WHAT YOU SHOULD KNOW ABOUT HDN. Provided by Grifols

Transcription

1 WHAT YOU SHOULD KNOW ABOUT HDN Provided by Grifols

2 2

3 PATIENT QUESTIONS AND ANSWERS What is hemolytic disease of the newborn (HDN)? If your body has produced antibodies to fight the antigens on your baby s red blood cells, a blood disorder called hemolytic disease of the newborn (HDN) sometimes called rhesus (Rh) disease can result. It is important to know that your body s production of these antibodies does not necessarily lead to HDN. But if it does, the results can be life-threatening, manifesting as anemia, jaundice, heart or liver problems, or mental retardation. Before any preventative treatment had been developed, HDN affected 1% of babies in second pregnancies born to Rh negative women in England and Wales. How common is HDN? Until the late 1960s, HDN due to Rh incompatibility was an important cause of fetal and neonatal morbidity and mortality. Mortality from HDN due to Rh incompatibility is now uncommon. What are Rh negative and Rh positive blood types and how are they important to my pregnancy? There are 2 main systems used for categorizing human blood: the ABO system and the Rh system. Individuals who are Rh positive have a particular protein (RhD antigen) attached to their red blood cells whereas individuals who are Rh negative do not. Whether you are Rh positive or Rh negative depends on the 2 Rh genes you inherited from your parents (we receive 1 gene from each parent that may be either positive or negative). If you are Rh negative and pregnant, there is a chance that your baby is Rh positive. 3

4 What can happen if I have a different Rh blood group than my baby? Having a different Rh blood group than your baby is only a potential problem if you are Rh negative and your baby is Rh positive. If a small amount of your baby s blood mixes with yours during pregnancy, your immune system may perceive this difference in blood type as a threat, producing antibodies that fight against your baby s blood. This process is called sensitization or alloimmunization, and once your body has made these antibodies, they cannot be removed. Sensitization is unlikely to affect your first pregnancy, but instead becomes a problem in any subsequent pregnancy if your baby is Rh positive. This is because the process of producing antibodies takes time. The initial antibodies you produce in your first pregnancy (IgM) cannot cross the placenta. These IgM antibodies are replaced by IgG antibodies which can cross the placenta and adversely affect future pregnancies. If I am Rh negative and am pregnant with an Rh positive baby, how likely am I to produce antibodies against my baby s blood? The most likely times you would produce antibodies occur when an exchange of blood between you and your baby is most likely: at delivery, after abortion, or after an invasive procedure (for example, amniocentesis). In a 2006 review of Rh testing, reviewers noted that without preventative treatment, 5%-15% of Rh negative pregnant women develop antibodies at delivery; 3%-6% after spontaneous abortion; and 2%-5% during amniocentesis. If no high-risk situations have occurred prior to delivery, without treatment 1%-2% of Rh negative pregnant women produce antibodies before birth due to hemorrhages of the baby s blood. What are anti-d (RhD immunoglobulin) injections and when are they recommended? Anti-D injections are given to pregnant women who are Rh negative as a means of preventing antibodies from forming against the baby s red blood cells. Anti-D injections are recommended after potentially sensitizing events that could result in a fetal/maternal hemorrhage: invasive procedures (amniocentesis), abdominal trauma, and delivery (C-section or vaginal). What are the risks of receiving anti-d (RhD immunoglobulin) injections? The injections are derived from human donor blood and are tested for hepatitis C and B, parvovirus B19, and HIV. The active substance in these injections is human anti-d immunoglobulin. Other ingredients may include human albumin, glycine, and sodium chloride. Since 2001, anti-d injections no longer contain thimerosal, which is mercury-derived. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. RhD immunoglobulin should be given with caution to patients with a history of prior systemic allergic reactions following the administration of human immunoglobulin preparations. 4

5 5

6 Will I need anti-d (RhD immunoglobulin) injections? HDN is only relevant to Rh negative pregnant women because of the chance that they may have an Rh positive baby. If you are Rh negative and are certain of paternity, a paternal blood test can be conducted. If both you and the baby s father are Rh negative, it is not possible for your baby to be Rh positive, and you will not need anti-d injections. There is also nonroutine testing called noninvasive prenatal diagnosis (NIPD) by which your baby s Rh status can be assessed. The accuracy of this testing has been reported to be between 94.8% and 100%. 6

7 CLINICAL QUESTIONS AND ANSWERS What are the current dosing recommendations for the administration of RhD immunoglobulin? Indications Postpartum prophylaxis preferably within 72 hours of delivery If volume of red blood cells that has entered the circulation 15 ml If large (>30 ml whole blood or 15 ml red blood cells) fetomaternal hemorrhage is suspected Antenatal prophylaxis At approximately 28 weeks gestation Postpartum, preferably within 72 hours of delivery, if infant is Rh positive Following miscarriage, abortion, or termination of ectopic pregnancy If pregnancy terminated at or beyond 13 weeks gestation Following amniocentesis at weeks gestation or during third trimester Following abdominal trauma in second or third trimester Transfusion Dosage 1500 IU IM Fetal red cell count should be performed to determine dosage. See complete prescribing information IU IM 1500 IU IM 1500 IU IM 1500 IU IM 1500 IU IM For dosage calculation, see complete prescribing information. If >15 ml of red blood cells are suspected due to fetomaternal hemorrhage, see postpartum prophylaxis above. If abdominal trauma, amniocentesis, or another adverse event required administration of RhD Immunoglobulin at weeks gestation, another 1500-IU dose should be given at weeks gestation. 7

8 If a patient fails to receive prophylactic RhD immunoglobulin at 28 weeks, when should she receive the first dose? The dose should be given as soon as possible after it is recognized that the dose was missed. In such a case the second dose should be delayed until 6 weeks after the first dose. Where is the best site for administration of the intramuscular injection? The deltoid muscle or the anterolateral thigh is the best site. The gluteal region should not be used as an injection site because of the risk of injury to the sciatic nerve. 8

9 COOMBS TEST The Coombs test detects Rh incompatibility between mother and fetus To detect HDN, the presence of maternal anti-rh immunoglobulin G (IgG) must be identified. In vivo, these antibodies destroy Rh positive fetal red blood cells (RBCs), but in vitro, they do not lyse cells or even cause agglutination, making them difficult to identify. Therefore, the Coombs test is used. This test uses antibodies that bind to human anti-d antibodies. Direct Coombs test: diagnoses HDN The direct Coombs test detects maternal anti-d antibodies that have already bound to fetal RBCs. First, a sample of fetal RBCs is washed to remove any unbound antibody (Ig). When the test antibodies (anti-ig) are added, they agglutinate any fetal RBCs to which maternal antibodies are already bound. This is called the direct Coombs test because the anti-ig binds directly to the maternal anti-d Ig that coats fetal RBCs in HDN. Indirect Coombs test: used in the prevention of HDN The indirect Coombs test finds anti-d antibodies in the mother s serum. If these were to come into contact with fetal RBCs they would hemolyze, and this may result in HDN. By finding maternal anti-d before fetal RBCs have been attacked, treatment can be given to prevent or limit the severity of HDN. For this test, the mother s serum is incubated with Rh positive RBCs. Then if any anti-d is present in the mother s serum, it will bind to the cells. The cells are then washed to remove all free antibodies. When anti-ig antibodies are added, they will agglutinate any RBCs to which maternal antibodies are bound. This is called the indirect Coombs test because the anti-ig finds indirect evidence of harmful maternal antibodies, requiring the addition of fetal RBCs to show the capacity of maternal anti-d to bind to fetal RBCs. 9

10 10

11 REFERENCES AND ADDITIONAL INFORMATION References: Socio-Economic Group, University of Warwick for Workpackage 6, SAFE Network of Excellence. A Review of Evidence on Noninvasive Prenatal Diagnosis (NIPD): Tests for Fetal RHD Genotype. Initial Report. University of Warwick; ac.uk/129/1/wrap_szczepura_rhdreportfinalversion_website_1.pdf. Accessed October 1, Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; Appendix I. Immunologists Toolbox. Available from: Barham-Floreani, J. Common Questions About Anti-D Injections. WellAdjusted. Accessed October 1, National Health & Medical Research Council. Guidelines on the prophylactic use of RhD immunoglobulin (Anti-D) in obstetrics. Commonwealth of Australia; Accessed October 1, Reid ME, Lomas-Francis C. The Blood Group Antigen FactsBook. New York: Academic Press, Data on file, Grifols. Additional Resource: American College of Obstetricians and Gynecologists: Contact Information: Customer Service Medical Information Reimbursement Support HelpLine M F 8:30 am to 5:30 pm (Eastern) 11