clinical topic updates

Safely Transfusing Patients With Sickle Cell Disease

by Stella T. Chou, MD

Overview

Red blood cell transfusions in sickle cell disease (SCD) may be used acutely to treat life-threatening complications or chronically as prophylaxis for first or recurrent ischemic stroke in patients at high risk. The judicious use of transfusion therapy is essential, and the recognition of transfusion risks such as delayed hemolytic transfusion reaction (DHTR) is key to transfusion safety.

Expert Commentary

Stella T. Chou, MD

Attending Physician, Division of Hematology and the Apheresis Program
Children’s Hospital of Philadelphia
Associate Professor, Department of Pediatrics
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

“Patients admitted for vaso-occlusive pain may have a decrease in hemoglobin levels, but we need to be judicious about transfusing these patients at a time when they are in a higher inflammatory state than at baseline, which seems to increase their risk of alloimmunization and DHTR.”

Stella T. Chou, MD

Red blood cell transfusion is often used in the inpatient setting for acute complications of SCD, including parvovirus infection, acute chest syndrome requiring respiratory support, and splenic sequestration. Importantly, transfusion is not indicated for uncomplicated vaso-occlusive pain episodes. Patients admitted for vaso-occlusive pain may have a decrease in hemoglobin levels, but we need to be judicious about transfusing these patients at a time when they are in a higher inflammatory state than at baseline, which seems to increase their risk of alloimmunization and DHTR. Chronic transfusion therapy in the outpatient setting is initiated in patients at high risk of ischemic stroke by abnormal transcranial Doppler screenings or a history of stroke. These patients typically receive transfusions every 3 to 5 weeks to reduce their risk of stroke, with a typical goal of maintaining their hemoglobin S level below 30%. Whether transfusion is acutely or chronically indicated, a major concern is alloimmunization and DHTRs; thus, we all need to be judicious with red blood cell therapy.

All patients with SCD should be transfused with red blood cells matched for Rh (C, E, or C/c, E/e) and K, in addition to ABO and RhD. Despite prophylactic antigen matching, patients still form antibodies to their transfused red blood cells, particularly against Rh antigens. A DHTR should be considered in those who present with pain and a significant drop in hemoglobin; typically, this occurs within 21 days of a transfusion with signs and symptoms of hemolysis, including fatigue from exacerbated anemia. We evaluate for an accelerated hemoglobin S percentage increase with a concomitant fall in hemoglobin A percentage by hemoglobin quantification, and we check for an elevation in lactate dehydrogenase and unconjugated bilirubin levels from the patient’s baseline. A transfusion reaction panel should be sent to the blood bank and will include screening for any newly formed antibodies. We avoid further transfusion if possible, and, if transfusion is necessary, we provide red blood cells lacking the offending antigen in addition to Rh and K matching. Recent guidelines from the American Society of Hematology note that acute and delayed HTRs are among the most concerning complications of transfusion support. The guidelines provide guidance on the management of severe HTRs and the prevention of HTRs in high-risk patients using immunosuppressive agents, including steroids, intravenous immunoglobulin, rituximab, and eculizumab.  

Another way to minimize transfusion risk is to reduce the need for transfusions. The practice of administering hydroxyurea to children aged 9 months and older has led to a significant decline in abnormal transcranial Dopplers in early childhood and a corresponding decrease in those requiring chronic transfusions. Evidence from the 2016 TWiTCH trial showed that a subset of patients with SCD can be safely transitioned to hydroxyurea for primary stroke prevention after 1 year of transfusion therapy. Although transfusions are required to manage the acute complications of SCD or to provide support during stem cell transplantation, I am optimistic that some of the recently approved agents and those that are still in clinical development will also decrease the need for transfusions in the future.

References

Chou ST, Alsawas M, Fasano RM, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327-355.

Chou ST, Liem RI, Thompson AA. Challenges of alloimmunization in patients with haemoglobinopathies. Br J Haematol. 2012;159(4):394-404.

Pirenne F, Yazdanbakhsh K. How I safely transfuse patients with sickle-cell disease and manage delayed hemolytic transfusion reactions. Blood. 2018;131(25):2773-2781.

Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016;387(10019):661-670.

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