The morbidity pattern of children with sickle cell disorders admitted to the Queen Elizabeth Hospital,Barbados (2009

Abstract

A retrospective study was conducted by examining all the medical files of all the children with sickle cell anaemia (Hb SS) admitted from 1 January 2009 to 31 December 2013. A total of 220 admission notes (59 patients aged 5 months–16 years) were analysed. Of these, 53.2% were boys; 85.8% of the patients had Hb SS. The most common reason for admission was vaso-occlusive crisis. Blood transfusions were used in 39.7% of admissions There were no deaths during the study period. We note the number of sickle cell-related admissions and morbidity has increased, along with an increase in the number of blood transfusions. The mortality rate for children with sickle cell in Barbados is low compared to other territories in the Caribbean and worldwide. The need for better comprehensive management protocols and universal screening should decrease the morbidity patterns seen in this study.

Keywords

Americas congenital disease sickle cell epidemiology

Introduction

Sickle cell disease (Hb SS) is an inherited haematological disorder in which haemoglobin S is present in the red blood cells.¹ In a previous audit done by St. John and Adomakoh, 75 medical patients were admitted to the paediatric department for Hb SS. The most common admission diagnosis was vaso-occlusive crisis (VOC) (57%). In this study, there were two inpatient deaths.² In a 1995 study of cord bloods in Barbados,³ the incidence of the Hb SS genotype was 2.01 (95% confidence interval [CI] = 0.24–7.21) per 1000 live births.⁵ Comparatively, in a cohort of 100,000 Jamaican neonates screened between 1973 and 1981, the incidence was 3.15 per 1000 live births.⁴

Hb SS has a chronic course of anaemia, as well as acute presentations such as VOC, dactylitis, sequestration, hyper haemolytic crisis, acute chest syndrome (ACS), aplastic crisis, priapism and cerebrovascular accidents. Chronic complications include an increased risk of infection, strokes, renal impairment, liver disease and delayed growth.¹ These clinical manifestations lead to high morbidity and mortality. VOCs are the most common crises or morbid events seen in patients with Hb SS.^5–7 Children with Hb SS frequently require blood transfusions to treat acute complications of the disease. Despite the obvious necessity for transfusion in many instances in Hb SS, there is an incidence of about 18% of allo-immunisation following blood transfusion in the sickle population.⁸

A major breakthrough in the management of Hb SS occurred in 1995 with the publication of the Multicentre Study of Hydroxyurea (MSH) in adults with severe sickle cell anaemia.⁹ This study was consolidated for use in children in 2009 by the Hydroxycarbamide in Young Children with Sickle Cell Anemia: (BABY HUG).¹⁰

Methods and design

This study is a population-based retrospective study of all children normally resident in Barbados who were aged 16 years and under, with Hb SS hospitalised between 1 January 2009 and 31 December 2013. The data obtained were entered into a Microsoft Access Database using Microsoft Access 2013. The database was then exported to SPSS Version 2.0 for statistical analysis. Ethical approval was obtained from the Internal Research Board of the University of the West Indies, as well as the Queen Elizabeth Hospital Ethics Committee.

Results

A total of 9709 patients were admitted to the paediatric medical and surgical wards at the Queen Elizabeth Hospital during the study period. In total, 44 (74.5%) had more than one admission throughout the five-year period. Of the patients with more than one admission, 41 (93.2%) had Hb SS and 23 (52.3%) were girls. Seventy-five (34%) of the admissions with Hb SS occurred within a three-month period of the previous admission. Over the study period, the mean number of admissions per patient was 3.7. There were 22 admissions with Hb SS in 2009, accounting for 10% of the sickle cell admissions over the five-year period. In subsequent years, there were 33 (15%) in 2010, 52 (23.6%) in 2011, 60 (27.3%) in 2012 and 53 (24.1%) in 2013 (Figure 1).

Figure 1.

The frequency of admissions for children with sickle cell disease for the period 2009-2013.

Admission by month and rainfall: During the five-year study period, the lowest number of admissions (8, 3.6%) occurred in the month of March (driest month with an average of 38 mm of rain). The highest number of admissions (31, 14.1%) occurred during September, which is the wettest month—averaging 158 mm of rain.¹¹

Sickle cell phenotypes on admission: Of the total admissions for Hb SS, there were 188 (85.5%) admissions with sickle cell anaemia (HbSS) and 14 (14.0%) with HbSC.

Age of Admission: The age of the patients was in the range of five months to 16 years. Ten (4.5%) were aged less than one year, 89 (40.5%) were aged 1–5 years, 92 (41.8%) were aged 6–10 years, 28 were aged 11–15 years. The mean age was 6.3 years (SD 3.8) (Figure 2). In total, 103 (46.8%) of the admissions were girls and 117 (53.2%) were boys. There was no significance in the average age of the girls versus boys.

Figure 2.

The age distribution of admissions of children with sickle cell disease for the period 2009-2013.

Hospitalization days and reasons for admission: A total of 1313 hospital admission days were studied. The longest duration of stay was 152 days. The mean length of stay was 6.1 (SD 11.2) days. Of the admissions, 29.5% required treatment in the intensive care unit, accounting for 306 days. The longest duration of stay in the intensive care unit was 34 days. Of the patients admitted to the intensive care unit, four (6.2%) required some form of ventilatory support, with the longest duration of ventilatory support being 15 days.

The most common reason for admission was a VOC, accounting for 31.9%. Twelve percent were due to lower respiratory tract infections (LRTI), 9.6% were due to ACS, 6.9% were due to splenic sequestration or hypersplenism, 6% were due to a febrile illness (which was usually viral in aetiology) and 5.7% were due to elective transfusions. Only one (0.3%) admissions was due to priapism (Table 1).

Table 1.

Reasons for admission to Hospital.

Reasons for admission	n	%
VOC	106	31.9
ACS	32	9.6
Splenic sequestration	23	6.9
Haemolytic crisis	10	3.0
Priapism	1	0.3
Dactylitis	5	1.5
Fever/viral illness	20	6.0
Upper respiratory tract infection	14	4.2
Lower respiratory tract infection	40	12.0
Gastrointestinal illness	16	4.8
Liver disease	6	1.8
Central nervous system illness	18	5.4
Elective surgical procedure	8	2.4
Elective transfusion	19	5.7
Other	14	4.2
Total	332	100.0

VOC, vaso-occlusive crisis; ACS, acute chest syndrome.

At the time of admission, 200 (90.9%) used folic acid, and of the 99 who were aged ≤ 5 years when admitted, 61 (61.6%) were on antibiotic prophylaxis. The use of hydroxyurea (HU) was documented in 38 admissions, accounting for 17.3% of total admissions or 13% of the patient cohort.

Transfusion and haemoglobin levels: The haemoglobin level on admission was in the range of 2–11 g/dL, with a mean of 7.9 g/dL (SD 1.6). During the study period, 87 (39.7%) admissions had blood transfusions. Of these, 42 (19.4%) had exchange transfusions, 33 (15.2%) had simple transfusions and ten (4.6%) required both types of transfusions. Nineteen (8.6%) admissions required more than one transfusion while hospitalised. There was only one patient who was receiving routine exchange transfusions.

Infections documented during admission: In total, 124 admissions were screened for infection during the period of hospitalisation. Three blood cultures were positive for microorganisms, which included yeast, extended spectrum beta-lactamase Klebsiella pneumonia and staphylococcus. One urine culture was positive for Staphylococcus hominis. There were two documented cases of dengue fever and analysis of cerebrospinal fluid revealed one case of herpes simplex virus.

Other sickle cell complications: Of the 59 patients, 23.7% in a total had a chronic complication related to sickle cell disease: 10.2% had cholelithiasis; 6.7% had cerebrovascular accidents; 3.3% had avascular necrosis of the hip and splenectomy before the study period. There were no deaths during the study period.

Discussion

Barbados, one of the English-speaking Caribbean countries, had a total population in 2012 of 283,000, of whom 21% were children aged under 16 years. The majority of the population is of Afro-Caribbean decent. Sickle cell disease occurs frequently in this population and the impact on health is probably under estimated.^11–14

In this retrospective study, we found that sickle cell disease continues to be a significant cause of morbidity among Barbadian children. The number of admissions with sickle cell disease has increased since the audit done by St. John and Lungu,³ recording 255 admissions representing 75 patients over that ten-year period. However, in this five-year study period, there were 220 admissions representing 59 patients. This may be due to the fact that parents and guardians have become more health and hospital conscious, as in other countries.¹⁴ It may also represent a change in the criteria for admission. Since these admissions reflect significant morbidity, there will be important implications for medical practice in terms of the efficacy of current prophylactic interventions and management protocols. There will also be financial implications for allocation of medical resources for the sickle cell population as a whole. On further analysis of the data, it was noted that during the period 2009–2012, the number of admissions per year of patients with sickle disease increased from 22 (10%) in 2009 to 60 (27.3%) in 2012. This trend was also seen in the total number of paediatric admissions, which increased from 1953 (20.1%) to 2139 (22.0%) in PubMed over that same time period. Although it has been determined that concurrent epidemics such as the H1N1 viral epidemic of 2009 may have affected the severity of sickle cell admissions,^16–18 this did not affect the number of admissions as seen in our data.

A blood transfusion was required in 87 admissions (39.7%) in this study. This is a significant increase compared to St John and Lungu's, in which only nine patients (12%) received a blood transfusion.³ The increasing number of blood transfusions may be a reflection of the lack of consistent transfusion protocols and variability of opinion by different managing paediatric teams.

Morbidity in sickle cell is often underestimated, since many patients are still treated at home or in outpatient settings. In Jamaica, for example, with the establishment of the Sickle Cell Day Unit, many of the patients who have VOCs are managed as day cases.¹⁹ As a result, VOCs account for only 8.8% of hospital admissions in Jamaica. In the UK & USA, VOCs account for the majority of sickle cell-related admissions with 80–90% being quoted in some studies.¹⁴ In Brazil, the commonest reason for hospitalisation is also VOC.^2,12,20 Meanwhile, in India and Africa febrile illnesses and infections were the most common cause.^14,15 In this study, the most frequent causes for admission were VOC in 106 (31.9%), lower respiratory tract infections in 40 (12%), ACS in 32 (14.5%) and splenic sequestration crisis in 23 (6.9%). Comparatively, in St. John and Lungu's study, the most frequent diagnoses were VOC in 146 (57%), pneumonia in 37 (14%), sequestration crisis in seven (3%) and haemolytic crisis in five (2%).³

It is very encouraging to note the zero-mortality rate over this five-year study. This decrease in mortality rate seen in this cohort compared to other territories in the Caribbean as well as worldwide^2,4,6,13,14 may be due to multiple factors including: early admissions from primary care sources; significant improvement in the general medical care of children over the last ten years including the presence of a dedicated Paediatric Intensive Care Unit at the Queen Elizabeth Hospital; earlier identification and management of children with sickle cell disease as a result of physician sensitivity and maternal testing during pregnancy for the sickle cell gene; parental understanding of the need to seek immediate medical care especially with febrile illnesses; and early antibiotic therapy of febrile episodes and immunisation with Haemophilus B and more recently the pneumococcal vaccine to all children starting at two months of age as part of the public health policy of Barbados. It has been well documented that infection is one of the leading causes of early childhood mortality (age < 3 years) in persons with sickle cell disease.^21–23 In this study, although infections were considered in the admission diagnosis, bacterial infections were only documented in three cases with blood cultures positive for yeast, extended spectrum beta-lactamase Klebsiella pneumonia and staphylococcus. This low rate of documented infection is also accounted for with the advent of penicillin prophylaxis. It is noted that in our study 61.6% admissions were on antibiotic prophylaxis. However, despite this, it is noted that more than one-quarter of these eligible children did not routinely receive this treatment and therefore remained at risk of invasive disease.

The occurrence of early vaso-occlusive complications (VOC and ACS) in the first five years of life has been shown to be predictive of an increase in painful episodes later in life.²⁰ The universal use of disease-modifying agents such as HU, use of chronic transfusion programs and judicious stem-cell transplantation will contribute to significant decline in the morbidity of this chronic disease.¹² It is this younger group which accounted for > 40% of admissions in this study and should be specifically targeted for the use of HU^21–29 and possible chronic transfusion therapy.¹⁰ However, worldwide there still remain several barriers to universal use of HU but due to the nature of this study we were unable to determine the barriers to the use of this therapy in our cohort.³⁰

The way forward can start with a coordinated effort between the departments of paediatrics and haematology to put in place guidelines for care of the sickle cell child, both in hospital and in the community. A recent collaboration between the Sick Children’s Hospital in Canada³¹ and the Sickle Cell Unit (SCU) of Jamaica has already begun with new updated guidelines suitable for Caribbean use. However, timely intervention hinges on early detection and regular follow-up; in the case of HbSS, this translates to newborn screening, followed by a comprehensive care regime for identified patients.⁵

Conclusion

The number of sickle cell-related admissions has increased throughout the years, both compared to 20 years ago and during sequential years during this study. This change perhaps indicates an increase in the morbidity patterns. There has been an increase in the number of blood transfusions among children with sickle cell done at the Queen Elizabeth Hospital compared to 20 years ago. Despite this, use of HU remains low. The mortality rate for children with sickle cell in Barbados is low compared to other territories in the Caribbean as well as worldwide.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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The morbidity pattern of children with sickle cell disorders admitted to the Queen Elizabeth Hospital,Barbados (2009–2013)

Abstract

Keywords

Introduction

Methods and design

Results

Discussion

Conclusion

Footnotes

Declaration of conflicting interests

Funding

References