Alison Chan, DO, Grace Fortes Monis, MD PhD

The blood bank occasionally will receive requests for a transfusion exchange in a neonate with hyperbilirubinemia. Neonates with hyperbilirubinemia may necessitate hospital admissions with approximately 5-10% of all neonates needing medical intervention. Neonatal hyperbilirubinemia can be due to unconjugated or conjugated bilirubin, with the former being more important for early detection and treatment to prevent serious complications such as bilirubin-induced encephalopathy. Unconjugated bilirubin is insoluble in the body and is tightly bound to serum albumin. There is a small fraction of unbound unconjugated bilirubin that can diffuse into tissues such as the brain leading to toxicity. Conjugated bilirubin is nontoxic as it is water soluble and can be easily excreted from the body. Common causes of unconjugated hyperbilirubinemia include hemolytic disease of the newborn, G6PD deficiency, resorption of a cephalohematoma, breast-feeding jaundice, breast-milk jaundice, Gilbert syndrome, and many more. Phototherapy is commonly used to convert unconjugated bilirubin into the water soluble and excretable form and can reduce the need for exchange transfusions. In more severe cases and urgent cases of hyperbilirubinemia an exchange transfusion using reconstituted whole blood can be considered.

Reconstituted whole blood, also known as reconstituted red blood cells, refer to the combination of red blood cells and plasma to achieve a specific volume of a targeted hematocrit. The literature suggests that the use of reconstituted whole blood for the exchange transfusion is immunologically safer and better than using whole blood. The benefits of an exchange transfusion include removal of serum unconjugated (indirect) bilirubin, possible circulating mother antibodies, and any antibody-coated neonate red cells from the circulation. Other benefits of using reconstituted whole blood include providing compatible red cells to correct the associated anemia and albumin which can bind additional bilirubin to further decrease the serum levels of indirect bilirubin. Reconstituted whole blood can also be used in exchange transfusions of neonates with severe anemia.

At UC Davis Medical Center, the decision to perform an exchange transfusion is determined by the clinical team. Although there is no cutoff at which the total bilirubin levels must reach to consider an exchange transfusion, the clinical team considers factors such as risk factors for development of severe hyperbilirubinemia, how quickly they need to remove the bilirubin, whether the infant is symptomatic with moderate or advanced clinical signs of bilirubin-induced neurologic dysfunction, and whether intensive phototherapy has failed, when making their decision. Tools that can be used to help determine the appropriate medical intervention for treating unconjugated bilirubinemia include the BIND score and the newborn hyperbilirubinemia assessment calculator. The BIND score determines the presence and severity of acute bilirubin encephalopathy in infants with no other identifiable etiologies for neurologic dysfunction. The newborn hyperbilirubinemia assessment calculator uses the total bilirubin level and presence of additional risk factors to stratify the infant into different groups and their recommended course of treatment.

Once the request for a reconstituted whole blood exchange transfusion is made, the transfusion medicine team is notified and at which they work with the clinical team to coordinate timing of the procedure. As part of the work flow, a type and screen and direct antiglobulin test need to be done on the neonate’s and mother’s blood to help select the appropriate red cell unit for reconstitution. It is important to have the mother’s type and screen so that a red cell unit lacking the antigens to any possible antibodies that the mother may have passively transferred to her baby is prepared. The red blood cell unit will be a type O unit that is leukocyte reduced, CMV negative, sickle cell trait negative, irradiated, washed, and crossmatch compatible. The red blood cells are washed and concentrated to achieve a high hematocrit before combining it with the plasma. The washed red cells are sent to hematology where the hematocrit is checked. Type AB, CMV negative, irradiated plasma is thawed out for the reconstitution. The final reconstituted whole blood product has a typical target hematocrit of 40-50%. The entire workflow can take up to 3 hours to prepare the reconstituted whole blood unit, but sometimes can be faster. A key consideration for this request is the timing since in some cases, the neonates are being transferred in from an outside hospital. Additionally, once the whole blood is reconstituted, it only has a shelf life of 24 hours from when the RBC unit was washed. In the case the reconstituted whole blood unit is no longer needed, the product is wasted since whole blood is not transfused to general patients. Thus, the certainty of completing the exchange transfusion must be determined by the clinical team. It is recommended that the total bilirubin should be checked to help make the decision. If the bilirubin is down trending, a reconstituted whole blood unit may not be necessary.

Key Points

  • The clinical team makes the ultimate decision to perform a reconstituted whole blood exchange transfusion.
  • The entire workflow can take up to 3 hours to prepare the reconstituted whole blood unit.
  • The reconstituted unit will expire 24 hours from the date and time that the unit of RBCs is washed.


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