Rho(D) Immune Globulin (RhoGAM)

Emergency & Prehospital

• Abdominal or pelvic trauma in an Rh(D)-negative pregnant patient: Give within 72 hr of injury. From 20 weeks, quantify fetomaternal hemorrhage (FMH). The result sets the total dose.
• Antepartum bleeding: From 12 weeks onward, count threatened miscarriage with an ongoing pregnancy, placenta previa and other antepartum hemorrhage.

ED / ICU / Transport

• Ectopic pregnancy: Labeled at any gestation. First-trimester use depends on the guideline.
• Miscarriage or induced abortion at 12 weeks or later: Spontaneous, medication or procedural. All three count.
• Molar pregnancy (hydatidiform mole): The labels for Rhophylac and WinRho cover it.
• Threatened miscarriage before 12 weeks: Labeled for RhoGAM, HyperRHO, Rhophylac and WinRho. Outside the ACOG 2024 update, practice varies, so follow local protocol.
• Pregnancy loss or abortion before 12 0/7 weeks: The 2024 American College of Obstetricians and Gynecologists (ACOG) update no longer recommends routine prophylaxis here. Offer it only through shared decision-making.
• Delivery of an Rh(D)-positive or untyped newborn: Give postpartum prophylaxis within 72 hr. The ABO group does not change that.
• Obstetric procedures: amniocentesis, chorionic villus sampling (CVS), cordocentesis, external cephalic version
• Rh-incompatible transfusion: An Rh(D)-negative patient who receives Rh(D)-positive red cells, platelets or granulocytes

Other Uses

• Routine antepartum prophylaxis: Give at 28 weeks to every unsensitized Rh(D)-negative patient whose fetus is Rh(D)-positive or untyped.
• Immune thrombocytopenia (ITP): Rh(D)-positive, non-splenectomized patients only. Hematology gives it as the IV products WinRho SDF (children and adults) or Rhophylac (adults). The alternative is IVIG.

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• RhoGAM Ultra-Filtered PLUS: 300 mcg (1,500 international units) in a prefilled syringe, IM only. MICRhoGAM 50 mcg was discontinued in 2024.
• HyperRHO Full Dose / Mini-Dose: 300 mcg and 50 mcg prefilled syringes, IM only. Mini-Dose is the only US 50 mcg product. Its label covers miscarriage or abortion up to 12 weeks only.
• Rhophylac: 300 mcg (1,500 international units) in a 2 mL prefilled syringe. IV or IM.
• WinRho SDF: Vials of 120, 300, 500, 1,000 and 3,000 mcg, IV or IM. The 120 mcg vial is its labeled postpartum dose and the dose after 34 weeks.
• Setting: Stocked in the ED, labor and delivery and the blood bank. EMS does not carry it.

Adult Dosing

Pediatric Dosing

Preparation & Administration

• IM site: Deltoid or anterolateral thigh. Avoid the gluteal region (sciatic nerve). Never give it subcutaneously. The needle must reach muscle. IM failure is reported with a body mass index (BMI) of 30 or more.
• Multiple syringes: Use separate sites, all at one time or spaced out, with the whole dose in within 72 hr.
• IV (Rhophylac, WinRho only): Never give RhoGAM or HyperRHO IV. WinRho: 2 mL every 5–15 seconds for Rh prophylaxis, over 3–5 min for ITP. Rhophylac ITP: 2 mL every 15–60 seconds.
• Before and after: Warm IV products to room temperature. Discard if cloudy. Observe at least 20 min. Give the patient the Rh card and record lot and time.

Contraindications

• Rh(D)-positive patients receiving it for Rh prophylaxis (ITP use is the exception)
• Prior anaphylaxis or severe systemic reaction to a human immune globulin product
• Rhophylac: IgA deficiency with anti-IgA antibodies and a history of hypersensitivity to Rhophylac
• WinRho: IgA deficiency with anti-IgA antibodies, or a history of hypersensitivity to WinRho or its components
• The newborn infant: Postpartum doses are for the mother only
• ITP use: autoimmune hemolytic anemia, existing hemolysis or high risk of hemolysis (WinRho)
• IV administration of IM-only products (RhoGAM, HyperRHO)

Precautions

• Already alloimmunized (immune anti-D): No benefit. The blood bank tells this apart from passive anti-D after a recent dose.
• Weak or discrepant D typing: Send RHD genotyping (Special Populations).
• Thrombocytopenia or bleeding disorders: An IM injection can bleed. Consider an IV product.
• Pre-existing anemia (ITP use): Hemolysis may make it worse.
• Corn allergy (WinRho): Avoid WinRho. It contains 10% maltose, and that maltose comes from corn.
• IV immune globulin risks (WinRho ITP dosing): Watch for acute renal failure, thrombosis and transfusion-related acute lung injury (TRALI). Correct volume depletion first. In at-risk patients, check renal function and infuse at the slowest practical rate (Special Populations).
• Human plasma product: Screening and viral inactivation reduce infection risk. They do not eliminate it.

Hold / Reassess If

• The Rh(D) type or antibody screen has not resulted: send type and screen first. The 72-hour window allows time for it.
• Urticaria, wheeze, chest tightness or hypotension: Stop the injection or infusion.
• ITP use: back pain, shaking chills, fever, dark urine or hematuria during the 8-hour observation. Stop and check for hemolysis.

Common

• Injection-site pain, swelling, induration, redness or warmth (most frequent)
• Mild fever, body aches, malaise, rash
• Nausea, dizziness, headache (each 0.5–0.7% in Rhophylac obstetric trials)
• Transient positive anti-C antibody screen (0.9%, Rhophylac)
• In the Rhophylac ITP trial, chills 35%, fever 31%, rising bilirubin 21% and headache 11%. WinRho trials ran lower, with headache 11%, chills 8% and fever 6%.

Serious / Life-Threatening

Overdose & Toxicity Management

• Rh(D)-negative patients: No overdose toxicity is known. Rhophylac has reported mcg/unit mix-ups without harm. Very large WinRho doses, given for a mismatched transfusion, have been followed by hemolysis.
• Rh(D)-positive patients (ITP, transfusion, wrong patient): Overdose raises the hemolysis risk. A WinRho mcg/unit mix-up in ITP caused fatal intravascular hemolysis. Monitor clinically and with labs as above.
• No antidote: Supportive care. For anaphylaxis, give epinephrine first. Antihistamines such as diphenhydramine are adjuncts only.

Clinically Significant Interactions

IV Compatibility

• WinRho SDF: Give it separately from other drugs. If you dilute it, use normal saline only, never D5W.
• Rhophylac: Check that the needle-free IV connector fits the glass syringe tip before use.
• There is no IV compatibility for IM-only products. Verify with an institutional compatibility resource.

• Pediatrics: Safety and effectiveness are not established in children, including for incompatible transfusion. Weigh the benefit, especially in girls. WinRho is labeled for pediatric ITP at adult per-kg doses. See the Pediatric Dosing table.
• Neonates: Contraindicated. An antepartum maternal dose can make the newborn's DAT weakly positive. Tell the nursery team.
• Pregnancy: The available evidence shows no fetal harm and no effect on later pregnancies or fertility. No animal reproduction studies exist. Do not withhold an indicated dose.
• Lactation: It can be used while breastfeeding. Immunoglobulins pass into milk.
• Older Adults: ITP use: fatal intravascular hemolysis has occurred most often in patients over 65 with cardiorespiratory, renal or prothrombotic comorbidity (WinRho label). Start at the low end of the dose range. Check renal function first and monitor closely. In the Rhophylac ITP trial, 19% were 65 or older, with no difference in safety or effect. Not studied for Rh prophylaxis.
• Renal Impairment: No dose adjustment is established. In ITP use, hemolysis can cause acute kidney injury, so watch creatinine and urine output. WinRho: if the patient has pre-existing renal insufficiency, diabetes, age over 65, sepsis or nephrotoxic drugs, check BUN and creatinine before the first infusion. In those patients, use the minimum practical infusion rate.
• Hepatic Impairment: No dose adjustment is established. IgG breaks down the way the body's own antibody does.
• Obesity / Dosing Weight: Rh prophylaxis doses are fixed. ITP doses use actual weight in kg, and entering pounds causes an overdose. At a BMI of 30 or more, make sure the IM needle reaches muscle, or use an IV product.
• Weak D and Partial D: Weak D types 1, 2 and 3 carry no sensitization risk, so they get no prophylaxis. For other weak D and partial D types, give as for Rh(D)-negative.
• Fetal RHD known: A conclusively Rh(D)-negative newborn makes postpartum prophylaxis unnecessary. Fetal RHD genotyping from cell-free DNA can answer that before birth where a validated assay is used and local protocol accepts it. SOGC 2024 supports this approach.

• Scope: Not an EMS drug. It is given in the ED, labor and delivery or ICU, on an RN or provider order. Practice varies by state and agency protocol. Your role is to recognize the need and hand it off.
• Storage & Stability: Refrigerate at 2–8 °C (36–46 °F). Do not freeze. Rhophylac must not sit at room temperature, and it stays in its carton to protect it from light.
• Pregnant Trauma: Report gestational age, Rh status if known from the prenatal record, mechanism and time of injury. Expect at least 4 hr of observation at the receiving facility, even after minor injury.
• Interfacility Transfer: Send whether anti-D was given, the product, the dose, the time and the KB result. If it has not been given, flag the time the 72-hour window closes.
• Handoff Essentials: Rh type, antibody screen result, sensitizing event and time, doses given, pending FMH quantification.

Mechanism of Action

• Passive IgG anti-D binds Rh(D)-positive fetal red cells in the maternal circulation. The spleen clears them before a primary immune response can form. With no maternal anti-D, later pregnancies are protected from hemolytic disease of the fetus and newborn. The exact mechanism is not fully known.
• Once sensitization has occurred, it has no effect.
• ITP: anti-D-coated Rh(D)-positive red cells occupy the splenic Fc receptors. The antibody-coated platelets are spared, so the platelet count rises. The cost is hemolysis, mild or sometimes severe.

Pharmacokinetics

• Half-life: about 16–31 days, depending on product and route (Rhophylac 16–18 days, WinRho 24–30 days, RhoGAM 31 days).
• Bioavailability: IM about 69% of IV (Rhophylac).
• Metabolism and Elimination: It is broken down like endogenous IgG. No renal or hepatic elimination pathway matters clinically.

Generic Name

Rho(D) immune globulin (human); anti-D immunoglobulin; RhIG

Brand Names

RhoGAM Ultra-Filtered PLUS (Kedrion); MICRhoGAM Ultra-Filtered PLUS (discontinued 2024); HyperRHO Full Dose and Mini-Dose (Grifols); Rhophylac (CSL Behring); WinRho SDF (Kamada)

Pharmacologic Class

Anti-D (anti-Rh) hyperimmune IgG from pooled human plasma

Therapeutic Class

Rh isoimmunization prophylaxis; ITP therapy (IV products)

Controlled Substance

Not controlled

ISMP High-Alert

No

Look-Alike / Sound-Alike

HyperRHO / HyperHEP B / HyperRAB (same-manufacturer immune globulins; ISMP lists their former names BayRho-D / BayHep B / BayRab). Strength mix-up: HyperRHO Mini-Dose 50 mcg / HyperRHO Full Dose 300 mcg

Error-Prone Abbreviations to Avoid

"IU" and "µg": write "international units" and "mcg" (1 mcg = 5 international units)