International Registry of Dengue Infection in Congenital Bleeding Disorders (DengueCBDR)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Severity of Bleeding
研究概览
简要总结
Dengue fever, a viral infection transmitted by Aedes mosquitoes, is a major health issue in tropical and subtropical regions. Around 20-30% of symptomatic patients developed Dengue Hemorrhagic Fever (DHF), which leads to impaired hemostasis, subsequently increasing the risk of bleeding.
The hemostatic abnormalities associated with dengue infection included vascular permeability, platelet dysfunction, and coagulation defects. Therefore, Individuals with underlying bleeding disorders are at increased risk of bleeding. Dengue infection in patients with hemophilia was reported, including six of 843 patients in the cohort with underlying hemophilia: five with hemophilia A and one with hemophilia B. Replacement therapy was more commonly used in patients with bleeding disorders and dengue than in patients with other febrile illnesses. All of them had bleeding during dengue infection. The mortality rate was high at 16%.
Despite the importance of this issue, there is a lack of registries or data-collection systems to determine the bleeding complications, the requirement for replacement therapy, and the outcome of dengue infection in congenital bleeding disorders (CBDs). Therefore, this research aims to establish a registry of dengue infections among individuals with CBDs.
The study is a multicenter, retrospective study from 1 January 2015 to 31 December 2025 and a prospective cohort study involving hospitals that treat individuals with CBDs and dengue. The registry format will be provided using REDCap system.
详细描述
Background:
The global incidence of dengue has markedly increased over the past two decades, posing a substantial public health challenge. From 2000 to 2019, the World Health Organization (WHO) documented a tenfold surge in reported cases worldwide, increasing from 500,000 to 5.2 million, with reported instances spreading across 129 countries.
Dengue fever, a viral infection transmitted by Aedes mosquitoes, is a major health issue in tropical and subtropical regions. Dengue virus (DENV) causes systemic infection in 25% of infected individuals. The symptoms include fever, rash, and, in severe cases, hemorrhagic manifestations. Around 20-30% of symptomatic patients developed Dengue Hemorrhagic Fever (DHF), which leads to increased vascular permeability, thrombocytopenia, and coagulopathy, which are known to increase the risk of bleeding. The most serious presentation is Dengue Shock Syndrome (DSS), which can cause substantial morbidity and mortality, particularly in vulnerable populations. One such vulnerable group is individuals with congenital bleeding disorders (CBDS), such as hemophilia, von Willebrand disease (vWD), platelet disorders, and other coagulation factor deficiencies.
Individuals with CBD have an inherent predisposition to bleeding complications, which could be exacerbated by the platelet dysfunction and vascular leakage associated with dengue infection. In addition, the interaction between the pathophysiology of dengue and bleeding disorders creates significant challenges in the diagnosis, management, and treatment of these individuals. Despite the importance of this issue, there is a lack of comprehensive registries or data-collection systems that track the incidence and outcomes of dengue infection among individuals with congenital bleeding disorders.
Dengue infection in patients with hemophilia was reported. A total of six patients in a cohort of 843 patients had underlying hemophilia; five with hemophilia A and one with hemophilia B. Replacement therapy was higher in patients with bleeding disorders with dengue, compared to other febrile illnesses. All of them had bleeding during dengue infection. The mortality rate was 16%. In addition, severe hemophilia patients presented with bleeding during the febrile stage while the platelet count was normal, then required factor replacement therapy. However, there is limited data on bleeding severity, replacement or prophylaxis protocols, and outcomes for this population.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients, aged ≥ 1 day old, diagnosed with CBDs (e.g., hemophilia, von Willebrand disease, and other coagulation factor deficiency) who are diagnosed with dengue infection, based on WHO criteria as follow;
- •Clinical dengue infection:
- •Symptoms of high sustained fever for 3-7 days with 2 of the following: headache, retroorbital pain, myalgia, arthralgia/bone pain, hemorrhagic manifestation, positive tourniquet test, leukopenia (WBC ≤5000/uL)
- •Probable dengue infection:
- •Positive dengue IgM
- •Definite dengue infection:
- •Seroconversion of dengue IgM between acute and convalescent serum OR Rising of dengue IgG (HAI) at least 4 folds between acute and convalescent serum OR Positive NS1 Ag or other dengue-specific antigen tests
- •Dengue hemorrhagic fever:
- •Dengue infection with signs of bleeding (including positive tourniquet test) with platelet count < 100,000/uL and with signs of leakage (one of the following):
- •Increase Hct at least 15-20% from baseline
- •Serum albumin < 35 g/L
- •Presence of pleural effusion or ascites
- •Dengue shock syndrome:
- •Narrow pulse pressure (< 20 mmHg)
- •Hypotension
- •Signs of poor tissue perfusion
- •Severity of DHF:
- •Grade I: Positive tourniquet test
- •Grade II: Spontaneous bleeding
- •Grade III: Circulatory failure (narrow pulse pressure ≤20 mmHg, hypotension, or signs of poor tissue perfusion)
- •Grade IV: Profound shock with undetectable blood pressure
排除标准
- •Patients with CBDs with dengue infection who are not willing to participate in the study
研究组 & 干预措施
Dengue infection in patients with congenital bleeding disorders
结局指标
主要结局
Severity of Bleeding
时间窗: Day of fever (Day 1) to Day 14 or Day of discharge from the hospital (if less than day 14)
Percentage of major and clinically relevant non-major bleeding (CRNMB) Major bleeding: Fatal bleeding, clinically overt bleeding associated with a decrease in Hgb of at least 20 g/L (2 g/ dL) in a 24-hour period, critical site bleeding such as retroperitoneal, pulmonary, pericardial, intracranial, or otherwise involves the central nervous system, bleeding that requires an intervention via an invasive procedure such as surgery in an operating suite, interventional radiology, or endoscopy Clinically relevant non-major bleeding (CRNMB): Bleeding that results in a medical or procedural intervention not meeting major bleeding criteria, examples include: hormonal therapy, tranexamic acid (TXA), iron, nasal packing, nasal cautery, laparoscopic arthroscopic retrograde cholangiopancreatography (LARC) placement, bleeding that results in hospitalization or increased level of care, overt bleeding for which a blood product is administered, and does not meet criteria for major bleeding
Amount of replacement therapy
时间窗: Day of fever (Day 1) to Day 14 or Day of discharge from the hospital (if less than day 14)
Percentage of patients receiving blood product, Percent of factor activity requirement during dengue infection
Mortality
时间窗: Day of fever (Day 1) to Day 14 or Day of discharge from the hospital (if less than day 14)
Percentage of mortality
次要结局
- Severity of bleeding among congenital bleeding disorders(Day of fever (Day 1) to Day 14 or Day of discharge from the hospital (if less than day 14))
- Mortality among congenital bleeding disorders(Day of fever (Day 1) to Day 14 or Day of discharge from the hospital (if less than day 14))
研究者
Nongnuch Sirachainan
Professor
Mahidol University