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UNIVERSIDAD AUTÓNOMA DE GUERRERO

   UNIDAD ACÁDEMICA FACULTAD DE MEDICINA

 ENGLISH CLASS: HEMOLYTIC DISEASE OF
 NEWBORN

 EQUIPO FISIOLOGÍA.

Mendoza McGinnis Gema Itzel
Villagómez Vélez Julio Andrés
Arzeta Serrano Laura Gabriela
Hernández Barrera Mario
Objectives
    The student is expected to learn about clinical
    symptoms, diagnosis, and treatment for hemolytic
    newborn disease.

    Reinforce everything learned in physiology class by
    applying a case study.

    Participate in a group dynamic to simplify the learning
    experience.
 Antibodies - Anticuerpos
 Shortened - acortado
 Ocurring - ocurriendo
 Ag Glutination - Glutinacion antigenico
 Inmunogenic - Inmunogenico
 Involves - Involucrar
 Phagocytic - Fagocitico
 Binding -
 Fristloorn -
 Microspheocytes - Microfeoscitos.
Hemolytic disease of the new born and fetus
   (HDN) is a destruction of the red blood
  cells (RBCs) of the fetus and neonate by
     antibodies produced by the mother

It is a condition in which the life span of the
  fetal/neonatal red cells is shortened due to
    maternal allo-antibodies against red cell
        antigens acquired from the father
Antibodies
   Five classes of antibodies
        IgM
        IgG

        IgA

        IgD

        IgE

   Blood groups specific antibodies are
        IgG
        IgM and rarely

        IgA
Blood group antibodies
   Blood group antibodies can be classified as
          Naturally occurring and immune antibodies
             Depending on presensitization



          Complete and incomplete antibodies
             Depends on agglutination of saline suspended
              red cells
             IgM is complete antibody; most naturally
              occurring antibodies are complete and of IgM
              class
             IgG is incomplete antibody
Antibodies of ABO system

   Anti- A

   Anti- B

   Anti- A1


   Anti- H
Antibodies of Rh system
   Naturally occurring
         Anti- E
         Occasionally anti-D and anti Cw




   Immune antibodies
         D antibodies are more immunogenic
         Other are anti c, E, e, C.

         Most common is anti- E

         After anti- D, anti- c is the common cause of HDN



(The vast majority of Rh antibodies are IgG and do not fix complement)
Complement
   Complements are series of proteins, present
    in plasma as an inactive precursors

   When activated and react sequentially with
    each other they mediate destruction of cells
    and bacteria

   Complement activation involves two stages
        Opsonization
        Lytic stage
Complement

   Antibodies can fix complement and cause rapid
    destruction of red cells

   Destruction depends on the amount of antibody
    and complement

   In ABO- incompatible transfusion no surviving A
    or B red cells can be seen after 1 hour of
    transfusion
          Why?
          Remember naturally occurring Abs. are IgM and fix
           complement mediating the hemolysis
Disease mechanism - HDN
   There is destruction of the RBCs of the
    fetus by antibodies produced by mother

          If the fetal red cells contains the corresponding
           antigen, then binding of antibody will occur to red
           cells


   Coated RBCs are removed by
    mononuclear phagocytic system
Neonatal
      liver is immature and
         unable to handle
              bilirubin

                              Unconjugated
                                bilirubin
                               Conjugated
                                bilirubin


Coated red blood cell
 are hemolysed in
      spleen
Clinical features
   Less severe form
     Mild   anemia

   Severe forms
     Icterus    gravis neonatorum (Kernicterus)
   Intrauterine death
     Hydrops  fetalis
        Oedematous, ascites, bulky swollen & friable
         placenta
        Pathophysiology
              Extravascular hemolysis with extramedullary
               erythropoiesis
              Hepatic and cardiac failure
Hemolytic disease of newborn HDN
BOFORE BIRTH
 Anemia (destruction of red cells)
 Heart failure
 Fetal death


AFTER BIRTH
 Anemia (destruction of red cells)
 Heart failure
 Build up of bilirubin
 Kernicterus
 Severe growth retardation
Rh HEMOLYTIC DISEASE OF
               NEWBORN
   Antibodies against
          Anti-D and less commonly anti-c, anti-E
 Mother is the case of anti-D is Rh -ve
  (negative)
 Firstborn infant is usually unaffected
 Sensitization of mother occurs
        During gestation
        At the time of birth

   All subsequent offspring inheriting D-antigen
    will be affected in case of anti-D HDN
Pathogenesis

             Fetomaternal Hemorrhage

Maternal Antibodies formed against Paternally derived
                       antigens

 During subsequent pregnancy, placental passage of
              maternal IgG antibodies

  Maternal antibody attaches to fetal red blood cells

            Fetal red blood cell hemolysis
Factors affecting immunization and
severity
   Antigenic exposure

   Host factors

   Antibody specificity

   Influence of ABO group
          ABO-incompatible Rh- positive cells will be hemolysed
           before Rh antigen can be recognized by the mother’s
           immune system
Diagnosis and Management
   Cooperation between

     Pregnant    patient

     Obstetrician


     Her   spouse

     Clinical   laboratory
Diagnosis and Management contd.
   Intrauterine transfusion
            Zone II or III
            Cordocentesis blood sample Hb less than 10g/dl
            Ultrasound evidence of hydrops

 Early delivery
 Phototherapy
 Newborn transfusion
        Exchange transfusion
        Effects of transfusion
            Removal of bilirubin
            Removal of sensitized RBCs, and antibodies
            Suppression of incompatible erythropoiesis
Mechanism of action
 Administered   antibodies will
  bind the fetal Rh- positive cells
 Spleen captured these cells by
  Fc-receptors
 Suppressor T cell response is
  stimulated
 Spleen remove anti-D coated
  red cells prior to contact with
  antigen presenting cells
  “antigen deviation”
ABO HEMOLYTIC DISEASE OF
            NEW BORN
   For practical purpose, only group O
    individuals make high titres IgG

   Anti-A and anti-B are predominantly IgM

   ABO antibodies are present in the sera of all
    individuals whose RBCs lack the
    corresponding antigens
ABO HDN contd.
   Signs and symptoms
          Two mechanism protects the fetus against anti-A and anti-B
               Relative weak A and B antigens o fetal red cells
               Widespread distribution of A & B antigen in fetal tissue diverting
                antibodies away from fetal RBCs
          Anemia is most of the time mild
          ABO- HDN may be seen in the first pregnancy

   Laboratory findings
          Differ from Rh- HDN; microspherocytes are characteristic of ABO-
           HDN
          Bilirubin peak is later; 1- 3 days after birth
          Collection of cord blood and testing eluates form red cells will
           reveal anti-A or anti-B

   Treatment
          Group O donor blood for exchange transfusion which is rarely
           required
Hemolytic Disease of Newborn Explained

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Hemolytic Disease of Newborn Explained

  • 1. UNIVERSIDAD AUTÓNOMA DE GUERRERO UNIDAD ACÁDEMICA FACULTAD DE MEDICINA ENGLISH CLASS: HEMOLYTIC DISEASE OF NEWBORN EQUIPO FISIOLOGÍA. Mendoza McGinnis Gema Itzel Villagómez Vélez Julio Andrés Arzeta Serrano Laura Gabriela Hernández Barrera Mario
  • 2. Objectives The student is expected to learn about clinical symptoms, diagnosis, and treatment for hemolytic newborn disease. Reinforce everything learned in physiology class by applying a case study. Participate in a group dynamic to simplify the learning experience.
  • 3.  Antibodies - Anticuerpos  Shortened - acortado  Ocurring - ocurriendo  Ag Glutination - Glutinacion antigenico  Inmunogenic - Inmunogenico  Involves - Involucrar
  • 4.  Phagocytic - Fagocitico  Binding -  Fristloorn -  Microspheocytes - Microfeoscitos.
  • 5.
  • 6.
  • 7.
  • 8. Hemolytic disease of the new born and fetus (HDN) is a destruction of the red blood cells (RBCs) of the fetus and neonate by antibodies produced by the mother It is a condition in which the life span of the fetal/neonatal red cells is shortened due to maternal allo-antibodies against red cell antigens acquired from the father
  • 9. Antibodies  Five classes of antibodies  IgM  IgG  IgA  IgD  IgE  Blood groups specific antibodies are  IgG  IgM and rarely  IgA
  • 10. Blood group antibodies  Blood group antibodies can be classified as  Naturally occurring and immune antibodies  Depending on presensitization  Complete and incomplete antibodies  Depends on agglutination of saline suspended red cells  IgM is complete antibody; most naturally occurring antibodies are complete and of IgM class  IgG is incomplete antibody
  • 11. Antibodies of ABO system  Anti- A  Anti- B  Anti- A1  Anti- H
  • 12. Antibodies of Rh system  Naturally occurring  Anti- E  Occasionally anti-D and anti Cw  Immune antibodies  D antibodies are more immunogenic  Other are anti c, E, e, C.  Most common is anti- E  After anti- D, anti- c is the common cause of HDN (The vast majority of Rh antibodies are IgG and do not fix complement)
  • 13. Complement  Complements are series of proteins, present in plasma as an inactive precursors  When activated and react sequentially with each other they mediate destruction of cells and bacteria  Complement activation involves two stages  Opsonization  Lytic stage
  • 14. Complement  Antibodies can fix complement and cause rapid destruction of red cells  Destruction depends on the amount of antibody and complement  In ABO- incompatible transfusion no surviving A or B red cells can be seen after 1 hour of transfusion  Why?  Remember naturally occurring Abs. are IgM and fix complement mediating the hemolysis
  • 15. Disease mechanism - HDN  There is destruction of the RBCs of the fetus by antibodies produced by mother  If the fetal red cells contains the corresponding antigen, then binding of antibody will occur to red cells  Coated RBCs are removed by mononuclear phagocytic system
  • 16. Neonatal liver is immature and unable to handle bilirubin Unconjugated bilirubin Conjugated bilirubin Coated red blood cell are hemolysed in spleen
  • 17. Clinical features  Less severe form  Mild anemia  Severe forms  Icterus gravis neonatorum (Kernicterus)  Intrauterine death  Hydrops fetalis  Oedematous, ascites, bulky swollen & friable placenta  Pathophysiology  Extravascular hemolysis with extramedullary erythropoiesis  Hepatic and cardiac failure
  • 18. Hemolytic disease of newborn HDN BOFORE BIRTH  Anemia (destruction of red cells)  Heart failure  Fetal death AFTER BIRTH  Anemia (destruction of red cells)  Heart failure  Build up of bilirubin  Kernicterus  Severe growth retardation
  • 19. Rh HEMOLYTIC DISEASE OF NEWBORN  Antibodies against  Anti-D and less commonly anti-c, anti-E  Mother is the case of anti-D is Rh -ve (negative)  Firstborn infant is usually unaffected  Sensitization of mother occurs  During gestation  At the time of birth  All subsequent offspring inheriting D-antigen will be affected in case of anti-D HDN
  • 20. Pathogenesis Fetomaternal Hemorrhage Maternal Antibodies formed against Paternally derived antigens During subsequent pregnancy, placental passage of maternal IgG antibodies Maternal antibody attaches to fetal red blood cells Fetal red blood cell hemolysis
  • 21.
  • 22. Factors affecting immunization and severity  Antigenic exposure  Host factors  Antibody specificity  Influence of ABO group  ABO-incompatible Rh- positive cells will be hemolysed before Rh antigen can be recognized by the mother’s immune system
  • 23. Diagnosis and Management  Cooperation between  Pregnant patient  Obstetrician  Her spouse  Clinical laboratory
  • 24. Diagnosis and Management contd.  Intrauterine transfusion  Zone II or III  Cordocentesis blood sample Hb less than 10g/dl  Ultrasound evidence of hydrops  Early delivery  Phototherapy  Newborn transfusion  Exchange transfusion  Effects of transfusion  Removal of bilirubin  Removal of sensitized RBCs, and antibodies  Suppression of incompatible erythropoiesis
  • 25. Mechanism of action  Administered antibodies will bind the fetal Rh- positive cells  Spleen captured these cells by Fc-receptors  Suppressor T cell response is stimulated  Spleen remove anti-D coated red cells prior to contact with antigen presenting cells “antigen deviation”
  • 26. ABO HEMOLYTIC DISEASE OF NEW BORN  For practical purpose, only group O individuals make high titres IgG  Anti-A and anti-B are predominantly IgM  ABO antibodies are present in the sera of all individuals whose RBCs lack the corresponding antigens
  • 27. ABO HDN contd.  Signs and symptoms  Two mechanism protects the fetus against anti-A and anti-B  Relative weak A and B antigens o fetal red cells  Widespread distribution of A & B antigen in fetal tissue diverting antibodies away from fetal RBCs  Anemia is most of the time mild  ABO- HDN may be seen in the first pregnancy  Laboratory findings  Differ from Rh- HDN; microspherocytes are characteristic of ABO- HDN  Bilirubin peak is later; 1- 3 days after birth  Collection of cord blood and testing eluates form red cells will reveal anti-A or anti-B  Treatment  Group O donor blood for exchange transfusion which is rarely required