Hemolytic disease of the newborn (anti-Kell)

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.

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.

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

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. 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.

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. This test is done noninvasively with ultrasound. By measuring the peak velocity of blood flow in the middle cerebral artery, a MoM (multiple of the median) score can be calculated. MoM of 1.5 or greater indicates severe anemia and should be treated with intrauterine transfusion (IUT). Fetal mortality was reduced by 36% in the IVIG and IUT group than in the IUT alone group. IVIG and plasmapheresis together can reduce or eliminate the need for an IUT. Plasmapheresis Plasmapheresis aims to decrease the maternal titer by direct plasma replacement. Plasmapheresis and IVIG together can even be used on women with previously hydropic fetuses and losses.

IUT Intrauterine Transfusion (IUT) is done either by intraperitoneal transfusion (IPT) or intravenous transfusion (IVT). IVT is preferred over IPT. IUTs are only done until 35 weeks. After that, the risk of an IUT is greater than the risk from post birth transfusion. Steroids Steroids are sometimes given to the mother before IUTs and early delivery to mature the fetal lungs. Phenobarbital Phenobarbital is sometimes given to the mother to help mature the fetal liver and reduce hyperbilirubinemia. Early Delivery Delivery can occur anytime after the age of viability.

Coombs after birth baby will have a direct coombs test run to confirm antibodies attached to the infant's red blood cells. This test is run from cord blood. In some cases, the direct coombs will be negative but severe, even fatal HDN can occur. An indirect coombs needs to be run in cases of anti C, anti c, Low retic is observed in infants treated with IUT and in those with HDN from anti Kell
Thrombocytes as thrombocytopenia is one of the complications of HDN, the thrombocyte count should be checked. Newborn Screening Tests Transfusion with donor blood during pregnancy or shortly after birth can affect the results of the Newborn Screening Tests. It is recommended to wait and retest 10–12 months after last transfusion. In some cases, DNA testing from saliva can be used to rule out certain conditions.

Suggestions have been made that women of child bearing age or young girls should not be given a transfusion with Kell1 positive blood. Donated blood is not currently screened (in the U. S. A.) for the Kell blood group antigens as it is not considered cost effective at this time. It has been hypothesized that IgG anti Kell1 antibody injections would prevent sensitization to RBC surface Kell1 antigens in a similar way that IgG anti D antibodies (Rho(D) Immune Globulin) are used to prevent Rh disease, but the methods for IgG anti Kell 1 antibodies have not been developed at the present time.

Phototherapy Phototherapy is used for cord bilirubin of 3 or higher. Some doctors use it at lower levels while awaiting lab results. IVIG IVIG has been used to successfully treat many cases of HDN. It has been used not only on anti D, but on anti E as well. IVIG can be used to reduce the need for exchange transfusion and to shorten the length of phototherapy. The AAP recommends "In isoimmune hemolytic disease, administration of intravenousγ globulin (0.5 1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34 51 μmol/L) of the exchange level If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms). Intravenous γ globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease."