ABC of Rh immunoglobulins :- Rh IgG, first released for general use in 1968, has been remarkably successful in the prevention of Rh incompatibility in the current preg if such inj is received by 28 weeks to a great extent & mostly in subsequent pregnancies . In the Rh-negative mother, the preparation is administered after a suspected fetomaternal hemorrhage.

The exact mechanism by which passive administration of Rh IgG prevents Rh immunization is unknown but possibly the immunoglobulins smear the Rh +ve foetal RBCs (platelates surfaces have no antigens for Rh) and such RBC smeared with anti D get hemolyzed at spleen and destroyed. .

The most likely hypothesis is that the Rh immune globulin coats the surface of fetal RBCs containing Rh antigens. Once produced, maternal Rh immunoglobulin G (IgG) antibodies persist for life and may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia

These exogenous antibody-antigen complexes cross the placenta before they can stimulate the maternal endogenous immune system B cells to produce IgG antibodies.

Rh IgG is the standard of care in the the risk of Rh incompatibility has been reduced from 10-20%( mothers who don’t receive Anti-D --unimmunized mothers) to less than 1%.

Because of its short half-life, Rh IgG routinely is administered once at 28-32 weeks' gestation and again within 72 hours after birth(if neonate is Rh +Ve) to all Rh-negative pregnant females as a part of routine prenatal and postnatal care.

The current recommendation is that every Rh-negative nonimmunized woman who presents to the L room with antepartum bleeding or potential fetomaternal hemorrhage should receive 300 mcg of Rh IgG IM. For every 30 mL of fetal whole blood exposed to maternal circulation, 300 mcg of Rh IgG should be administered. A lower 50-mcg dose preparation of Rh IgG is available and recommended for Rh-negative females who have termination of pregnancy in the first trimester when fetomaternal hemorrhage is believed to be minimal.

What will be the dose schedule of anti-D ?? Dosage Forms & Strengths

Preparations are 1) 50 mcg 2) 300 mcg also expressed / dispensed in several courtiers as

1,500 Units/2 mL

1,500 Units/1.3 mL

2,500 Units/2.2 mL

5,000 Units/4.4 mL

15,000 Units/13 mL

Antepartum: 1500 IU~300 mcg IV/IM at 28-30 weeks of gestation

Postpartum: 1500 IU IV/IM within 72 hr

If both given risk reduced to 0.1%

If unable to give within 72 hr, give within 28 days; do not withhold

If >15 mL of Rho+ fetal RBC present in mother's circulation, multiple 1500 IU doses are required

Obstetric Conditions (Abortion/Miscarriage)

1500 IU IV/IM x1 within 72 hr

Hyper RHO/MicRhoGAM: If abortion within 13 weeks give 250 IU/50 mcg (minidose)

Rh Incompatibility

Updated: Mar 15, 2017

· Author: Leon Salem, MD, MS; Chief Editor: Bruce M Lo, MD, MBA, CPE, RDMS, FACEP, FAAEM, FACHE more...

· Share

The Rh factor (ie, Rhesus factor) is a red blood cell surface antigen that was named after the monkeys in which it was first discovered. Rh incompatibility, also known as Rh disease, is a condition that occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells, leading to the development of Rh antibodies.

Rh incompatibility can occur by 2 main mechanisms. The most common type occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma,^[1]invasive obstetric procedures, or normal delivery.

Rh incompatibility can also occur when an Rh-negative female receives an Rh-positive blood transfusion. In part, this is the reason that blood banks prefer using blood type "O negative" or "type O, Rh negative," as the universal donor type in emergency situations when there is no time to type and crossmatch blood.

The most common cause of Rh incompatibility is exposure from an Rh-negative mother by Rh-positive fetal blood during pregnancy or delivery. As a consequence, blood from the fetal circulation may leak into the maternal circulation, and, after a significant exposure, sensitization occurs leading to maternal antibody production against the foreign Rh antigen.

Once produced, maternal Rh immunoglobulin G (IgG) antibodies persist for life and may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia.^[2]Although the Rh blood group systems consist of many antigen subtypes (eg, D, C, c, E, e), the D antigen is the most immunogenic; therefore, it most commonly is involved in Rh incompatibility.

Dosage Forms & Strengths

50 mcg

300 mcg

1,500 Units/2 mL

1,500 Units/1.3 mL

2,500 Units/2.2 mL

5,000 Units/4.4 mL

15,000 Units/13 mL

Administer to Mother to Prevent Hemolytic Disease in Newborn

Antepartum: 1500 IU~300 mcg IV/IM at 28-30 weeks of gestation

Postpartum: 1500 IU IV/IM within 72 hr

If both given risk reduced to 0.1%

If unable to give within 72 hr, give within 28 days; do not withhold

If >15 mL of Rho+ fetal RBC present in mother's circulation, multiple 1500 IU doses are required

Obstetric Conditions (Abortion/Miscarriage)

1500 IU IV/IM x1 within 72 hr

HyperRHO/MicRhoGAM: If abortion within 13 weeks give 250 IU/50 mcg (minidose)

Immune Thrombocytopenic Purpura (Nonsplenectomized Rho(D)-Positive Patients)

Initial, Hgb >10 g/dL: 250 IU/kg IV once

Initial, Hgb <10 g/dL: 125-200 IU/kg IV once

Additional doses: 125-300 IU/kg IV PRN

Infuse IV over 3-5 min

If unresponsive to intital dose and Hgb <8 g/dL, use an alternate treatment

Incompatible Transfusions

WinRho SDF

· Exposure to Rh(D) positive whole blood

· IM: 12 mcg (60 IU)/mL blood

· IV: 9 mcg (45 IU)/mL blood

Rhophylac

· 20 mcg (100 IU)/2 mL blood (or 1 mL erythrocyte concentrate) IV/IM

Interactions

Enter a drug nameand Rho(D) immune globulin

No Results

All InteractionsSort By:

Frequency Not Defined

Tenderness

Allergic reaction

Urticaria

Angioedema

Rare elevation in total bilirubin secondary to rapid RBC destruction when given following transfusion mismatch

Black Box Warnings

Intravascular Hemolysis (IVH) with WinRho SDF

· Intravascular hemolysis (IVH) leading to death has been reported in patients treated for ITP with WinRho SDF

· IVH can lead to clinically compromising anemia and multisystem organ failure including acute respiratory distress syndrome (ARDS)

· Serious complications, including severe anemia, acute renal insufficiency, renal failure and disseminated intravascular coagulation (DIC) have also been reported

· Monitor closely in health care setting for at least 8 hr after administration

· Perform dipstick urinalysis at baseline, 2 hr, and 4 hr after administration and prior to end of the monitoring period

· Alert patients to signs and symptoms of IVH, including back pain, shaking chills, fever, and discolored urine or hematuria

· Absence signs and/or symptoms of IVH within 8 hr do not indicate IVH cannot occur subsequently

· Post-treatment laboratory tests should be performed if IVH suspected and include plasma hemoglobin, urinalysis, haptoglobin, LDH, and plasma bilirubin (direct and indirect)

Contraindications

Hemolytic Disease

· Rho(D)+

· Rho(D) negative women who are Rh immunized

· Hypersensitivity to immune globulins

Immune Thrombocytopenic Purpura

· Rho(D) negative individuals

· Splenectomized individuals

· Hypersensitivity to plasma products

· Autoimmune hemolytic anemia

· Pre-existing hemolysis or high risk for hemolysis

· Do not use WinRho SDF in patients with IgA deficency with antibioies against IgA

Cautions

NEVER GIVE TO NEONATE

Do not administer IM for ITP

WinRho SDF: risk of rare but potentially fatal intravascular hemolysis in ITP pts

Maltose-containing IVIG products (eg WinRho SDF) may give false highs in certain glucose-testing systems

Avoid live vaccines for 3 mth

IgA deficiency

Avoid gluteal IM if possible, if not inject only in upper outer quadrant

Pregnancy & Lactation

Pregnancy Category: C

Lactation: not known if excreted in breast milk, no adverse effects reported

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Anti-Rho(D) immune globulins from human donors

Pharmacokinetics

Peak Plasma Time: 5-10 d (IM); 2 hr (IV)

Peak Plasma Concentration: 18-19 ng/mL (IM); 36-48 ng/mL (IV)

Half-Life: 24-30 days

Vd: 8.59 L (IM)

Bioavailability: 69% (IM)

IM

Administer to mother, not to infant

Administer into the deltoid muscle or upper outer side of the thigh

Do not use gluteal region as routine inj site (risk of injury to sciatic nerves), however if necessary, use only the upper, outer quadrant of gluteal muscle

The plunger of the syringe should be drawn back before injection to ensure that the needle is not in a blood vessel

If blood or any unusual discoloration is present in the syringe, withdraw needle &discard syringe; administer new dose of Rho(D) IGIM at a different site using a new syringe & needle

Do not adminster RhoD IGIM by IV; however, RhoD IGIV may be administered IM

Do NOT administer IM for ITP treatment

WinRho SDF: dilute 600 IU & 1500 IU in 1.25 mL supplied diluent(s); for 5000 IU vial, use 8.5 mL

IV

For Rh suppression, administer to mother & not infant

Reconstitute vial contents with appropriate volume of NS by injecting supplied diluent (NS) slowly onto the inside wall of the vial & swirl vial gently until the lyophilized pellet has dissolved

Do not shake vial. Inspect for particulate matter and discoloration prior to administration

For 600 IU or 1500 IU vials, use 2.5 mL diluent; for 5000 IU vial, use 8.5 mL

Do not administer with other drugs

Administer direct injection Rhophylac at 2 mL/15-60 sec; WinRho SDF 1500 IU/5-15 sec

Images

Patient Handout

Formulary

Adding plans allows you to compare formulary status to other drugs in the same class.

Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.

· Dosing & Uses

· Interactions

· Adverse Effects

· Warnings

Pathophysiology

The amount of fetal blood necessary to produce Rh incompatibility varies. In one study, less than 1 mL of Rh-positive blood was shown to sensitize volunteers with Rh-negative blood. Conversely, other studies have suggested that 30% of persons with Rh-negative blood never develop Rh incompatibility, even when challenged with large volumes of Rh-positive blood. Once sensitized, it takes approximately one month for Rh antibodies in the maternal circulation to equilibrate in the fetal circulation. In 90% of cases, sensitization occurs during delivery. Therefore, most firstborn infants with Rh-positive blood type are not affected because the short period from first exposure of Rh-positive fetal erythrocytes to the birth of the infant is insufficient to produce a significant maternal IgG antibody response.

The risk and severity of sensitization response increases with each subsequent pregnancy involving a fetus with Rh-positive blood. In women who are prone to Rh incompatibility, the second pregnancy with an Rh-positive fetus often produces a mildly anemic infant, whereas succeeding pregnancies produce more seriously affected infants who ultimately may die in utero from massive antibody-induced hemolytic anemia.

Risk of sensitization depends largely upon the following 3 factors:

1. Volume of transplacental hemorrhage

2. Extent of the maternal immune response

3. Concurrent presence of ABO incompatibility

The incidence of Rh incompatibility in the Rh-negative mother who is also ABO incompatible is reduced dramatically to 1-2% and is believed to occur because the mother's serum contains antibodies against the ABO blood group of the fetus. The few fetal red blood cells that are mixed with the maternal circulation are destroyed before Rh sensitization can proceed to a significant extent.

Rh incompatibility is only of medical concern for females who are pregnant or plan to have children in the future. Rh-positive antibodies circulating in the bloodstream of an Rh-negative woman otherwise have no adverse effects.

Frequency

United States

Only 15% of the population lack the Rh erythrocyte surface antigen and are considered Rh-negative. The vast majority (85%) of individuals are considered Rh positive. Rh sensitization occurs in approximately 1 per 1000 births to women who are Rh negative. The Southwest United States has an incidence approximately 1.5 times the national average, which likely is caused by immigration factors and limited access to medical care since blood typing is a routine part of prenatal care. Even so, only 17% of pregnant women with Rh-negative blood who are exposed to Rh-positive fetal blood cells ever develop Rh antibodies.

Mortality/Morbidity

During the course of Rh incompatibility, the fetus is primarily affected. The binding of maternal Rh antibodies produced after sensitization with fetal Rh-positive erythrocytes results in fetal autoimmune hemolysis. As a consequence, large amounts of bilirubin are produced from the breakdown of fetal hemoglobin and are transferred via the placenta to the mother where they are subsequently conjugated and excreted by the mother. However, once delivered, low levels of glucuronyl transferase in the infant preclude the conjugation of large amounts of bilirubin and may result in dangerously elevated levels of serum bilirubin and severe jaundice.

Mildly affected infants may have little or no anemia and may exhibit only hyperbilirubinemia secondary to the continuing hemolytic effect of Rh antibodies that have crossed the placenta.

Moderately affected infants may have a combination of anemia and hyperbilirubinemia/jaundice.

In severe cases of fetal hyperbilirubinemia, kernicterus develops. Kernicterus is a neurologic syndrome caused by deposition of bilirubin into central nervous system tissues. Kernicterus usually occurs several days after delivery and is characterized by loss of the Moro (ie, startle) reflex, posturing, poor feeding, inactivity, a bulging fontanelle, a high-pitched shrill cry, and seizures. Infants who survive kernicterus may go on to develop hypotonia, hearing loss, and mental retardation.

A very serious life-threatening condition observed in infants affected by Rh incompatibility is erythroblastosis fetalis, which is characterized by severe hemolytic anemia and jaundice. The most severe form of erythroblastosis fetalis is hydrops fetalis, which is characterized by high output cardiac failure, edema, ascites, pericardial effusion, and extramedullary hematopoiesis. Newborns with hydrops fetalis are extremely pale with hematocrits usually less than 5. Hydrops fetalis often results in death of the infant shortly before or after delivery and requires an emergent exchange transfusion if there is to be any chance of infant survival.

Complications

Emergent delivery of an infant with hydrops fetalis should be as nontraumatic as possible. Ideally, a neonatologist who is prepared to perform an exchange transfusion should attend to the infant immediately.^[4]

Race

Approximately 15-20% of white patients, as opposed to 5-10% of black patients, have the Rh-negative blood type.

Among individuals of Asian and American Indian descent, the incidence of Rh-negative blood type is less than 5%.

Clinical PresentationMS; Chief Editor: Bruce M Lo, MD, MBA, CPE, RDMS, FACEP, FAAEM, FACHE more...

· Share

· Feedback

History

Obtain the following history:

· History of prior blood transfusion

· Rh blood type of the mother

· Rh blood type of the father (55% of Rh-positive men are genetically heterozygous for the Rh antigen and, therefore, produce Rh-negative offspring when mating with Rh-negative women 50% of the time.)

· Previous pregnancies, including spontaneous and elective abortions

· Previous administration of Rh IgG (RhoGAM)

· Mechanism of injury in cases of maternal trauma during pregnancy

· Presence of vaginal bleeding and/or amniotic discharge

· Previous invasive obstetric procedures, such as amniocentesis, cordocentesis, chorionic villous sampling, or ectopic pregnancy

Note that a large fetal-maternal hemorrhage may occur without symptoms and with little or no evidence of trauma. Therefore, a high index of suspicion is warranted and a low threshold for treatment is indicated.

Physical

Evaluation of the vital signs and primary survey of the airway and cardiovascular system are indicated to ensure maternal stability.

A thorough pelvic examination is required.

In situations in which abdominal and/or pelvic trauma is a consideration, inspect for evidence of bruising that may suggest the possibility of significant fetomaternal hemorrhage.

When an infant with an Rh-negative mother is delivered in the emergency department, a thorough physical examination of the infant must be performed after initial stabilization, and a neonatal clinician must be consulted immediately.

Physical findings may vary from mild jaundice to extreme pallor and anemia with hydrops fetalis. Causes

Factors that influence an Rh-negative pregnant female's chances of developing Rh incompatibility include the following:

· Ectopic pregnancy

· Placenta previa

· Placental abruption

· Abdominal/pelvic trauma

· In utero fetal death

· Any invasive obstetric procedure (eg, amniocentesis)

· Lack of prenatal care

· Spontaneous abortion

Differential Diagnoses

Diagnostic Considerations

Potential reasons for postpartum clinical failures include the following:

· Failure to type the patient's blood during the ED visit

· Failure to administer Rh IgG when indicated

· Error in typing the mother's or infant's blood

· Unrecognized fetomaternal hemorrhage

· Inadequate Rh IgG dosage for the volume of fetomaternal hemorrhage

Other conditions to consider in patients with suspected Rh incompatibility include the following:

· ABO incompatibility

· Autoimmune hemolytic anemia

· Microangiopathic hemolytic anemia

· Spherocytosis

· Hereditary enzyme deficiencies

· Alpha thalassemia

· Chronic fetomaternal hemorrhage

· Twin-twin transfusion

· Erythroblastosis fetalis

· Hydrops fetalis

Laboratory Studies

Prenatal emergency care

Determination of Rh blood type is required in every pregnant female. In a pregnant woman with Rh-negative blood type, the Rosette screening test often is the first test performed. The Rosette test can detect alloimmunization caused by very small amounts of fetomaternal hemorrhage.

When a high clinical suspicion of large fetomaternal hemorrhage is present (>30 mL blood), the Kleihauer-Betke acid elution test can be performed. The Kleihauer-Betke test is a quantitative measurement of fetal red blood cells in maternal blood, and it can be valuable for determining if additional amounts of Rh IgG should be administered.

Dose:--The amount of Rh IgG required for treatment after sensitization is at least 20 mcg/mL of fetal RBCs.

Point-of-care blood tests have become available for use in the emergency department and have been shown to have very high sensitivity and specificity in determining Rh status.

Obtaining maternal Rh antibody titers can be helpful for future follow-up care of pregnant females who are known to be Rh negative and may be initiated from the ED. High levels of maternal Rh antibodies suggest that Rh sensitization has occurred, and further studies, such as amniocentesis and/or cordocentesis, may be necessary to evaluate the health of the fetus.

Postnatal emergency care

Immediately after the birth of any infant with an Rh-negative mother in the ED or prehospital setting, examine blood from the umbilical cord of the infant for ABO blood group and Rh type, measure hematocrit and hemoglobin levels, perform a serum bilirubin analysis, obtain a blood smear, and perform a direct Coombs test.

A positive direct Coombs test result confirms the diagnosis of antibody-induced hemolytic anemia, which suggests the presence of ABO or Rh incompatibility.

Elevated serum bilirubin measurements, low hematocrit, and elevated reticulocyte count from the neonate can help determine if an early exchange transfusion is necessary.

An emergent exchange transfusion, preferably performed in a neonatal intensive care setting with experience in this procedure, is required in infants born with erythroblastosis fetalis, hydrops fetalis, or kernicterus.

Other testing

Perform fetal monitoring in cases of suspected fetal distress. Abnormal fetal heart tones and ultrasonographic evidence of fetal or placental injury are indications of worsening fetal condition requiring emergent delivery, ideally in a center specializing in high-risk obstetric care.

Rh-negative blood and a suspected fetomaternal hemorrhage varies depending on the presentation of the patient and the gestational age of the fetus.

If the mother has Rh-negative blood and has not been sensitized previously, administer human anti-D immune globulin (Rh IgG or RhoGAM) and refer the woman for further evaluation.

If the mother has been sensitized previously, as determined by elevated level of maternal Rh antibodies, administration of Rh IgG is of no value.

In this situation, prompt referral to a center that specializes in high-risk obstetrics is warranted.

When an infant with Rh incompatibility is delivered in the ED, a more aggressive approach is required, centering on respiratory and hemodynamic stabilization of the infant and determining the need for an emergent exchange transfusion and phototherapy.

Stress the importance of early prenatal care to each pregnant female who presents to the ED. Early administration of Rh IgG in conjunction with early prenatal care is the best means to prevent Rh incompatibility

Referrals and consultations

After administering Rh IgG in the ED, promptly refer the Rh-negative pregnant mother of an Rh-positive fetus to an institution equipped for high-risk obstetric care.

Refer every pregnant female with Rh incompatibility to a medical center specializing in high-risk obstetric care

Medication Summary

Rh IgG, first released for general use in 1968, has been remarkably successful in the prevention of Rh incompatibility. In the Rh-negative mother, the preparation is administered after a suspected fetomaternal hemorrhage. The exact mechanism by which passive administration of Rh IgG prevents Rh immunization is unknown. The most likely hypothesis is that the Rh immune globulin coats the surface of fetal RBCs containing Rh antigens. These exogenous antibody-antigen complexes cross the placenta before they can stimulate the maternal endogenous immune system B cells to produce IgG antibodies.

Since Rh IgG became the standard of care in the United States, the risk of Rh incompatibility has been reduced from 10-20% to less than 1%. Because of its short half-life, Rh IgG routinely is administered once at 28-32 weeks' gestation and again within 72 hours after birth to all Rh-negative pregnant females as a part of routine prenatal and postnatal care.

The current recommendation is that every Rh-negative nonimmunized woman who presents to the ED with antepartum bleeding or potential fetomaternal hemorrhage should receive 300 mcg of Rh IgG IM. For every 30 mL of fetal whole blood exposed to maternal circulation, 300 mcg of Rh IgG should be administered. A lower 50-mcg dose preparation of Rh IgG is available and recommended for Rh-negative females who have termination of pregnancy in the first trimester when fetomaternal hemorrhage is believed to be minimal.

Next: Blood derived product

What to Read

· Overview

Workup

HomeRhesus disease is a condition where antibodies in a pregnant woman's blood destroy her baby's blood cells. It's also known as haemolytic disease of the foetus and newborn (HDFN).

Rhesus disease doesn't harm the mother, but it can cause the baby to become anaemic and develop jaundice.

Read about the signs of rhesus disease in a baby.

What causes rhesus disease?

Rhesus disease only happens when the mother has rhesus negative blood (RhD negative) and the baby in her womb has rhesus positive blood (RhD positive). The mother must have also been previously sensitised to RhD positive blood.

Sensitisation happens when a woman with RhD negative blood is exposed to RhD positive blood, usually during a previous pregnancy with an RhD positive baby. The woman’s body responds to the RhD positive blood by producing antibodies (infection-fighting molecules) that recognise the foreign blood cells and destroy them.

If sensitisation occurs, the next time the woman is exposed to RhD positive blood, her body produces antibodies immediately. If she's pregnant with an RhD positive baby, the antibodies can cross the placenta, causing rhesus disease in the unborn baby. The antibodies can continue attacking the baby's red blood cells for a few months after birth.

Read more about the causes of rhesus disease.

Preventing rhesus disease

Rhesus disease is uncommon these days because it can usually be prevented using injections of a medication called anti-D immunoglobulin.

All women are offered blood tests as part of their antenatal screening to determine whether their blood is RhD negative or positive. If the mother is RhD negative, she'll be offered injections of anti-D immunoglobulin at certain points in her pregnancy when she may be exposed to the baby's red blood cells. This anti-D immunoglobulin helps to remove the RhD foetal blood cells before they can cause sensitisation.

If a woman has developed anti-D antibodies in a previous pregnancy (she's already sensitised) then these immunoglobulin injections don't help. The pregnancy will be monitored more closely than usual, as will the baby after delivery.

Read more about preventing rhesus disease and diagnosing rhesus disease.

Treating rhesus disease

If an unborn baby does develop rhesus disease, treatment depends on how severe it is. A blood transfusion to the unborn baby may be needed in more severe cases. After delivery, the child is likely to be admitted to a neonatal unit (a hospital unit that specialises in caring for newborn babies).

Treatment for rhesus disease after delivery can include a light treatment called phototherapy, blood transfusions, and an injection of a solution of antibodies (intravenous immunoglobulin) to prevent red blood cells being destroyed.

If rhesus disease is left untreated, severe cases can lead to stillbirth. In other cases, it could lead to brain damage, learning difficulties, deafness and blindness. However, treatment is usually effective and these problems are uncommon.

Read more about treating rhesus disease and the potential complications of rhesus disease.

Page last reviewed: 11 June 2018
Next review due: 11 June 2021

1. Next:

2. Health A to Z

3. Rhesus disease

Symptoms-Rhesus disease

1. Overview

2. Symptoms

3. Causes

4. Diagnosis

5. Treatment

6. Complications

7. Prevention

Rhesus disease only affects the baby, and the mother won't experience any symptoms.

The symptoms of rhesus disease depend on how severe it is. Around 50% of babies diagnosed with rhesus disease have mild symptoms that are easily treatable.

Signs in an unborn baby

If your baby develops rhesus disease while still in the womb, they may become anaemic because their red blood cells are being destroyed faster than usual by the antibodies.

If your baby is anaemic, their blood will be thinner and flow at a faster rate. This doesn't usually cause any noticeable symptoms, but it can be detected with an ultrasound scan known as a Doppler ultrasound.

If the anaemia is severe, complications of rhesus disease, such as internal swelling, may be detected during scans.

Signs in a newborn baby

The two main problems caused by rhesus disease in a newborn baby are haemolytic anaemia and jaundice. In some cases, the baby may also have low muscle tone (hypotonia) and they may be lacking in energy.

If a baby has rhesus disease, they won't always have obvious symptoms when they're born. Symptoms can sometimes develop up to 3 months afterwards.

Haemolytic anaemia

Haemolytic anaemia occurs when red blood cells are destroyed. This happens when the antibodies from the mother's RhD negative blood cross the placenta into the baby's blood. The antibodies attack the baby's RhD positive blood, destroying the red blood cells.

In the newborn baby, this may cause pale skin, increased breathing rate, poor feeding or jaundice.

Jaundice

Jaundice in newborn babies turns their skin and the whites of their eyes yellow. In babies with dark skin, the yellowing will be most obvious in their eyes or on their palms and soles.

Jaundice is caused by a build-up of a chemical called bilirubin in the blood. Bilirubin is a yellow substance that's made naturally in the body when red blood cells are broken down. It's normally removed from the blood by the liver, so it can be passed out of the body in urine.

In babies with rhesus disease, the liver cannot process the high levels of bilirubin that build up as a result of the baby's red blood cells being

auses-Rhesus disease

1. Overview

2. Symptoms

3. Causes

4. Diagnosis

5. Treatment

6. Complications

7. Prevention

Rhesus disease is caused by a specific mix of blood types between a pregnant mother and her unborn baby.

Rhesus disease can only occur in cases where all of the following happen:

the mother has a rhesus negative (RhD negative) blood type
the baby has a rhesus positive (RhD positive) blood type
the mother has previously been exposed to RhD positive blood and has developed an immune response to it (known as sensitisation)

Blood types

There are several different types of human blood, known as blood groups, with the 4 main ones being A, B, AB and O. Each of these blood groups can either be RhD positive or negative.

Whether someone is RhD positive or RhD negative is determined by the presence of the rhesus D (RhD) antigen. This is a molecule found on the surface of red blood cells.

People who have the RhD antigen are RhD positive, and those without it are RhD negative. In the UK, around 85% of the population are RhD positive.

How blood types are inherited

Your blood type depends on the genes you inherit from your parents. Whether you're RhD positive or negative depends on how many copies of the RhD antigen you've inherited. You can inherit one copy of the RhD antigen from your mother or father, a copy from both of them, or none at all.

You'll only have RhD negative blood if you don't inherit any copies of the RhD antigen from your parents.

A woman with RhD negative blood can have an RhD positive baby if her partner's blood type is RhD positive. If the father has two copies of the RhD antigen, every baby will have RhD positive blood. If the father only has one copy of the RhD antigen, there's a 50% chance of the baby being RhD positive.

Sensitisation

An RhD positive baby will only have rhesus disease if their RhD negative mother has been sensitised to RhD positive blood. Sensitisation occurs when the mother is exposed to RhD positive blood for the first time and develops an immune response to it.

During the immune response, the woman's body recognises that the RhD positive blood cells are foreign and creates antibodies to destroy them.

In most cases, these antibodies aren't produced quickly enough to harm a baby during the mother's first pregnancy. Instead, any RhD positive babies the mother has in the future are most at risk.

How does sensitisation occur?

During pregnancy, sensitisation can happen if:

small numbers of foetal blood cells cross into the mother's blood
the mother is exposed to her baby's blood during delivery
there's been bleeding during the pregnancy
an invasive procedure has been necessary during pregnancy – such as amniocentesis, or chorionic villus sampling (CVS)
the mother injures her abdomen (tummy)

Sensitisation can also occur after a previous miscarriage or ectopic pregnancy, or if a RhD negative woman has received a transfusion of RhD positive blood by mistake (although this is extremely rare).

How sensitisation leads to rhesus disease

If sensitisation occurs, the next time the woman is exposed to RhD positive blood her body will produce antibodies immediately.

If she's pregnant with an RhD positive baby, the antibodies can lead to rhesus disease when they cross the placenta and start attacking the baby's red blood cells.

Rhesus disease can largely be prevented by having an injection of a medication called anti-D immunoglobulin.This can help to avoid a process known as sensitisation, which is when a woman with RhD negative blood is exposed to RhD positive blood and develops an immune response to it.

Blood is known as RhD positive when it has a molecule called the RhD antigen on the surface of the red blood cells.

Read more about the causes of rhesus disease.

Anti-D immunoglobulin

The anti-D immunoglobulin neutralises any RhD positive antigens that may have entered the mother's blood during pregnancy. If the antigens have been neutralised, the mother's blood won't produce antibodies .Such anti-D be offered anti-D immunoglobulin if it's thought there's a risk that RhD antigens from her baby have entered mothers blood – for example, if she experience any bleeding, if she have an invasive procedure (such as amniocentesis), or if you experience any abdominal injury.

Anti-D immunoglobulin is also administered routinely during the third trimester of your pregnancy if your blood type is RhD negative. This is because it's likely that small amounts of blood from your baby will pass into your blood during this time.

This routine administration of anti-D immunoglobulin is called routine antenatal anti-D prophylaxis, or RAADP (prophylaxis means a step taken to prevent something from happening).

Routine antenatal anti-D prophylaxis (RAADP)

There are currently two ways you can receive RAADP:

a 1-dose treatment: where you receive an injection of immunoglobulin at some point during weeks 28 to 30 of your pregnancy
a 2-dose treatment: where you receive 2 injections; one during the 28th week and the other during the 34th week of your pregnancy

There doesn't seem to be any difference in the effectiveness between the 1-dose or 2-dose treatments. Your local clinical commissioning group (CCG) may prefer to use a 1-dose treatment, because it can be more efficient in terms of resources and time.

When will RAADP be given?

RAADP is recommended for all pregnant RhD negative women who haven't been sensitised to the RhD antigen, even if you previously had an injection of anti-D immunoglobulin.

As RAADP doesn't offer lifelong protection against rhesus disease, it will be offered every time you become pregnant if you meet these criteria.

RAADP won't work if you've already been sensitised. In these cases, you'll be closely monitored so treatment can begin as soon as possible if problems develop.

Anti-D immunoglobulin after birth

After giving birth, a sample of your baby's blood will be taken from the umbilical cord. If you're RhD negative and your baby is RhD positive, and you haven't already been sensitised, you'll be offered an injection of anti-D immunoglobulin within 72 hours of giving birth.

The injection will destroy any RhD positive blood cells that may have crossed over into your bloodstream during the delivery. This means your blood won't have a chance to produce antibodies and will significantly decrease the risk of your next baby having rhesus disease.

Complications from anti-D immunoglobulin

Some women are known to develop a slight short-term allergic reaction to anti-D immunoglobulin, which can include a rash or flu-like symptoms.

Although the anti-D immunoglobulin, which is made from donor plasma, will be carefully screened, there's a very small risk that an infection could be transferred through the injection.

However, the evidence in support of RAADP shows that the benefits of preventing sensitisation far outweigh these small risks. Unborn babies

If rhesus disease causes severe anaemia in an unborn baby, it can lead to:

foetal heart failure
fluid retention and swelling (foetal hydrops)
stillbirth

Blood transfusions given to a baby in the womb (intrauterine transfusions [IUT]), can be used to treat anaemia in an unborn baby. However, this treatment also carries some risks of complications. It can lead to an early labour that begins before the 37th week of pregnancy and there's a 1 in 50 risk of miscarriage or stillbirth.

Newborn babies

Rhesus disease causes a build-up of excessive amounts of a substance called bilirubin. Without prompt treatment, a build-up of bilirubin in the brain can lead to a neurological condition called kernicterus. This can lead to deafness, blindness, brain damage, learning difficulties, or even death.

Treatment for rhesus disease is usually effective in reducing bilirubin levels in the blood, so these complications are uncommon.

Blood transfusions

The risk of developing an infection from the blood used in blood transfusions is low, because all the blood is carefully screened. The blood used will also be matched to the baby's blood type, so the likelihood of your baby having an adverse reaction to the donated blood is also low.

However, there may be a problem with the transfusion itself. For example, the tube (catheter) used to deliver the blood can become dislodged, causing heavy bleeding (haemorrhage) or a blood clot.

Generally, the risks associated with blood transfusions are small and don't outweigh the benefits of treating a baby with anaemia.

Page last reviewed: 11 June 2018
Next review due: 11 June 2021

Around half of all cases of rhesus disease are mild and don't usually require much treatment. However, your baby will need to be monitored regularly, in case serious problems develop.

In more severe cases, a treatment called phototherapy is usually needed and blood transfusions may help to speed up the removal of bilirubin (a substance created when red blood cells break down) from the body.

In the most serious cases, a blood transfusion may be carried out while your baby is still in the womb and a medication called intravenous immunoglobulin may be used when they're born if phototherapy isn't effective.

If necessary, the baby may be delivered early using medication to start labour (induction) or a caesarean section, so treatment can start as soon as possible. This is usually only done after about 34 weeks of pregnancy.

Phototherapy

Phototherapy is treatment with light. It involves placing the newborn baby under a halogen or fluorescent lamp with their eyes covered.

Alternatively, they may be placed on a blanket containing optical fibres through which light travels and shines onto the baby's back (fibre optic phototherapy).

The light absorbed by the skin during phototherapy lowers the bilirubin levels in the baby's blood through a process called photo-oxidation. This means that oxygen is added to the bilirubin, which helps it to dissolve in water. This makes it easier for the baby's liver to break down the bilirubin and remove it from the blood.

During phototherapy, fluids will usually be given into a vein (intravenous hydration) because more water is lost through your baby's skin and more urine is produced as the bilirubin is expelled.

Using phototherapy can sometimes reduce the need for a blood transfusion.

Blood transfusions

In some cases, the levels of bilirubin in the blood may be high enough to require one or more blood transfusions.

During a blood transfusion, some of your baby's blood is removed and replaced with blood from a suitable matching donor (someone with the same blood group). A blood transfusion normally takes place through a tube inserted into a vein (intravenous cannula).

This process helps to remove some of the bilirubin in the baby's blood and also removes the antibodies that cause rhesus disease.

It's also possible for the baby to have a transfusion of just red blood cells to top up those they already have.

Blood transfusion to an unborn baby

If your baby develops rhesus disease while still in the womb, they may need to be given a blood transfusion before birth. This is known as intrauterine foetal blood transfusion.

An intrauterine foetal blood transfusion requires specialist training and is not available in all hospitals. You may therefore be referred to a different hospital for the procedure.

A needle is usually inserted through the mother's abdomen (tummy) and into the umbilical cord, so donated blood can be injected into the baby. An ultrasound scanner is used to help guide the needle to the right place.

Local anaesthetic is used to numb the area, but you'll be awake during the procedure. A sedative may be given to keep you relaxed and your baby may also be sedated to help stop them moving during the procedure.

You may need more than one intrauterine foetal blood transfusion. Transfusions can be repeated every 2 to 4 weeks until your baby is mature enough to be delivered. They may even reduce the need for phototherapy after birth, but further blood transfusions could still be necessary.

There's a small risk of miscarriage during an intrauterine foetal blood transfusion, so it's usually only used in particularly severe cases.

Intravenous immunoglobulin

In some cases, treatment with intravenous immunoglobulin (IVIG) is used alongside phototherapy if the level of bilirubin in your baby's blood continues to rise at an hourly rate.

The immunoglobulin is a solution of antibodies (proteins produced by the immune system to fight against disease-carrying organisms) taken from healthy donors. Intravenous means that it's injected into a vein.

Intravenous immunoglobulin helps to prevent red blood cells being destroyed, so the level of bilirubin in your baby's blood will stop rising. It also reduces the need for a blood transfusion.

However, it does carry some small risks. It's possible that your baby may have an allergic reaction to the immunoglobulin, although it's difficult to calculate how likely this is or how severe the reaction will be.

Concerns over possible side effects, and the limited supply of intravenous immunoglobulin, mean that it's only used when the bilirubin level is rising rapidly, despite phototherapy sessions.

Intravenous immunoglobulin has also been used during pregnancy, in particularly severe cases of rhesus disease, as it can delay the need for treatment with intrauterine foetal blood transfusions.

Page last reviewed: 11 June 2018
Next review due: 11 June 2021

Previous:DiagnosisBlood tests

A blood test should be carried out early on in your pregnancy to test for conditions such as anaemia, rubella, HIV and hepatitis B.

Your blood will also be tested to determine which blood group you are, and whether your blood is rhesus (RhD) positive or negative (see causes of rhesus disease for more information).

If you're RhD negative, your blood will be checked for the antibodies (known as anti-D antibodies) that destroy RhD positive red blood cells. You may have become exposed to them during pregnancy if your baby has RhD positive blood.

If no antibodies are found, your blood will be checked again at 28 weeks of pregnancy and you'll be offered an injection of a medication called anti-D immunoglobulin to reduce the risk of your baby developing rhesus disease (see preventing rhesus disease for more information).

If anti-D antibodies are detected in your blood during pregnancy, there's a risk that your unborn baby will be affected by rhesus disease. For this reason, you and your baby will be monitored more frequently than usual during your pregnancy.

In some cases, a blood test to check the father's blood type may be offered if you have RhD negative blood. This is because your baby won't be at risk of rhesus disease if both the mother and father have RhD negative blood.

Checking your baby's blood type

It's possible to determine if an unborn baby is RhD positive or RhD negative by taking a simple blood test during pregnancy.

Genetic information (DNA) from the unborn baby can be found in the mother's blood, which allows the blood group of the unborn baby to be checked without any risk. It's usually possible to get a reliable result from this test after 11 to 12 weeks of pregnancy, which is long before the baby is at risk from the antibodies.

If your baby is RhD negative, they're not at risk of rhesus disease and no extra monitoring or treatment will be necessary. If they're found to be RhD positive, the pregnancy will be monitored more closely so that any problems that may occur can be treated quickly.

In the future, RhD negative women who haven't developed anti-D antibodies may be offered this test routinely, to see if they're carrying an RhD positive or RhD negative baby, to avoid unnecessary treatment.

Monitoring during pregnancy

If your baby is at risk of developing rhesus disease, they'll be monitored by measuring the blood flow in their brain. If your baby is affected, their blood may be thinner and flow more quickly. This can be measured using an ultrasound scan called a Doppler ultrasound.

If a Doppler ultrasound shows your baby's blood is flowing faster than normal, a procedure called foetal blood sampling (FBS) can be used to check whether your baby is anaemic. This procedure involves inserting a needle through your abdomen (tummy) to remove a small sample of blood from your baby. The procedure is performed under local anaesthetic, usually on an outpatient basis, so you can go home on the same day.

There's a small (usually 1-3%) chance that this procedure could cause you to lose your pregnancy, so it should only be carried out if necessary.

If your baby is found to be anaemic, they can be given a transfusion of blood through the same needle. This is known as an intrauterine transfusion (IUT) and it may require an overnight stay in hospital.

FBS and IUT are only carried out in specialist units, so you may need to be referred to a different hospital to the one where you are planning to have your baby.

Read more about treating rhesus disease.

Diagnosis in a newborn baby

If you're RhD negative, blood will be taken from your baby's umbilical cord when they're born. This is to check their blood group and see if the anti-D antibodies have been passed into their blood. This is called a Coombs test.

If you're known to have anti-D antibodies, your baby's blood will also be tested for anaemia and jaundice. Dosage Forms & Strengths

50 mcg

300 mcg

1,500 Units/2 mL

1,500 Units/1.3 mL

2,500 Units/2.2 mL

5,000 Units/4.4 mL

15,000 Units/13 mL

Administer to Mother to Prevent Hemolytic Disease in Newborn

Antepartum: 1500 IU~300 mcg IV/IM at 28-30 weeks of gestation

Postpartum: 1500 IU IV/IM within 72 hr

If both given risk reduced to 0.1%

If unable to give within 72 hr, give within 28 days; do not withhold

If >15 mL of Rho+ fetal RBC present in mother's circulation, multiple 1500 IU doses are required