Homozygous sickle cell disease related mortality in Senegal (2011–2020)

Abstract Homozygous sickle cell disease (HSCD) is characterized by multiorgan morbidity and an increased risk of early death. We aim to describe the mortality rate, causes, and risk factors of death in HSCD between 2011 and 2020. We conducted a retrospective study with a duration of 10 years in the cohort of 2348 HSCD patients. The mortality rate was determined by reporting the number of deaths to the total number of patients followed in the year. Sociodemographic, clinical, biological data and causes of death were studied. Death risk factors were determined by a bivariate analysis comparing deceased and living HSCD patients. The mean age of death was 26 years (3–52). The sex ratio was 1.2. The mortality rate was 2.76%. The death rate was high in 2011 (3.2%) and low in 2020 (0.17%). We observed a significant reduction of mortality of 94.6%. Most of the common causes of death were acute anemia (40%), acute chest syndrome (24.6%), and infections (20%). Risk factors of death were age, vaso‐occlusive crises ≥3, acute chest syndrome, blood transfusion, and chronic complications. Mortality among HSCD has significantly decreased over the past 10 years in Senegal, and the main causes of death were acute anemia, acute chest syndrome, and infections.


INTRODUCTION
Homozygous sickle cell disease (HSCD) is characterized by very high morbidity and mortality especially in Africa due to diagnosis delay and precarious means of care [1]. This morbidity is expressed by the occurrence of acute complications witch the most formidable and often causes of death are acute anemia, acute chest syndrome, infections, stroke, and chronic degenerative complications of fatal such as chronic renal failure, heart failure, and pulmonary artery hypertension [2,3]. evaluated mortality in HSCD dates back to 2003 and involved a small cohort of 108 HSCD patients followed on average for 5 years, showed a death rate of 4.6% [5]. In this view, it is necessary to study mortality, causes, and risk factors of death on a larger cohort of HSCD patients.

METHODS
We realized a retrospective study including 65 HSCD patients who died of complications related to HSCD between 2011 and 2020 of a

Characteristics baseline of HSCD death patients
The sex ratio (M/F) was 1.

Mortality, causes of death, mean age, and sex ratio of HSCD patients
Between 2011 and 2020, the global mortality was 2.76% (65 deaths for 2348 HSCD patients followed). The death rate per year was high in TA B L E 1 Mortality and number of HSCD patients followed per year (2011-2020)

Risk factors for death in HSCD patients
The factors significantly associated with death were age between 20 and 40 years, the number of VOC ≥3, acute chest syndrome, blood transfusion history, and chronic complications (Table 3).

DISCUSSION
We show through this study that the death rate in HSCD is 2.76% over a period of 10 years, and that acute anemia, acute chest syndrome, and infections are the main causes of death. We also note that the mortality is gradually decreased from 3.2% (2011) to 0.17% (2020). This result is Statistically significant values are put in bold.
lower than that reported in a previous study where the mortality rate was 4.6% [5]. This reduction in mortality of HSCD is due to the progress in improving the care of patients with the reduction of mean age at diagnosis, early care in hematology, antibiotic prophylaxis in children up to 5 years old, opening clinical hematology for the early management of HSCD emergencies and the organization of a multidisciplinary follow in Senegal.
We note a higher mortality rate in men with a sex ratio of 1.2 but without a significant difference in the mean age of death (25.7 years for men and 26.5 years for women). Although HSCD is responsible for a significant excess risk of maternal death mainly due to serious complications of HSCD [15].
Nevertheless, mortality in HSCD remains high in Africa and particularly in children under 5 years [6]. In developed countries, this mortality is low because of the progress related to newborn screening, hydroxyurea treatment, long-term transfusion programs, and allogeneic bone marrow transplantation [7,11,16].
The main causes of death were acute anemia, acute chest syndrome, and infections. Three main etiologies worsening anemia in HSCD are hyperhemolysis, splenic sequestration occurring in children under 5 years, and acute erythroblastopenia due to parvovirus B19. In our series, acute anemia was mainly related to hyperhemolysis caused by an infectious disease such as malaria, sepsis, and tuberculosis and prolonged VOC. In Nigeria, a study shows a lower rate of death from acute anemia (31%), of which splenic sequestration was the main cause of death [17]. However, in the United States, only 1.36% of HSCD deaths were due to splenic sequestration [18]. This high mortality linked to acute anemia in Africa is due to the management delay which can be explained by a diagnosis delay and the unavailability of red blood cell concentrates in extreme emergency [1].
Acute chest syndrome was the second cause of death in our study, compared to developed countries, where it is the leading cause of HSCD death, but at lower rates around 5% of deaths [19]. This difference can be explained by the diagnosis difficulties of acute chest syndrome and the delay in treatment in Africa. Acute chest syndrome related mortality is due to the rapid onset symptoms of chest tightness causing premature HSCD death if emergency care is not begun.
Oxygen therapy and single or exchange blood transfusion are the mainstays of treatment of acute chest syndrome [20,21]. Several studies demonstrated the benefit of transfusion exchange with a 40% reduction in mortality because it improves microvascular perfusion and increases oxygen transport capacity [22,23].
Infectious complications represent one of the most frequent complications in HSCD with a peak frequency in children [24]. They constituted 78% of the causes of death among SCD in Africa [25] and 45% of deaths in Brazil [26]. In our study, infections are responsible for 20% of HSCD deaths. They were mainly due to malaria and pulmonary infections, while in Nigeria meningitis is predominantly responsible for 13.2% of HSCD deaths [27].
Other causes of HSCD deaths consisted of chronic renal failure, ischemic stroke, and cholecystectomy complications. Sickle cell nephropathy appears increasingly as a common complication and has long-term serious consequences for patient survival [14,28]. Chronic renal failure in HSCD was responsible for 9.2% of deaths, lower than in developed countries [22]. It has a poor prognosis in Africa due to the unavailability of renal transplantation and little easy access to symptomatic treatment by dialysis [29]. Microalbuminuria assay should be performed regularly in HSCD anemia to detect renal failure to start early treatment before kidney failure sets in.
Strokes are common in HSCD especially in childhood and are responsible for high mortality reaching over 25% [26].
HSCD deaths associated with biliary lithiasis were associated with acute cholecystitis, but especially postsurgical complications of cholecystectomy. The risk of death is real in the immediate aftermath of a cholecystectomy, hence the importance of strict and adequate monitoring [30].
Other HSCD chronic complications related to cardiovascular injuries such as heart failure and pulmonary hypertension are often responsible for HSCD deaths [31]. Other studies have shown the influence of severe anemia with an increase in HSCD deaths [32].
The risk factors associated with death were age between 20 and 40 years, the number of VOC ≥3, acute chest syndrome, priapism, blood transfusion history, and chronic complications. Most of these factors have already been reported in other studies except priapism [12,13].

CONCLUSION
Mortality among HSCD has significantly decreased over the past 10 years in Senegal reflecting the progress in HSCD management, and the main causes of death were acute anemia, acute chest syndrome, and infections. We, therefore, recommend early diagnosis and emergency management of these acute complications, particularly, in Africa.