Transfusion medicine
Therapeutic apheresis
Red blood cell exchange

Topic Completed: 1 January 2014

Minor changes: 24 February 2021

Copyright: 2002-2021,, Inc.

PubMed Search: Erythrocytapheresis "loattrfree full text"[sb]

Huy Phu Pham, M.D., M.P.H.
Garrett S. Booth, M.D., M.S.
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Cite this page: Pham HP, Booth GS Red blood cell exchange. website. Accessed April 19th, 2021.
Definition / general
  • Red blood cell (RBC) exchange and erythrocytapheresis:
    • The process of removing RBCs from a patient and exchanging with replacement fluids, most commonly allogeneic donor RBCs
    • When the replacement fluid is saline or albumin, the procedure is called erythrocytapheresis
    • Both RBC exchange and therapeutic erythrocytapheresis can be performed on an automated device or manually
  • High performance liquid chromatography (HPLC):
    • Analytic chemistry instrument used to separate and quantify components
  • Hemoglobin S (HgbS):
    • Using HPLC, the percentage of cells that are hemoglobin S can be identified
    • This percentage is used in the fraction of cell remaining (FCR) calculation
    • Without an accurate HgbS percentage in an emergent clinical situation, estimates of 95 - 100% HbgS can be used when calculating the FCR, assuming that the patient has not been transfused in the past 3 months
  • FCR - Fraction of cells remaining:
    • A calculation derived from the following mathematical formula:
      • FCR = desired percentage of cells at conclusion of procedure/actual percentage of cells now
    • The typical goal in patients with sickle cell disease is a HgbS percentage of 30% or less
      • Example: target end point of 30% HbS RBCs/100% HbS at beginning = FCR of 30%
  • Sickle cell disease (HgbSS, HgbSC, HgbS/Thal):
    • Affects nearly 100,000 patients in the U.S., with an incidence of approximately 1 in 500 African American births and 1 in 36,000 Hispanic American births
    • The sickle cell trait (HgbSA) frequency is ~1/10
  • Babesia:
    • A tick borne parasite that can be found in the Northeast and upper Midwest U.S.
  • Hereditary hemochromatosis (HH):
    • A genetic defect found most frequently in individuals of Northern European heritage, with historical rates of nearly 5% in Utah
Vascular access
  • Automated RBC exchange can be performed either with peripheral IV access or with a central venous catheter (CVC)
  • For patients undergoing chronic transfusion support, often a CVC is used to ensure adequate venous access
  • For emergent procedure although there is an increased risk of infection, femoral catheter can be used because it can be relatively easy to place
  • The American Society for Apheresis (ASFA) delineates RBC exchange indications by the acuity of the clinical situation
  • For acute cases:
    • Stroke - Category I
    • Acute chest syndrome - Category II
    • Priapism - Category III
    • Multiorgan failure - Category III
    • Splenic sequestration - Category III
  • For chronic RBC exchange, the ASFA categories are:
    • Stroke prophylaxis - Category II
    • Vaso-occulsive crisis - Category III
    • Preoperative management - Category III
Adverse events
  • Exposure to blood products always carries an infectious and noninfectious complication rate (see discussion in the Transfusion transmitted disease section)
  • However, with the additional number of RBC units needed in an exchange, there are additional concerns for minor RBC antigen alloimmunization, hypocalcemia reactions secondary to excess citrate exposure from the allogeneic blood products as well as hypothermia due to the refrigerated products
  • Insertion of CVC also carries risk
Clinical features
  • ASFA guidelines can be broken down by acute indications and nonacute / chronic ASFA recommendations
  • The diagnosis of sickle cell disease is made by HPLC and hemoglobin electrophoresis
  • The diagnosis of babesiosis is made by combination of travel history and laboratory evidence of hemolysis and the presence of intracellular parasites
  • The diagnosis of hereditary hemochromatosis is made by combination of medical and family history as well as laboratory evidence of iron overload and molecular analysis HfE gene mutation C282Y
  • Laboratory assessment both pre-RBC and post-RBC exchange is critical
  • In order to determine the volume of RBCs used in an exchange procedure, the current HgbS percentage needs to be identified via HPLC
  • Alternatively, if the hemoglobin solubility testing (Sickledex test) is negative, then the HgbS percentage must be less than 20%
  • Using the HPLC result the FCR can be calculated
  • The end hemoglobin level (or HCT) must also be relayed during a procedure; thus, a complete blood count needs to be performed
  • For emergent RBC exchange procedures, it is critical to lower the HgbS percentage to < 30% to lessen the risk of stroke
  • Confirmation of the exchange goals can be assessed by CBC / HPLC approximately 30 - 60 minutes following the procedure
  • The end HCT should be < 36% to avoid any potential hyperviscosity; typically, it is 30%
  • Depending on which anticoagulant preservative solution is used, the HCT of the RBC replacement fluid differs
    • i.e. the HCT of RBCs stored in CPD, CP2D and CPDA-1 is ~75% compared to 60% for RBCs stored in additive solution (AS)
    • The apheresis machine will calculate the volume of RBC replacement fluid based on patient's data (height and weight), replacement RBCs HCT, initial and end HCT and the desired FCR of the procedure
  • Red blood cell units used during the exchange should be ABO / Rh compatibile
  • Additionally, minor RBC antigen matching for the RhCE and Kell antigens has proven to reduce alloimmunization
  • However, extended phenotype matching has not been demonstrated to be cost effective based on a recent Markov model simulation
Radiology description
  • Only needed in acute chest syndrome diagnosis
  • Xray confirmation of CVC should be performed if an IJ or subclavian line is used
  • Babesiosis:
    • Although the main therapy is antibiotics, RBC exchange is used to lower the level of parasitemia rapidly
    • Typically, it is performed in patients with parasitemia > 10%
    • 2 BV exchange can be done to reduce the parasitemia to 10 - 15% of the preprocedural level
    • The decision to repeat the procedure depends on the patient's condition
    • Similar rationale for performing RBC exchange in patients with severe malaria with a parasitemia > 10% has been suggested; however, from a recent meta-analysis, the CDC no longer recommends this procedure
  • Sickle cell disease:
    • In acute complications, such as stroke, acute chest or multiorgan failure, RBC exchange is preferred over simple transfusion because it can rapidly lower HgbS percentage without increasing blood viscosity and volume overload
    • Typically, 1 BC exchange can achieve the goal of HgbS < 30%
    • For patients receiving chronic exchange, it is typically performed every 6 - 8 weeks to maintain the HgbS between 30 - 50%
    • Long term chronic exchange transfusion is advantageous over simple transfusion by reducing iron overload; however, it has more risk of blood product exposure
    • To date, no evidence supports one method of chronic transfusion over the other
  • Hemochromatosis:
    • Erythrocytaphersis can be used to remove excess iron in patients with hereditary hemochromatosis
    • Each erythrocytapheresis removes 2 - 3 times the iron and RBCs removed by simple phlebotomy
    • It can be performed every 2 - 3 weeks until the ferritin level < 50 ng/dL
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