Anti-D immunoglobulin

Mechanism

Mechanism of Action

Anti-D immunoglobulin is a concentrated sterile solution of IgG immunoglobulins of human plasma origin containing specific antibodies directed against the erythrocyte surface Rh (D) antigen.

Physiology of Immune Suppression by Clearance

1. Opsonization and Clearance: Following a fetomaternal hemorrhage event in which fetal erythrocytes expressing the Rh (D) antigen enter the bloodstream of an Rh-negative mother, the infused anti-D immunoglobulin rapidly binds to the D antigen epitopes of the fetal red blood cells.
2. Destruction in the spleen: Erythrocytes opsonized by exogenous IgG antibodies are selectively recognized by the Fc receptors of macrophages in the maternal spleen, being captured and destroyed by phagocytosis before they reach the lymphoid follicles.
3. Prevention of alloimmunization: By being destroyed early, the mother's B lymphocytes are prevented from recognizing the foreign D antigen, completely preventing the process of alloimmunization of memory cells and the subsequent synthesis of their own IgG anti-D antibodies capable of crossing the placenta in future pregnancies, preventing the development of Hemolytic Disease of the Newborn (Erythroblastosis). Fetal).

Pharmacokinetics

Pharmacokinetics

• Routes of administration: Deep intramuscular (exclusively in deltoid or gluteal forceps) or slow intravenous (brands approved specifically for IV infusion in cases of bleeding risk or thrombocytopenia).
• Absorption: After IM injection, the concentration of serum antibodies is progressively detected starting 2 hours after injection, reaching maximum levels in 5 to 10 days.
• Distribution: Reduced and stable volume of distribution, confined to the lymphatic and vascular space. It residually crosses the placental barrier in trace amounts incapable of inducing significant clinical hemolysis in the fetus.
• Metabolism: Nonspecific cellular catabolism in the reticuloendothelial system through lysosomal degradation to free amino acids.
• Half-life (t_1/2): Approximately 21 to 30 days, which allows a prenatal dose administered at week 28 to remain active, protecting the mother until full-term delivery.

Indicators and dose

Indications

• Active prevention of Rh (D) alloimmunization in Rh (D)-negative adult women who are not previously sensitized (anti-D antibodies negative in the indirect Coombs test) in situations of:
  - Routine systematic prenatal prophylaxis (at 28 weeks of gestation).
  - Immediate postpartum prophylaxis after the birth of a confirmed Rh (D)-positive newborn (within the first 72 hours of birth).
  - Prophylaxis after obstetric events of potential active fetomaternal hemorrhage: spontaneous or induced abortion, threatened abortion with active bleeding, ectopic pregnancy, blunt gestational abdominal trauma, or diagnostic invasion procedures (amniocentesis, chorionic villus biopsy or external cephalic version).

Dosing and Precision Adjustment

• Systematic prenatal prophylaxis: 300 µg (1,500 IU) by IM or slow IV route once in week 28 of gestation.
• Standard postpartum prophylaxis: 300 µg (1,500 IU) IM or IV administered as soon as possible within the first 72 hours after delivery of an Rh-positive fetus (if the 72-hour interval is exceeded, the effectiveness decreases but it should still be injected until day 14-28 postpartum).
• First trimester events (abortion, amniocentesis < 12 weeks): Reduced dose from 50 to 150 µg IM.
• Suspected massive feto-maternal hemorrhage: In cases of placental abruption or severe abdominal trauma, a standard dose of 300 µg is insufficient (it only neutralizes up to 15 mL of compact fetal erythrocytes or 30 mL of whole fetal blood). Quantitative Kleihauer-Betke testing or flow cytometry should be performed to quantify actual fetal blood loss and calculate the additional required cumulative dose of anti-D immunoglobulin.

Pregnancy and Breastfeeding

Specifically indicated for prophylactic administration during pregnancy safely and without described fetal risks. Compatible with breastfeeding.

Security

Contraindications

• Rh (D)-positive women.
• Rh (D)-negative women who are previously confirmed actively sensitized (positive anti-D antibody titer in baseline indirect Coombs test, where prophylaxis is useless and Doppler ultrasound management of the fetal middle cerebral artery is required to monitor fetal anemia).
• Known underlying hypersensitivity to human immunoglobulin preparations of plasma origin.
• Patients with selective IgA deficiency (high risk of development of anti-IgA antibodies and systemic anaphylaxis reactions).

Adverse Effects (ADR)

• Local Reactions: Pain, erythema, indurated edema and hypersensitivity at the IM injection site (common but mild).
• Systemic: Moderate transient fever, tension headache, myalgia and self-limited general malaise.
• Severe hypersensitivity (Rare): Generalized urticaria, dyspnea and systemic anaphylactic shock.