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Rhesus Isoimmunisation

Rhesus isoimmunization occurs when an Rh-negative mother carries an Rh-positive baby and fetal-maternal hemorrhage of Rh-positive fetal red blood cells into the mother's circulation triggers the formation of anti-D antibodies. This can sensitize the mother and cause hemolytic anemia in subsequent Rh-positive pregnancies if the anti-D antibodies cross the placenta and destroy fetal red blood cells. Administering RhoGAM (anti-D immunoglobulin) to the mother during and after pregnancy can prevent sensitization by neutralizing any Rh-positive fetal red blood cells that enter her circulation. Close monitoring and medical management is required for sensitized Rh-negative mothers to prevent harm to

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Rhesus isoimmunization
Basic – Blood group & Rhesus 2 most important blood group systems ABO group Rhesus group
ABO blood group No No Yes Yes AB Yes Yes No No O No Yes Yes No B Yes No No Yes A Anti-B Anti-A Antigen B Antigen A ABO blood type
Rhesus blood group No No Rhesus –ve No Yes Rhesus +ve D-antibody D-Antigen D D D D D D D D D D D D D D D D
Epidemiology <1% Asians 5-10% African-Americans (Blacks) 15% Caucasian Racial variation in incidence of Rh negative
Basic - isoimmunization Occurs when: Mother is Rh –ve Baby is Rh +ve Fetomaternal haemorrhage occurs Antepartum haemorrhage Falls or closed abdominal trauma Intrauterine death External cephalic version Invasive prenatal diagnosis (e.g. amniocentesis, chorionic villus sampling)
Basic - Isoimmunization Fetomaternal haemorrhage – fetal RBC enter maternal circulation Formation of antibodies to D antigen (anti-D) - sensitization Later in pregnancy or next pregnancy, anti-D crosses placenta Anti-D attacks fetal Rh +ve RBCs and are destroyed by the immune system – haemolytic anaemia
Importance Rh –ve mothers are at risk of developing Rh isoimmunization if the fetus is Rh +ve If a mother has been sensitized before, there is a risk of the Rhesus +ve fetus developing hemolytic anaemia and in severe cases, hydrops fetalis
How to prevent isoimmunization? Prevent mother from forming Anti-D antibodies by giving RhoGAM (Anti-D antibodies)
Why RhoGAM? Prophylactic anti-D Ig has resulted in a substantial fall in perinatal mortality and morbidity from rhesus D disease
Rhesus +ve men 55% are heterozygous (Dd) – 50% chance of Rh-positive fetus 45% are homozygous (DD) – 100% chance of Rh-positive fetus
Risk of isoimmunisation 0.1-0.2% Postpartum + antepartum RhoGAM 1-2% Postpartum RhoGAM 8% Subsequent pregnancy - untreated 16% 1 st Rh-incompatible pregnancy – untreated Risk of isoimmunisation
Indications for RhoGAM Miscarriage All therapeutic termination – irregardless of gestational age or methods (medical or surgical) All surgical evacuation (ERPOC @ S&C) Threatened miscarriage >12 weeks Threatened miscarriage <12 weeks with Heavy or repeated bleeding Abdominal pain
Indications for RhoGAM Ectopic pregnancy Conditions a/w fetomaternal haemorrhage Antepartum haemorrhage Falls or closed abdominal trauma Intrauterine death External cephalic version Invasive prenatal diagnosis (e.g. amniocentesis, chorionic villus sampling)
Not indicated Complete spontaneous miscarriage <12 weeks Threatened miscarriage <12 weeks POA (with cessation of bleeding before 12 weeks POA) Reason – unlikely to cause significant FMH
RhoGAM – Dosage & administration Dose Before 20 weeks : 250 IU After 20 weeks : 500 IU Postpartum : At least 500 IU Note : Kleihauer test should be performed when anti-D Ig is given after 20 weeks To estimate volume of FMH Additional anti-D Ig if FMH > 4 mL fetal cells (125 IU prevents immunization with 1 ml fetal cells)
RhoGAM – Dosage & administration Route : Deep IM injection – preferably deltoid muscle Timing : Postpartum – <72 hours May still be given if presented later (10-14 days)
Clinical setting Refer to hospital as early as possible if: Rhesus negative pregnant mother (either 1 st time detected or known rh –ve previously) Known rhesus negative with risk of FMH (e.g. threatened miscarriage, APH, fall, abdominal trauma, etc.)
Clinical setting Screened for maternal anti-D (sensitization) – Indirect Coomb’s test At booking Just before 28 weeks If not sensitized, RhoGAM is administered: 500 IU at 28 & 34 weeks 1,500 IU at 28 weeks only No need to check Indirect Coomb’s test after Rhogam as it may be positive due to Rhogam itself Postnatal RhoGAM is still given
Clinical setting If sensitized, close monitoring of: Fetus Anti-D level Timing and mode of delivery depending of status of fetus
Oxford Rhesus Therapy Unit mx guidelines 34+ Yes 2 > 16.0 34-38 Yes 2 10.1-16.0 36-38 No 2 4.1-10.0 Term No 2 0.5 - 4.0 Term No 4 < 0.5 Gestation at which delivery advised Invasive testing Repeat antibody quantitation (weeks) Anti-D quantitation (IU/ml)
Non-invasive fetal monitoring Ultrasound – features of hydrops Ascites Pleural effusion Soft tissue/scalp edema Cardiomegaly Hepatomegaly Doppler – middle cerebral artery FKC CTG
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