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A case of Exchange Transfusion in new
born infant with Neonatal Jaundice and
Rh incompatibility
in integration with Dept. of Paediatrics
Presenter- Dr. Shiny Kajal
PG 2nd Year
Dept. Of Immunohematology & Blood Transfusion
ABO-Rh Typing
•1 EDTA Vial sample was received at Blood
centre on 15/01/24 of a 3 day old neonate.
•ABO-Rh typing- O Positive with
DAT 4+ Positive
• Requisition forms for 1 Whole Blood, 1 PRBC, 1FFP was received on 15/01/2024 at 6pm along with 1
EDTA and 1 Plain vial sample.
Clinical Diagnosis mentioned - Neonatal Jaundice
Indication mentioned- Exchange Transfusion
Clinical History
Dept. of Paediatrics
On following up the case-
Relevant Immunohemat history-
•Mother- O negative G3P1L1A1
•H/O IvIg during first pregnancy present (verbal information)
•2nd pregnancy- Abortion- no IvIg administered
•Blood group of offsprings- unknown
Transfusion Management
Volume
•Birth Weight of neonate- 2.6 kgs
•Blood volume of neonates>2kgs- 80mL/kg = 2.6 x 80 = 208 mL
•Volume for Double Volume exchange transfusion= 2x208= 416mL+20-30mL for
the tubing = 440-450mL
•2 cycles of Double Volume Exchange transfusion were performed in the patient.
15/01/2024- 1st Double Volume E.T
Requisition Component Preparation Pre
transfusion
Testing
Issue Transfusion
Monitoring
Received at
6 pm
A reconstituted whole blood
in form of PRBC and FFP
mixed in ratio 7:3 (as
requested by the department)
was prepared using the Sterile
connecting device.
PRBC- 310 mL O Neg
FFP- 140mL O Neg
Cross
matched
with
mother’s as
well as
patient’s
sample-
Compatible
The unit
was issued
at 8.30 pm
Vol- 450mL
TAT- 2.5 hrs
No
transfusion
reaction
reported
16/01/2024- 2nd Double Volume E.T
Requisition Component
Preparation
Pre transfusion
Testing
Issue Transfusion
Monitoring
A requisition for 1 unit of
O Negative Fresh Whole
blood was received at
10.00 am
Indication-
Bilirubin dropped from
34.1 to 26.4mg/dL. It was
still above 20 mg/dL
which indicated 2nd
exchange transfusion.
Donor for the same was
arranged via our blood
centre’s rare donor
registry by contacting a
known O negative donor
amongst Adesh hospital
staff.
Cross matched with
mother’s as well as
patient’s sample-
Compatible.
The unit was tested by
Chemiluminescence
Immunoassay
The unit was issued
at 2.26pm
Volume- 430 mL
TAT- 4 hrs
No transfusion
reaction
reported
18/01/2024
Requisition Component
Preparation
Pre transfusion
Testing
Issue Transfusion
Monitoring
A requisition for 1 unit of
Fresh Frozen Plasma was
received at 3 pm.
The demand form was
received at 4.10 pm
Indication- Derranged INR
The unit was thawed
at 37 degrees C.
Minor Cross match
was Compatible.
The unit was issued at
5.00 pm
Volume- 102 mL
TAT- 1 hour
No transfusion
reaction
reported
Follow up at Blood centre- Patient
Parameter Before ET After ET
Direct
Antiglobulin
Test
4+ Positive Negative
Antibody
screening
3+ Panel II
2+ Panel III
Negative
DAT Pre and Post ET
Antibody screening
Post ET
Antibody screening
Pre ET
Follow up at Blood centre- Mother
•ICT- Positive
•DCT- Negative
•ANTIBODY SCREENING- Positive
•Inference- Possible alloimmunization in mother
Lab investigations- Pre & Post ET
Technique for Exchange Transfusion
Dept. of Paediatrics
Technique
•The transfusion is given at a rate of about 5 mL/min and even more slowly in the
case of a hydropic foetus (2–3 mL/min)
•5% of the infant’s blood volume is removed and replaced during a 3- to 5 min
cycle.
•The exchange transfusion should not be performed rapidly because sudden
hemodynamic changes may affect cerebral blood flow and shift intracranial
pressure, contributing to ICH.
•A total double-volume exchange transfusion typically takes 90 to 120 minutes.
Single Line exchange transfusion Double Line exchange transfusion
AABB Standards
Reconstituted Whole Blood
•Reconstituted whole blood consists of RBCs combined with ABO-compatible FFP,
which can be used for neonate exchange transfusion.
•The conventional approach to reconstitute Universal Donor R.W.B- is to combine group
O RBCs and group AB FFP to achieve a 50% ± 5% hematocrit of the final product.
•The volumes of the two components before pooling can be adjusted to achieve a desired
hematocrit level.
•Following reconstitution, the product can be stored at 1 to 6 C for up to 24 hours.
•Exchange transfusion of a neonate/infant is also considered a massive transfusion
•“Massive transfusion” is defined as the administration of 8 to 10 RBC units in an
adult patient in less than 24 hours or acute administration of 4 to 5 RBC units
within 1 hour or replacement of at least 50% of blood volume.
•Exchange transfusion is preferred to be done with fresh whole blood or red cells
that are usually less than 14 days old (as fresh as possible)
Characteristics of the reconstituted whole blood
•The reconstitution procedure must only be performed in Transfusion Services in
a closed system, using appropriate formulae to obtain the desired Hct.
•The product has the same metabolic and haemostatic characteristics as fresh
whole blood but lacks platelets.
Introduction to Exchange Transfusion
•An exchange transfusion involves gradual removal of patient’s blood and
simultaneous replacement with allogenic donor blood.
•Besides hyperbilirubinemia, the use of ET has been extended in the management of
•hydrops fetalis
•congenital leukaemia
•disseminated intravascular coagulation
•severe neonatal sepsis
•sclerema neonatorum
•Hyperammonaemia
•Polycythaemia
•fluid and electrolyte imbalance
The aim of ET is to:
•Lower serum bilirubin level to reduce the risk of kernicterus (most common
indication) in patients not responsive to phototherapy and/ or IVIG.
•To remove infants affected red blood cells and circulating maternal antibodies to
reduce red cell destruction, e.g., in HDFN.
•To correct anaemia
•Remove bacteria, bacterial toxins, and circulating pro-inflammatory cytokines
(e.g., in sepsis)
Exchange Transfusion for Hyperbilirubinemia
•Exchange transfusion in neonates involves replacement of 1 or 2 whole-blood volumes.
•The primary purpose of this therapy is to treat excessively high levels of unconjugated bilirubin
(hyperbilirubinemia).
•In high concentrations, bilirubin may cross the blood brain barrier; concentrates in the basal
ganglia and cerebellum of preterm and full-term infants; and cause irreversible damage, known
as “kernicterus,” to the central nervous system.
• Phototherapy (use of fluorescent blue lights) is the current treatment of choice for
hyperbilirubinemia; Exchange Transfusion is reserved for patients who fail phototherapy.
Two critical objectives of exchange transfusions are-
•the removal of unconjugated bilirubin
•maximization of albumin binding of residual bilirubin.
In addition, in antibody mediated hemolytic processes, exchange therapy removes both
free antibody and antibody- coated red cells, replacing them with antigen-negative red
cells.
Kernicterus And Bilirubin
•Exchange transfusion needs to be performed before the development of kernicterus.
•In full-term infants, kernicterus develops at bilirubin levels >25 mg/dL.
•However, in ill VLBW infants, kernicterus can occur at bilirubin levels as low as 8 to
12 mg/dL. OPHISTHOTONUS
Volume And Hematocrit
Considerations
•A double-volume exchange in neonates necessitates the infusion of 2 volumes of
approximate Blood volume of neonate.
•The unit’s hematocrit should be approximately 45% to 60%, and the unit should
have sufficient plasma (based on estimated blood volume) to provide clotting
factors.
•If the neonate’s condition requires a higher post exchange transfusion hematocrit,
a small-volume RBC transfusion may be given or a unit with a higher hematocrit
can be used for the initial exchange transfusion.
Transfusion and Bilirubin
•A double-volume exchange transfusion (two 85mL/kg transfusions for full-term
infants and two 100-mL/kg transfusions for VLBW/preterm infants) removes
approximately 70% to 90% of the circulating red cells and approximately 50% of
the total bilirubin.
•However, after the first exchange transfusion, bilirubin levels may rise again
because of a re-equilibration of the extravascular tissue and plasma bilirubin,
which may necessitate another exchange transfusion.
Possible complications of ET
Vascular- air emboli/thrombosis
Cardiac- volume overload, cardiac arrest
Electrolytes- hyperkalemia, hypocalcemia, acidosis
Coagulation disorders- thrombocytopenia
Infectious- bacteremia/CMV/Sepsis
Hemolytic disease of the fetus and
newborn
•HDFN is the destruction of the red blood cells (RBCs) of a fetus/neonate by antibodies
produced by the mother.
•The mother can be stimulated to form RBC antibodies naturally (ABO), by previous
pregnancy, or transfusion (RBC alloimmunization).
•Incidence of the disease caused by anti-D has decreased since 1968 with the introduction
of RhIG.
•Despite the decrease in HDFN, RhD continues to remain an important cause of
incompatibility.
Antigens which can cross placenta
•Rh(D) is the most potent immunogen, in that a 200-mL transfusion of Red Blood
Cells (RBCs) stimulates anti-D in about 85% of D-negative individuals, except
those who are immunosuppressed.
•Unlike HDFN caused by anti-D, HDFN caused by anti-K uniquely results in
destruction of fetal erythropoietic precursors in addition to hemolysis.
•Other antibodies that have been less commonly reported to cause moderate or
severe disease include E, k, Kpa, Kpb, Ku, Jsa, Jsb, Jka, Fya, Fyb, S, s, and U
HDFN Haemolysis
•Hemolysis occurs when the maternal antibody binds to a fetal red cell antigen,
causing attachment to the Fc receptor of macrophages in the spleen of the fetus.
•The rate of hemolysis and severity of disease are determined by the IgG
subclass, amount of antibody, and number of antigenic sites on the red cells.
•The subclasses IgG1 and IgG3 are more efficient in causing hemolysis than
IgG2 or IgG4.
•Transportation of IgG1 and IgG3 across the placenta is mediated by the Fc
receptor beginning in the second trimester and continuing until birth.
Pathophysiology
Anemia
Fetal Death
Kernicterus
Screening and Dosing for RhIG
•The risk of a D-negative mother becoming immunized by a D-positive fetus can be
reduced from about 16% to less than 0.1% by the appropriate administration of RhIG.
•Antepartum Administration-The American College of Obstetricians and Gynecologists
(ACOG) recommends RhIG administration at 28 weeks’ gestation because 92% of women
who develop anti-D during pregnancy do so at or after 28 weeks.
•Postpartum Administration- Postpartum RhIG should be given to the mother within 72
hours of delivery.
DGHS Guidelines
Indian guidelines for dose
Current Practice
•There is steep decline in the incidence of HDFN following the introduction of
maternal anti-D Ig prophylaxis, more effective antenatal monitoring and
treatment, and the use of intensive phototherapy and intravenous immunoglobulin
postnatally has made red cell exchange transfusion an uncommon procedure that
should only be performed by experienced staff.
Indian guidelines
Take Home Message
An early recognition and diagnosis
is the first and most crucial step
towards a successful treatment.
References
1. https://www.transfusionguidelines.org/transfusion-
handbook/10-effective-transfusion-in-paediatric-
practice/10-2-neonatal-transfusion
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607607/
3. Exchange transfusion in neonatal hyperbilirubinemia: A
single Centre experience from Northern India
https://pubmed.ncbi.nlm.nih.gov/31636029/
4. DGHS Transfusion Medicine Technical Manual 3rd
edn.November 2022
5. AABB Technical manual- 21st edition 2023
6. NACO guidelines- Division of Blood Transfusion Services
Ministry of Health and Family Welfare
7. Rossi’s Principles of Transfusion Medicine, Edition 4

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A case presentation of Exchange Transfusion in new born infant with Neonatal Jaundice and Rh incompatibility

  • 1. A case of Exchange Transfusion in new born infant with Neonatal Jaundice and Rh incompatibility in integration with Dept. of Paediatrics Presenter- Dr. Shiny Kajal PG 2nd Year Dept. Of Immunohematology & Blood Transfusion
  • 2. ABO-Rh Typing •1 EDTA Vial sample was received at Blood centre on 15/01/24 of a 3 day old neonate. •ABO-Rh typing- O Positive with DAT 4+ Positive
  • 3. • Requisition forms for 1 Whole Blood, 1 PRBC, 1FFP was received on 15/01/2024 at 6pm along with 1 EDTA and 1 Plain vial sample. Clinical Diagnosis mentioned - Neonatal Jaundice Indication mentioned- Exchange Transfusion
  • 5. On following up the case- Relevant Immunohemat history- •Mother- O negative G3P1L1A1 •H/O IvIg during first pregnancy present (verbal information) •2nd pregnancy- Abortion- no IvIg administered •Blood group of offsprings- unknown
  • 7. Volume •Birth Weight of neonate- 2.6 kgs •Blood volume of neonates>2kgs- 80mL/kg = 2.6 x 80 = 208 mL •Volume for Double Volume exchange transfusion= 2x208= 416mL+20-30mL for the tubing = 440-450mL •2 cycles of Double Volume Exchange transfusion were performed in the patient.
  • 8. 15/01/2024- 1st Double Volume E.T Requisition Component Preparation Pre transfusion Testing Issue Transfusion Monitoring Received at 6 pm A reconstituted whole blood in form of PRBC and FFP mixed in ratio 7:3 (as requested by the department) was prepared using the Sterile connecting device. PRBC- 310 mL O Neg FFP- 140mL O Neg Cross matched with mother’s as well as patient’s sample- Compatible The unit was issued at 8.30 pm Vol- 450mL TAT- 2.5 hrs No transfusion reaction reported
  • 9. 16/01/2024- 2nd Double Volume E.T Requisition Component Preparation Pre transfusion Testing Issue Transfusion Monitoring A requisition for 1 unit of O Negative Fresh Whole blood was received at 10.00 am Indication- Bilirubin dropped from 34.1 to 26.4mg/dL. It was still above 20 mg/dL which indicated 2nd exchange transfusion. Donor for the same was arranged via our blood centre’s rare donor registry by contacting a known O negative donor amongst Adesh hospital staff. Cross matched with mother’s as well as patient’s sample- Compatible. The unit was tested by Chemiluminescence Immunoassay The unit was issued at 2.26pm Volume- 430 mL TAT- 4 hrs No transfusion reaction reported
  • 10. 18/01/2024 Requisition Component Preparation Pre transfusion Testing Issue Transfusion Monitoring A requisition for 1 unit of Fresh Frozen Plasma was received at 3 pm. The demand form was received at 4.10 pm Indication- Derranged INR The unit was thawed at 37 degrees C. Minor Cross match was Compatible. The unit was issued at 5.00 pm Volume- 102 mL TAT- 1 hour No transfusion reaction reported
  • 11. Follow up at Blood centre- Patient Parameter Before ET After ET Direct Antiglobulin Test 4+ Positive Negative Antibody screening 3+ Panel II 2+ Panel III Negative DAT Pre and Post ET Antibody screening Post ET Antibody screening Pre ET
  • 12. Follow up at Blood centre- Mother •ICT- Positive •DCT- Negative •ANTIBODY SCREENING- Positive •Inference- Possible alloimmunization in mother
  • 13. Lab investigations- Pre & Post ET Technique for Exchange Transfusion Dept. of Paediatrics
  • 14.
  • 15. Technique •The transfusion is given at a rate of about 5 mL/min and even more slowly in the case of a hydropic foetus (2–3 mL/min) •5% of the infant’s blood volume is removed and replaced during a 3- to 5 min cycle. •The exchange transfusion should not be performed rapidly because sudden hemodynamic changes may affect cerebral blood flow and shift intracranial pressure, contributing to ICH. •A total double-volume exchange transfusion typically takes 90 to 120 minutes.
  • 16. Single Line exchange transfusion Double Line exchange transfusion
  • 18. Reconstituted Whole Blood •Reconstituted whole blood consists of RBCs combined with ABO-compatible FFP, which can be used for neonate exchange transfusion. •The conventional approach to reconstitute Universal Donor R.W.B- is to combine group O RBCs and group AB FFP to achieve a 50% ± 5% hematocrit of the final product. •The volumes of the two components before pooling can be adjusted to achieve a desired hematocrit level. •Following reconstitution, the product can be stored at 1 to 6 C for up to 24 hours.
  • 19. •Exchange transfusion of a neonate/infant is also considered a massive transfusion •“Massive transfusion” is defined as the administration of 8 to 10 RBC units in an adult patient in less than 24 hours or acute administration of 4 to 5 RBC units within 1 hour or replacement of at least 50% of blood volume. •Exchange transfusion is preferred to be done with fresh whole blood or red cells that are usually less than 14 days old (as fresh as possible)
  • 20. Characteristics of the reconstituted whole blood •The reconstitution procedure must only be performed in Transfusion Services in a closed system, using appropriate formulae to obtain the desired Hct. •The product has the same metabolic and haemostatic characteristics as fresh whole blood but lacks platelets.
  • 21. Introduction to Exchange Transfusion •An exchange transfusion involves gradual removal of patient’s blood and simultaneous replacement with allogenic donor blood. •Besides hyperbilirubinemia, the use of ET has been extended in the management of •hydrops fetalis •congenital leukaemia •disseminated intravascular coagulation •severe neonatal sepsis •sclerema neonatorum •Hyperammonaemia •Polycythaemia •fluid and electrolyte imbalance
  • 22. The aim of ET is to: •Lower serum bilirubin level to reduce the risk of kernicterus (most common indication) in patients not responsive to phototherapy and/ or IVIG. •To remove infants affected red blood cells and circulating maternal antibodies to reduce red cell destruction, e.g., in HDFN. •To correct anaemia •Remove bacteria, bacterial toxins, and circulating pro-inflammatory cytokines (e.g., in sepsis)
  • 23. Exchange Transfusion for Hyperbilirubinemia •Exchange transfusion in neonates involves replacement of 1 or 2 whole-blood volumes. •The primary purpose of this therapy is to treat excessively high levels of unconjugated bilirubin (hyperbilirubinemia). •In high concentrations, bilirubin may cross the blood brain barrier; concentrates in the basal ganglia and cerebellum of preterm and full-term infants; and cause irreversible damage, known as “kernicterus,” to the central nervous system. • Phototherapy (use of fluorescent blue lights) is the current treatment of choice for hyperbilirubinemia; Exchange Transfusion is reserved for patients who fail phototherapy.
  • 24. Two critical objectives of exchange transfusions are- •the removal of unconjugated bilirubin •maximization of albumin binding of residual bilirubin. In addition, in antibody mediated hemolytic processes, exchange therapy removes both free antibody and antibody- coated red cells, replacing them with antigen-negative red cells.
  • 25. Kernicterus And Bilirubin •Exchange transfusion needs to be performed before the development of kernicterus. •In full-term infants, kernicterus develops at bilirubin levels >25 mg/dL. •However, in ill VLBW infants, kernicterus can occur at bilirubin levels as low as 8 to 12 mg/dL. OPHISTHOTONUS
  • 26. Volume And Hematocrit Considerations •A double-volume exchange in neonates necessitates the infusion of 2 volumes of approximate Blood volume of neonate. •The unit’s hematocrit should be approximately 45% to 60%, and the unit should have sufficient plasma (based on estimated blood volume) to provide clotting factors. •If the neonate’s condition requires a higher post exchange transfusion hematocrit, a small-volume RBC transfusion may be given or a unit with a higher hematocrit can be used for the initial exchange transfusion.
  • 27. Transfusion and Bilirubin •A double-volume exchange transfusion (two 85mL/kg transfusions for full-term infants and two 100-mL/kg transfusions for VLBW/preterm infants) removes approximately 70% to 90% of the circulating red cells and approximately 50% of the total bilirubin. •However, after the first exchange transfusion, bilirubin levels may rise again because of a re-equilibration of the extravascular tissue and plasma bilirubin, which may necessitate another exchange transfusion.
  • 28. Possible complications of ET Vascular- air emboli/thrombosis Cardiac- volume overload, cardiac arrest Electrolytes- hyperkalemia, hypocalcemia, acidosis Coagulation disorders- thrombocytopenia Infectious- bacteremia/CMV/Sepsis
  • 29. Hemolytic disease of the fetus and newborn •HDFN is the destruction of the red blood cells (RBCs) of a fetus/neonate by antibodies produced by the mother. •The mother can be stimulated to form RBC antibodies naturally (ABO), by previous pregnancy, or transfusion (RBC alloimmunization). •Incidence of the disease caused by anti-D has decreased since 1968 with the introduction of RhIG. •Despite the decrease in HDFN, RhD continues to remain an important cause of incompatibility.
  • 30. Antigens which can cross placenta •Rh(D) is the most potent immunogen, in that a 200-mL transfusion of Red Blood Cells (RBCs) stimulates anti-D in about 85% of D-negative individuals, except those who are immunosuppressed. •Unlike HDFN caused by anti-D, HDFN caused by anti-K uniquely results in destruction of fetal erythropoietic precursors in addition to hemolysis. •Other antibodies that have been less commonly reported to cause moderate or severe disease include E, k, Kpa, Kpb, Ku, Jsa, Jsb, Jka, Fya, Fyb, S, s, and U
  • 31. HDFN Haemolysis •Hemolysis occurs when the maternal antibody binds to a fetal red cell antigen, causing attachment to the Fc receptor of macrophages in the spleen of the fetus. •The rate of hemolysis and severity of disease are determined by the IgG subclass, amount of antibody, and number of antigenic sites on the red cells. •The subclasses IgG1 and IgG3 are more efficient in causing hemolysis than IgG2 or IgG4. •Transportation of IgG1 and IgG3 across the placenta is mediated by the Fc receptor beginning in the second trimester and continuing until birth.
  • 33. Screening and Dosing for RhIG •The risk of a D-negative mother becoming immunized by a D-positive fetus can be reduced from about 16% to less than 0.1% by the appropriate administration of RhIG. •Antepartum Administration-The American College of Obstetricians and Gynecologists (ACOG) recommends RhIG administration at 28 weeks’ gestation because 92% of women who develop anti-D during pregnancy do so at or after 28 weeks. •Postpartum Administration- Postpartum RhIG should be given to the mother within 72 hours of delivery.
  • 36. Current Practice •There is steep decline in the incidence of HDFN following the introduction of maternal anti-D Ig prophylaxis, more effective antenatal monitoring and treatment, and the use of intensive phototherapy and intravenous immunoglobulin postnatally has made red cell exchange transfusion an uncommon procedure that should only be performed by experienced staff.
  • 38.
  • 39.
  • 40.
  • 41. Take Home Message An early recognition and diagnosis is the first and most crucial step towards a successful treatment.
  • 42. References 1. https://www.transfusionguidelines.org/transfusion- handbook/10-effective-transfusion-in-paediatric- practice/10-2-neonatal-transfusion 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607607/ 3. Exchange transfusion in neonatal hyperbilirubinemia: A single Centre experience from Northern India https://pubmed.ncbi.nlm.nih.gov/31636029/ 4. DGHS Transfusion Medicine Technical Manual 3rd edn.November 2022 5. AABB Technical manual- 21st edition 2023 6. NACO guidelines- Division of Blood Transfusion Services Ministry of Health and Family Welfare 7. Rossi’s Principles of Transfusion Medicine, Edition 4