Research Article: Characteristics and predictors for gastrointestinal hemorrhage among adult patients with dengue virus infection: Emphasizing the impact of existing comorbid disease(s)

Date Published: February 20, 2018

Publisher: Public Library of Science

Author(s): Wen-Chi Huang, Ing-Kit Lee, Yi-Chun Chen, Ching-Yen Tsai, Jien-Wei Liu, Tyler M. Sharp.


Gastrointestinal (GI) bleeding is a leading cause of death in dengue. This study aims to identify predictors for GI bleeding in adult dengue patients, emphasizing the impact of existing comorbid disease(s).

Of 1300 adults with dengue virus infection, 175 (mean age, 56.5±13.7 years) patients with GI bleeding and 1,125 (mean age, 49.2±15.6 years) without GI bleeding (controls) were retrospectively analyzed.

Among 175 patients with GI bleeding, dengue hemorrhagic fever was found in 119 (68%) patients; the median duration from onset dengue illness to GI bleeding was 5 days. Gastric ulcer, erythematous gastritis, duodenal ulcer, erosive gastritis, and hemorrhagic gastritis were found in 52.3%, 33.3%, 28.6%, 28.6%, and 14.3% of 42 patients with GI bleeding who had undergone endoscopic examination, respectively. Overall, nine of the 175 patients with GI bleeding died, giving an in-hospital mortality rate of 5.1%. Multivariate analysis showed age ≥60 years (cases vs. controls: 48% vs. 28.3%) (odds ratio [OR]: 1.663, 95% confidence interval [CI]: 1.128–2.453), end stage renal disease with additional comorbidities (cases vs. controls: 1.7% vs. 0.2%) (OR: 9.405, 95% CI: 1.4–63.198), previous stroke with additional comorbidities (cases vs. controls: 7.4% vs. 0.6%) (OR: 9.772, 95% CI: 3.302–28.918), gum bleeding (cases vs. controls: 27.4% vs. 11.5%) (OR: 1.732, 95% CI: 1.1–2.727), petechiae (cases vs. controls: 56.6% vs. 29.1%) (OR: 2.109, 95% CI: 1.411–3.153), and platelet count <50×109 cells/L (cases vs. controls: 53.1% vs. 25.8%) (OR: 3.419, 95% CI: 2.103–5.558) were independent predictors of GI bleeding in patients with dengue virus infection. Our study is the first to disclose that end stage renal disease and previous stroke, with additional comorbidities, were strongly significant associated with the risk of GI bleeding in patients with dengue virus infection. Identification of these risk factors can be incorporated into the patient assessment and management protocol of dengue virus infection to reduce its mortality.

Partial Text

Dengue is the most common mosquito-borne arboviral disease in the world [1]. The World Health Organization (WHO) estimates that 50–100 million people are infected annually and over 2.5 billion people living in tropical and subtropical regions worldwide are at risk [2]. The clinical manifestations of dengue virus (DENV) infection vary greatly, ranging from asymptomatic, self-limiting febrile illness, dengue fever (DF) and dengue hemorrhagic fever (DHF) to dengue shock syndrome (DSS), the most severe form of DENV infection [1,2]. Of note, the number of dengue cases is increasing globally, both among travelers as well as those residing in endemic regions [1,2]. One of the most vital challenges for physicians caring for dengue patients is the early identification of those in whom the disease will evolve to its severe form. Remarkably, a variety of dengue-related complications have been reported in dengue-affected patients, with bleeding as one of the major ones, which contributes to its morbidity and mortality [3–7]. In 2009, the WHO released revised dengue guidelines that proposed mucosal bleeding as one of warning signs of severe dengue, and severe bleeding as one category of severe dengue [8]. The most common bleeding manifestations in dengue are epistaxis, gum bleeding, and cutaneous hemorrhages [1]; however, gastrointestinal (GI) bleeding was reported to be an indicator of poor prognosis in dengue-affected patients [5–7]. Sam et al [7] noted that 56% of fatal cases experienced GI bleeding, and other reports [3] have shown that 45.5% of fatal patients had GI bleeding. Yet, little information is available about the risk factors for GI bleeding in adult patients with DENV infection [9,10]. Early recognition of risk factors for GI bleeding and prompt initiation of appropriate treatment is important in the treatment of dengue-affected patients, which in turn can potentially reduce morbidity and mortality. In this report, we aimed to describe the clinical and laboratory presentations of patients with GI bleeding and identification of clinical predictors associated with GI bleeding in adult dengue-affected patients, emphasizing the impact of existing comorbid disease(s). Our findings should be helpful to physicians regarding the decision of hospital admission for a patient with DENV infection and providing timely management, particularly in resource-poor settings.

The incidence of GI bleeding in dengue patients was found to vary from 5% to 30% [16–18]. In our study, the prevalence of GI bleeding in adult patients with DENV infection during the study period was 13.5%. Notably, the fatality rate was 5.1% and 0.3% in adult dengue-affected patients with and without GI bleeding, respectively. Furthermore, once massive GI bleeding developed, the fatality rate can be as high as 29%. Our study highlights the urgent need for improving clinicians’ awareness of this potentially fatal complication. Despite the time interval from dengue illness onset to presentation between the patients with and without GI bleeding differ significantly (median, 4 days vs. 3 days), the importance of continuous analyses of the relevant findings to assist clinicians early prediction of GI bleeding in dengue-affected populations cannot be overemphasized.




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