biology

Hemolytic disease of the newborn (anti-RhE)

Hemolytic disease of the newborn (anti-RhE) is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Hemolytic disease of the newborn (anti-RhE) rather than just read about it. In short: Hemolytic disease of the newborn (anti-RhE) is caused by the anti-RhE antibody of the Rh blood group system. The anti-RhE antibody can be naturally occurring, or arise following immune sensitization after a blood transfusion or pregnancy.

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Reference excerpt

Hemolytic disease of the newborn (anti-RhE) is caused by the anti-RhE antibody of the Rh blood group system. The anti-RhE antibody can be naturally occurring, or arise following immune sensitization after a blood transfusion or pregnancy. The anti-RhE antibody is quite common especially in the Rh genotype CDe/CDe; it usually only causes a mild hemolytic disease, but can cause a severe condition in the newborn. It can occur with other antibodies, usually the anti-Rhc antibody, which can also cause a severe hemolytic disease. One study done by Moran et al., found that titers are not reliable for anti-E. Their most severe case of hemolytic disease of the newborn occurred with titers 1:2. Moran states that it would be unwise routinely to dismiss anti-E as being of little clinical consequence.

Presentation

Complications High at birth or rapidly rising bilirubin Prolonged hyperbilirubinemia Bilirubin-induced neurological dysfunction Cerebral palsy Kernicterus Thrombocytopenia Hemolytic anemia – must not be treated with iron Late onset anemia – must not be treated with iron. Can persist up to 12 weeks after birth.

Mechanism Hemolytic disease of the fetus and newborn (HDN) is a condition where the passage of maternal antibodies results in the hemolysis of fetal/neonatal red cells. The antibodies can be naturally occurring such as anti-A, and anti-B, or immune antibodies developed following a sensitizing event. Isoimmunization occurs when the maternal immune system is sensitized to red blood cell surface antigens. The most common causes of isoimmunization are blood transfusion, and fetal-maternal hemorrhage. The hemolytic process can result in anemia, hyperbilirubinemia, neonatal thrombocytopenia, and neonatal neutropenia. With the use of RhD Immunoprophylaxis, (commonly called Rhogam), the incidence of anti-D has decreased dramatically and other alloantibodies are now a major cause of HDN.

Antibody specific One study done by Moran et al., found that titers are not reliable for anti-E. Their most severe case of hemolytic disease of the newborn occurred with titers 1:2. Moran states that it would be unwise routinely to dismiss anti-E as being of little clinical consequence. In the case of anti-E, the woman should be checked around 28 weeks to see if she has developed anti-c as well.

Testing Testing for HDN involves blood work from both mother and father, and may also include assessment with amniocentesis and Middle Cerebral Artery scans.

Mother Blood testing for the mother is called an indirect Coombs test (ICT) or an indirect agglutination test (IAT). This test tells whether there are antibodies in the maternal plasma. If positive, the antibody is identified and given a titer. Critical titers are associated with significant risk of fetal anemia and hydrops. Titers of 1:8 or higher is considered critical for Kell. Titers of 1:16 or higher are considered critical for all other antibodies. After critical titer is reached, care is based on MCA scans. If antibodies are low and have a sudden jump later in pregnancy, an MCA scan is warranted. If the titer undergoes a 4 fold increase, it should be considered significant regardless of if the critical value has been reached. Maternal titers are not useful in predicting fetal anemia after the first affected gestation and should not be used for the basis of care. Titers are tested monthly until 24 weeks, after which they are done every 2 weeks. "In only 2 situations are patients not monitored identically to patients who are Rh sensitized. The first is that of alloimmunization to the c, E, or, C antigens. Some concern exists that hemolysis may occur in these patients with a lower than 1:16 titer. Thus, if the initial titer is 1:4 and stable but increases at 26 weeks' gestation to 1:8, assessment with MCA Doppler velocity at that point is reasonable. However, if the patient presents in the first trimester with a 1:8 titer that remains stable at 1:8 throughout the second trimester, continued serial antibody titers are appropriate. The second situation in which patients should not be treated identically to patients who are Rh D sensitized is that of Kell isoimmunization because several cases of severe fetal hemolysis with anti-Kell antibodies have occurred in the setting of low titers." In the case of a positive ICT, the woman must carry a medical alert card or bracelet for life because of the risk of a transfusion reaction.

Father Blood is generally drawn from the father to help determine fetal antigen status. If he is homozygous for the antigen, there is a 100% chance of all offspring in the pairing to be positive for the antigen and at risk for HDN. If he is heterozygous, there is a 50% chance of offspring to be positive for the antigen. This test can help with knowledge for the current baby, as well as aid in the decision about future pregnancies. With RhD, the test is called the RhD genotype. With RhCE, and Kell antigen it is called an antigen phenotype.

Fetus There are three possible ways to test the fetal antigen status. Free cell DNA, amniocentesis, and chorionic villus sampling (CVS). Of the three, CVS is no longer used due to risk of worsening the maternal antibody response. Once antigen status has been determined, assessment may be done with MCA scans.

Cell-free DNA can be run on certain antigens. Blood is taken from the mother, and using PCR, can detect the K, C, c, D, and E alleles of fetal DNA. This blood test is non-invasive to the fetus and is an easy way of checking antigen status and risk of HDN. Testing has proven very accurate and is routinely done in the UK at the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. For US patients, blood may be sent to either of the labs. In the US, Sensigene is done by Sequenome to determine fetal D status. Sequenome does not accept insurance in the US, but US and Canadian patients have had insurance cover the testing done overseas. Amniocentesis is another recommended method for testing antigen status and risk for HDN. Fetal antigen status can be tested as early as 15 weeks by PCR of fetal cells. CVS is possible as well to test fetal antigen status but is not recommended. CVS carries a higher risk of fetal maternal hemorrhage and can raise antibody titers, potentially worsening the antibody effect.

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Worked examples

Example 1 — a first encounter with Hemolytic disease of the newborn (anti-RhE)

Start with the simplest possible case. Write down what Hemolytic disease of the newborn (anti-RhE) claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Hemolytic disease of the newborn (anti-RhE) before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Hemolytic disease of the newborn (anti-RhE) ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Hemolytic disease of the newborn (anti-RhE)

In research: Hemolytic disease of the newborn (anti-RhE) appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Hemolytic disease of the newborn (anti-RhE) in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Hemolytic disease of the newborn (anti-RhE) is common in secondary-school and first-year university syllabi. It links to neighbouring topics Acquired hemolytic anemia, Disorders originating in the perinatal period, Haemorrhagic and haematological disorders of fetus and newborn, so understanding it makes those chapters shorter.
In everyday life: Look for Hemolytic disease of the newborn (anti-RhE) outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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Frequently asked questions

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