Hemolytic Disease of the Fetus and Newborn

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Author: Pat Letendre, MEd
Reviewers: Laurie Bjerklie, MA, MLS(ASCP)CM and Marissa Wildung, MLS(ASCP)CM

This course provides information on the significant aspects of hemolytic disease of the fetus and newborn (HDFN), including its laboratory investigation and prevention. It offers a broad overview of various important topics, including causative antibodies, laboratory findings in severe HDFN, and pre- and postnatal treatments. Rh immune globulin (RhIg) is covered in depth, as it prevents the most severe form of HDFN and is one of the most significant success stories in modern medicine.

Continuing Education Credits

Objectives

  • Interpret typical clinical symptoms and associated laboratory test results and relate findings to the pathogenesis of HDFN and its treatment.
  • Describe the progression of HDFN due to anti-D historically and the effect of Rh immune globulin (RhIG) and other factors on its incidence.
  • Compare and contrast ABO HDFN and HDFN due to anti-D and other antibodies in terms of clinical symptoms, fetal monitoring procedures, laboratory investigation, typical test results, and criteria for donor RBC transfusions.
  • Identify current best practices for perinatal testing programs and investigation of HDFN using serologic tests done on the mother, father, and fetus/newborn.
  • Discuss the criteria for administration, dosage calculation, and causes of failures of RhIG.
  • Describe the principles, uses, and limitations of the rosette test, Kleihauer-Betke test, and flow cytometry used in perinatal testing programs.

Course Outline

  • Pathophysiology of HDFN and Blood Group Systems Most Commonly Implicated in the Disease
      • Introduction to HDFN
      • Development of Anti-D
      • Factors Affecting Production of Anti-D
      • Primary versus Secondary Response
      • Pathophysiology in Severe HDFN Due to Anti-D
      • HDFN Due to Anti-D
      • ABO HDFN
      • ABO HDFN: Diagnostic Tests
      • ABO HDFN: Expected Findings
      • ABO HDFN: Treatment
      • True or False: ABO incompatibility between a D-negative mother and a D-positive fetus eliminates the possibility of HDFN due to anti-D.
      • HDFN Due to Other Antibodies
      • Phototherapy helps to prevent which symptom of HDFN?
      • For which of the following antibodies is the DAT most likely to be negative when testing a newborn for possible HDFN?
      • True or False: Kernicterus due to high levels of unconjugated bilirubin can cause brain damage in newborns suffering from severe HDFN.
  • Fetal Monitoring and HDFN Treatments
      • Fetal Monitoring
      • Prenatal Treatment
      • Choosing Donor RBCs for IUT and IVT
      • Postnatal Treatment: Exchange Transfusion
      • Criteria for Transfused Red Blood Cells
      • Other Postnatal Treatment
      • True or False: The following are criteria for donor RBCs to be used for an exchange transfusion related to both ABO HDFN and HDFN due to anti-D:Less t...
      • Which procedure used to obtain a fetal blood sample to monitor the severity of HDFN can also be used to deliver intravenous transfusions?
  • Perinatal Testing Programs
      • Purpose of Perinatal Testing
      • HDFN Diagnosis and Management
      • Newborn Serologic Testing Protocols
      • Molecular Genotyping
      • Molecular Genotyping: Differentiating Between Weak D and Partial D
      • Determining Risk for HDFN Using Molecular Genotyping
      • For which of these reasons would a molecular method be used to determine a pregnant patient's Rh type?
      • True or False: A Rh-negative pregnant patient has produced anti-D, and the physician has decided to use molecular typing to determine if the fetus is ...
      • Follow-up Investigative Tests (Mother)
      • Follow-up Investigative Tests (Father)
      • Follow-up Investigative Tests (Fetus)
      • Follow-up Investigative Tests (Newborn)
      • True or False: Maternal antibody titer is a reliable indicator of fetal disease.
  • Review of Rh Immune Globulin
      • RhIG Prophylaxis
      • RhIG Uses
      • RhIG and Variants of D
      • RhIG Policies for Weak D
      • Clinical Relevance of D Phenotypes
      • RhIG 'Failures'
      • Passive Anti-D Following RhIG Administration
      • Protocols to Deal with RhIG-Derived Anti-D
      • True or False: When given during pregnancy, RhIG may cross the placenta and sensitize fetal D-positive RBCs.
      • True or False: Ectopic pregnancy is an indication for administering RhIG to an Rh-negative patient.
      • An Rh-positive individual has produced an anti-D antibody. Which D variant possesses the ability to stimulate this production of anti-D?
      • What dose of RhIG can suppress immunization of 30 mL of D-positive whole blood?
  • Post-Delivery Testing of RhIG Candidates
      • Overview of Fetomaternal Hemorrhage
      • Screening for Fetomaternal Hemorrhage
      • Rosette Test
      • Quantifying FMH
      • Kleihauer-Betke Test
      • Flow Cytometry
      • Calculating RhIG Dosage
      • Which of the following tests are suitable for quantifying the size of fetomaternal hemorrhage (FMH)?
      • True or False: A rosette test may be falsely positive if the mother is weak-D positive.
      • The appropriate dosage of Rh immune globulin (RhIG) to administer post-delivery to an Rh-negative mother delivering an Rh-positive child is calculated...
  • Conclusion
      • Summary
      • Resources
  • References
      • References

Additional Information

Level of Instruction: Intermediate
Intended Audience: Medical laboratory scientists, medical laboratory technicians, laboratory supervisors, and laboratory managers. This course is also appropriate for MLS and MLT students and pathology residents.
Author Information: Pat Letendre, MEd, is a laboratory scientist, educator, and consultant. She consults in the areas of transfusion medicine, education, professional development, and the use of the Internet in education. Ms. Letendre is the Webmaster for Canada's transfusion safety officers and the TraQ website coordinator. She holds a Master of Education degree in adult education from the University of Alberta and a Bachelor of Science degree from the University of Manitoba.  
The author has no conflict of interest to disclose.
Reviewer Information:
Laurie Bjerklie, MA, MLS(ASCP)CM, is a Lead Education Developer. She earned a B.S. in Medical Laboratory Science from the University of North Dakota and an M.A. in Curriculum and Instruction from Saint Xavier University. She has over 15 years of experience in higher education and has held program director and faculty positions in both MLT and MLS programs.
Marissa Wildung, MLS(ASCP)CM, is a Laboratory Supervisor with nine years of experience as a Medical Laboratory Scientist and a Faculty Instructor for an MLT/Phlebotomy Program in Central Minnesota. Marissa holds a Bachelor’s in Medical Laboratory Science from the University of Cincinnati and is pursuing a Master's in Business Administration from St. Cloud State University.

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Figure 1. Primary vs. secondary immune response
Figure 5. Kleihauer-Betke test positive with blue arrows indicating fetal cells, <br>red arrows indicating maternal cells (ghost cells)
Figure 3. Rosette test positive