Impact of hospitalized vaso-occlusive crises in the previous calendar year on mortality and complications in adults with sickle cell disease: a French population-based study

Abstract

Background: Historically, sickle cell disease (SCD) patients experiencing frequent hospitalized vaso-occlusive crises (HVOC) have been associated with increased mortality, yet recent data reflecting the widespread use of hydroxyurea and advancements in disease management remain limited. Our study aims to assess the association between HVOC and mortality or severe complications in patients with SCD in this new treatment landscape.

Methods: This was a retrospective observational cohort study using the French national health data system. Between 01-01-2012 and 12-31-2018, all SCD patients ≥16 years old (ICD-10 codes D57.0-2) were included and followed until 12-31-2018. HVOC was defined as a hospitalization of ≥1 night with primary diagnosis of SCD with crisis, following an emergency room visit. The association between HVOC and severe complications was assessed with a Cox proportional hazards model.

Findings: In total, 8018 patients (56.6% females; 4538/8018) were included. The 2018 SCD standardized one-year period prevalence was 17.9 cases/100,000 person-years [17.4; 18.3]. The mean rate was 0.84 (1.88) HVOC/person-year. In 2018, 70% (5323/7605), 22% (1671/7605), and 8% (611/7605) of patients experienced 0, 1-2, or 3+ HVOCs, respectively. The median survival time between HVOCs was 415 days [386; 439]. Overall, 312 patients died (3.9%) with a mean age of 49.8 (19.4). Compared to patients without HVOC, the hazard ratios of death in patients with 1-2 or 3+ HVOCs the year prior to death were 1.67 [1.21; 2.30] and 3.70 [2.30; 5.93], respectively. Incidence of acute chest syndrome, pulmonary embolism, osteonecrosis, and sepsis increased with the HVOCs category, but not stroke. In 2018, 29.5% (180/611) of patients with 3+ HVOCs did not take hydroxyurea.

Interpretation: Patients must be closely monitored during their hospitalizations to intensify treatment and check treatment compliance. Innovative therapies are also required.

Funding: The study was funded by Novartis.

Keywords: France; Mortality; Sickle cell disease; Vaso-occlusive crisis.

Fig. 1

French standardized one-year period prevalence sickle-cell disease rate in patients aged 16 and above.

Fig. 2

Hospitalized vaso-occlusive crisis (HVOC) evolution across years.

Fig. 3

Hospitalizations and emergency room visits per patient, per category of hospitalized vaso-occlusive crisis, per calendar year. HVOC, hospitalized vaso-occlusive crisis; ER, emergency room visit.

Fig. 4

Kaplan Meier curve of the probability of patients with one hospitalized vaso-occlusive crisis (HVOC) during the study period of staying without a second HVOC.

Fig. 5

Hazard ratio of the risk of death and the HVOC category the calendar year before death. HVOC, hospitalized vaso-occlusive crisis (visit to the ER followed by a hospital stay of ≥1 night with a primary diagnosis of D57.0).

Fig. 6

Hazard ratio of the risk of sickle-cell disease severe complications and the HVOC category the calendar year before. HVOC, hospitalized vaso-occlusive crisis (visit to the ER followed by a hospital stay of ≥1 night with a primary diagnosis of D57.0).