The epidemiology of very severe anaemia in sickle cell disease in Tanzania: a prospective cohort study.

Background: Anaemia in sickle cell disease (SCD) is a significant cause of morbidity and mortality, but few studies have reported on the burden and outcome of very severe anaemia. This study described the epidemiology of very severe anaemia by determining the prevalence and incidence, investigating associated clinical and laboratory factors, and assessing outcomes in SCD.

Methods: A 10-year prospective cohort study involving SCD patients of all ages was conducted at Muhimbili National Hospital in Tanzania between 2004 and 2013. SCD included Homozygous SS-Sickle cell anaemia and Sβ⁰ thalassemia at clinics and during hospitalization visits. Very severe anaemia was defined as Haemoglobin <5 g/dL at steady-state which was a period when a patient was stable with no blood transfusion in past 3 months or accute pain report in the previous month.

Findings: There were 28,293 (92.9%) clinic visits and 2158 hospitalisations amongst 3586 patients. Mean haemoglobin concentration at clinic was 7.4 g/dL, (95% CI: 7.4-7.5) compared to hospitalisation [6.4 g/dL, 95% CI: 6.3-6.5], p < 0.001. Prevalence of very severe anaemia at the clinic was 4.1%, and 23.8% during hospitalization, while the overall incidence was 114.1 (95% CI: 108.2-120.2) events per 1000 person years. Risk ratio of dying for patients with very severe anaemia was 4.78 times higher (95% CI: 3.65-6.25, p < 0.001) than in individuals without very severe anaemia. The risk ratio for mortality was highest in children aged <2 years, and was decreasing steadily with increase in age, from HR = 0.73 (95% CI: 0.39-1.35) in children aged 2-4 years to HR of 0.38 (95% CI: 0.20-0.71) in patients in age group 10-17 years when compared to those aged 0-1 years. Mortality risk ratio was higher (HR = 6.76 [95% CI: 4.31-10.62, p < 0.001]) in patients with steady-state haemoglobin <5 g/dL and presenting with very severe anaemia before death compared to those with steady state haemoglobin ≥5 g/dL and haemoglobin ≥5 g/dL before death.

Interpretation: The burden of very severe anaemia in SCD was high, especially during hospitalization, and was independent predictor of mortality. There is an urgent need to improve prevention, diagnosis, and interventions for very severe anaemia in SCD in Africa. More research to elucidate the aetiology and mechanisms of anaemia in this population is required.

Funding: Government of the United Republic of Tanzania, Wellcome Trust, United Kingdom (JKM 072064; Project grant 080025, Strategic award 084538).