Chukwuma I. Onyeije, M.D.<br />Atlanta Perinatal Associates<br />Rh (Rhesus) Isoimmunization:Perinatal Implications and Ma...
A copy of this lecture can also be found at:http://onyeije.net/present/rhdis<br />
Objectives<br />Review Terminology<br />Review Major Blood Group Antigens<br />Review Minor Blood group antigens<br />Over...
Rh Disease<br />Alloimmunization<br />Isoimmunization<br />HDFN<br />ErythroblastosisFetalis<br />Confusing Terminology<br />
Rh (Rhesus) Isoimmunization:<br />
Red blood cell<br />antigens <br />and <br />antibodies.<br />Pathophysiology<br />
INTRODUCTION:<br />Four blood types ( A, B, AB, and O)<br />Each blood type is additionally classified according to the pr...
Rh Incompatibility<br />Occurs when there is a different Rh blood type between that of the pregnant mother (Rh negative) a...
Rh Incompatibility<br />Exposure to fetal ANTIGENS causes the mother to produce ANTIBODIES<br />
The placenta usually acts as a barrier to fetal blood entering the maternal circulation.<br />
Fetal cells can enter  the maternal circulation through a “break” in the “placental barrier”.<br />
Maternal production of Rhesus antibodies following introduction of Rhesus positive blood<br />
Maternal production of Rhesus antibodies following introduction of Rhesus positive blood<br />
Causes of RBC Transfer: “A break in the barrier”<br />Abortion/Ectopic Pregnancy<br />Partial molar pregnancy<br />Blighte...
IMMUNIZED PREGNANCY<br />NON-IMMUNIZED PREGNANCY<br />Rh Incompatibility<br />
Pathophysiology<br />After first antigenic exposure, memory B lymphocytes recognize appearance of RBC’s containing the ant...
Pathophysiology- Fetal Events<br />Maternal antibodies cross the placenta & attach to fetal RBC’s- leading to RBC destruct...
METABOLISM OF BILIRUBIN:<br />
JAUNDICE DOES NOT OCCUR BEFORE DELIVERY:<br />
* Hemolysis/Anemia is basis of MCA-PSV<br />** Increased Bilirubuin is basis of Delta OD-450<br />*<br />*<br />
What’s harmless?<br />What’s dangerous?<br />Antigen Nomenclature<br />
CDE (Rhesus) System<br />Clinically Important<br />Includes c, C, D, e, E<br />Rh negative status indicates the absence of...
Other Antibodies<br />Antigens such as A, P, Le (a), M, I, IH, and Sd (a) are innocuous<br />Most are IgM<br />Lewis antib...
Antibodies Associated with HDFN<br />Anti-c, Anti-D, Anti-E, and Anti-Kell<br />
Antibodies Associated with HDFN<br />RhoGAM has decreased HDFN caused by anti-D<br />Anti-D antibody is still MOST COMMON ...
Minor RBC Antigens<br />Kell is most common of minor <br />Responsible for 10% of cases of severe antibody-mediated anemia...
Minor RBC Antigens<br />Duffy antigens Fy(a) and Fy(b)<br />Only anti-Fy(a) antibody associated with HDFN- may range from ...
Minor Antigens<br />MNS system = M, N, S, s, U antigens<br />Anti-M and anti-N naturally occurring- no clinical significan...
Clinical Management<br />Routine blood type screen<br />Repeat Ab screen at 24-28 weeks for Rhnegative women PRIOR to rece...
Clinical Management For Positive Antibody Screen<br />Determine risk factors for isoimmunization<br />Past pregnancies<br ...
Clinical Management For Positive Antibody Screen<br />Obtain antibody titer<br />Consider invasive testing at titer of 1:3...
Clinical Management For Positive Antibody Screen<br />If AB titer remains below critical titer…<br />Invasive testing can ...
Clinical Management Fetal Testing<br />Obtain amniocytes to determine fetal blood type <br />When father is heterozygous f...
Normal and Abnormal MCA Dopplers<br />
The Middle Cerebral Artery<br />Should be examined close to its origin in the internal carotid artery. <br />The angle of ...
MCA Doppler and Fetal Anemia<br />Fetuses with anemia show an increased peak velocity of systolic blood flow in the middle...
MCA Doppler and Fetal Anemia<br />Method:<br />MCA closest to the maternal skin should be measured using a minimal angle o...
Clinical Management (cont)<br />Perform serial amniocenteses to measure delta OD450 <br />AND<br />Plot values on Liley Cu...
Delta OD450<br />Spectral analysis of amniotic fluid at 450 nm measures change in OD<br />Measures the level of bilirubin ...
RhIsoimmunized Pregnancy Worksheet<br />
Cordocentesis<br />Gold standard for detection of fetal anemia<br />Complications<br />2.7% total risk of fetal loss<br />...
Advantages of MCA-PSV<br />Non-invasive<br />NO risk for worsening isoimmunization<br />Utility with alloantibodies other ...
Caution Regarding MCA-PSV<br />From:  http://youtu.be/FGUFC39Bgu0<br />
Review of Management for RhIsoimmunization<br />Monthly indirect coombs titer (in first sensitized pregnancy)<br />If crit...
Prevention (cont)<br />Give 300 mcg dose within 72 hrs of delivery to unsensitizedRh (-) women (Rh positive infant)<br />A...
Prevention<br />Test for excessive fetal-maternal hemorrhage after blunt trauma, abruption, cordocentesis, and bleeding as...
SUMMARY<br />Remember the instances in which to consider RhoGAM<br />SAB, TAB, threatened AB (controversial), ectopic, pre...
SUMMARY<br />Anti-D still most common cause of red cell alloimmunization, despite RhoGAM<br />Kell = most common minoranti...
References<br />Gabbe Obstetrics – Normal and Problem  Pregnancies, 4th edition.<br />Creasy R., Resnik R., Iams J., Mater...
Kleihauer-Betke Test<br />% fetal RBC in maternal circulation<br />Fetal erythrocytes contain Hbg F which is more resistan...
Kleihauer Calculations<br />Fetal red cells = MBV X maternal Hct X % fetal cells in KB<br />                              ...
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Rh Rhesus Isoimmunization

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A presentation on Rh Isoimmunization presented by Chukwuma Onyeije, M.D.

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Rh Rhesus Isoimmunization

  1. 1. Chukwuma I. Onyeije, M.D.<br />Atlanta Perinatal Associates<br />Rh (Rhesus) Isoimmunization:Perinatal Implications and Management<br />
  2. 2. A copy of this lecture can also be found at:http://onyeije.net/present/rhdis<br />
  3. 3. Objectives<br />Review Terminology<br />Review Major Blood Group Antigens<br />Review Minor Blood group antigens<br />Overview of Clinical Management<br />Discuss Prevention Strategies<br />Q&A<br />
  4. 4. Rh Disease<br />Alloimmunization<br />Isoimmunization<br />HDFN<br />ErythroblastosisFetalis<br />Confusing Terminology<br />
  5. 5. Rh (Rhesus) Isoimmunization:<br />
  6. 6.
  7. 7. Red blood cell<br />antigens <br />and <br />antibodies.<br />Pathophysiology<br />
  8. 8.
  9. 9. INTRODUCTION:<br />Four blood types ( A, B, AB, and O)<br />Each blood type is additionally classified according to the presence or absence of the Rh factor<br />
  10. 10. Rh Incompatibility<br />Occurs when there is a different Rh blood type between that of the pregnant mother (Rh negative) and that of the fetus (Rh positive)<br />
  11. 11. Rh Incompatibility<br />Exposure to fetal ANTIGENS causes the mother to produce ANTIBODIES<br />
  12. 12. The placenta usually acts as a barrier to fetal blood entering the maternal circulation.<br />
  13. 13. Fetal cells can enter the maternal circulation through a “break” in the “placental barrier”.<br />
  14. 14. Maternal production of Rhesus antibodies following introduction of Rhesus positive blood<br />
  15. 15. Maternal production of Rhesus antibodies following introduction of Rhesus positive blood<br />
  16. 16. Causes of RBC Transfer: “A break in the barrier”<br />Abortion/Ectopic Pregnancy<br />Partial molar pregnancy<br />Blighted ovum<br />Antepartumbleeding<br />Procedures (amniocentesis, cordocentesis, CVS)<br />External version<br />Platelet transfusion<br />Abdominal trauma<br />Inadvertent transfusion Rh+ blood<br />Postpartum (Rh+baby)<br />
  17. 17. IMMUNIZED PREGNANCY<br />NON-IMMUNIZED PREGNANCY<br />Rh Incompatibility<br />
  18. 18. Pathophysiology<br />After first antigenic exposure, memory B lymphocytes recognize appearance of RBC’s containing the antigen in subsequent pregnancies<br />
  19. 19. Pathophysiology- Fetal Events<br />Maternal antibodies cross the placenta & attach to fetal RBC’s- leading to RBC destruction<br />Sequestration by macrophages in fetal spleen (extravascularhemolysis) produces fetal anemia<br />
  20. 20. METABOLISM OF BILIRUBIN:<br />
  21. 21. JAUNDICE DOES NOT OCCUR BEFORE DELIVERY:<br />
  22. 22. * Hemolysis/Anemia is basis of MCA-PSV<br />** Increased Bilirubuin is basis of Delta OD-450<br />*<br />*<br />
  23. 23. What’s harmless?<br />What’s dangerous?<br />Antigen Nomenclature<br />
  24. 24. CDE (Rhesus) System<br />Clinically Important<br />Includes c, C, D, e, E<br />Rh negative status indicates the absence of D antigen<br />87% of Caucasians carry the D antigen<br />
  25. 25. Other Antibodies<br />Antigens such as A, P, Le (a), M, I, IH, and Sd (a) are innocuous<br />Most are IgM<br />Lewis antibodies and cold agglutinins of I are prevalent but not clinically significant<br />“Lewis Lives”<br />
  26. 26. Antibodies Associated with HDFN<br />Anti-c, Anti-D, Anti-E, and Anti-Kell<br />
  27. 27. Antibodies Associated with HDFN<br />RhoGAM has decreased HDFN caused by anti-D<br />Anti-D antibody is still MOST COMMON CAUSE of red cell isoimmunization<br />
  28. 28. Minor RBC Antigens<br />Kell is most common of minor <br />Responsible for 10% of cases of severe antibody-mediated anemia<br />Mechanism of anemia two-fold<br /> 1. Hemolysis<br /> 2. Suppression of erythropoiesis<br />**Transfuse women with Kell(-) blood**<br />
  29. 29. Minor RBC Antigens<br />Duffy antigens Fy(a) and Fy(b)<br />Only anti-Fy(a) antibody associated with HDFN- may range from mild to severe<br />“Duffy Dies”<br />We treat sensitization to minor RBC antigens similar to those with Rhisoimmunization<br />
  30. 30. Minor Antigens<br />MNS system = M, N, S, s, U antigens<br />Anti-M and anti-N naturally occurring- no clinical significance<br />Anti-S, anti-s, and anti-U antibodies ~ mild to severe HDFN<br />
  31. 31. Clinical Management<br />Routine blood type screen<br />Repeat Ab screen at 24-28 weeks for Rhnegative women PRIOR to receiving RhoGAM<br />If Abscreen is (+), identify antibody and potential for HDFN<br />
  32. 32. Clinical Management For Positive Antibody Screen<br />Determine risk factors for isoimmunization<br />Past pregnancies<br />Transfusions<br />Shared needles<br />Determine father’s RBC antigen status and zygosity<br />If paternity unknown or father is (+) for antigen, fetus is at RISK<br />
  33. 33. Clinical Management For Positive Antibody Screen<br />Obtain antibody titer<br />Consider invasive testing at titer of 1:32 or greater by indirect Coombs (1:16 most often used)<br />
  34. 34. Clinical Management For Positive Antibody Screen<br />If AB titer remains below critical titer…<br />Invasive testing can be deferred<br />Evaluate serial Ab titers<br />Serial titers are NOT necessary before 18-20 weeks<br />If critical titer noted at first visit, amnio for delta OD450 at 22-24 weeks<br />
  35. 35. Clinical Management Fetal Testing<br />Obtain amniocytes to determine fetal blood type <br />When father is heterozygous for the antigen responsible for alloimmunization<br />When paternal status is unknown<br />MCA-PSV can be used as early as 18 weeks~ if greater than 1.5 MoM, consider fetal blood sampling<br />
  36. 36. Normal and Abnormal MCA Dopplers<br />
  37. 37. The Middle Cerebral Artery<br />Should be examined close to its origin in the internal carotid artery. <br />The angle of the ultrasound beam and the direction of blood flow should be zero degrees. <br />The risk of anemia is highest in fetuses with a peak systolic velocity of 1.5 times the median or higher. <br />
  38. 38.
  39. 39. MCA Doppler and Fetal Anemia<br />Fetuses with anemia show an increased peak velocity of systolic blood flow in the middle cerebral artery (MCA) <br />MCA Doppler is useful in the determination of fetal anemia in Rh-isoimmunizedpregnancies<br />MCA Doppler is also used to follow fetal response to intrauterine transfusion and to assist in timing subsequent transfusions.<br />
  40. 40. MCA Doppler and Fetal Anemia<br />Method:<br />MCA closest to the maternal skin should be measured using a minimal angle of insonation<br />The Doppler gate is placed over the vessel as it bifurcates from the carotid siphon. <br />Serial MCA Doppler studies can be used to generate a curve that plots MCA peak systolic velocity as a function of gestational age. <br />After 35 weeks' gestation, accuracy in determining MCA PSV appears to decrease; therefore, at this gestational age amniocentesis for deltaOD450 is indicated.<br />
  41. 41. Clinical Management (cont)<br />Perform serial amniocenteses to measure delta OD450 <br />AND<br />Plot values on Liley Curve<br />“Belt and Suspenders” Approach<br />
  42. 42. Delta OD450<br />Spectral analysis of amniotic fluid at 450 nm measures change in OD<br />Measures the level of bilirubin and predicts severity of hemolytic disease after 27 weeks<br />Delivery or intrauterine transfusion if delta OD450 falls into zone III or upper zone II<br />
  43. 43. RhIsoimmunized Pregnancy Worksheet<br />
  44. 44. Cordocentesis<br />Gold standard for detection of fetal anemia<br />Complications<br />2.7% total risk of fetal loss<br />Reserved for patients with increased MCA-PSV or delta OD450<br />
  45. 45. Advantages of MCA-PSV<br />Non-invasive<br />NO risk for worsening isoimmunization<br />Utility with alloantibodies other than Rh-D, including anti-Kell antibodies<br />
  46. 46. Caution Regarding MCA-PSV<br />From: http://youtu.be/FGUFC39Bgu0<br />
  47. 47. Review of Management for RhIsoimmunization<br />Monthly indirect coombs titer (in first sensitized pregnancy)<br />If critical titer reached, determine paternal and fetal antigen status<br />Amniocentesis and delta OD450 OR MCA-PSV<br />** For 2nd or greater sensitized pregnancy, initiate amnio or MCA at 18-20 weeks**<br />
  48. 48. Prevention (cont)<br />Give 300 mcg dose within 72 hrs of delivery to unsensitizedRh (-) women (Rh positive infant)<br />ACOG: 300 mcg at 28 weeks UNLESS father known to be Rh(-)<br />
  49. 49.
  50. 50. Prevention<br />Test for excessive fetal-maternal hemorrhage after blunt trauma, abruption, cordocentesis, and bleeding assoc. with previa<br />KleihauerBetke<br />Give RhoGAM for partial molar pregnancy, SAB, TAB, ectopic, chorionic villus sampling, amniocentesis, external version<br />
  51. 51. SUMMARY<br />Remember the instances in which to consider RhoGAM<br />SAB, TAB, threatened AB (controversial), ectopic, previa/bleeding, abruption, partial molar, CVS, blunt trauma, cordocentesis<br />Clinically important antibodies: Anti-c, Anti-D, Anti-E, and Anti-Kell, Rarely Anti-Duffy Fy(a)<br />Usually not associated with severe HDFN:<br />, ABO incompatibilities, Anti-Duffy(Fy-b) antibodies, (Duffy Fy-a causes mild to severe HDFN), Anti-A, Anti-P, Anti-M, Anti-I, Anti-IH, Anti-Sd(a)<br />
  52. 52. SUMMARY<br />Anti-D still most common cause of red cell alloimmunization, despite RhoGAM<br />Kell = most common minorantigen<br />Critical titer most often used is 1:16 by indirect Coombs<br />Amnio with delta OD450 & MCA-PSV<br />Antibody screens and indications for RhoGAM<br />
  53. 53. References<br />Gabbe Obstetrics – Normal and Problem Pregnancies, 4th edition.<br />Creasy R., Resnik R., Iams J., Maternal Fetal Medicine Principles and Practice, 5th edition.<br />ACOG Compendium 2005<br />Harkness U., Spinnato J., Prevention and Management of RhDisoimmunization. Clinics in Perinatology, Dec 2004 31:4.<br />Pereira L., Jenkins T., Conventional management of maternal red cell alloimmunization compared with management by Doppler assessment of MCA-PSV. American Journal of Obstetrics and Gynecology, Oct 2003 189:4.<br />Cohen D., Hemolytic disease of the newborn: RBC alloantibodies in pregnancy and associated serologic issues. Up to Date, Oct 2004.<br />Barss V., Moise K., Significance of minor red blood cell antibodies during pregnancy. Up to Date, Apr 2005.<br />Online resources:<br />www.austincc.edu/mlt/bb/bb_HDN.ppt<br />http://www.perinatology.com/Archive/Isoimmunization.htm<br />http://emedicine.medscape.com/article/273995-overview<br />http://www.nlm.nih.gov/medlineplus/ency/article/001600.htm<br />
  54. 54.
  55. 55. Kleihauer-Betke Test<br />% fetal RBC in maternal circulation<br />Fetal erythrocytes contain Hbg F which is more resistant to acid elution than HbgA so after exposure to acid, only fetal cells remain & can be identified with stain<br />1/1000 deliveries result in fetal hemorrhage > 30ml<br />Risk factors only identify 50%<br />
  56. 56.
  57. 57. Kleihauer Calculations<br />Fetal red cells = MBV X maternal Hct X % fetal cells in KB<br /> newborn Hct<br />MBV – maternal blood volume (usually 5000ml)<br />Fetal cells X 2 = whole blood<br />
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