Spleen size in homozygous sickle cell disease: trends in a birth cohort using ultrasound

Abstract

Objectives: To provide ultrasound baselines for spleen length in homozygous sickle cell disease (HbSS) and in normal controls with a HbAA genotype. Methods: The Jamaican cohort study identified 311 babies with HbSS and 246 matched HbAA controls during the screening of 100,000 consecutive deliveries in Kingston, Jamaica from 1973 to 1981. Ultrasonography commenced in 1988 when the youngest patients were aged 6 years at which time deaths, emigrations and default had reduced the numbers to 206 HbSS and 89 controls. It continued annually until 2000. Results: The spleen was visualized in all HbAA controls but in only 1103/2138 (52%) scans in HbSS. Where available, mean splenic lengths were significantly lower in HbSS (77–103 mm in males, 70–83 mm in females) compared to normal controls (89–101 mm in males, 86–95 mm in females). Assessed by statistical modelling after adjusting for body height, the splenic ratio (splenic length/body height) declined over the age range 12–20 years in HbSS, consistent with progressive splenic fibrosis. Genetic factors known to inhibit sickling, α thalassaemia and fetal haemoglobin level (HbF) significantly reduced the decline in splenic ratio. Clinical splenomegaly was an insensitive measure of splenic enlargement as only 50% of patients aged 18 years and above with spleens measuring ≥150 mm on ultrasonography had palpable spleens. Conclusions: An age-related decline in splenic length occurred in HbSS and occurred more slowly with genetic factors known to inhibit sickling. The standards provided may be of value in assessing minor degrees of subclinical acute splenic sequestration. (241 words) Advances in knowledge These are the first standards available for splenic length in HbSS. They may be useful in detecting red cell sequestration, not apparent from clinical splenomegaly and also provide a model for identifying factors inhibiting vaso-occlusion.

Determinants of splenic preservation among patients with sickle cell disease in North‐Eastern Nigeria

“…In our study, the spleen was visualised on ultrasonography among all the children under 5 years, but declined in prevalence with successively older age groups, so that only about a quarter of patients had their spleens visualised on ultrasonography after the age of 15 years. A similar pattern was noted recently among a large Jamaican birth cohort of patients with SCD (n = 2138); non-visualised spleens increased with age from 34% in those aged 6.0-7.9 years to 72% in those aged 24 years and older [20]. In contrast, a study among SCD children in the United Kingdom (n = 100) showed that only 5.6% of children aged 6-10 years and 19.4% of children aged 11-16 years had no visible spleen on ultrasonography [21].…”

“…Lower frequencies have been found in Asia (11%) [33], the Middle-East (6.1%) [12] and the United States (9%) [21]. The variability of splenic nonvisualisation on ultrasonography in the different geographic location may partly be explained by the presence of genetic factors known to inhibit sickling, such as alphathalassaemia and HbF [11,20], improvement in clinical care and outcomes in SCD [21,32], and also environmental factors that results in the frequent exposure to organisms known to cause spleen enlargement including malaria and bacterial infections [34,35].…”

“…One of these studies from South‐West Nigeria among children with SCD demonstrated higher levels of HbF in children with visualised spleens compared to those without visible spleens ( p = 0.012) [39]. Similarly, studies among patients with SCD in Saudi Arabia and Jamaica have demonstrated high HbF levels in patients with visualised spleens compared to those without visible spleens on ultrasonography [12, 20]. Other studies from Africa [40–42] which all used abdominal palpation to detect splenomegaly, found no relationship between the presence of palpable spleens and HbF.…”

Acute splenic sequestration in HbSS: observations from the Jamaican birth cohort

“…Potential weaknesses include the diligence of different doctors recording splenomegaly, difficulties of assessment in sometimes sick children and that clinical splenic enlargement imperfectly reflects spleen size on ultrasonography. 25 The prevalence of ASS in the Jamaican cohort at 35% exceeded the 10% reported from the cooperative study in the USA, 26 7% in western Saudi Arabia 27 and 16% in a French study. 15 All studies used similar definitions for ASS, and the greater frequency in the cohort may reflect clinically mild cases from auditing serial haematology, a hypothesis consistent with the relatively benign clinical course, 90 out of 183 (49%) events resolving without admission and 90 out of 183 (49%) without transfusion.…”

“…Following up children from birth created a novel challenge as the early establishment of haemolysis in HbSS, also qualified for the accepted diagnosis of ASS. Potential weaknesses include the diligence of different doctors recording splenomegaly, difficulties of assessment in sometimes sick children and that clinical splenic enlargement imperfectly reflects spleen size on ultrasonography 25. The prevalence of ASS in the Jamaican cohort at 35% exceeded the 10% reported from the cooperative study in the USA,26 7% in western Saudi Arabia27 and 16% in a French study 15.…”