Correlation of Dengue Warning Signs during Febrile Phase with Rotational Thromboelastometry, Cortisol and Feritin.

Dengue mortality remains high despite monitoring against warning signs (WS). The associations of WS at febrile phase (FP) and hemorrhage at defervescence with the levels and kinetics of ROTEM, platelet count, cortisol, and ferritin were analyzed. Patients with confirmed dengue serology and WS in two centers were screened (n = 275) and 62 eligible patients were recruited prospectively over 9 months. "Vomiting" was the commonest WS (62.9%), with shortened clotting time (CT) INTEM (p = 0.01). "Hematocrit increase" showed significant prolonged CT INTEM, EXTEM, and FIBTEM (p < 0.05). "Platelet decrease" showed reduced platelet function and reduced clot amplitude at 10 min (A10) and maximum clot firmness (MCF) in INTEM and EXTEM (p < 0.001). The kinetics were reduced in platelet count, CT EXTEM, and cortisol (p < 0.05) but increased in CT INTEM (p = 0.03). At FP, "vomiting", "hematocrit increase", and "platelet decrease" demonstrated impaired CT, clot strengths A10/MCF and platelet functions. Majority (60/62, 96.7%) had non-severe outcomes, consistent with increase in cortisol kinetics. In conclusion, "vomiting", "hematocrit increase" and "platelet decrease" at FP correlated with ROTEM. No conclusion could be made further regarding ferritin and cortisol. Larger study is required to study "hematocrit increase" with ROTEM as a potential marker for hemorrhage.

Prediction of mortality in severe dengue cases.

BACKGROUND: Increasing incidence of dengue cases in Malaysia over the last few years has been paralleled by increased deaths. Mortality prediction models will therefore be useful in clinical management. The aim of this study is to identify factors at diagnosis of severe dengue that predicts mortality and assess predictive models based on these identified factors. METHOD: This is a retrospective cohort study of confirmed severe dengue patients that were admitted in 2014 to Hospital Kuala Lumpur. Data on baseline characteristics, clinical parameters, and laboratory findings at diagnosis of severe dengue were collected. The outcome of interest is death among patients diagnosed with severe dengue. RESULTS: There were 199 patients with severe dengue included in the study. Multivariate analysis found lethargy, OR 3.84 (95% CI 1.23-12.03); bleeding, OR 8.88 (95% CI 2.91-27.15); pulse rate, OR 1.04 (95% CI 1.01-1.07); serum bicarbonate, OR 0.79 (95% CI 0.70-0.89) and serum lactate OR 1.27 (95% CI 1.09-1.47), to be statistically significant predictors of death. The regression equation to our model with the highest AUROC, 83.5 (95% CI 72.4-94.6), is: Log odds of death amongst severe dengue cases = - 1.021 - 0.220(Serum bicarbonate) + 0.001(ALT) + 0.067(Age) - 0.190(Gender). CONCLUSION: This study showed that a large proportion of severe dengue occurred early, whilst patients were still febrile. The best prediction model to predict death at recognition of severe dengue is a model that incorporates serum bicarbonate and ALT levels.

Evaluation of creatine kinase and liver enzymes in identification of severe dengue.

BACKGROUND: Existing biomarkers such as AST, ALT and hematocrit have been associated with severe dengue but evidence are mixed. Recently, interests in creatine kinase as a dengue biomarker have risen. These biomarkers represent several underlying pathophysiological processes in dengue. Hence, we aimed to assess AST, ALT, CK and hematocrit in identification of severe dengue and to assess the correlational relationship amongst common biomarkers of dengue. METHODS: This was a retrospective cohort study of confirmed dengue patients who were warded in Kuala Lumpur Hospital between December 2014 and January 2015. CK, AST, ALT, hematocrit, platelet count, WBC and serum albumin were taken upon ward admission and repeated at timed intervals. Composite indices based on admission AST and ALT were analyzed. Correlation coefficients and coefficients of determination were computed. RESULTS: Among the 365 cases reviewed, twenty-two (6%) patients had severe dengue. AST and ALT were found to be good at identification of severe dengue. The AST2/ALT composite index was the most accurate (AUC 0.83; 95% CI 0.73 - 0.93). Optimal cutoff was 402 with a sensitivity of 59.1% (95% CI: 36.4 - 79.3%) and specificity of 92.4% (95% CI: 89.1 - 95.0%). Modified cutoff of 653 had a sensitivity of 40.9% (95% CI: 20.7 - 63.7%) and specificity of 97.4% (95% CI: 95.1 - 98.8%). Our analyses also suggested that several underlying biological processes represented by biomarkers tested were unrelated despite occurring in the same disease entity. Also, markers of plasma leakage were discordant and AST was likely hepatic in origin. CONCLUSIONS: The composite index AST2/ALT may be used as a marker for identification of severe dengue based on admission AST and ALT, with two choices of cutoff values, 402 and 653. AST is most likely of liver origin and CK does not provide additional value.