Hemolytic disease of newborn Dr. Tariq M.Roshan Dept. of Hematology PPSP.
-
Upload
jemima-dalton -
Category
Documents
-
view
245 -
download
11
Transcript of Hemolytic disease of newborn Dr. Tariq M.Roshan Dept. of Hematology PPSP.
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
Conjugatedbilirubin
Unconjugatedbilirubin
Neonatalliver is immature and
unable to handle bilirubin
Coated red blood cellare hemolysed in
spleen
Pathogenesis; beforebirth
Pathogenesis; afterdelivery
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 HDNBOFORE 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
Blood film of a fetus affected by HDN showing polychromasiaand increased number of normaoblasts
N
P
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)
PercutaneousUmbilical bloodsampling
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 RBCsRh-negativve units for Rh-negative caseWhole blood group OBlood 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 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
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