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Immune hydrops


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Erythroblastosis fetalis/ Immune hydrops

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Immune hydrops

  1. 1. Immune Hydrops fetalis Dr. Vinayak V. Kodur 3rd year DM resident L.T.M. General Hospital
  2. 2. History • Hippocrates in 400 bc, had discribed erythroblastosis fetalis • First clinical report - Attributed to a French midwife who delivered twins in 1609. • The first twin was hydropic and stillborn; the second died of kernicterus. • 1940 Landsteiner et al discovered Rh antigen. • In 1941, Levine et al observed that RhD negative mother exposed to when RhD positive erythrocytes, she forms antibodies that cause red blood cell hemolysis.
  3. 3. History • In 1948, Wiener postulated that transplacental passage of RhD-positive fetal blood into the maternal circulation trigger the production of antibodies against fetal cells • Thus it supported an immunologic rationale for the therapeutic use of exchange transfusion. • Freda and coworkers efficacy of anti-D IgG in Rh negative volunteers.
  4. 4. • Some basics in Microbiology..
  5. 5. Rh Antigen • The Rh system includes antigens encoded by two genes on chromosome 1p36.13-1p34.3. • Although this system comprises more than 40 discrete antigens, only five of them are clinically relevant: D, C, c, E, and e. • “D” is dominant and in clinical sympatomatology whenever present the person is called Rh +Ve, while one having small dd is non effective hence taken as Rh -Ve . • Rh –Ve persions ---India 5- 10 % 0f population –it is least in Japan < 2% and 15 % in Europe and USA.
  6. 6. DCT and ICT
  7. 7. Kleihauer Betke Test.. • Based on acid elution technique. Fetal and maternal RBCs have different response to citrate acid phosphate buffer solution. • Maternal cells (adult Hb ) get eluded leaving behind only cell membrane and hence appear as swollen round large “GHOST CELLS” against normal fetal cells whose Hb remain unaltered hence look as red refractile round cells .
  8. 8. Kleihauer Betke Test • If in 50 low power fields of maternal peripheral blood 80 fetal RBC’s are found- it is estimated that 4ml of fetomaternal hemorrhage has occurred. • For 1ml of fetal blood 10ug of Rh anti D is needed. Thus 300ug anti D will be sufficient for 30 ml of fetal blood which has entered the maternal circulation.
  9. 9. Kleihauer Betke Test..
  10. 10. Characteristics of Rh - Immunoglobins • IgM • Saline antibodies • Agglutinate Rh +ve RBCs when suspended in saline. • Appear first –before 24 weeks– and then decline • Larger molecule. • Can not cross placenta hence can not cause hemolytic disease of new born. • Agglutinate with Rh +Ve RBCs when suspended in 20% Albumin solution. • Appear later than saline antibodies & continue to increase as pregnancy advances. • Small Molecule. • It crosses the placenta. • Causes hemolytic disease of newborn .
  11. 11. Hydrops Fetalis
  12. 12. Hydrop fetalis • Hydrops fetalis is a condition in the fetus characterized by an abnormal collection of fluid with at least two of the following: • Edema (fluid beneath the skin, more than 5 mm). • Ascites (fluid in abdomen) • Pleural effusion (fluid in the pleural cavity, the fluid-filled space that surrounds the lungs) • Pericardial effusion (fluid in the pericardial sac, covering that surrounds the heart) • Polyhydramnios • Placentomegaly
  13. 13. Hydrop fetalis • Hydrops fetalis is typically diagnosed during ultrasound evaluation for other complaints such as : • Polyhydramnios • Size greater than dates • Fetal tachycardia • Decreased fetal movement • Abnormal serum screening • Antenatal hemorrhage
  14. 14. Etiology • Hydrops fetalis is found in about 1 per 2,000 births and is categorized as : • Immune hydrops • Nonimmune hydrops
  15. 15. Immune hydrops • Accounts for 10-24%of cases • Maternal antibodies against red-cells of the fetus cross the placenta and coat fetal red cells which are then destroyed (hemolysis) in the fetal spleen.
  16. 16. Non-immune hydrops • Accounts for 76 -90% of cases • Any other cause besides immune. • In general nonimmune hydrops (NIH) is caused by a failure of the interstitial fluid (the liquid between the cells of the body) to return into the venous system . • Non-immune is now becoming more and more common.
  17. 17. Hematologic causes • Isoimmunization (hemolytic disease of the newborn, erythroblastosis) • Rh (most commonly D; also C, c, E, e) • Kell (K1, k2, Kp, Js[B]) • ABO • MNSs • Duffy (Fyb ) • Anti-D, anti-E, and antibodies directed against other Rh antigens comprise the majority of antibodies responsible for hemolytic disease of the newborn .
  18. 18. Feto- maternal haemorrhage During Antenatal Period • O.1mlof fetal RBCs are found in 5-15 % of women’s circulation by 8 weeks of gestation. • 75% cases it is always < 1ml . • 1% show atleast 5ml fetal RBCs. • 0.25% have more than 30ml of fetal RBCs • Only 1.5 % women get sensitised in Antenatal period . • It can be prevented by anti D therapy in antenatal period ---at 28-30 and 34-36 weeks of gestation and repating it after delivery.
  19. 19. Rh Sensitization • Fetomaternal transfusion has been documented in 7%, 16%, and 29% of patients in their first, second, and third trimesters, respectively. • In the peripartum period, the incidence of fetomaternal hemorrhage can be as high as 50%. • As little as 0.2 mL of fetal blood is sufficient to cause maternal anti-D sensitization.
  20. 20. Immune Hydrops Fetalis • First pregnancy proceeds normally as Rh -ve mother is usually not sensitized. • Feto -placental maternal transfusion occurs at the time of placental separation. • Amnioscentesis , threatened abortion, ectopic pregnancy, MTP, D&E, abruptio placenta, APH , External podalic version, IPV, LSCS, CVS. • In subsequent pregnancy the fetal RBCs entering in maternal circulation may be destroyed /or some of them may have booster effect for maternal sensitization.
  21. 21. Immune Hydrops • Maternal Immunoglobins G cross the placenta and destroy fetal RBCs . • In mild cases, the fetus has haemolytic disease resulting in anaemia with mild icterus. • In severe cases fetus develops hydrops fetalis. • If IgG titers are high the disease process may start even in early period of gestation --- resulting in IUFD.
  22. 22. Degree of Risk of Developing isoimmunisation according to period of gestation Gestational period % After 1st trimester abortion 2 % After MTP ( mid trimester ) 4-5% At term after Delivery— Rh competability 16% 2% at the time of delivery , 7% will develop anti D antibodies by the 6 months of delivery , 7% get sensibilized e.g. they develop anti D slowly and very low titre which becomes detactable and measurable in next prgnancy. ABO incompetable 1.5 -2 %
  23. 23. Why all babies are not affected in Rh –Ve mother • Volume of fetomaternal trnsfusion may be too low to sensitise. • Immunological non responders ---pregnancy induced suppression of immune system –30%. • ABO Major group incompetability. • Rh set up of the fetal blood may change the Rh – antigenicity ( stimulus )
  24. 24. Hydrops fetalis • Occasionally hydrops may be due to other erythrocyte antigen apart from Rh D antigen. • These include –major A.B.O. incompatibility and minor blood group antigens ---C D E, Kell , Jk, S, c , and Duffy. • If issoimmunization occurs , then the titers of antibodies are monitored at appropriate intervals depending on the levels and rapidity with which they are changing ( either every 2 or 4 weeks).
  25. 25. Pathophysiology • In immune hydrops, excessive and prolonged hemolysis causes anemia, which in turn stimulates marked marrow erythroid hyperplasia • It also stimulates extramedullary hematopoiesis in the spleen and liver with eventual hepatic dysfunction
  26. 26. Pathophysiology • The precise pathophysiology of hydrops remains unknown • Theories includes • Heart failure form profound anemia and hypoxia • Portal hypertension due to hepatic parenchymal disruption caused by extramedullary hemopoiesis • Decreased colloid oncotic pressure resulting from liver dysfunction and hypopreteinemia
  27. 27. Pathophysiology • The degree and duration of anemia is the major factor causing and influencing the severity of ascites • Secondary factors include hypoproteinemia caused by liver dysfunction and capillary endothelial leakage resulting from tissue hypoxia, both of these lead to protein loss and decreased colloid oncotic pressure
  28. 28. Pathophysiology Severe anemia Hepatic extramedullary hematopoeisis Decreased production of plasma proteins Decreased plasma COP
  29. 29. Pathophysiology Congestive heart failure Increased central venous pressure Increased capillary hydrostatic pressure
  30. 30. Pathophysiology Severe tissue hypoxia Endothelial cell damage Capillary leak of fluid & protein
  31. 31. Decreased COP Increased CVP Capillary leak Increased fluid efflux from intravascular space
  32. 32. Pathophysiology • There may be cardiac enlargement and pulmonary hemmorrhage • Fluid collects in the fetal thorax, abdominal cavity, or skin • The placenta is markedly edematous, enlarge, and boggy. It contains large, prominent cotyledons and edematous villi
  33. 33. Pathophysiology • Pleural effusions may be so severe as to restrict lung development, which causes pulmonary compromise after birth • Ascites, hepatomegaly, and splenomegaly may lead to severe labor dystocia • Severe hydropic changes are easily seen with sonography
  34. 34. Pathophysiology • Fetuses with hydrops may die in utero from profound anemia and circulatory failure • One sign of severe anemia and impending death is the sinusoidal fetal heart rate pattern • Hydrops placental changes leading to placentomegaly can cause preeclampsia
  35. 35. Pathophysiology • The liveborn hydropic infant appears pale, edematous, and limp at birth and usually requires resuscitation • The spleen and liver are enlarged, and there may be widespread ecchymosis or scattered petechiae • Dyspnea and circulatory collapse are common
  36. 36. Placenta of Hydropic Pregnancy Placenta of Normal Pregnancy
  37. 37. Associated complication • Polyhydramnios • Placenta abruption • Uterine atony • Pre-mature labour • Hydropic, theickened placenta (> 6 cm) • Retained placenta • Preeclapsia
  38. 38. Associated complication • In an attempt to compensate for the fetal hypoxia, placenta increases in size and sometimes also penetrate deeper into the myometrium. • Thus causes the morbid adherence of placenta and can cause the problems for third stage of labor necessitating the manual removal of Placenta.
  39. 39. Associated complication • Mirror syndrome • The mother develops preeclampsia along with severe edema that is similar to that of the fetus • Caused by vascular changes in the swollen, hydropic placenta, this likely related to antiangiopenic factors produced by hyperplacentosis
  40. 40. History • A history suggesting the presence of any of the following factors should trigger an extensive diagnostic study for hydrops fetalis: • Maternal history • Rh negative (d;d) blood type • Known presence of isoimmune blood group antibodies • Prior administration of blood products • Risks of illicit drug use
  41. 41. History • Family history • Hydramnios in earlier pregnancies • Prior hydrops fetalis • Previous fetomaternal transfusion • Previous fetal death • Jaundice in other family members or in previous child • Treatment given in previous child if jaundiced or hydropic.
  42. 42. Manifestation Of Erythroblastosis Fetalis • Depending upon the degree of fetal RBCs haemolysis - --It may be - • Hydrops Fetalis: Fetus is severely affected. • Neonatal Jaundice: Relatively less affected. • Congenital Anaemia: mildly affected . Baby develops anaemia ; jaundice is not so evident or mild , prognosis is good. • 30% cases with hydrops die in utero. (IUFD)
  43. 43. Laboratory Studies • Assessments generally proceed from low-risk noninvasive tests to higher-risk invasive techniques as required for precise and complete diagnosis to properly manage the individual pregnancy.
  44. 44. Maternal laboratory studies • Assessment of maternal blood type (red cells) and antibody screen (identification, and quantitation when indicated, of maternal plasma antibodies) • Qualitative and quantitative estimates of the proportion of red cells containing fetal hemoglobin in the maternal circulation Kleihauer Betke test.
  45. 45. Laboratory Studies • Ultrasonogram with Doppler measurement of the peak systolic velocity (PSV) in the fetal middle cerebral artery (MCA) to assess for fetal anemia. • At cut off point of 1.5 multiples of median, MCA- PSV is found to correlate with moderate to severe anemia, with a sensitivity of 100% and a false positive rate of 12% • An accurate and noninvasive means of diagnosing fetal anemia in patients with Rh isoimmunization.
  46. 46. Normal four Chamber Cardiac View
  47. 47. Pericardial Effusion Heart
  48. 48. Body wall edema in a hydropic fetus
  49. 49. Fetal Ascites
  50. 50. Hydrocele can be an early manifestation in hydrops
  51. 51. Laboratory Studies • Fetal 2D echocardiogram with doppler • Amniocentesis for fetal karyotype and Liley`s chart • Fetal percutaneous blood sampling to confirm the hemoglobin just before intrauterine transfusion.
  52. 52. Liley’s chart
  53. 53. Prophylaxis
  54. 54. Immunoprophylaxis • Routine antenatal Rh antibody therapy is recommended to Rh negetive women married to Rh+ve partner. • 300 ug ,im in deltoid muscle at 28-30 weeks and 34-36 weeks of gestation. • 100 ug, im is given after bleeding in 1st trimester. • Higher dose if any precipitating factor or procedure likely to cause feto placental hemorrhage. • 300ug anti D is sufficient to neutralize 15 ml of have fetal cell/ 30ml of whole blood.
  55. 55. • When a Rh(D) negative mother receives RhD-Ig during pregnancy, especially as routine prophylaxis at 28-30 and 34-36 weeks gestation: • Rh(D) positive infant may be born with a positive DCT but have no evidence of haemolysis • Maternal sample will often show anti-D reactivity, as the half-life of passive RhD-Ig in the absence of significant FMH, is approximately 21 days.
  56. 56. Antepartum Monitoring • Follow up of the fetus will depend on the gestational age of the fetus, and the mother's wishes regarding intervention. • If treatment has been successful or hydrops is resolving spontaneously, the fetus may be followed with repeat sonograms every 1 to 2 weeks and antenatal testing.
  57. 57. Algorithm
  58. 58. Algorithm
  59. 59. Treatment
  60. 60. Treatment Intrauterine Blood Transfusion • Blood Transfusion to Fetus • Intra-peritoneal • Intra-venous • Umbilical Vein • Hepatic Vein
  61. 61. Intrauterine Transfusion • The goal of IUT is to achieve a posttransfusion hematocrit of 50-60%. • Indications for the first IUT: • Ultrasound evidence of hydrops fetalis. • cordocentesis shows severe anemia (hemoglobin < 10 g/dL, hematocrit < 30%) • Spectrophotometry of amniotic fluid shows high bilirubin level,
  62. 62. Intra-venous.. • Give antenatal steroids for lung maturity • Use of antibiotics and tocolytics before procedure no evidence for it. • Fetal paralysis with pancuronium can be done • 20-22 gauge echogenic tip needle • Site 1. near the placental insertion of cord • 2. Free loop of cord • 3. Intrahepatic portion of hepatic vein • 4.Umbilical artery
  63. 63. Intra-venous.. • Fetal blood confirmed by high MCV (>110) • Volume of blood transfused depends on EFW, fetal hematocrit(HCT), HCT of blood transfused • Overall procedure related fetal loss 1%. • Emergency delivery in 24 hrs of procedure and subsequent perinatal death 1.8% • HCT falls 1% per day and repeat transfusion generally within 2 weeks.
  64. 64. Intra-peritoneal.. • Usually done < 18weeks or when intravenous transfusion technically impossible because fetal position or location of umbilical cord. • Infused RBCs are absorbed into the circulation of subdiaphragmatic lymphatic lacunae and right lymphatic duct • Fetal respiration is important to occur. • Complete absorption takes 150hrs (6days)
  65. 65. Intra-peritoneal • Less effective when hydrops present • 16-20 gauge Touhy needle used • Needle inserted in between umbilicus and bladder • Catheter tip should be free in abdominal cavity and confirmed with injected saline. • Bowman formula for infused blood volume = (gestation in weeks -20) * 10 ml. Repeat transfusion generally 9-12 days
  66. 66. IUT.. • Complications: serial IUT risk to the mother and the fetus such as preterm labor, premature rupture of membranes, chorioamnionitis, fetal bleeding, fetal bradycardia, and fetal death. • Fetomaternal hemorrhage which may increase maternal alloimmunization and worsen the outcome.
  67. 67. IUT • After one IUT, the timing of the next IUT is usually planned arbitrarily after 2-3 weeks depending on previous posttransfusion hematocrit, considering a fall in hematocrit of 1% per day
  68. 68. Treatment • Invasive Procedures • Drainage Procedures: • Shunts • Large Pleural Effusions • Ascities • All invasive procedures carry an inherent increased risk of fetal demise or pre-mature labor.
  69. 69. Delivery • Mild Rh isoimmunisation 37 completed weeks • Severe cases • Last transfusion should be given 30-32 weeks with delivery between 32-34 weeks with steroids given to accelerate FLM. • Intra-uterine transfusion to be continued till 35 weeks and delivery at 37 weeks • Oral phenobarbitone can be given to mother strating 1 week prior to anticipated delivery.
  70. 70. Delivery • The fetus should be delivered at tertiary care center with neonatologists and other appropriate specialists. • There is no evidence that delivery by cesarean section has a marked effect on outcome. • Cord blood should be obtained at delivery for hemoglobin concentration and direct Coombs testing
  71. 71. Delivery • A postmortem evaluation should be performed in all cases of hydrops that result in neonatal death. One study showed that a combined approach of a thorough antenatal assessment and autopsy may be more likely to determine the cause of non- immune hydrops .
  72. 72. Counseling
  73. 73. Counseling • Long term prognosis depends on underlying cause and severity of the heart failure. • If the cause of NIH cannot be determined, the perinatal mortality is approximately 50% • Prognosis is much poorer if diagnosed at less than 24 weeks , pleural effusion is present, or structural abnormalities are present . • Pulmonary hypoplasia is a common cause of death in neonates with plerual effusions. • Fetal hydrops associated with a structural heart defect is associated with an almost 100% mortality rate.
  74. 74. Counseling • If early in pregnancy (less than 24 weeks) with no treatable cause the option of termination may be a consideration. • Recurrence is uncommon unless related to blood group incompatibility (isoimmunization) or inheritable disorder.
  75. 75. Thank You
  76. 76. Grand Mother theory • Rh –ve(dd) fetus rarely may be exposed to maternal D antigen as result of materno fetal haemorrhage and may become sensitized in their intra uterine life. When such girl at her adult age has pregnancy with Rh +ve fetus , the very first fetus may suffer from HDFN . this mechanism of isoimmunisation is called GRAND MOTHER THEORY.
  77. 77. Amnestic Response • In a previously sensitized / sensibilized women the antibody titer may rise to high level in subsequent pregnancy. • This may occur in d-negative fetus also.