Patients with sickle cell disease (SCD) experience a wide range of complications thought to be due to the systemic impact of chronically inflamed vasculature, ongoing haemolysis, multi-cellular adhesion and ischemic damage. These complications impact the health-related quality of life and the life expectancy. One of the most impactful complications is the vaso-occlusive crisis (VOC). Evidence of the relationship between VOC occurrence and the incidence of SCD-related complications is still emerging.
To assess the association between hospitalised VOC rates and acute and chronic complications in SCD patients.
This study was a retrospective observational cohort study using the French national health insurance's claims database. This database gathers information on hospital records, and primary and secondary care. Between 01-01-2012 and 12-31-2018, all patients 16 years and older suffering from SCD (through a hospital record or Long-Term Disease status with diagnostic ICD-10 codes D57.0-2) were included in the study. Participants were followed-up for at least one year and until 12-31-2018.
A hospitalised VOC was defined as a hospital stay of at least one night with a primary or related diagnosis of sickle-cell anaemia with crisis (D57.0), preceded by a transit through the emergency room. The VOC annual rate was defined as the total number of VOCs during the follow-up divided by the number of follow-up years. Patients were categorised by the annual rate of VOCs they experienced into three groups: <1; 1 to <3; ≥3 VOCs per year.
Complications  known to be experienced by patients with SCD and leading to a hospitalisation were identified during the follow-up using ICD-10 codes reported in the hospital discharge records. Cox proportional hazards models using age as the time scale were used to study the effect of the annualized rate of hospitalised VOCs on the risk of complications, adjusted for sex.
A total of 17,726 patients were included in the study, of which 65.3% were female -a high proportion partly due to inclusion of women at time of pregnancy hospital stay. Ages ranged from 16 to 99 years and the average age was 35.0 years (±17.8). Overall, 90.3%, 7.4%, and 2.3% of patients experienced <1, 1 to <3, or ≥3 VOCs per year during the follow up period, respectively.
Over a median follow up of 7 years, the most common complications requiring a hospital admission were acute chest syndrome (ACS) (18%), sepsis (16%), acute kidney injury (12%), gallstones (10%), and eye disorder (7%).
During the follow-up period, compared to <1 hospitalised VOC per year, patients with a rate of ≥3 hospitalised VOCs per year had a statistically significant higher risk of inpatient treated complications: a 19.2 [95%CI 16.0;22.9]-time increase in the risk of osteonecrosis, 16.7[95%CI 12.0;23.2] of pulmonary hypertension, 16.4 [95%CI 13.2;20.5] of pulmonary embolism, 13.3 [95%CI 12.0;14.8] of ACS, 12.8 [95%CI 8.2;20.2] of heart failure, 12.0 [95% CI 10.0;14.4] of eye disorder, 10.0 [95% CI 8.9;11.2] of sepsis, 9.7 [95% CI 8.3;11.4] of acute kidney injury, 6.7 [95% CI 5.7;7.9]of gallstones, 6.3 [95% CI 4.3;9.0] of priapism, 6.1 [95% CI 4.6;8.0] of liver complication, 5.9 [95% CI 4.3;8.0] of central nervous system complications, 3.4 [95% CI 2.0;5.8] of dialysis, 3.2 [95% CI 2.2;4.6] of stroke..
Patients frequently experiencing VOCs are at much greater risk of hospitalization for some chronic complications compared to patients rarely experiencing VOCs. The highest association were found for osteonecrosis and pulmonary hypertension or embolism. It could be an additional reason to reinforce treatment of SCD patients with recurrent VOCs.
 ACS, Sepsis, Acute Kidney Injury, Gall stones, Eye disorder, Osteonecrosis, Liver complication, Stroke, Pulmonary embolism, Dialysis, Central nervous system, Pulmonary hypertension, Heart failure, Priapism, Kidney transplantation, Cardiomegaly
Arlet: Novartis company: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Addmedica: Research Funding. Lennon: HEVA: Ended employment in the past 24 months; IQVIA (contractor to JANSSEN Pharmaceuticals): Current Employment; WHO International Agency for Research on Cancer: Ended employment in the past 24 months. Bailey: Novartis pharmaceuticals: Current Employment. Herquelot: Pharmaceuticals and medical devices companies (BMS, MSD, Merck Sante, Janssen, Cook, Novartis, Pfizer, Takeda, ...): Other: Grants or contracts for our CRO from pharmaceutical and MD industries for research study. Lamarsalle: Pharmaceutical and medical devices comapnies (BMS, BSCI, AstraZeneca, Janssen, Merck, Novartis, Pfizer, Roche, ...): Other: Grants or contracts for our CRO from pharmaceutical and MD industries for research study. Raguideau: Pharmaceutical and medical devices companies (BMS, MSD, Merck Sante, Janssen, Cook, Novartis, Pfizer, Takeda, ...): Other: Grants or contracts for our CRO from pharmaceutical and MD industries for research study. Bartolucci: ADDMEDICA, NOVARTIS, ROCHE, GBT, Bluebird, EMMAUS, HEMANEXT, AGIOS: Consultancy; NOVARTIS, ADDMEDICA, JAZZPHARMA: Other: Lecture fees; Novartis: Other: Steering committee; ADDMEDICA, foundation Fabre, NOVARTIS, Bluebird: Consultancy, Research Funding; INNOVHEM: Other: Cofounder.
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