Chronic pain persists in adults with sickle cell disease despite regular red cell transfusions.

BACKGROUND: Pain affects over 50% of adults with sickle cell disease (SCD), and this pain is largely managed outside of the hospital. While chronic transfusion therapy is used to decrease the rate of acute pain events in patients with SCD, less is known about its impact on the day-to-day experience of pain. To address this knowledge gap, we provided pain diaries to patients with SCD receiving chronic transfusion. PATIENTS AND METHODS: A convenience sample of chronically-transfused adults with SCD successfully completed a diary over the course of at least 2 transfusion events. Patients receiving simple transfusions and red cell exchanges were included. Pain was rated on a scale of 0 to 10 each day, and patient laboratory values, co-morbidities, and hospital utilization were also obtained using the electronic medical record. The mean pain scores pre- and post-transfusion were evaluated using both a random effects-expectation maximization regression tree analysis and a generalized linear mixed regression model. RESULTS: Ten subjects (63%) in this cohort were defined as having chronic pain, while the remaining four (27%) subjects had episodic pain. Despite chronic transfusion and a suppressed HbS% (22.5% (16.5-25.9)), 10 patients (63%) continued to report nearly daily pain, and on almost 70% of diary days, the pain was significant (≥5/10). When the relationship between HbS% and reported pain intensity was examined, no association was found. DISCUSSION: These results suggest that, even with regular transfusions and a low HbS%, daily pain persists in many adults with SCD.

Erythropoietic drive is the strongest predictor of hepcidin level in adults with sickle cell disease.

Levels of hepcidin, a key modulator of iron metabolism, are influenced by erythropoiesis, iron, and inflammation, all of which may be increased in patients with sickle cell disease (SCD). The objectives of this study were to determine: 1) the variation in hepcidin level, and 2) the relative contribution of erythropoietic drive, iron, and inflammation to differences in hepcidin level in an adult cohort with SCD. In a prospective study, cross-sectional measurements of hepcidin, reticulocyte percentage, erythropoietin, ferritin, and high-sensitivity CRP were obtained. A regression tree analysis was used to measure the association between these interacting factors and hepcidin level. The cohort was comprised of 40 adults with SCD. Median age was 26years, 68% were female, and all had HbSS. Hepcidin values ranged from 30ng/ml to 326ng/ml, with a median of 87ng/ml. Regression tree analysis demonstrated that reticulocyte percentage, erythropoietin, ferritin and hs-CRP all were associated with hepcidin. The highest hepcidin values were found in subjects with low reticulocyte percentage and erythropoietin. In conclusion, erythropoietic drive, iron status, and inflammation all contribute to variation in hepcidin level. The strongest contributor is erythropoietic drive. Future studies could determine whether suppression of erythropoiesis with chronic transfusion influences hepcidin level.