A Retrospective Review of Secondary Hemophagocytic Lymphohistiocytosis (HLH) and Dengue-associated HLH from a Teaching Hospital in Singapore.

Real-world data on the outcome of Asian patients with secondary hemophagocytic lymphohistiocytosis (HLH), especially on dengue-associated HLH, are limited to small case series. This is a retrospective records review of adult patients with secondary HLH between 2015 and 2020. Thirty-two adult patients were followed up for a median of 6.6 months (range 0.1 - 75 months). 15 had underlying lymphomas, and 12 had viral infections. Hemophagocytosis was seen in 28 of 29 patients with a bone marrow biopsy. 100% and 76.5% of patients with and without an underlying malignancy required HLH-directed therapy and blood product transfusion. 12 of 15 patients with lymphomas were treated with additional chemotherapy. Patients with malignancy-associated HLH had poorer survival than non-malignancy-associated HLH (median overall survival (OS) 1.5 months versus not reached, p-value 0.003). The 1-year survival rates of patients with malignancy-associated HLH, HLH with unknown etiologies, and infection-associated HLH were 0.133 (95% CI: 0.036 - 0.484), 0.400 (95% CI: 0.137 - 1.000) and 0.833 (95% CI: 0.647 - 1.000), respectively. Malignancy significantly increased the risk of death compared to infection-associated HLH (HR 9.37, p-value 0.003). Eight patients were diagnosed with dengue-associated HLH with a median HSCORE of 240 (98-99% probability of HLH). Their mean ferritin was 34,740 ng/mL. Three patients required blood product transfusion, 5 required corticosteroids and/or etoposide, with a median duration of treatment of 31 days. Their overall survival rate was 87.5%. Our study highlights the stark contrast in the survival of secondary HLH patients with and without an underlying malignancy. We also present one of the world's most extensive case series of dengue-associated HLH.

Clinical and health-related quality of life outcomes of transfusion-dependent thalassaemia patients in Singapore.

INTRODUCTION: Transfusion-dependent thalassaemia is associated with complications related to iron overload from frequent red cell transfusions which affect quality of life. We collected data on the clinical outcomes, complications, socioeconomic status and health-related quality of life (HRQoL) of transfusion-dependent thalassaemia patients in Singapore, and analysed the associations between clinical and socioeconomic factors with development of transfusion-related complications and HRQoL scores. MATERIALS AND METHODS: This was a cross-sectional study of transfusion-dependent thalassaemia patients treated at four major public hospitals in Singapore. Clinical information was obtained from retrospective reviews of medical records. Socioeconomic data and patient-reported compliance to iron chelators were obtained from prospective interviews of patients or caregivers using a questionnaire. A validated, disease-specific HRQoL instrument, the TranQOL, was administered to patients and caregivers during a routine clinic or transfusion visit. RESULTS: Liver iron loading was the most common transfusion-related complication and occurred in 79% of patients. Cardiac iron loading was noted in 28.3% and endocrine complications were present in 34.2%. Liver iron loading was significantly associated with higher mean ferritin level. Cardiac iron loading was significantly associated with increasing age, higher mean ferritin level and type of iron chelator. Endocrine complications were associated with increasing age, higher mean ferritin level, type of iron chelator and poorer patient-reported compliance to iron chelators. The lowest TranQOL scores were reported by caregiver parents of patients aged less than 18 years. Lower TranQOL scores were significantly associated with increasing age, especially in the 31-50 age cohort, and with reception of social assistance. CONCLUSION: The main morbidities noted in transfusion-dependent thalassaemia patients in Singapore are from complications associated with iron loading. The cohort of older thalassaemia patients aged 31-50 experienced significantly higher rates of cardiac iron loading, endocrine complications and lower TranQOL scores compared to younger age cohorts.

Hereditary thrombophilia in an unselected cohort of venous thrombosis patients in Singapore.

AIM: Hereditary thrombophilic markers are commonly screened among patients diagnosed as having venous thromboembolism, but optimal patient selection and the goals of screening may differ between populations. Determining the patterns of hereditary thrombophilia may improve screening strategies. METHOD: An unselected cohort of venous thromboembolism patients in three tertiary institutions in Singapore was prospectively tested for the prevalence of deficiencies of protein C, protein S, antithrombin III, factor V Leiden and prothrombin 20210 gene mutations. RESULTS: Among 384 patients screened, the prevalences of protein S, protein C and antithrombin III were 9.20%, 1.18% and 4.19% respectively. Only one patient was positive for the factor V Leiden mutation and none tested positive for the prothrombin 20210 gene mutation. At least 1 in 9 patients (11.52%, 95% CI 8.20 to 15.93) will test positive for one of the above markers in an unselected group of 269 patients who completed all tests. The exclusion of patients with clinical risk factors did not improve the detection rates, in comparison with those with obvious provoking clinical risk factors (11.72%, 95% CI 7.36 to 18.06 vs 11.29%, 95% CI 6.73 to 18.18). When upper age limits were set for thrombophilia screening by decades, a statistical difference in the likelihood of a positive thrombophilia screen between younger and older patient was seen for patients below 40 (p<0.001). CONCLUSION: In Singapore and countries with similar demographics, hereditary thrombophilia screening should be confined to testing for protein C, protein S and antithrombin III.