Background: Timely anti-D immunoglobulin (anti-D) administration to rhesus (Rh)-negative, non-sensitized, pregnant women prevents Rh-D alloimmunization and future pregnancy morbidities. Reported hypersensitivity reactions to anti-D and published protocols for subsequent anti-D are limited, ranging from avoidance to 3-step graded administration. We report the first slow infusion protocol of anti-D given during pregnancy for a patient with previous clinical reactions. Informed consent for publication was obtained.

Case Report: A healthy, 25-week-pregnant, G5P2, Rh-negative, 32-year-old woman was seen at BC Women’s Hospital for anti-D administration. During her first pregnancy, she acutely developed nausea, tinnitus, dyspnea, rash, and presyncope after her first dose of anti-D. Symptoms improved with antihistamine and systemic steroids. Tryptase levels were not available. Her serum IgA level was normal. Intradermal skin testing to anti-D (1:100 and 1:10 dilutions) performed by a local allergist was negative. Instead of the usual administration of 2 mL per 5 to 15 seconds by IV push, her postpartum anti-D was given successfully in a 3-step graded administration (10%, 30%, 60% every 30 minutes) with pre-treatment (diphenhydramine and prednisone) as per prior case reports. She was re-challenged with a single-step administration of anti-D after the miscarriage of her second pregnancy but developed the same symptoms. For subsequent pregnancies, anti-D was given by 3-step graded administration with pretreatment.

With her current pregnancy, we proposed a slow infusion protocol with loratadine and prednisone pretreatment. Anti-D was diluted in 100 mL of normal saline (3 mcg/mL) and started at 20 mL/hour; rate was doubled every 15 minutes until 160 mL/hour, then completed to a cumulative dose of 300 mcg (Table 1). Total infusion time was 69 minutes, as compared to 60 minutes with 3-step graded administrations. She tolerated the infusion with no side effects.

Conclusion: Anaphylaxis to anti-D was reported previously; negative intradermal skin test suggests a non-IgE mediated mechanism. Avoiding anti-D carries risk of developing alloimmunization; conversely, rechallenging the product may result in life-threatening reactions. The proposed slow infusion protocol may be an additional method to safely give anti-D to patients with prior hypersensitivity reactions. Infusions can be stopped immediately upon symptom onset and may even be preferable to graded administration.