The role of serum ferritin in predicting plasma leakage among adults and children with dengue in Sri Lanka: a multicentre, prospective cohort study

Abstract

BACKGROUND: Early prediction of plasma leakage helps in timely management of dengue. Currently, there are no defined early predictors of plasma leakage, and identified parameters are late predictors. Raised ferritin is associated with severe dengue, but its clinical utility early in the disease to predict severe dengue is not previously reported. We studied the efficacy of day 3 or 4 serum ferritin in predicting plasma leakage among adults and children with dengue in Sri Lanka. METHODS: We conducted a prospective cohort study in four hospitals in Sri Lanka from June 2022 to June 2023. Consecutive and consenting patients admitted with dengue fever were included in the study. Patients with comorbidities where ferritin could be abnormal were excluded. Serum ferritin levels were prospectively measured daily until day 8 of the illness. Physician-diagnosed plasma leakage, defined as rising haematocrit ≥ 20% from baseline or ultrasound evidence of pleural effusion or ascites, was the main outcome. Data were collected using a proforma by perusing medical records. Prediction of plasma leakage by day 3 or 4 ferritin was studied using receiver operating characteristic curves (ROC). FINDINGS: We studied 209 patients with dengue, of which 118 (56.5%) were males and median age was 20 years (IQR 9.0-40.5). Out of 209 patients, 70 (33.5%) developed plasma leakage. Median [IQR] ferritin levels on day 3 (926 [400-2752]) and day 4 (1249 [588-3005]) in patients who developed plasma leakage were higher than ferritin levels in patients who did not develop plasma leakage (p < 0.001) (day 3: 273 [101-620]) and (day 4: 506 [220-1226]). Performance of day 3 or 4 ferritin in predicting plasma leakage showed an area under the ROC of 0.78 (95% CI 0.70-0.85). The highest serum ferritin of day 3 or 4 had a positive predictive value of 52% and a negative predictive value of 84%. INTERPRETATION: Day 3 or 4 ferritin levels correctly predicted plasma leakage status in 78% of the study samples. Serum ferritin levels measured on day 3 or 4 can be used as an early predictor of plasma leakage in dengue. FUNDING: University of Kelaniya Internal Research Grants 2022 (Grant reference number: RP/03/04/13/01/2022).