HEMOLYTIC ANEMIA EXTRACORPUSCULAR DEFECTS

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

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• CAUSES
• I.Immune
• A. A. Isoimmune
• Hemolytic disease of the newborn
• incompatible blood transfusion
•  
• B. B. Autoimmune lgG only c3 only mixed lgG
  and C3
• 1. Idiopathic
• a.Warm antibody
• b. Cold antibody
• c.                  c. Cold warm (Donath
  Landsteiner antibody)

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 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
SECONDARY
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• 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

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• Nonimmune
• Idiopathic
• 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

• 4.

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• Microangiopathic hemolytic anemia thrombotic
  thrombocytopenic purpura, hemolytic uremic
  syndrome, chronic relapsing schestocytstic
  hemolytic anemia, burns, postcardiac surgery,
  march hemoglobinuria.

• Miscellaneous Wilsons disease, erythropoietic
  porphyria, osteopetrosis, hypersplenism

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• HEMOLYTIC DISEASE OF THE NEWBORN
• ØImmune 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.
• ØThe spectrum of pathologic conditions resulting
  from minimal anemia or hyperbilirubinemia to
  hydrops fetalis.

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• ETIOLOGY AND PATHOGENESES
• Ø      Rh disease is most significant clinically
  because of its severity, although ABO hemolytic
  disease is about twice as common.
• Ø      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
  .
• Ø      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.
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• It is during delivery that larger boluses,
  greater than 0.2 ml, enter the maternal
  circulation.

  Ø      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. Ø      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.
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• 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.

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• INVESTIGATOINS
• ü      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.
• ü      Bone marrow Erythroid hyperplasia is
  invariably present.
• ü      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.
• ü      Serum bilirubin - Cord bilirubin levels
  are not high and levels in excess of 4 mg/dl are
  evidence of severe disease.

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• THERAPY
• üPrevention 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.
• üAdministration 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.

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• 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
•  

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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.
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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.  
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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
37C, and resultant hemolysis is called warm
antibody-induced hemolytic anemial. Rarely, warm
reacting lgM antibodies may be responsible.
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• 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

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•  
• 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
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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.
a.                 High dosage corticosteroid
therapy should be maintained for several days.
Threafter, corticosteroid therapy in the form of
prednisone should be slowly tapered off over a 3
to 4 week period.
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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.  
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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
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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.

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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.  
 
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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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