Children with Sickle Cell Disease on Chronic Red Cell Transfusion Experience Fewer Hospitalizations for Acute Vaso-Occlusive Episodes Irrespective of the Indication for Transfusion

While there is strong evidence that chronic red cell transfusion is effective in preventing primary stroke and reducing the risk of recurrent stroke in sickle cell disease (SCD), it is less clear whether chronic transfusions will prevent admissions for other acute vaso-occlusive complications, including pain, priapism and/or acute chest syndrome. To our knowledge, no study to date has investigated the effect of chronic transfusion on the frequency of admissions for acute vaso-occlusive complications in children with all diagnoses of SCD and treated with chronic transfusion for a variety of indications. In addition, this study included a special focus on the effect of chronic transfusion on children who were transfused specifically for recurrent vaso-occlusive episodes.

We performed a single-site retrospective chart review. We selected subjects from all children aged 0 to 19 years who were treated (lived in the Milwaukee area) and followed by the Wisconsin Sickle Cell Center at Children’s Hospital of Wisconsin from 1984 to May 2014 (n=695 subjects). Data was extracted from any individual who was enrolled in a chronic transfusion program for a minimum of six months. Data on admissions for painful vaso-occlusive crises, acute chest syndrome (ACS), other SCD complications as well as sickle diagnosis, age at time of transfusion, CBC, reticulocyte count, and percent sickle hemoglobin (HbS%) were collected for 24 months prior to onset of transfusion and for all months during transfusion until the age of 19 yrs. Unless otherwise indicated, all statistical analyses on extracted data were done by paired Student’s t-Test.

We extracted data from 103 unique subjects for 108 chronic transfusion programs (as defined above); 5 subjects were chronically transfused twice, separated by at least 4 years without chronic transfusion. 55% were female; average age was 8.6 ± 5.6 (mean ± SD) years and the sickle diagnosis included 94% SS, 3% SC, 2% Sβ°-Thalassemia and 1% SD. The indication for transfusion included pain (n=31), priapism (n=6), ACS (n=5), central nervous system complications (n=37, including stroke, TIA, and abnormal TCD), splenic sequestration (n=25), pulmonary hypertension (n=2), retinopathy (n=1) and osteomyelitis (n=1). The hemoglobin level increased from a baseline of 7.6 ± 2.2 gm/dL to 9.6 ± 0.8 gm/dL during transfusion (p<0.0001, paired t-Test). HbS% was also reduced from a baseline of 84.2 ± 10.8% to 35.8 ± 0.3% during transfusion (p<0.0001). We found that rate of admissions for acute painful episodes, including priapism, dropped from 2.2 ± 2.9 admits/yr during the 24 months pre-transfusion to 1.0 ± 1.9 admits/yr during transfusion (p<0.0001). Similarly, the rate of admission for ACS decreased from 0.3 ± 0.5 admits/yr for 24 months pre-transfusion to 0.1 ± 0.3 admits/yr during transfusion (p=0.0001).

Subanalyses were performed on specific indications for transfusion. For children transfused due to frequent acute vaso-occlusive complications (pain, priapism and ACS were arbitrarily included in this group), the average age at initiation of transfusion was 11.9 ± 4.4 yr, and admissions for acute painful episodes dropped from 4.0 ± 3.2 admits/yr during the 24 months pre-transfusion to 2.1 ± 2.6 admits/yr during transfusion (p=0.003). When the indication for transfusion was splenic sequestration (age 2.3±2.7 yr), the admission rate for acute painful episodes did not change (0.8±1.7 vs 0.3±0.5 admits/yr, p= 0.14). For children transfused for CNS complications (age 8.5±4.6 yr), the admission rate for pain improved from 0.9±1.3 to 0.2±0.5 admissions/yr (p=0.007).

In agreement with previous studies, our data also showed an increase in the rate of admissions for pain (nontransfused) as subjects aged (r²=0.19, p<0.0001). Thus, the significant improvement in admission rate for pain during transfusion, while the child continues to age, further accentuates the impact of transfusion on the natural history of pain in SCD.

In summary, our data suggest that chronic transfusion reduces hospital admissions for pain and acute chest syndrome in children with SCD. Our data also support the notion that chronic transfusion is an effective treatment to prevent not only stroke, but also other painful, life-threatening and life-limiting complications of sickle cell disease.