A Brief Review of Transfusion Practice in Sickle Cell Disease (SCD)
by Laurie J Sutor, MD, MBA
When to transfuse. Consensus recommendations support transfusion for the prevention and treatment of stroke in high-risk patients. There is also some evidence that transfusion is helpful in patients to treat acute chest syndrome and for splenic sequestration with anemia. However, transfusion has not shown to be helpful routinely for treatment of pain crises, priapism, acute renal failure, or in pregnant women. Transfusion may be used pre-operatively to bring the hemoglobin level to 10 g/dL prior to surgery involving anesthesia. Patients receiving chronic transfusion to prevent stroke should maintain a HbS level below 30%. Patients receiving infrequent transfusions should avoid surpassing a hemoglobin level of 10 g/dL or risk the hyperviscosity syndrome.
How closely to match the blood. Since these patients are at high risk for forming alloantibodies, there is much discussion on prophylactically matching antigens of the donor blood to the patient to prevent alloantibody formation. An NHLBI expert panel as well as the British Society of Haematology guidelines both recommend prophylactically matching for Rh (D, C, c, E, e) and Kell antigens. Other institutions try to match for all of the clinically significant antigens for which the patient could make antibodies. Which strategy the facility chooses is often based on the resources available to that institution. A very recent (2019) publication by Fasano et al in Transfusion Medicine Reviews, that looked at 303 different publications on red cell matching in SCD, found that none of the studies were prospective randomized controlled trials to compare different matching strategies and therefore, high quality evidence is lacking to scientifically make a recommendation one way or another. Low quality observational studies support extended matching to decrease the risk of alloimmunization.
When to use molecular genotyping. Any patient who is at high risk for having serological problems should have a complete red cell phenotype done, and the sickle cell patient certainly falls into this category with so many forming multiple red cell alloantibodies. Up to one third or more of sickle cell patients make alloantibodies after transfusion. Serological testing, while readily available, is labor intensive and somewhat subjective in its interpretation. Molecular red cell typing provides the advantage of providing a panel of a larger number of red blood cell antigens screened for at one time. The one used at our facility looks for 29 polymorphisms-predicting 37 phenotypes, representing 10 red blood cell groups. Molecular typing also works in patients recently transfused, those with positive direct antiglobulin tests, and for others with complex serological problems. It is also advantageous when commercial serologic reagents are not available for certain red cell antigens. Casas et al showed improved accuracy of red cell typing when DNA methods were used (see references). Fasano’s review of the literature mentioned above did not find any randomized controlled trials to compare the use of molecular genotyping and serological testing on rates of alloimmunization or cost.
When to do simple transfusion vs. red cell exchange. The advantage of red cell exchange (virtually always by apheresis technology) is that the sickle cells can be removed and normal cells supplied without significantly increasing the hemoglobin and increasing the viscosity of the blood. In addition, in these patients who often require multiple, chronic transfusions, iron can be removed through exchange transfusion-decreasing the dangerous accumulation that can be seen with life-long transfusion. On the other hand, exchange transfusion requires more expensive resources which are not available at all hospitals and clinics, and also can result in the need for more matched units and increased donor exposures. In general, red cell exchange should be performed in sickle cell patients needing chronic transfusion whenever possible, as the advantages outweigh the disadvantages if this option is available.
What are the different types of red cell exchange? Few facilities perform manual red cell exchange these days, so the choices are really between traditional automated red cell exchange and isovolemic hemodilution followed by automated red cell exchange. At least one apheresis instrument currently on the market has a program designed to perform the hemodilution type of red cell exchange without manual intervention. The advantages of the isovolemic hemodilution type of procedure are that it can increase the interval between exchange procedures (from approximately 4-5 weeks to 6-8 weeks) and requires less units of red cells per treatment. It also may improve iron removal over traditional red cell exchange. It does this by removing some of the patient’s blood and replacing it with normal saline prior to the start of the red cell exchange. It is recommended that patients undergo traditional red cell exchange at least once to demonstrate they can tolerate an apheresis procedure, before proceeding to hemodilution.
References:
Yawn BP, Buchanan GR, Afenyi-Annan AN et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members.
JAMA 2014; 312(10):1033-48.
Davis BA, Allard S, Qureshi A et al. Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects. Br J Haematol 2017;
176:179-91.
Vichinsky EP, Earles A, Johnson RA et al. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med 1990; 322:1617-21.
Fasano RM, Meyer EK, Branscomb J, White MS, Gibson RW, Eckman JR. Impact of red blood cell antigen matching on alloimmunization and transfusion
complications in patients with sickle cell disease: a systematic review. Trans Med Rev 2019; 33:12-23.
Danielson CFM. The role of red blood cell exchange transfusion in the treatment and prevention of complications of sickle cell disease. Ther Apher 2002;
6(1):24-31.
Casas J, Friedman DF, Jackson T et al. Changing practice: red cell typing by molecular methods for patients with sickle cell disease. Transfusion 2015;
55(6):1388-93.
Feldman A, Siniard R, Staley E et al. Cost savings with isovolemic hemodilution red cell exchange in sickle cell disease patients: a single center experience.
Am J Clin Pathol 2016; 146:327.
Sarode R, Matevosyan K, Rogers ZR et al. Advantages of isovolemic hemodilution-red cell exchange therapy to prevent recurrent stroke in sickle cell anemia
patients. J Clin Apher 2011; 26(4):200-7.