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Rh isoimmunization

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Rh isoimmunization

  2. 2.  ISOIMMUNIZATION: A process by which immune antibodies are produced in a person by the entry of an antigen of another individual of same species, the former lacking the antigen.
  3. 3. Rh- Iso imunization Definition known as: Rhesus incompatibility ,Rhesus disease RhD Hemolytic Disease of the Newborn. -When Rh– mother gets pregnant to Rh+ fetus —she may be sensitized to Rh antigen and develop antibodies. These will cross the placenta and cause hemolysis of fetal red blood cells.
  4. 4. HISTORY  1609-description of hydrops fetalis.  1939-Levine and Stetson discovered atypical aglutinin.  1940-Landsteiner and wiener Rh-antigen.  1941-Levine discover Rh-antidody.
  5. 5. Rhesus factor (1940): Agglutinogen (C,D,E) - mainly D C,D,E - dominant antigen c,e - recessive antigen Person lack D-antigen called Rh-ve
  6. 6. - Rh positive (85%) - homozygous (DD) (35%), or heterozygous (Dd) (50%) - Rh negative (15%) - Incidence of Rh-ve in far east is about 1% Examples of Rh factor: (CDe=R1) , (Cde=r) (cDE=R2) Other systems:  Kell.  Lweis,  Deigo,  luther,  Duffy,  MNS,
  7. 7.  Kell is most common of minor gr.  Responsible for 10% of cases of severe antibody-mediated anemia  Only anti-Fy(a) antibody associated with HDFN- may range from mild to sever.
  8. 8. INCIDENCE OF Rh-ve  Chinese and Japanese 1% North American Indian 1—2% Indo-Eurasian 2% india 5% African American 4 - 8% Caucasian 15 - 16% Basque 30 - 35%
  9. 9. Rh-isoimmunization occurs A. Mismatched blood transfusion. B. Rh-negative women bearing Rh- positive fetous with feto-maternal hemorrhage.
  10. 10. CAUSE OF FMH Feto-maternal haemorrhage: during pregnancy leakage of fetal cells in the maternal circulation (Rh+ fetal cells in Rh- maternal circulation) Examples: 1.Abortion 2.APH 3.E.C.V. 4.Cordocentesis, 5.CVS, 6.Amniocentesis
  11. 11. CAUSE OF FMH 7.Severe preeclampsia 8.Ectopic pregnancy 9.Caesarean section 10.Manual removal of placenta 11.Silent feto-maternal hage
  12. 12. Pathophysiology  Rh-isoimmunization is due to D antigen in more than 90% of cases. Occasionally result of other than Rh group like anti- Kell and anti- Duffy
  13. 13. Pathophysiology  Following feto-maternal hemorrhage.  Initial response is forming IgM antibodies for the short period (6wks-6month) o Followed by production of IgG on subsequent pregnancy which crosses placenta.  IgG antibodies adhere to the antigen site on the surface of erythrocytes causing hemolysis.  The excessive removal of circulatory RBCs leads to severe anemia and hypoxia.
  14. 14. IGM antibodies 1. Cleared by Macrophage 2. Plasma stem cells Fetal Anaemia Mother Placental Primary Response •6 wks to 6 M. •IGM.
  15. 15. Anti - D Macroph. antigen Presenting cell T- helper cell B cell Fetal Anaemia Mother Placental Secondary Response •Small amount •Rapid •IgG IgG
  16. 16.  Rh Antibodies  Antibodies Coated Red Cells  Destruction of Fetal Cells by Fetal RES  Fetal Anemia  Fetal Hypoxia and Stimulate of Erythropoitin  Extra Medullary red Cells Synthesis  Hepato spleenomegally  Hepatic Cell Failure  Hypoproteinemia, Increased Intrahepatic Pressure, Portal hypertension  Ascetic, Edema, hypoxia, Placental Thickness, Polyhydramnios, Pericardial effusion
  17. 17. Development of Rhesus antibodies: depends on : 1- Inborn inability to respond to Rh-antigenic stimulus. 2- Protection if ABO incompatible 110 3- Strength of Rh antigen stimumlus (CDe=R1) 4- Volume of leaking feta blood (0.1ml) 5- Immunological nonresponders found in 30% of Rh-negative women.
  18. 18. 1- If ABO is incompatible:  Red blood cells is easily destroyed, so not reaching enough immunological component to cause antibody response and reaction.  The risk of sensitization after ABO incompatible pregnancy is only 2%.
  19. 19. - If ABO is compatible: Rh+ fetal cells  remain in circulation (life span) until removed by (R.E.S)  destroyed  liberating antigen (D)  isoimmunization
  20. 20. Macroph. Antigen Presenting Cell T-Hellper B-cell Anti-D Anti - A Anti - B Mother Infant A Rh positive B Rh Positive“O” Rh positive Group “O” Rh Negative Placenta
  21. 21. Fetomaternal hemorrhage as a reason of Rh –isoimmunization has been documented in: 6.7% in the first trimester.  13.9% in the second trimester  29% in the third trimester.
  22. 22.  Amount needed for sensitisation 0.1ml FMH/ML SENSITIZATION% 0.1 1 0.5 - 1 25 >5 65
  23. 23. Complications  Hydrops fetalis And Stillbirth.  Icterus gravis neonatorum.  Neonatal Jaundice.  Compilations Of Neonatal Kernicterus (Lethargy, Hypertonicity, Hearing Loss, Cerebral Palsy And Learning Disability)  Congenital Anemia of newborn.
  24. 24. ICTERUS GRAVIS NEONATORUM  Less severe form of hemolytic disease.  Baby born alive without jaundice but soon develops within 24 hrs of birth.
  25. 25. Kernicterus Concentration of bilirubin in the newborn blood exceeds 20mg/100ml or in-term fetus – > 342 mmoll/L in pre-term fetus – >205 mmoll/L, Billirubin crosses the BBB and damage the basal nuclei of brain.
  26. 26. Screening and diagnosis  Maternal blood grouping, Rh-typing and antibody screening at their 1st pre-natal visit.  Presence of anti-D antibodies in serum is diagnostic of maternal Rh- alloimmunization.
  27. 27. Antibody screening in mother  Should be done in…. I. Rh-negative women who have received anti-D immune globulin. II. Rh-positive mother who have… --blood transfusion. --unexplained fetal loss. --infant with unexplained jaundice.
  28. 28. Gold Standard Test  Indirect Coombs: -mix Rh(D)+ cells with maternal serum -anti-Rh(D) Ab will adhere -RBC’s then washed & suspended in Coombs serum (antihuman globulin) -RBC’s coated with Ab will be agglutinated  Direct Coombs: -mix infant’s RBC’s with Coombs serum -maternal Ab present if cells agglutinate
  29. 29.  If indirect coombs test is positive, the father’s Rh should be tested.  Serial maternal Anti D titers should be done every 2- 4 weeks.  If titer is less than 1/16 the fetus is not at risk.  If titer is more than 1/16 then severity of condition should be evaluated.
  30. 30.  USG : detection of hydropic change.  CVS  Amniocentasis  Cordocentesis  MCA-PSV
  31. 31. USG  Confirmation of gestational age.  Early detection of hydrops when finding one or more of the following: Ascites, pleural effusion, pericardial effusion, skin edema.  Increase placental size,  Hepato-spleenomegally.
  32. 32. USG FINDINGS
  33. 33. Fetal Ascites
  34. 34. Rh- Iso imunization Body wall edema hydropic fetus
  35. 35. MCA-PSV  Non-invasive  Mother not put at risk for worsening alloimmunization  Can be used with alloantibodies other than RhD, including anti-Kell antibodies
  36. 36. Biophysical surveillance Middle cerebral artery peak velocity
  37. 37. Biophysical surveillance Middle Cerebral Artery peak systolic velocity B = moderate-severe anaemia A = mild anaemia C = no anaemia C
  38. 38. CVS  To know fetal Rh genotype.  Advantage: early detection.  Disadvantage: --more complicated. --increase severity of alloimmunization if baby Rh +
  39. 39. AMNOCENTESIS  Methode of choice for detection of Rh factor of fetous and amniotic fluid bilirubin.  Critical titre/previous affected infant.  Bilirubin correlates with fetal hemolysis.  Spectophotometric analysis optical density of amniotic fluid @ ▲OD 450nm.  Data plotted on Liley curve.
  40. 40. CORDOCENTESIS  More complicated procedure..  Fetal Rh phenotype can be known rapidly by blood bank serology.  Gold standard for detection of fetal anemia  Greater morbidity and mortality  2.7% total risk of fetal loss
  41. 41. Diagram of cordocentesis procedure Cordocentesis -
  42. 42. MANAGEMENT
  43. 43.  Rh-negative women categorized in two groups. I. Rh-negative non-immunized women. II. Rh-negative immunized women. immunized against -D-antigens -non D-Rh antigens -other blood group system
  44. 44. The aim of antenatal management  To predict which pregnancy is at risk  To predict whether or not the fetus is severely affected.  To correct anemia and reverse hydrops by intrauterine transfusion.  To deliver the baby at the appropriate time, weighing the risks of prematurity against these of intrauterine transfusion.
  45. 45. OBJECTIVES A. Non immunized women– prevention of allo-immunization. B. Immunized women— a. early detection. b. adequet treatment of fetal anemia.
  46. 46. Rh-negative non immunized Phenotype of father Rh-positive Ante-partum sensitization of Ab screening at 20,24,28 wks GA. Rh-negative Baby Rh- negative Manage as normal pregnancy
  47. 47. Cont… Antibody screening at 20,24& 28wks ga No anti-Ab detected Pt should received anti-D-immunoglobin at 28wks of GA. If anti-D antibodies detected Manage as Rh-negative immunised women At times of delivery to determine the mother’s eligibility for a second dose of anti-D immunoglobin
  49. 49. Management based on--- A. First affected prenancy. B. Previous affected pregnancy.
  50. 50. FIRST AFFECTED PREGNANCY  Should have antibody triter every 4 wks. A. If triter≥critical level - amniocntasis - MCA-PSV. B. If triter<critical level upto 36 wks of gestation,should deliverd between 38-40wks.
  51. 51. Sudden elevation of Ab-triter when GA>34WKS <37WKS amniocentasis Lung imaturity Contineu pregnancy if bilirubin<0.05 with serial amniocentasis weekly Lung maturity Lung maturity delivery
  52. 52. PREVIOUS AFFECTED PREGNANCY a. Maternal anti-D triter not predict the fetal anemia b. MCA-PSV to determine the anemia. c. Serial amniocentasis.
  53. 53. PREVIOUS AFFECTED PREGNANCY a. Maternal anti-D triter not predict the fetal anemia b. MCA-PSV to determine the anemia. c. Serial amniocentasis. TRITER LEVEL PAST OBSTETRIC HISTORY % OF IUD <64 NEGATIVE 4% <64 POSITIVE 32% >64 NEGATIVE 17.2% >64 POSITIVE 68.7%
  54. 54. Suggested management after amniocentesis for ΔOD 450 Serial Amniocentesis Lily zone I Lower Zone II Upper Zone II Zone III Hydramnios & Hydrops Repeat Amniocentesis every 2-4 weeks Delivery at OR near term Repeat Amniocentesis in 7 days or FBS Hct < 30% Hct > 30% Intrauterine Transfusion Repeat Sampling 7 to 14 days Fetal hematocrit<30% Fetal hematocrit>30% Intrauterine Transfusion Follow with fetal Blood sampling & USG DELIVERY WHEN LUNG MATURE Fetal blood sampling
  55. 55. LILEY’S CHART
  58. 58. Transfusion therapy Intraperitoneal  First done in 1963  Instill blood through needle or epidural catheter  Volume to transfuse = (G.A.-20) x 10ml.  Generally, repeat in ~ 10 days, then every 4wks.  Risk of death about 4% per procedure.  Not effective in hydropic fetus.  Some advocate combined approach (IPT and IVT)
  59. 59. Transfusion therapy Intravascular  Goal is to have post-transfusion Hct 40-45%  Can infuse about 10 ml/min  Goal:keep Hct>25%  Estimate requirement based on EFW and pre- transfusion Hct  Repeat in 1 wk., then about every 3 wkly.  Fetal loss about 1.5% per procedure
  60. 60. Direct fetal intravascular transfusion
  61. 61.  Other therapies: A. Plasmapheresis : tried to remove several liters of maternal plasma with anti-D antibodies. B. High dose i.v immunoglobulin : 1000mg/kg weekly.
  63. 63. Pregnant women undergo cesarean section in isoimunization:  Severe form of hemolytic infant disease in the term or 34-35 weeks after previous antenatal prevention of fetal hyaline membranes syndrome;
  64. 64. Measures to be taken  Use abdominal packs in the sides of the uterus before opening the lower segment to prevent spilled blood from the placenta to inter the peritoneal cavity.  Let the placenta to be delivered spontaneous using control cord traction without squeezing the uterus.  … A void avulsions of the cord.
  65. 65.  undergo delivery in the term of 37-38 weeks of gestation.  Induction of labor is performen by prostaglandin (in the case of “unripe” uterine cervix) or by intravenous oxytocin infusion administration (in the case of “ripe” uterine cervix). Vaginal delivery in Rh-isoimmunization
  66. 66. Vaginal delivery in Rh-isoimmunization  During labor:  No fundal pushing in 1st or 2nd stage of labor.  With hold inj methergin after ant. shoulder delivery.  Early cord clamping and no milking.  No uterine massage or squeeze in 3rd stage.  Let the placenta to be delivered spontaneous to avoid avulsions of the cord.  Protect the vaginal and perineal wounds and laceration from being exposed to the fetal blood spilled from cord
  67. 67.  At birth  Maternal blood a. antibodies by indirect Comb's test ( ICT ).. b. fetal red blood cells in maternal circulation  Cord blood sample ( Neonatal blood sample ) for a. antibodies by Direct Comb's test ( DCT ) b. Infant blood group and rh-typing. c. Infant bilirubin level d. Infant Hb & Hct level
  68. 68. Rh- Iso imunization Prevention - Screening of all pregnant mothers to Rh D antigen and antibody screening for Rh D negative mother. Word of Vincent Freda the rule of thumb should be to administer anti-D immunoglobin when in doubt rather than to withhold it.
  69. 69. Prophylactic anti D immunoglobulin To be given  All Rh – mothers after delivery if the fetus is Rh+  At 28, 32 weeks of pregnancy or after 40wks if pregnancy contineued  After abortion, amniocentesis, abruption, ectopic pregnancy.
  70. 70. Rh- Iso imunization Prevention The standard dose of anti D is 0.3 mg —will eradicate 15 ml of fetal red blood cells (routine for all Rh –ve pregnancies) within 3 days of delivery. -If more feto-maternal bleeding is suspected as in abruption or ante partum hemorrhage-Do Kleihauer –Betke test to estimate the amount of fetal red cells in maternal circulation and re-calculate the dose of the anti-D.
  71. 71. Kleihauer-Betke test measure amount of feto-maternal haemorrhage. PRINCIPLE: Adult hemoglobin, but not fetal hemoglobin, is soluble in a citrate buffer with pH 3.2 and will elute out of the red cell.  (critical volume)  isoimmunization represented by 5 fetal cells in 50 low power microscopic field of peripheral maternal blood.  So 1 ml is represented by 20 fetal cells
  72. 72. method  Prepare patient blood smears  Fix smears in 80% ethanol  Incubate slides in citrate buffer  Stain smears with erythrosine  Count fetal cells on patient slid  Red cells containing Hgb F stain bright  pink due to erythrosin stain ,Negative staining, adult red cells that contained Hgb A,appear as pale, ghost cells.
  73. 73. Kleihauer Calculations  %Fetal red cells = fetal cell counted in total slids x 100 total maternal cell %fetal red cell x 5000ml(MBV) volume of FMH = 100 MBV – maternal blood volume (usually 5000ml) volume of FMH VIAL REQUIRS = 30
  74. 74. positive cells on the Kleihauer-Betke stain  Post-partum mothers following a transplacental hemorrhage  • Newborns/infants less than 6 months old  • Hereditary persistence of hemoglobin F  • Disorders that compensate with hemoglobin F such as beta thal major or  sickle cell disease
  75. 75.  Other test: to detect FMH  Flow cytometry  Rosette test  Enzyme linked antiglobulin test  Surrogate test
  76. 76. Immunoglobulin (RhoGAM) prophylaxis (RhIgG) Schedules  Spon.abortionBefore 12wks – RCOG,UK- no dose require Austalian soc.- 50 μg RhIgG Canadian soc.- 120 μg RhIgG  2nd trimester abortion- 50 μg RhIgG  Threatened abortion- 1st trimester - not requir 2nd trimester- 50 μg RhIgG (should be repeated 6wkly if heavy bleeding)
  77. 77.  A minimum dose of 50 μg RhIgG is recomendate upto 19wks+6days GA.  After 20wks minimum dose 125 μg RhIgG .
  78. 78.  Antepartum (RAADP)regimen.  Two dose 500IU at 28 and 34wks GA.  Single dose 1500IU at 28 wks GA.  Postpartum <72 hr - 300 μg RhIgG; IT can be given upto 28 days of delivery 0.3% require > 300 μg RhIgG
  79. 79. prophylaxis Hydatidiform mole complete mole-controversial. patrial mole-anti-D to be given.
  80. 80. Following BTL-controversial. given….  women wants new partner desire for IVF.  In future if major accident occurs and Rh- blood not available at emergency.
  81. 81.  300 μg anti-D neutralizes 30 mL fetal Rh-positive blood (15 mL packed fetal RBC)
  82. 82. Management of sensitized newborn Mild anemia (Hb <14gm/dl, cord bilirubin>4 mg/dl)--- Phototherapy -Moderate to severe---- Exchange transfusion. -Mild Hydrops improves in 88% of cases -Severe hydrops—Mortality is 39%

Notas do Editor

  • C
  • mannage as Rh-negative immunized women
  • At times of delivery to determine the mother’s eligibility for a second dose of anti-D immunoglobin