A 32-year-old Rh-negative woman (G3P2) presents at 18 weeks of gestation with vaginal bleeding. Ultrasound confirms a threatened miscarriage with fetal cardiac activity present. Her previous two pregnancies were uncomplicated vaginal deliveries of Rh-positive infants. She received anti-D prophylaxis after both deliveries. Indirect Coombs test today is negative. What is the most appropriate immediate management?

Explanation

## Anti-D Prophylaxis in First and Second Trimester Bleeding **Key Point:** Any potentially sensitizing event (miscarriage, threatened miscarriage, ectopic pregnancy, molar pregnancy, termination, amniocentesis, CVS) in an Rh-negative unsensitized woman requires anti-D prophylaxis. The dose and need for Kleihauer–Betke testing depend on gestation and clinical context. ### Sensitizing Events and Anti-D Requirements | Event | Gestation | Anti-D Dose | Kleihauer–Betke | |-------|-----------|-------------|------------------| | Threatened miscarriage | <12 weeks | 100–250 IU (optional) | Not required | | Threatened miscarriage | 12–20 weeks | 500 IU | Perform if bleeding significant | | Miscarriage/termination | <12 weeks | 100–250 IU (optional) | Not required | | Miscarriage/termination | 12–20 weeks | 500 IU | Perform if bleeding significant | | Miscarriage/termination | >20 weeks | 500 IU | Always perform | | Ectopic/molar pregnancy | Any | 500 IU | Always perform | **High-Yield:** At 18 weeks with threatened miscarriage, the standard dose is 500 IU anti-D intramuscularly. Kleihauer–Betke should be performed to quantify fetomaternal hemorrhage and determine if additional anti-D is needed (1 IU per fetal red cell or 125 IU per mL fetal whole blood). **Clinical Pearl:** The negative ICT confirms this woman is unsensitized and eligible for prophylaxis. Her previous Rh-positive deliveries with appropriate anti-D prophylaxis have not resulted in sensitization, but she remains at risk with this current bleeding episode. **Warning:** Do NOT defer anti-D prophylaxis based on the assumption that ICT will be checked at 28 weeks. Each sensitizing event requires immediate anti-D administration. Waiting increases the risk of active sensitization. ### Mechanism Fetomaternal hemorrhage during threatened miscarriage can expose maternal circulation to fetal red blood cells. Anti-D prevents maternal B-cell sensitization by coating these cells, preventing immune recognition. **Mnemonic:** **SEAT** = **S**ensitizing **E**vents in **A**ny **T**rimester require anti-D in unsensitized Rh-negative women.