Patients with SCD Face Early Death Despite Improved Survival Rates

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A recent, retrospective multi-center study evaluated risk factors linked with mortality among children and adults with sickle cell disease (SCD) admitted to three hospitals between 2006 and 2020.¹

These factors, including male gender, low fetal hemoglobin (HbF), rapid drop in hemoglobin and platelet counts, and increases in white blood cell count, LDH, ferritin, and C-reactive protein, correlated significantly with mortality in the population with SCD.

“In summary, the ability to identify the risk factors that are associated with increased mortality among SCD patients permits accurate prognostication and provides effective prophylactic management strategies,” wrote the investigative team, led by Salam Alkindi, department of hematology, college of medicine and health sciences, Sultan Qaboos University.

Both in Oman, where the study was conducted, and globally, SCD is a notable public health crisis linked with increasing morbidity and mortality.² Recurrent episodes of vaso-occlusion define the condition, with painful episodes, hemolytic anemia, and increased infection risk impacting survival rates. These rates have improved in recent years, with ≥95% of patients reaching adulthood in the developed world, owing to better newborn screening programs and treatment in later life.³

Despite survival improvements in SCD, patients continue to be lost prematurely, ranging from sepsis, painful episodes bringing about acute chest syndrome (ACS), and stroke. In the current analysis, Alkindi and colleagues evaluated death from three hospitals over 15 years to examine the primary causes of death and related risk factors in patients with SCD.

The retrospective analysis enrolled 123 patients (41 female) with a median age of 27 years, who died during the study period. Data were obtained from the electronic patient record, identifying demographics, season during death, and previous SCD manifestations. Analysis was also performed on hematologic, biochemical, and radiological parameters at baseline and during the terminal event, including antibiotic use, ventilatory support, and blood and exchange transfusions.

More than six painful episodes of VOCs were identified in approximately one-fifth of the study cohort (17.9%) —most patients had a significant history of SCD-related complications, including ACS (52.8%), splenic sequestration (21.1%), right upper quadrant syndrome (19.5%), and stroke (13.8%).

At the terminal admission, fever, cough abnormal findings in chest examination, and reduced O2 saturation were observed in 68.3%, 24.4%, 53.6%, and 49.6% of the population, respectively. Hematologic-related laboratory parameters showed a significant drop in the median hemoglobin and platelet counts from baseline and an increase in white blood cell counts (P <.05).

Regarding the biochemical parameters, there was a significant rise in the median C-reactive protein levels, serum bilirubin levels, and serum LDL levels at admission to the hospital to the time of the terminal event (P <.05). Chest X-ray was abnormal at more than half (57.7%) of patients—a CT scan was performed in only 94 patients but the majority were abnormal (89.3%).

Antibiotics were provided to all patients, while simple and exchange blood transfusions were given in 118 (96.9%) and 115 (93.5%) patients, respectively. Approximately two-thirds (66.6%) of patients required non-invasive ventilatory support.

At the terminal event, 32 (26%) patients died within 24 hours of hospital admission. Causes of death included sepsis (40%), ACS associated with multi-organ failure (26%), and miscellaneous causes (34%), including cardiac events, pulmonary embolism, stroke, and some at home.

Overall, mortality was significantly correlated with a cutoff of basal hemoglobin, basal white blood cell count, and HbF of 7 gm/dL, 15 x 10⁹/L, and 8.55, respectively. Most patients who died (72.4%) had an HBF <8.5%. Serum LDH, ferritin, and C-reactive protein also correlated significantly with mortality during the terminal event.

Although improvements have been made to survival rates in SCD, Alkindi and colleagues pointed to the high premature death rate seen in males in this study. Among the study population, the overall proportion of death among males was doubled that of females (66% vs. 33%).

“SCD is a complex condition, with life-threatening complications that interfere with the patient’s normal life owing to repeated painful episodes, and the associated multi-system involvement,” they wrote. “Although this is a retrospective study, however, it identified that ACS and sepsis were the most important preventable risk factors associated with mortality in this SCD patient cohort.”

References

1. _{Alkindi S, Al-Jadidi S, Al-Adawi S, et al. Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death. Sci Rep. 2024;14(1):8584. Published 2024 Apr 13. doi:10.1038/s41598-024-58328-9}
2. _{Colombatti R, Birkegård C, Medici M. PB2215: GLOBAL EPIDEMIOLOGY OF SICKLE CELL DISEASE: A SYSTEMATIC LITERATURE REVIEW. Hemasphere. 2022;6(Suppl ):2085-2086. Published 2022 Jun 23. doi:10.1097/01.HS9.0000851688.00394.f4}
3. _{Telfer P, Coen P, Chakravorty S, et al. Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica. 2007;92(7):905-912. doi:10.3324/haematol.10937}