Vitamin D useful indicator of medication adherence in SCD 

Vitamin D levels in children with sickle cell anaemia are a valuable indicator of medication adherence, the recent Haematology Association of Ireland Annual Meeting heard.

Presenting at the conference, Dr Helen Fogarty, Children’s Health Ireland at Crumlin, said that sickle cell disease (SCD) is the most common hereditary haematological disorder worldwide, caused by a single amino acid substitution in the beta-globin gene. She noted that it is a truly multisystem condition, with complications such as stroke occurring in up to 10 per cent of children, while pulmonary hypertension, cardiac disease, and renal failure may develop later in life.

In discussing treatment options, Dr Fogarty outlined the benefits and limitations of hydroxyurea (HU) for patients with SCD. The drug has more than 30 years of safety and efficacy data and is routinely recommended for children with sickle cell anaemia from nine months of age. However, as it is a daily medication requiring regular blood tests and clinic visits, adherence can be challenging.

Blood transfusion (BT) in SCD remains the “gold standard” intervention for children at high risk of stroke and is superior to HU, the meeting was told.

“However, regular blood transfusions are a significant time commitment,” requiring hospital attendance every three to four weeks.

“Iron overload is an inevitable consequence of blood transfusion, requiring iron chelation therapy to avoid cardiac and hepatic iron overload, and eventually cardiac failure.”

Chelation compliance is critical for the ongoing safety of transfused children, Dr Fogarty added. Adherence to iron chelation is monitored by checking ferritin levels and by performing dedicated MRI scans – FerriScan. However, these scans are expensive and frequently difficult to access.

“Given the pitfall in classical methods of monitoring adherence, we sought to explore an alternative biomarker,” Dr Fogarty said.

Patients with SCD are known to have an increased incidence of vitamin D deficiency, and osteoporosis. Therefore, year-round supplementation with vitamin D is routinely recommended in SCD.

“In Crumlin, we check patients’ vitamin D levels twice yearly in the spring and autumn and we adjust the vitamin D supplementation dose accordingly,” she said. She outlined that levels less than 30nmol/L were defined as deficient, with levels between 30 and 50 defined as insufficient, while levels greater than 50 were consistent with a sufficient vitamin D status.

“We hypothesised that vitamin D levels may provide a surrogate marker of overall medication adherence in [children with] sickle cell anaemia,” she continued. To test this, children with sickle cell anaemia on either a HU or the BT programme were examined.

Vitamin D levels were collected in spring and autumn of 2023 and 2024 and compared with ferritin levels in the BT group and with mean corpuscular volume (MCV) and HbF% in the HU group. In total, 232 children were included, with an almost equal gender distribution (51 per cent male, 49 per cent female). The median patient age was 16.1 years (range 2–22 years). More than half (55 per cent) were on the BT programme, and these patients were statistically significantly older than the 45 per cent on HU, with a median age of 17 versus 15 years.

In the HU group, vitamin D insufficiency was present in just over a third (35 per cent), with 6 per cent found to be deficient. The foetal haemoglobin (HbF) percentage was significantly higher in children with sufficient vitamin D levels compared with those with vitamin D insufficiency. Furthermore, MCV was significantly higher in children with sufficient vitamin D levels than in those with insufficient levels.

“Looking at the transfusion cohort, it was quite staggering that despite all of these children being prescribed year-round vitamin D supplementation, almost 50 per cent had vitamin D insufficiency. Vitamin D deficiency was identified in 18 per cent.”

Ferritin levels were significantly higher in children with insufficient vitamin D levels compared with those with sufficient levels, correlating inversely with vitamin D concentrations.

In the overall cohort, vitamin D levels were higher in spring than in autumn across both 2023 and 2024. “Intuitively one might have expected the levels to be higher in the autumn following the summer months,” said Dr Fogarty. Vitamin D levels were significantly higher in the HU group than the BT group and were also higher in females than in males.

“However, perhaps the most highly statistically significant result was the difference between those aged less than 16 and those older. Those younger than 16 had significantly higher vitamin D levels than those above 16. This is probably one of the most clinically relevant findings also, because as patients age and become more autonomous, adherence to medication really declines.”

Discussing some of the study’s findings, Dr Fogarty said the higher vitamin D levels in spring versus autumn suggested adherence during winter months. “This may reflect the erroneous belief that supplementation in the summer is unnecessary, and perhaps contributes to seasonal vitamin D insufficiency or deficiency.”

She asked if patients were not taking their vitamin D supplementation during the summer, was this true of other medications?

The significantly higher vitamin D levels in females and children aged less than 16 years highlighted that males and adolescents are most at risk of poor medication adherence, reflecting prior published work.

In conclusion, Dr Fogarty said she hoped she had convinced her colleagues that vitamin D levels provide a useful surrogate of overall medication adherence in SCD. The importance of year-round vitamin D supplementation, including during summer months, must be emphasised.

“Males and adolescents really need to be prioritised for targeted interventions and education to improve medication adherence,” she added.