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856 Part VI: The Erythrocyte Chapter 55: Alloimmune Hemolytic Disease of the Fetus and Newborn 857

double-volume exchange depends on the total blood volume (TBV) unavailable, some centers wash the RBCs and transfuse as soon as pos-
recognizing differences in term and preterm infants: sible after washing to avoid hyperkalemia. Additionally, the RBC units
• Double-blood-volume exchange volume (term) = 85 mL/kg × 2, or should be leukoreduced, gamma irradiated, and sickle-negative. 113
170 mL/kg Potential complications of exchange transfusion include hypoc-
• Double-blood-volume exchange volume (preterm) = 100 mL/kg × 2, alcemia, hyperglycemia, hypoglycemia, thrombocytopenia, dilutional
coagulopathy, neutropenia, disseminated intravascular coagulation,
or 200 mL/kg umbilical venous and/or arterial thrombosis, necrotizing enterocolitis,
To perform the exchange transfusion, aliquots of the reconsti- and infection. Thrombocytopenia and hypocalcemia are reported to be
tuted whole blood product are administered while equal amounts of the most common complications (incidence ranging from 29 to 47 per-
the infant’s blood are withdrawn. Careful attention not to exceed 2 mL/ cent). 114,115 Thrombocytopenia results from a dilutional effect of replac-
kg per minute (continuous) or 5 mL/kg at a time over 3 to 10 minutes ing platelet rich neonatal WB with platelet-deficient reconstituted WB.
(discontinuous technique) is required to prevent rapid fluctuations in Infants who may be thrombocytopenic from severe HDFN or other
arterial and intracranial pressure. 108 comorbidities should be monitored closely after an exchange transfu-
The indications for “early” exchange transfusions performed sion as they may require platelet transfusion. Hypocalcemia occurs as
within the first 12 hours of life have remained essentially unchanged a result of the citrate load infused, which an immature neonatal liver
over the last 45 years, with minor modifications. Cord hemoglobin has difficulties metabolizing. In anticipation of hypocalcemia, ionized
levels equal to or less than 11 g/dL, cord bilirubin levels equal to or calcium levels should be monitored throughout the exchange transfu-
greater than 5.5 mg/dL, and rapidly rising total serum bilirubin (TSB) sion procedure, and intravenous calcium replacement may be needed in
equal to or greater than 0.5 mg/dL per hour despite phototherapy are sick preterm infants. Furthermore, attempts should be made to correct
commonly used criteria for early exchange transfusions. Early exchange conditions that may potentiate the symptoms of hypocalcemia such as
transfusion has the advantage of replacing sensitized RBCs with normal alkalosis, hypothermia, hypomagnesemia, and hyperkalemia. 116
RBCs, thereby removing not only bilirubin but also the source of future In a retrospective review of exchange transfusions performed in
bilirubin. Because bilirubin is distributed in the extracellular fluids, two neonatal intensive care units between 1981 and 1995, the risk of
efficiency is enhanced by removing sensitized cells early in the process. death or permanent serious sequelae was reported to be as high as 12
Newborns that have been treated with serial IUTs until term often do percent in sick infants, compared with less than 1 percent in healthy
not require exchange transfusions; however, late anemia is common infants. Adverse outcomes were more frequent in exchanges done on
because of IUT-induced erythropoietic suppression, which may last for preterm infants younger than 32 weeks, infants with other significant
many weeks after delivery. 109 comorbidities, and when umbilical catheters were used rather than
“Late” exchange transfusions are performed when serum biliru- other means of central venous access. Another center reported no
117
bin levels threaten to exceed approximately 20 to 22 mg/dL in term increase in the number of complications and no exchange transfusion–
infants. The American Academy of Pediatrics (AAP) Subcommittee on related deaths over a 21-year period, even though there was a decline
Hyperbilirubinemia provided revised guidelines for exchange transfu- in the frequency of exchange transfusions performed over the years.
115
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sion in infants 35 or more weeks’ gestation. In view of the fact that Careful clinical judgment is required to balance the potential risk of
bilirubin levels rise steadily from birth and peak at approximately 72 adverse events from exchange transfusion with the risk of bilirubin
to 96 hours of age, exchange transfusion should be considered if serum encephalopathy in neonates who are premature, sick, or both.
bilirubin levels reach 15 mg/dL in an infant of 35 weeks’ gestation or
17 mg/dL in an infant of 38 weeks’ gestation despite intensive photo- Phototherapy
therapy. Immediate exchange transfusion is recommended in infants Phototherapy is the mainstay of treatment for unconjugated hyperbiliru-
showing signs of acute bilirubin encephalopathy, even if bilirubin levels binemia; the objective of treatment is preventing bilirubin neurotoxicity.
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are falling. Conjugated or direct bilirubin values are not subtracted Exposure of bilirubin to light results in structural and configurational
from total bilirubin levels when considering levels for exchange trans- isomerization of bilirubin to less toxic and less lipophilic products that
fusions. Exchange transfusions are performed at lower bilirubin levels are excreted efficiently without hepatic conjugation. The effectiveness
in premature infants, particularly those with hypoxemia, acidosis, and of phototherapy is influenced by the wavelength and irradiance of light,
hypothermia, but little data are available to guide intervention in these the surface area of exposed skin, and the duration of exposure. Intensive
infants. In infants with birth weights of at least 1500 g, exchange trans- phototherapy involves the use of high levels of irradiance (≥30 μW/cm )
2
fusions usually are performed at TSB of 13 to 16 mg/dL but may be con- in the 430- to 490-nm band, delivered to as much of the infant’s surface
sidered even at levels as low as 8 to 9 mg/dL in sick babies of 24 weeks’ area as possible. Intensive phototherapy effectively reduces bilirubin
gestation. The bilirubin-to-albumin ratio (mg/dL:g/dL), considered levels and decreases the need for exchange transfusions for hyperbiliru-
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to be a surrogate measure of free bilirubin, may provide additional data binemia in ABO and Rh HDN. 118,119 Early and intensive phototherapy
in determining the need for exchange transfusion in both term and pre- should be initiated in infants with moderate or severe hemolysis or in
term neonates. 112 infants with rapidly rising bilirubin levels (>0.5 mg/dL per hour). In
Blood components chosen for the exchange transfusion should be full-term infants (at least 38 weeks’ gestation) with HDFN, intensive
ABO and Rh compatible (Rh-negative in Rh HDN), negative for offend- phototherapy should be initiated if TSB levels are 5 mg/dL or greater at
ing antibody(ies), and crossmatch compatible with maternal serum. In birth, 10 mg/dL at 24 hours after birth, or approximately 13 to 15 mg/dL
the case of ABO HDN, O RBCs should be chosen for exchange out of at 48 to 72 hours after birth. Phototherapy is recommended at lower
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concern that the more developed A or B antigens on any transfused levels for preterm or sick infants. Therapy often is initiated at TSB less
adult donor RBCs may more avidly bind maternal anti-A or anti-B and than 5 mg/dL in preterm infants with HDFN so as to avoid potentially
may result in hemolysis. Either reconstituted whole blood (WB) (e.g., risky exchange transfusions. 110,111
RBCs plus fresh-frozen plasma [FFP]) or stored WB if available can be
used for neonatal exchange transfusions. The RBCs are reconstituted Other Therapies
with AB or compatible plasma to a final hematocrit of 50 to 60 per- A number of small studies have reported on the successful administra-
cent. Fresh (<7 days) RBCs should be used. When fresh RBC units are tion of high-dose IVIG as an adjuvant treatment to standard therapy

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