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Rho (D) Immune Globulin (RhoGAM) uses in Obstetrics: What you need to know!

Rho (D) Immune Globulin (RhoGAM) is a biologic antibody derived from human plasma1. It is a medication that targets the rhesus D antigen found on the surfaces of red blood cells1. By doing so, it prevents a rhesus negative mother’s blood from making antibodies that attack the rhesus-positive blood of the foetus and neonate. It also treats idiopathic thrombocytopenic purpura in patients who are rhesus positive. We also use it among rhesus-negative individuals who have received rhesus-positive blood1,2,3.

The rhesus factor is a vital feature of the red blood cells. It indicates whether two different individuals’ blood is compatible upon mixing it, say, that of the mother and the baby. If the two blood systems are incompatible, haemolysis will occur when such blood is mixed. It’s called rhesus factor D, alias RhD antigen. It is a protein that we find on the surfaces of red blood cells. When people have the RhD antigen, they then carry rhesus positive blood. And if they lack it, they carry rhesus-negative blood3. People can carry blood groups A+, B+, AB+, and O+ if their red cells carry the rhesus D antigen1. The reverse is true for those that don’t have it. Their blood groups are thus designated, A-, B-, AB-, and O-.

Approximately 16% of the global population are rhesus negative. About 15% of the European population are rhesus negative3. In Uganda, the prevalence is between 2% and 4%4,5.

All expectant mothers must undergo a blood test to ascertain their blood group, as well as their rhesus status3. We raise no concerns when a rhesus-positive mother is pregnant, regardless of the rhesus status if the foetus. Surprisingly, about half of the rhesus negative expectant mothers carry rhesus negative foetuses. It’s the other half that has a rhesus-positive foetus3. Because, we cannot deduce the rhesus status of the baby until they are born, we raise a red flag for every rhesus negative expectant mother; thus, they receive Rho (D) immune globulin.

When the baby’s rhesus-positive blood mixes with that of the mother, the mother’s immune system may be sensitised to produce anti-D antibodies against the baby’s rhesus positive blood1,3. Exposure can be due to injuries to the placenta or umbilical cord during childbirth or during pregnancy de novo after a procedure like an amniocentesis3. The maternal immune system is sensitised to attack the subsequent babies, but not the first baby or pregnancy3. We administer the Rho (D) immune globulin to these mothers to prevent such a catastrophe.

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All rhesus negative non-sensitised mothers carrying an incompatible foetus must receive the Rho (D) immune globulin1,3. We also use it as prophylaxis in such mothers routinely during the subsequent pregnancies during antepartum and postpartum periods1; obstetric complications like ectopic pregnancy threatened abortion, and foetal death in the second or third trimester; spontaneous or induced abortion1; and after invasive obstetric procedures6. A rhesus negative expectant mother who afflicts abdominal trauma that involves maternal foetal haemorrhage must receive RhoGAM. All rhesus negative individuals who happen to receive rhesus positive blood must get RhoGAM to prevent haemolysis2.

We think that RhoGAM suppresses the immune response and formation of antibodies against RhD antigen in rhesus incompatible people. However, how it achieves this remains a mystery7,8. To acquire the maximal effect among expectant mothers, we provide the first dose between 28 and 30 weeks of gestation, and the second dose within 72 hours after delivery of the baby1,3,9. For all other obstetric conditions, we give a single dosage within 72 hours after the incident9. When administered appropriately, RhoGAM reduces the incidence of haemolytic disease of the foetus and new-born to less than 1%2,9,10. We typically administer 300mcg (1500 IU) intramuscularly or intravenously9. We do not give intramuscular injections to patients with idiopathic thrombocytopenic purpura1,9. In instances when more than 15mL of rhesus positive foetal red cells exist in the maternal circulation, we provide multiple 300mcg of RhoGAM9. We do not withhold the medication, in case we’ve forgotten, we can administer it within 28 days following the incident – the sooner, the better9. To boost the levels of RhoGAM in the subsequent pregnancies, we give it after every 12 weeks.

Because RhoGAM is a drug, a few adverse effects exist, though rare11,9. They include,

-headache

-chills

-fever

-dizziness

-infection

-hypertension

-drowsiness

-shivering

-excessive sweating

-anaemia

-increased lactate dehydrogenase enzyme

-reduced haptoglobins

-increased bilirubin levels

-abdominal and back pain

-injection site infection

-antibody development

-hyperkinetic muscle activity

-disseminated intravascular coagulopathy

-intravascular haemolysis

-acute kidney injury

-death.

Because of the above adverse effects, we recommend monitoring a patient before and after administering RhoGAM12. Monitor all patients for not less than 20 minutes after the prophylactic use of RhoGAM. For those that have idiopathic thrombocytopenic purpura, monitor them for about eight hours. Do a complete blood count with differential count: RhD antigen and antibody screen, reticulocyte count, urinalysis, serum creatinine and blood urea nitrogen before administering the medication. Following treatment, repeat the complete blood count 1 to 3 days later, urinalysis after 1 to 2 hours – preferably urine dipstick unless it is positive for blood. Only carry out serum creatinine and blood urea nitrogen levels if the patient’s haemoglobin levels fall by 1g/dL or more. In case, you suspect intravascular haemolysis, do lactate dehydrogenase levels, Haptoglobin and bilirubin levels.

As we conclude, we said earlier on that only half of the rhesus negative mothers carry rhesus positive foetuses. It implies that 50% of the rhesus-positive expectant mothers unnecessarily receive RhoGAM. We can prevent this through a prenatal blood test where we draw a mother’s blood3. We trace the foetus’ cell-free DNA. We use it to determine whether the unborn baby is rhesus positive or not. The prenatal test is 100% for singleton pregnancies, but it’s not useful for multiple pregnancies. It is widely available, but the maternal foetal societies have not yet recommended it.

In a nutshell, prenatal administration of RhoGAM to rhesus negative obstetric patients prevent haemolytic disease of the foetus and new-born. It inhibits the mother’s immune system from being sensitised once it gets exposed to the foetal rhesus positive blood. RhoGAM is vital as a viable treatment option among patients with idiopathic thrombocytopenic purpura. A dose at 28 to 30 weeks of gestation and a second one 72 hours after delivery of the baby reduces the probability of immune sensitisation to less than 1%. The expectant mother must receive the medication in every pregnancy she carries. We note that we can defer the second dose to a mother after delivery if we sample the baby’s blood, and we find it rhesus negative.  We need more research to ascertain the feasibility of the prenatal blood test such that expectant mothers do not unnecessarily receive the Rho (D) immune globulin.

IAmDrSsekandi

MBChB (MUK), Graduate Fellow, Department of Physiology, Makerere University Founder and Content Creator Peer reviewer, Associate Editor

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