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G.E. Linder and S.T. Chou
transfusion is convenient, requires one point of peripheral venous access, and utilizes fewer red cell units. Additionally, simple transfusion does not require special- ized personnel or devices. Drawbacks of simple transfu- sion include risks of volume overload and hyperviscosity. Simple transfusion invariably leads to iron overload over time, necessitating treatment with iron chelation or alter- ation in transfusion modality.
Red cell exchange (RCE) procedures involve removal of the patient’s red cells and replacement with cells from the donor. RCE can be provided via automated (erythrocyta- pheresis) or manual methods. Manual RCE is performed using a series of repeated phlebotomies and transfusions, is time-consuming, and provides less consistent control of fluid balance during the procedure.8 Erythrocytapheresis requires apheresis machines and operators with technical expertise and may only be available at specialty centers. Since RCE typically replaces one or two times the patient’s total red cell volume, a higher volume of replace- ment cells is required. Despite increased exposure to donors with RCE compared to simple transfusion, several studies have shown no increase in alloimmunization rates associated with RCE.9,10 Limited studies indicate that RCE is cost-effective and may decrease hospitalization rates.8,11 Red cell replacement volume and hematocrit can be tight- ly controlled with RCE, allowing for significant reduc- tions in HbS levels, while minimizing or preventing iron loading.12
Erythrocytapheresis requires draw and return lines. Venous access must allow a steady flow of blood and withstand the high negative pressures of the draw line. Most adult patients have an adequate peripheral venous access to support RCE, but smaller pediatric patients often require central venous access. Indwelling catheters incur additional risks of infection and thromboembolic events.13
RCE can be further modified to include isovolemic hemodilution, a process that includes initial removal of the patient’s red cells and replacement with normal saline or albumin followed by RCE. RCE with isovolemic hemodilution is not recommended in patients with recent or severe cerebrovascular or cardiopulmonary disease. Potential benefits of isovolemic hemodilution include improved efficiency of RCE, reduced number of red cell units per exchange, and decreased procedure frequency, however a recent meta-analysis found little evidence to support the use of RCE with isovolemic hemodilution over RCE without isovolemic hemodilution.2
RCE is recommended over simple transfusion for acute ischemic stroke, severe acute chest syndrome, for patients with high baseline hematocrits requiring transfu- sion, and for chronically transfused patients with signifi- cant iron overload. Guidelines published by the American Society of Hematology (ASH) suggest using automated RCE in all patients with SCD receiving chronic transfu- sion therapy; however, individualized decisions for patients should consider availability of compatible red cell units and venous access.2
General transfusion considerations
Prior to transfusion, an extended red cell antigen pro- file, including typing for C/c, E/e, K/k, Fya/Fyb, Jka/Jkb, M/N, and S/s, should be obtained for all patients with
SCD.2 An antigen profile performed by genotyping is pre- ferred, as it provides increased accuracy for C and Fyb antigen expression in this population.2 Serological pheno- typing may be inaccurate if the patient has been trans- fused in the preceding 3 months. Extended red cell anti- gen profiles guide antigen matching and evaluation of positive antibody screens.
It is critical to obtain a patient’s antibody history from all hospitals that provided prior transfusions. The majori- ty of antibodies are not detectable 6 to 12 months after initial identification.14,15 Knowledge of antibody history is necessary to avoid re-exposure to implicated antigens and reduce risk of hemolytic transfusion reactions.
Leukocyte reduction decreases the transmission of cytomegalovirus as well as the occurrence of HLA alloim- munization and febrile non-hemolytic transfusion reac- tions and is standard practice at most transfusion services treating patients with SCD.16 Irradiation prevents transfu- sion-associated graft-versus-host disease and is required for patients undergoing hematopoietic stem cell trans- plantation.16 Patients with SCD should receive transfu- sions negative for sickle cell trait. This aids accurate mon- itoring of post-transfusion HbS levels, a parameter uti- lized in chronic exchange programs and when assessing possible delayed hemolytic transfusion reactions (DHTR).1
Indications for transfusion in sickle cell disease
Transfusions are a key component of managing SCD- associated complications (Table 1). Patients can experi- ence acute exacerbations of anemia due to parvovirus- induced red cell aplasia, splenic and hepatic sequestra- tion, and vaso-occlusive episodes. Transfusion therapy should be based on symptomatic anemia and hemody- namic compromise rather than hemoglobin value.1 Transfusion is also utilized to decrease the HbS level rap- idly in patients experiencing stroke, acute chest syndrome (ACS), and multiorgan failure. The benefit of transfusion has not been well studied for pulmonary hypertension, priapism, and leg ulcers. Transfusion is not indicated for uncomplicated vaso-occlusive episodes.
Neurological complications
Cerebrovascular accidents are a significant source of morbidity and mortality in patients with SCD. Prior to implementation of routine screening, between 4-11% of patients experienced a stroke within the first two decades of life, and, without further therapy, two-thirds of patients developed recurrent stroke within 36 months.17,18 The landmark Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) identified children at high risk of stroke using transcranial Doppler to detect elevated internal carotid or middle cerebral artery blood flow velocity.6 Among a randomized cohort of 130 patients, those receiving chronic transfusion therapy had a 92% lower risk of stroke than those in the standard-of- care arm. In the STOP II study, children whose transcra- nial Doppler findings had normalized after receiving transfusion therapy for 30 months were randomized to continue or stop chronic transfusion therapy.7 The study was terminated early after a significant proportion of the children who stopped receiving transfusions developed
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haematologica | 2021; 106(7)