When should anti-D (Rho(D) immune globulin) be administered in the event of a miscarriage?

Anti-D Administration for Miscarriage

In care settings where RhD testing and anti-D administration are logistically feasible, offer both RhD testing and RhIg to all unsensitized Rh-negative women with spontaneous or induced abortion at <12 weeks gestation, as existing data do not convincingly demonstrate the safety of withholding RhIg for first-trimester pregnancy losses. 1

Physiologic Rationale

The recommendation to administer anti-D even in early pregnancy is based on critical developmental biology:

• Fetal red blood cells display RhD antigens from as early as 6 weeks of gestation, making maternal sensitization physiologically possible even in very early pregnancy 1, 2
• Fetomaternal hemorrhage occurs in 48% of threatened abortions, 36% of complete abortions, and 22% of incomplete abortions 2
• Without prophylaxis, the consequences of RhD alloimmunization include hemolytic disease of the fetus/newborn, need for fetal transfusion, fetal hydrops, stillbirth, and preterm delivery 2

Dosing Protocol by Gestational Age

Before 12 Weeks Gestation

• Administer 50 μg (minimum dose) of RhIg within 72 hours of the miscarriage or bleeding event 1, 2, 3
• If the 50 μg dose is unavailable, use the standard 300 μg dose 2, 3
• Some guidelines recommend 120 μg as the minimum dose, which is the lowest currently available in Canada 3

After 12 Weeks Gestation

• Administer 300 μg of RhIg within 72 hours 3, 4

Timing Window

• Optimal administration is within 72 hours of the event 3, 4
• If not given within 72 hours, still administer anti-D as soon as recognized, up to 28 days after the event 1, 3

High-Risk Scenarios Requiring Heightened Vigilance

Certain clinical presentations warrant particular attention for RhIg administration:

• Heavy or recurrent bleeding 2, 5
• Associated abdominal pain 2, 5
• Bleeding occurring near 12 weeks gestation 2
• Uterine instrumentation (D&C), which increases fetomaternal hemorrhage risk, particularly in primigravidas requiring greater cervical dilation 2

In a study of women presenting with threatened miscarriage <12 weeks, 74.1% presented with either abdominal pain or heavy/recurrent bleeding, indicating substantial risk 5

Evidence Quality and Guideline Divergence

There is notable divergence in international guidelines that warrants discussion:

Supporting Administration (SMFM, ACOG Position)

• The Society for Maternal-Fetal Medicine (2024) explicitly states that existing guidelines "do not convincingly demonstrate the safety of withholding RhIg for first-trimester abortions or pregnancy losses" 1
• Given the devastating consequences of RhD alloimmunization and the low risks of RhIg administration, prevention of maternal sensitization is essential 1, 2
• The mechanism of RhIg effectiveness is well-established: postpartum administration reduces alloimmunization from 13-17% to 1-2%, and this same mechanism applies to first-trimester exposures 2

Opposing View (SFP, WHO)

• The Society of Family Planning and World Health Organization recommend against routine RhD testing and RhIg for spontaneous/induced abortion <12 weeks 1
• However, these recommendations are based primarily on logistical and access considerations rather than evidence of safety 1, 2
• A Cochrane review found insufficient data to evaluate the practice, with only one small RCT of 48 women that failed to show differences due to inadequate sample size 6

Clinical Resolution of Controversy

The absence of high-quality evidence demonstrating safety of withholding RhIg, combined with the known presence of fetal RhD antigens from 6 weeks and documented fetomaternal hemorrhage rates, supports administration in the first trimester when feasible. 1, 2

Practical Implementation Algorithm

Step 1: Determine Rh Status

• Check Rh status on all women presenting with miscarriage or threatened abortion 3
• If Rh status is unknown and testing is unavailable, administer RhIg if clinically indicated, as the risks of administration are low compared to potential consequences of sensitization 2

Step 2: Assess for Prior Sensitization

• Confirm the patient is unsensitized (no anti-D antibodies) 1, 3
• Women with "weak D" (Du-positive) should not receive anti-D 3

Step 3: Administer Appropriate Dose

• <12 weeks: 50 μg (or 120 μg/300 μg if unavailable) 1, 2, 3
• ≥12 weeks: 300 μg 3, 4
• Administer within 72 hours, but up to 28 days if delayed 1, 3

Step 4: Consider Quantitative Testing for High-Risk Events

• For events with potential significant placental trauma (abruption, blunt abdominal trauma, placenta previa with bleeding), consider quantitative testing for fetomaternal hemorrhage 3
• If FMH exceeds the amount covered by the standard dose, give additional 10 μg anti-D per 0.5 mL of fetal RBCs 3, 4

Critical Pitfalls to Avoid

• Do not assume early gestational age eliminates risk – fetal RBCs with D-antigen are present from 6 weeks onward 1, 2
• Do not withhold RhIg for "minimal" bleeding – bleeding severity does not reliably predict fetomaternal hemorrhage volume 2
• Do not fail to document Rh status – in one A&E study, Rh status was recorded in only 13.3% of cases, and 86.6% were discharged without checking 5
• Do not delay beyond 72 hours without attempting late administration – RhIg can still be given up to 28 days post-event 1, 3

Special Circumstances

When RhD Testing Creates Barriers to Care

• In settings where requiring RhD testing could delay abortion care or pose logistical barriers, prioritize completing the abortion 2
• Counsel patients on implications of unknown blood type and possible risks of non-administration 2
• If clinically indicated and testing unavailable, administer RhIg empirically 2

Supply Limitations

• If RhIg supply is limited, prioritize postpartum patients and antenatal patients at later gestational ages 2