What Are Those Blood Group Antigens and Isn't There Some Treatment I Can Give?

Patient Presentation
A 3-day-old female came to clinic because the parents felt she wasn’t feeding as well as she should. She had been feeding every 2-3 hours but her mother only began lactating a couple of hours previously. She was urinating and having bowel movements per her parents. They denied any temperature instability and felt she was alert. The past medical history showed she was a 36 0/7 week premature infant born by spontaneous vaginal delivery to a first time mother with a history of anti-C antibody. She had been discharged from an outside hospital 12 hours previously. Birthweight was 2550 g and bilirubin level was 5.2 at 14 hours of age. The family history was negative for premature births, spontaneous abortions, hematological, oncological, or gastrointestinal diseases. The review of systems was otherwise negative. The pertinent physical exam showed a tired appearing infant who was markedly jaundiced over her entire skin. Her weight was 2410 g. Other growth parameters were 50%. She had moist mucous membranes. Her head had a small bruise that crossed the midline of the distal occiput that was 2 cm in size and soft. Her abdomen was soft with no hepatosplenomegaly. The rest of her examination was normal.

The diagnosis of hyperbilirubinemia in a premature infant with possible alloantibodies was made. The initial work-up of a bilirubin showed a bilirubin of 18.9 at 71 hours of life. She was begun on phototherapy and further evaluation and treatment started. However a repeat bilirubin level two hours later had increased to 19.2 which is just below the level for exchange transfusion, so she was transferred to the neonatal intensive care unit for probable hemolytic disease of the newborn. The patient’s clinical course showed that she was aggressively treated with phototherapy, hydration, and antibiotics for possible sepsis (cultures were eventually negative). She was also treated with intravenous immunoglobulin for possible alloimmunization, even though her Coombs test and blood smear were negative. There was no evidence of platelet or leukocyte problems. She was taken off phototherapy 2 days later and was able to be discharged home on day 3. She was to followup with her physician in 2-3 days.

Hemolytic disease of the newborn is usually considered if there is a severe or rapidly developing hyperbilirubinemia, a maternal positive antenatal antibody screening or severely anemic or hydropic fetus, a positive direct Coombs test, hemolysis seen on blood smear, or prolonged hyperbilirubinemia. A differential diagnosis of the multiple causes of unconjungated hyperbilirubemia can be found in a previous case, and a review of the epidemiology of Rh negative HDN can also be found in another previous case.

Learning Point
Causes of severe unconjungated hyperbilirubinemia due to red blood cells causes includes:

  • Major Blood Group Antigen
    • ABO incompatibility
    • Rhesus group incompatibility (Anti-D, Anti-C and Anti-E)
  • Minor Red Blood Cell Antigens
    • Anti-Duffy
    • Anti-Kell
    • Anti-Kidd
    • Anti-MNS system (Anti-U)
  • Enzyme Disorders
    • Glucose-6-phosphate dehydrogenase deficiency
    • Pyruvate kinase deficiency
    • Trisephophate isomerase deficiency
    • Disorders of glycolysis pathway
  • Hemoglobinopathies
    • Alpha Thalassemia
    • Globin chain variants, especially alpha and gamma
  • Membrane Disorders
    • Hereditary elliptocytosis
    • Hereditary spherocytosis
    • Hereditary pyropoikilocytosis
    • Hereditary stomatocytosis

The Rhesus antigen D (RhD) is the most important clinically because it is developed early in gestation, it is immunogenic, a significant percentage of the Caucasian population is RhD negative and the RhD antibody can cause fetal hemolysis.

Data for use of intravenous immunoglobulin (IVIG) began to be published approximately 20 years ago. Two recent systematic reviews have advocated for the judicious use of IVIG as an effective and safe treatment for reducing the need for exchange transfusion in HDN. The American Academy of Pediatrics guidelines for treatment of jaundice also recommends use of IVIG if the bilirubin continues to increase despite intensive phototherapy or if the level is within 2-3 mg/dl of exchange transfusion levels.

Questions for Further Discussion
1. How would you treat isoimmune thrombocytopenia?
2. What is the differential diagnosis of conjugated hyperbilirubinemia?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Jaundice and at Pediatric Common Questions, Quick Answers for this topic: Jaundice.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Hadley AG. Laboratory assays for predicting the severity of haemolytic disease of the fetus and newborn.
Transpl Immunol. 2002 Aug;10(2-3):191-8.

American Academy of Pediatrics Clinical Practice Guideline Statement. Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics. 2004;114:297-316. Available from the Internet at: http://aappolicy.aappublications.org/cgi/content/full/pediatrics;114/1/297 (cited 9/11/09).

Murray NA, Roberts IA. Haemolytic disease of the newborn.
Arch Dis Child Fetal Neonatal Ed. 2007 Mar;92(2):F83-8.

Alcock GS, Liley H. Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No.: CD003313. DOI: 10.1002/14651858.CD003313.

Walsh S, Molloy EJ. Towards evidence based medicine for paediatricians. Is intravenous immunoglobulin superior to exchange transfusion in the management of hyperbilirubinaemia in term neonates? Arch Dis Child. 2009 Sep;94(9):739-41.

ACGME Competencies Highlighted by Case

  • Patient Care
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital