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Red cell transfusion and alloimmunization in SCD
Table 1. Summary of indications for transfusion therapy in patients with sickle cell disease.
Indication
Transient aplastic crisis
Acute multisystem organ failure
Acute hepatic sequestration
Acute splenic sequestration
Acute splenic sequestration, recurrent Acute ischemic stroke
Primary stroke prevention Secondary stroke prevention Moderate acute chest Severe acute chest
Acute chest, recurrent
Preoperative with > 1 hour with general anesthesia Pregnancy with complications
Pregnancy, uncomplicated
Prior to hematopoietic stem cell transplant Uncomplicated vaso-occlusive episode
Priapism
Leg ulcers
Avascular necrosis
Transfusion method
Simple
Simple or exchange*
Simple or exchange
Simple via small volume aliquots of 3-5 mL/kg
Simple as a bridge to splenectomy
Exchange > simple
Simple or exchange
Simple or exchange
Simple or exchange
Exchange
Simple or exchange
Simple or exchange
Simple or exchange
Simple or exchange
Simple or exchange
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Level of support
Expert consensus
Expert consensus
Expert consensus
Expert consensus
Expert consensus Observational studies; expert consensus Randomized clinical trial
Randomized clinical trial
Expert consensus
Expert consensus
Hydroxyurea preferable
Randomized clinical trial
Expert consensus
Under investigation
Under investigation
Transfusion not recommended
Transfusion not recommended
Transfusion not recommended
Transfusion not recommended
*The British Committee for Standards in Haematology recommend exchange transfusion for acute multisystem organ failure. Red cell exchange may be preferred for severe, acute multisystem organ failure.
high-risk transcranial Doppler findings or overt stroke in contrast to none of the children in the continued-transfu- sion arm. Discontinuing transfusions in the STOP II trial was also associated with higher occurrence of silent cere- bral infarcts.19
More recently, the Transcranial Doppler with Transfusions Changing to Hydroxyurea (TWiTCH) trial explored transitioning patients with abnormal transcra- nial Doppler findings but no severe vasculopathy and at least 1 year of chronic transfusions to hydroxyurea versus continuation of chronic transfusions.20 Neither treatment group developed new stroke or evidence of new cerebral infarcts on magnetic resonance imaging, and hydrox- yurea therapy at maximum tolerated dose was deter- mined to be non-inferior to standard transfusions. Hydroxyurea can be considered as an alternative therapy for selected patients on chronic transfusion for primary stroke prevention.
The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) study was a multicenter ran- domized trial comparing transfusions plus chelation to hydroxyurea and phlebotomy in pediatric patients with a history of stroke and iron overload.21 The primary com- posite endpoint of the study included quantitative liver iron content and stroke recurrence rate. The study closed early after interim analysis indicated that liver iron con- tent was not significantly different between groups. Importantly, although within the range of the study’s non-inferiority margin, there was an imbalance of seven strokes in the hydroxyurea arm compared to no strokes in the subjects receiving transfusions.
Silent cerebral infarcts are common in children with SCD and are associated with cognitive deficits and poor educa- tional attainment.22 A history of silent cerebral infarcts pre- dicts an increased risk of recurrent infarct, in the form of both other silent cerebral infarct and overt stroke.23,24 The
Silent Infarct Transfusion trial showed that chronic transfu- sion therapy reduced the incidence of recurrent cerebral infarction in children with SCD.25 However, this study did not compare the efficacy of hydroxyurea to chronic trans- fusion, so implementation of chronic transfusion for patients with silent cerebral infarcts has not been robust given the availability of hydroxyurea and the burdens of chronic transfusion therapy.
Erythrocytapheresis is the preferred transfusion modal- ity for acute stroke given its ability to decrease HbS levels rapidly while limiting effects on serum viscosity. In set- tings of both acute cerebral ischemia and stroke preven- tion, maintenance of HbS level ≤30% has been the stan- dard of care.26
Acute chest syndrome
Acute chest syndrome (ACS) is one of the most com- mon complications of SCD and is a leading cause of hos- pitalization and death.27 ACS is defined as a new pul- monary infiltrate on chest radiograph in the presence of respiratory symptoms, hypoxia, chest pain, or fever. Episodes can be triggered by infection, fat embolism, atelectasis, and infarction.27 The clinical course and spec- trum of the disease are variable. While studies defining standardized criteria to assess ACS severity are lacking, patients with significant hypoxia or rapidly declining hemoglobin are considered to have severe disease.2
Simple transfusion provided early in the course of mod- erate ACS often prevents progression of the disease and the need for RCE.28-31 The ASH 2020 guidelines recog- nized the paucity of large-scale studies but suggest RCE over simple transfusion for patients with severe ACS, rap- idly progressive ACS, or ACS in patients with high base- line hemoglobin.2
Recurrent episodes of ACS can lead to chronic lung dis- ease including pulmonary hypertension and fibrosis.
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