Trajectories of hepatic and coagulation dysfunctions related to a rapidly fatal outcome among hospitalized patients with dengue fever in Tainan, 2015

PLoS Negl Trop Dis. 2019 Dec 5;13(12):e0007817. doi: 10.1371/journal.pntd.0007817. eCollection 2019 Dec.

Abstract

Background: Hepatic dysfunction and coagulopathy are common in acute dengue illness. We analyzed the trajectories of the above parameters in the survivors and fatal patients in the outbreak in Tainan, 2015.

Methods: A retrospective study was conducted using data from a tertiary hospital between January and December 2015. Multilevel modeling (MLM) was used to identify the changes in aminotransferase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (aPTT), and platelet counts from Day 0 to Day 7 of the onset of dengue infection. The machine-learning algorithm was used by purity measure assumption to calculate the accuracy of serum transaminases and coagulation variables to discriminate between the fatal and survival groups.

Results: There were 4,069 dengue patients, of which 0.9% died in one week after illness onset (i.e., early mortality). Case fatality rate was the highest for those aged ≥70 years. Both AST and ALT values of the fatal group were significantly higher than those of the survivor group from Day 3 (AST median, 624 U/L vs. 60 U/L, p < 0.001; ALT median, 116 U/L vs. 29 U/L, p = 0.01) of illness onset and peaked on Day 6 (AST median, 9805 U/L vs. 90 U/L, p < 0.001; ALT median, 1504 U/L vs. 49 U/L, p < 0.001). AST ≥ 203 U/L, ALT ≥ 55 U/L, AST2/ALT criteria ≥337.35, or AST/platelet count ratio index (APRI) ≥ 19.18 on Day 3 of dengue infection had a high true positive rate, 90%, 78%, 100%, or 100%, respectively, of early mortality. The platelet counts of the fatal group declined significantly than those of the survivor group since Day 3 of illness onset (median, 19 x103/μl vs. 91 x103/μl, p < 0.01), and aPTT values of the fatal group significantly prolonged longer since Day 5 (median, 68.7 seconds vs. 40.1 seconds, p < 0.001).

Conclusions: AST, ALT, and platelet counts should be monitored closely from Day 0 to Day 3 of dengue infection, and aPTT be followed up on Day 5 of infection to identify the individuals at risk for early mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Blood Coagulation Tests / methods*
  • Child
  • Child, Preschool
  • Dengue / diagnosis*
  • Dengue / epidemiology
  • Dengue / mortality*
  • Dengue / pathology
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Liver Function Tests / methods*
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Platelet Count
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Taiwan / epidemiology
  • Tertiary Care Centers
  • Young Adult

Substances

  • Aspartate Aminotransferases
  • Alanine Transaminase

Grants and funding

This work was supported by the Ministry of Science and Technology, Taiwan (https://www.most.gov.tw/en/public, grant number: MOST 107-2634-F-006-001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.