents
a.                    Antimetabolites : azathioprine, 6-
mercaptopurine, and thiroguanine
b.                  Alkylating agents: chlorambucil and
cyclophosphamide.
c.        Mitotic inhibitos: vincristine and vinblastine

7.    Immunosuppressive therapy: Cyclosporine

8.    Hormonal therapy : danazol, (synthetic
androgen). which has a masculinizing effect. Appears to
be due to decreased expression of macrophage Fcy
receptor activity;
COLD AUTOIMMUNE HEMOLYTIC ANEMIA
       IgM antibodies are found less often in association
with hemolysis in the pediatric age group. The destruction
of red blood cells is usually triggered by cold exposure.
Cold hemagglutinin disease usually occurs during 1.
Mycoplasma pneumoniae infection             2. Infectious
mononucleosis, 3. cytomegalovirus            4. mumps..



CLINICAL FEATURES
      Similar to those in warm autoimmune hemolytic
anemia but are less marked.
TREATMENT
       Treatment consists of control of the underlying
disorder. 1. Blood Transfusions may be necessary ;
warming the blood to 370 C during administration by means
of a heating coil or water bath is indicated to avoid further
temperature activation of antibody.
       If the anemia is severe, a trial of cytotoxic drug
therapy is appropriate. Alkylating agents such as
cyclophosphamide and chlorambucil.          Treatment with
corticosteroids or splenectomy is generally not effective.
Plasmapheresis is a valuable approach to reducing the
level of cold agglutinins.
DONATH LANDSTEINER COLD HEMOLYSIS
       An unusual igG antibody with anti –P specificity, is
responsible. This antibody, although uncommon, is most
frequently found in children with viral infections. Hemolysis
in this syndrome is most commonly intravascular as a
result of the unusual complement activating efficiency of
this IgG antibody. Hemolysis, which is usually mild, may
occasionally be severe but resolves as the infection clears.

MICROASGIOGRAPHIC HEMOLYTIC ANEMIA
      The blood smear is characterized by the presence
of buu erythrocytes, schistocytes, helmet cells, and
microspheocytes.
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