Transcript HDNewborn

Hemolytic disease
of newborn
Dr. Tariq M.Roshan
Dept. of Hematology
PPSP
Objectives
Definition & characteristics
 ABO vs Rh hemolytic disease of the
newborn

Pathogenesis
 Incidence
 Blood types of mother and baby
 Severity of disease
 Laboratory data
 Prevention
 Rh immune globulin
 Tests for feto-maternal hemorrhage
 Exchange transfusion protocol

Hemolytic disease of newborn
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

Biochemistry of antibodies

Made from four
polypeptide chains



Two light (L) chains
Two identical heavy (H)
chains
Each class has
immunologically
distinct heavy chain
Biochemistry of antibodies
IgG1 IgG2 IgG3 IgA
IgM
IgE
Compliment
fixation
++
+
+++
-
+++
-
Placental
transfer
++
+
+
-
-
-
Lymphocyte /
macrophage
FcR binding
+
-
+
-
-
-
Blood group antibodies

Blood group antibodies can be classified as

Naturally occurring and immune antibodies


Depending on presensitization
Cold and warm antibodies
Thermal range of antibodies
 Most natural Abs are cold & some e.g wide thermal range like
Anti A and Anti B
 Most immune Abs are warm and can destroy red cell in-vivo


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



Naturally occurring
Immune
Anti- B


Naturally occurring
Immune

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)
Antibodies from other blood group
systems

Anti- K
Kell blood group system
 Usually is immune antibody
 Warm Ab


Anti- Jka
Kidd blood group system
 Usually is immune antibody
 Warm Ab

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
Pathogenesis; before
birth
Pathogenesis; after
delivery
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
P
N
Blood film of a fetus affected by HDN showing polychromasia
and increased number of normaoblasts
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
Recommended obstetric practice
History; including H/O previous pregnancies
or and disease needing blood transfusion
 ABO and Rh testing
 Antibody detection;

To detect clinically significant IgG Ab which reacts at
370C
 Repeat testing required at 24 or 28 weeks if first test
negative

Antibody specificity
 Parental phenotype
 Amniocyte testing


Antibody titres


Difference of 2 dilutions or score more
than 10 is significant
Amniocentesis and
cordocentesis


Concentration of bilirubin
Spectrophotometric scan


Indirect method
 Increasing or un-change OD as
pregnancy advance shows
worsening of the fetal hemolytic
disease
Fetal blood sample can be taken and
tested for

Hb, HCT, blood type and DCT (Direct
Coombs test)
Percutaneous
Umbilical blood
sampling
Liley graph
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

Diagnosis and Management contd.

Selection of blood
 Group
O RBCs
 Rh-negativve units for Rh-negative case
 Whole blood group O
 Blood less than 7 days old
Diagnosis and Management contd.
Prevention of Rh- HDN

Prevention of active immunization
Administration of corresponding RBC antibody
(e.g anti-D)
 Use of high-titered Rh-Ig (Rhogam)


Calculation of the dose

Kleihauer test for fetal Hb
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





Anemia is most of the time mild
ABO- HDN may be seen in the first pregnancy
Laboratory findings




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
Differ from Rh- HDN; microspherocytes are characteristic of ABOHDN
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
HDN- due to other antibodies

Anti-c


Usually less severe than that cause by Anti-D
Anti-K

May cause severe fetal anemia
 Blood
transfusion for the treatment should
lack the appropriate antigen
Summary.

Hemolytic disease of newborn occurs when IgG
antibodies produced by the mother against the
corresponding antigen which is absent in her,
crosses the placenta and destroy the red blood
cells of the fetus.

Proper early management of Rh- HDN saves
lives of a child and future pregnancies

ABO- HDN is usually mild

Other blood group antigens can also cause HDN