Rh Disease Summary

Pathophysiology

  • RhD-negative mother + RhD-positive fetus
  • Fetomaternal haemorrhage → sensitization
  • IgG antibodies cross placenta → fetal hemolysis
  • Can lead to hydrops fetalis and fetal death

Anti-D Immunoglobulin

  • Prevents anti-D antibody formation
  • Destroys RhD-positive fetal RBCs
  • Administer within 72 hours of sensitizing event
  • Up to 10 days if deadline missed

Sensitizing Events

  • Amniocentesis, CVS, cordocentesis
  • Antepartum haemorrhage
  • External cephalic version
  • Abdominal trauma
  • Miscarriage/termination
  • Delivery (all types)

Dosing Guidelines

  • <12 weeks: 250 IU (limited indications)
  • 12-20 weeks: 250 IU minimum
  • >20 weeks: 500 IU minimum
  • RAADP: 28 weeks ± 34 weeks
  • Postnatal: 500 IU minimum

FMH Testing

  • Required after 20 weeks gestation
  • Significant if ≥4 mL fetal blood
  • Follow-up at 48h (IV) or 72h (IM)
  • Continue until fetal cells cleared

Special Situations

  • IUD: Administer within 72h of diagnosis
  • Cell salvage: 1500 IU minimum
  • Unknown status: Continue prophylaxis

Rhesus D Disease

Immune-mediated hemolytic disease of the fetus and newborn caused by Rh D incompatibility

Pathophysiology

Passage of fetal cells into the maternal circulation and fetomaternal haemorrhage (FMH) is a frequent occurrence, detectable in 65% of pregnancies either antenatally or in the early postnatal period.

Immune Sensitization Process

Primary Sensitization

  • Sensitization with as little as 0.1 mL of RhD-positive fetal RBCs
  • Generation of B lymphocyte clones recognizing foreign RBC antigen
  • Production of immunoglobulin G (IgG)
  • Formation of memory B lymphocytes

Secondary Response

  • Memory B cells activated in subsequent pregnancy
  • Differentiation into plasma cells producing IgG
  • Maternal IgG crosses placenta
  • Attachment to fetal RBCs expressing antigen

Fetal Consequences

Hemolysis & Anaemia

  • Fetal RBCs sequestered by macrophages in spleen
  • Extravascular haemolysis occurs
  • Progressive fetal anaemia develops

Compensatory Mechanisms

  • Increased extramedullary haematopoiesis
  • Hepatosplenomegaly
  • Portal hypertension
  • Cardiac compromise

Severe Complications

  • Tissue hypoxia and hypoviscosity
  • Increased brain perfusion
  • Hydrops fetalis (fluid in serous compartments)
  • Intrauterine fetal death

Critical threshold: Extreme fetal haemoglobin deficits of 70 g/L (7 g/dL) or greater can lead to hydrops fetalis and intrauterine fetal death without intervention.

Anti-D Immunoglobulin Prophylaxis

Anti-D immunoglobulin is prepared from plasma taken from rhesus-negative donors who have been immunised against the anti-D antigen. The aim is to prevent anti-D antibody formation in Rh D negative mothers.

Mechanism of Action

Immunological Protection
  1. Small amounts of anti-D IgG antibody administered
  2. Antibodies 'mop up' and destroy Rh D positive fetal red cells
  3. Prevents fetal cells from sensitising the mother
  4. Eliminates antigenic stimulus for primary immune response

Timing of Administration

Situation Timing Notes
Standard sensitizing events Within 72 hours Optimal protection window
Missed deadline Up to 10 days Some protection still offered
Follow-up after IV dose 48 hours Check fetal cell clearance
Follow-up after IM dose 72 hours Check fetal cell clearance

Clinical Guidelines for Anti-D Administration

Potentially Sensitizing Events

Invasive Procedures

  • Amniocentesis
  • Chorionic villus biopsy
  • Cordocentesis
  • External cephalic version
  • In-utero therapeutic interventions

Bleeding Events

  • Antepartum haemorrhage
  • Uterine (PV) bleeding in pregnancy
  • Threatened miscarriage
  • Miscarriage

Other Events

  • Abdominal trauma (sharp/blunt)
  • Ectopic pregnancy
  • Evacuation of molar pregnancy
  • Intrauterine death and stillbirth
  • Therapeutic termination of pregnancy
  • Delivery (all modes)
  • Intra-operative cell salvage

Gestational Age-Based Dosing

Gestation Dose FMH Testing Notes
< 12 weeks 250 IU minimum Not required Limited indications only
12-20 weeks 250 IU minimum Not required All sensitizing events
> 20 weeks 500 IU minimum Required Additional doses if FMH ≥4mL

Routine Antenatal Anti-D Prophylaxis (RAADP)

All D negative pregnant women who have not been previously sensitised should be offered routine antenatal prophylaxis with anti-D Ig (RAADP).

Regimen Options

Single Dose Regimen

  • Administered at around 28 weeks
  • Convenient for patient compliance
  • Standard approach in many centers

Two-Dose Regimen

  • Given at 28 and 34 weeks
  • May provide more consistent protection
  • Alternative option

Important: The 28-week sample for blood group and antibody screen must be taken prior to the first routine prophylactic anti-D Ig injection being given.

Postnatal Management

Delivery Protocol
  1. Perform ABO and Rh D typing on cord blood
  2. If baby is D positive, offer at least 500 IU anti-D Ig
  3. Administer within 72 hours following delivery
  4. Test maternal samples for FMH
  5. Give additional doses as guided by FMH tests

Special Clinical Situations

Fetomaternal Haemorrhage (FMH) Testing

A FMH test detects fetal cells in the maternal circulation and estimates the volume of FMH to allow calculation of additional anti-D doses required to clear the fetal cells.

Significant FMH

  • ≥4 mL fetal blood considered significant
  • Requires follow-up FMH sample
  • Additional anti-D doses if volume exceeds coverage
  • Continue until fetal cells no longer detectable

Monitoring Protocol

  • Follow-up sample at 48h after IV anti-D
  • Follow-up sample at 72h after IM anti-D
  • Presence of free anti-D doesn't indicate adequate prophylaxis
  • Continue additional doses until fetal cells cleared

Complex Scenarios

Situation Management Additional Considerations
Intrauterine Death (IUD) Administer anti-D within 72h of diagnosis Irrespective of time of subsequent delivery
Intra-operative Cell Salvage 1500 IU minimum after reinfusion FMH test 30-45min after reinfusion
Detected Anti-D Determine if immune or passive Continue prophylaxis if uncertain origin

Critical documentation: Maintain auditable records of issue and administration to allow full traceability of anti-D immunoglobulin.