biology

Hemolytic disease of the newborn (anti-Kell)

Hemolytic disease of the newborn (anti-Kell) 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-Kell) rather than just read about it. In short: Hemolytic disease of the newborn (anti-Kell1) is the second most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective.

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Reference excerpt

Hemolytic disease of the newborn (anti-Kell1) is the second most common cause of severe hemolytic disease of the newborn (HDN) after Rh disease. Anti-Kell1 is becoming relatively more important as prevention of Rh disease is also becoming more effective. Hemolytic disease of the newborn (anti-Kell1) is caused by a mismatch between the Kell antigens of the mother and fetus. About 91% of the population are Kell1 negative and about 9% are Kell1 positive. A fraction of a percentage are homozygous for Kell1. Therefore, about 4.5% of babies born to a Kell1 negative mother are Kell1 positive. The disease results when maternal antibodies to Kell1 are transferred to the fetus across the placental barrier, breaching immune privilege. These antibodies can cause severe anemia by interfering with the early proliferation of red blood cells as well as causing alloimmune hemolysis. Very severe disease can occur as early as 20 weeks gestation. Hydrops fetalis can also occur early. The finding of anti-Kell antibodies in an antenatal screening blood test (indirect Coombs test) is an indication for early referral to a specialist service for assessment, management and treatment.

Presentation

Complications High at birth or rapidly rising bilirubin Prolonged hyperbilirubinemia Bilirubin Induced Neuorlogical Dysfunction Cerebral Palsy Kernicterus Neutropenia 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.

Cause Mothers who are negative for the Kell1 antigen develop antibodies after being exposed to red blood cells that are positive for Kell1. Over half of the cases of hemolytic disease of the newborn owing the anti-Kell antibodies are caused by multiple blood transfusions, with the remainder due to a previous pregnancy with a Kell1 positive baby.

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 Anti-Kell can cause severe anemia regardless of titer. Anti-Kell suppresses the bone marrow, by inhibiting the erythroid progenitor cells.

anti-Kell2, anti-Kell3 and anti-Kell4 antibodies Hemolytic disease of the newborn can also be caused by anti-Kell2, anti-Kell3 and anti-Kell4 IgG antibodies. These are rarer and generally the disease is milder.

Diagnosis 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. Titers of 1:4 or higher is considered critical for Kell (compared to 1:16 for most other antibodies) and is considered to confer a high risk of fetal anemia. Such high titers may be managed by weekly follow-up by obstetric ultrasound, assessing the peak systolic velocity of the fetal middle cerebral arterial (MCA), amniotic fluid volume, as well as fetal signs of anemia or hydrops.

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 3 possible ways to test the fetal antigen status. Cell-free 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 used the determine the Rh antigen of the fetus when the mother is Rh negative. Blood is taken from the mother during the pregnancy, 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. For patients in the United States, BillionToOne, Inc. based in Menlo Park, California offers a non-invasive prenatal test (NIPT) called Unity that can used to determine the fetal Rh antigen for mothers who are Rh negative. Because Unity is the only test in the world that uses next generation sequencing (NGS) to determine the fetal antigen, it is the only test that can screen for the fetal Rh antigen as early as the 10th week of gestation. For patients in the UK testing is offered through the International Blood Group Reference Laboratory in Bristol. Sanequin laboratory in Amsterdam, Netherlands also performs this test. The European tests for fetal Rh antigen utilize qPCR or real-time PCR technology; therefore, testing has to wait until at least the 20th week of gestation. Sensigene used to be offered by Sequenome to determine the fetal Rh antigen. However, this test has been taken off the market. 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-Kell)

Start with the simplest possible case. Write down what Hemolytic disease of the newborn (anti-Kell) 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-Kell) 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-Kell) 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-Kell)

In research: Hemolytic disease of the newborn (anti-Kell) 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-Kell) 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-Kell) 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-Kell) 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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