Rhesus_Isoimmunisation_Presentation_Final.pptx

Rh in pregnancy

1. RHESUS ISOIMMUNISATION A Comprehensive Review of Pathogenesis, Diagnosis, and Management Presented by: GameGlitch BigBoss Date: July 23, 2025

2. Learning Objectives Define Rh isoimmunisation and understand the Rh system Describe the pathogenesis and prevalence of Rh alloimmunisation Identify fetal/neonatal and maternal complications Outline diagnostic approaches and investigations Discuss management strategies including fetal anemia treatment Review prevention protocols and counselling approaches Address social gaps and ethical considerations

3. Definition of Rh Isoimmunisation Process by which fetal Rh+ erythrocytes enter circulation of Rh- mother Causes maternal production of IgG antibodies against Rh antigens Antibodies cross placenta and destroy Rh+ fetal erythrocytes Results in hemolytic disease of fetus and newborn (HDFN) Also known as Rhesus sensitization or alloimmunization Preventable condition with proper Anti-D prophylaxis

4. Historical Background & Significance 1940: Discovery of Rh factor by Landsteiner and Wiener 1960s: Introduction of Anti-D immunoglobulin (RhoGAM) 1970s: Implementation of routine prophylaxis Before RhoGAM: 13-16% alloimmunization rate in at-risk pregnancies After RhoGAM: 0.5-1.8% alloimmunization rate Prevented countless cases of HDFN and fetal deaths One of the great success stories of modern obstetrics

5. The Rh Blood Group System Second most important blood group system after ABO Contains >50 antigens, 5 main clinically significant 36 different blood group systems, 360 antigens recognized Located on chromosome 1 (RHD and RHCE genes) Highly immunogenic, especially D antigen Prevalence varies by ethnicity and geography

6. The Five Main Rh Antigens (DCCEe) D antigen: Most immunogenic, determines Rh+/- C antigen: Encoded by RHCE gene c antigen: Antithetical to C antigen E antigen: Encoded by RHCE gene e antigen: Antithetical to E antigen RHD gene: Encodes D antigen RHCE gene: Encodes C/c and E/e antigens

7. Rh Phenotypes and Inheritance DCCee (R1R1): 45.71% - most common phenotype DCcee (R1R0): 30.48% DCcEe (R1R2): 11.43% DccEe (R2R0): 4.76% dccee (rr): 0.95% - Rh-negative phenotype Inheritance: Autosomal codominant pattern Independent of other blood group genes Inherited as haplotypes

8. Prevalence of Rh-Negative Blood Type Non-Hispanic White Americans: 15% Rh-negative African Americans: 7% Rh-negative Hispanic Americans: 7% Rh-negative Native Americans: 10% Rh-negative Asian Americans: 1% Rh-negative Overall: 85% of population is Rh-positive Significant geographic and ethnic variations

9. D Variants and Weak D >200 D antigen variants exist Weak D: Reduced D antigen expression Partial D: Missing portions of D antigen Some variants can cause alloimmunization Testing challenges in blood banking May require specialized typing methods Clinical significance varies by variant type

10. Prevalence of Rh Alloimmunisation Overall prevalence: ~1% of pregnancies Developed countries: 0.5-1.8% Developing countries: Up to 5-10% Southwest US: 1.5x national average Varies by population and healthcare access Higher in areas with limited Anti-D access Immigration factors affect regional rates

11. Pathogenesis - Primary Sensitization 1. Fetomaternal hemorrhage occurs 2. Fetal Rh+ cells enter maternal circulation 3. Maternal immune system recognizes foreign antigen 4. Primary immune response initiated 5. Memory B cells formed Usually occurs at delivery Can happen during pregnancy (trauma, procedures) As little as 0.1 mL can sensitize

12. Pathogenesis - Secondary Response Subsequent Pregnancy Process: 1. Re-exposure to Rh+ fetal cells 2. Rapid secondary immune response 3. IgG antibody production 4. Antibodies cross placenta 5. Fetal red cell destruction begins Characteristics: Faster and more robust response Higher antibody titers, Earlier onset in pregnancy

13. Factors Affecting Severity Maternal Factors: • Antibody titer levels • IgG subclass distribution • Previous obstetric history • Immune system responsiveness Fetal Factors: • Antigen density on RBCs • Gestational age • Fetal immune system maturity • Placental transfer efficiency

14. Fetal Complications - Overview Spectrum of Disease: • Mild: Minimal anemia, no symptoms • Moderate: Anemia with compensated hemolysis • Severe: Hydrops fetalis, heart failure • Fatal: Intrauterine fetal death Pathophysiology: • Antibody-mediated hemolysis • Compensatory extramedullary hematopoiesis • Progressive anemia and hypoxia

15. Hydrops Fetalis - Definition Definition: Abnormal fluid accumulation in ≥2 fetal compartments: • Ascites • Pleural effusion • Pericardial effusion • Skin edema (anasarca) Pathophysiology: • Severe anemia (Hb <7 g/dL below normal) • High-output cardiac failure • Capillary leak syndrome • Hypoalbuminemia

16. Hydrops Fetalis - Clinical Features Ultrasound Findings: • Fetal ascites • Pleural effusions • Pericardial effusion • Skin thickening >5mm • Polyhydramnios • Placentomegaly Prognosis: • 50% mortality if untreated • Better outcomes with early intervention

17. Icterus Gravis Neonatorum Definition: Severe neonatal jaundice due to massive hemolysis Pathophysiology: 1. Continued hemolysis after birth 2. Overwhelming bilirubin production 3. Immature hepatic conjugation 4. Risk of kernicterus Clinical Features: • Jaundice within 24 hours • Rapidly rising bilirubin levels • Hepatosplenomegaly

18. Fetal Anemia - Pathophysiology Mechanism: • Antibody-coated RBCs removed by spleen • Decreased RBC lifespan • Compensatory increase in erythropoiesis • Progressive anemia development Compensatory Mechanisms: • Extramedullary hematopoiesis • Increased cardiac output • Tissue hypoxia adaptation

19. Fetal Anemia - Assessment Diagnostic Methods: • Middle cerebral artery (MCA) Doppler • Peak systolic velocity measurement • Cordocentesis (if indicated) • Serial ultrasound monitoring MCA Doppler: • Non-invasive assessment • >1.5 MoM indicates moderate-severe anemia • Serial measurements guide management

20. Maternal Complications During Pregnancy: • Anxiety and psychological stress • Need for intensive monitoring • Risk of invasive procedures Delivery Complications: • Increased cesarean section rate • Neonatal intensive care needs • Postpartum hemorrhage risk Long-term: • Recurrence in future pregnancies • Need for specialized care

21. Diagnosis - Initial Assessment First Prenatal Visit: • Blood type and Rh determination • Antibody screening (Indirect Coombs) • Partner blood typing • Obstetric history review Antibody Screen Positive: • Antibody identification • IgG vs IgM determination • Initial titer measurement • Risk stratification

22. Diagnostic Tests and Critical Titers Laboratory Tests: • Indirect Coombs test (antibody screening) • Direct Coombs test (neonatal) • Antibody titration • Kleihauer-Betke test (FMH quantification) Critical Titers: • Anti-D: Usually 1:16 or 1:32 • Anti-c: 1:8 • Anti-E: 1:8 • Anti-Kell: Any detectable level

23. Investigations for Complications Fetal Assessment: • Serial MCA Doppler studies • Detailed ultrasound examination • Biophysical profile • Cordocentesis (if indicated) Maternal Monitoring: • Serial antibody titers • Complete blood count • Liver function tests • Psychological support assessment

24. Management - Current Case with Fetal Anemia Case Scenario: Fetal Anemia Present Immediate Actions: 1. Confirm diagnosis with MCA Doppler 2. Assess gestational age 3. Multidisciplinary team consultation 4. Prepare for intervention Treatment Options: • Intrauterine transfusion (IUT) • Early delivery (if ≥32 weeks) • Intensive neonatal care preparation

25. Intrauterine Transfusion Protocol Indications: • MCA Doppler >1.5 MoM • Evidence of fetal anemia • Gestational age <32 weeks Procedure: • Ultrasound-guided cordocentesis • O-negative, CMV-negative, irradiated blood • Target hematocrit 40-50% Monitoring: • Post-procedure MCA Doppler • Repeat IUT as needed

26. Management Protocol for Rh-negative Mother Antepartum Care: • Routine Anti-D at 28 weeks (300 μg) • Additional Anti-D after sensitizing events • Serial antibody monitoring • Fetal surveillance protocols Delivery Management: • Cord blood sampling • Neonatal assessment • Anti-D within 72 hours (if baby Rh+) Postpartum: • Neonatal monitoring • Future pregnancy counseling

27. Social & Healthcare System Gaps Access Issues: • Limited Anti-D availability in developing countries • Cost barriers for specialized care • Geographic disparities in expert centers Education Gaps: • Healthcare provider knowledge • Patient awareness • Community understanding System Challenges: • Blood bank infrastructure • Laboratory capabilities • Referral networks

28. Prevention - Anti-D Immunoglobulin Routine Prophylaxis: • 28 weeks gestation: 300 μg IM • Within 72 hours of delivery: 300 μg IM • After sensitizing events: Variable dose Effectiveness: • 99% effective when properly administered • Reduced HDFN incidence by >95% • Cost-effective intervention Mechanism: • Prevents maternal sensitization • Clears fetal cells before immune response

29. Counselling Approaches Pre-conception Counseling: • Risk assessment • Partner testing • Family planning discussions • Genetic counseling referral Antenatal Counseling: • Disease explanation • Treatment options • Risk-benefit discussions • Emotional support Postpartum Counseling: • Future pregnancy risks • Prevention strategies

30. Ethical Considerations & Future Directions Ethical Issues: • Informed consent for procedures • Resource allocation • Quality of life considerations • Termination counseling Future Directions: • Non-invasive fetal RhD genotyping • Improved Anti-D products • Gene therapy research • Global access initiatives Conclusion: Rh isoimmunisation remains significant but is largely preventable

31. Key Take-Home Messages 1. Rh isoimmunisation is preventable with proper Anti-D prophylaxis 2. Early detection and monitoring are crucial for optimal outcomes 3. MCA Doppler is the gold standard for fetal anemia assessment 4. Intrauterine transfusion can be life-saving in severe cases 5. Multidisciplinary approach improves maternal and fetal outcomes 6. Global access to Anti-D remains a challenge 7. Counselling and education are essential components of care

32. Questions & Discussion Thank you for your attention! Questions and Discussion Contact Information: GameGlitch BigBoss Date: July 23, 2025

33. Rh System Antigens Structure Five main Rh antigens: D, C, c, E, e D antigen most immunogenic Genetic control by RHD and RHCE genes

34. Pathogenesis Flowchart Primary sensitization during first pregnancy Secondary response in subsequent pregnancies Maternal antibodies cross placenta

35. RhoGAM Prevention Anti-D immunoglobulin prevents sensitization Given at 28 weeks and within 72 hours of delivery 99% effective when properly administered