Characterising the Loss of Haemostasis in Haemorrhagic Fever With Renal Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 62
- 主要终点
- Change in Reaction Time (R) on thromboelastography from admission to follow-up (3-7 days), assessing clot initiation and its association with haemostatic dysfunction in HFRS.
研究概览
简要总结
Hantaviruses are globally distributed viruses that cause haemorrhagic fever with renal syndrome (HFRS) in Europe, a disease characterised by acute kidney failure and, in some cases, significant bleeding complications. The mechanisms underlying clotting abnormalities in HFRS remain poorly understood. This study aims to investigate the pathological mechanisms of clotting dysfunction in hospitalised HFRS patients, assess the impact of different hantavirus types on disease severity, and evaluate the accuracy of a severity scoring system developed in China for predicting mortality in European patients.
Hospitalised patients with laboratory-confirmed HFRS will be prospectively recruited from University Medical Centre Ljubljana, Slovenia. Blood samples will be analysed for routine laboratory markers, thromboelastography (TEG) will assess real-time clotting function, and transcriptomic analysis will identify hantavirus strains and gene expression patterns linked to disease severity. Patients will be stratified into haemorrhagic and non-haemorrhagic groups, with statistical analyses comparing clinical and laboratory parameters to identify predictors of bleeding risk. Findings from this study may contribute to improved risk stratification and potential therapeutic targets for HFRS.
详细描述
Hantaviruses are globally distributed viruses that are transmitted to humans through the inhalation of viral particles found in the urine and faeces of infected rodents. In Europe, hantaviruses cause haemorrhagic fever with renal syndrome (HFRS), a disease characterised by acute kidney failure and, in some cases, significant bleeding complications. Despite advances in understanding HFRS, the mechanisms underlying these bleeding abnormalities remain poorly understood. Several hypotheses suggest that hantaviruses may interfere with the function of blood clotting factors, but definitive evidence is lacking.
Slovenia, a country in southern Europe, has one of the highest incidences of HFRS relative to its population, with recent years seeing large outbreaks. Discussions with leading hantavirus experts in Slovenia have highlighted the urgent need for further research, particularly to understand why some patients with HFRS develop severe bleeding complications. Currently, no licensed treatments exist for HFRS, raising concerns about future outbreaks, which are expected to become more frequent due to climate change. By investigating the mechanisms leading to clotting dysfunction, this study aims to identify potential targets for future therapeutic interventions.
This study will explore the pathological mechanisms driving clotting abnormalities and bleeding in hospitalised patients with HFRS. Additionally, it will assess whether different hantavirus types influence disease severity and haemorrhagic complications and evaluate the applicability of a severity scoring system-originally developed for HFRS cases in China-in predicting outcomes among Slovenian patients.
Patients with laboratory-confirmed HFRS will be prospectively recruited from University Medical Centre Ljubljana, Slovenia. Blood samples will be collected at multiple time points during their illness and tested for standard laboratory markers, including clotting factors, blood cell counts, kidney function, and liver function. Additionally, thromboelastography (TEG) will be performed to assess real-time clotting dynamics, providing a more detailed evaluation of clotting abnormalities.
An additional blood sample will undergo transcriptomic analysis using nanopore sequencing. This will identify the specific hantavirus strain in each patient and analyse gene expression patterns associated with disease severity and bleeding risk. Patients will also be assigned a severity score based on their clinical presentation, laboratory results, and symptoms, using a scoring system developed in China to predict HFRS-related mortality. This study will evaluate the reliability of this scoring system in a European cohort.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18 or older, including pregnant women
- •Laboratory-confirmed HFRS (serology and/or RT-PCR)
- •Willing and able to provide informed consent
排除标准
- •Patients under 18 years of age
- •Co-infections with other pathogens
- •Pre-existing coagulation disorders
- •Use of anticoagulant medication
- •Inability or refusal to provide consent
结局指标
主要结局
Change in Reaction Time (R) on thromboelastography from admission to follow-up (3-7 days), assessing clot initiation and its association with haemostatic dysfunction in HFRS.
时间窗: Baseline and 3-7 days later
Reaction time (R): The amount of time between the start of the test and the beginning of coagulation. Measured in minutes (min). Measured according to standardised assay on the TEG 6s haemostasis analyser.
Change in K-Time (K) on thromboelastography from admission to follow-up (3-7 days), evaluating clot kinetics and fibrin polymerisation in relation to haemostatic abnormalities in HFRS.
时间窗: Baseline and 3-7 days later
K-time (K): The speed of formation of the clot from Reaction Time (R) to a specific clot strength. Measured in minutes (min). Measured according to standardised assay on the TEG 6s haemostasis analyser.
Change in Alpha Angle (α-Angle) on thromboelastography from admission to follow-up (3-7 days), reflecting fibrin build-up and clot formation rate in patients with HFRS.
时间窗: Baseline and 3-7 days later
Alpha Angle (α-Angle): The speed of clot strengthening. Measured in degrees (°). Measured according to standardised assay on the TEG 6s haemostasis analyser.
Change in Maximum Amplitude (MA) on thromboelastography from admission to follow-up (3-7 days), assessing overall clot strength and platelet contribution to clot stability in HFRS.
时间窗: Baseline and 3-7 days later
Maximum Amplitude (MA): The ultimate strength of the clot. Measured in millimetres (mm). Measured according to standardised assay on the TEG 6s haemostasis analyser.
Change in Lysis 30 (LY30) on thromboelastography from admission to follow-up (3-7 days), measuring fibrinolysis and clot breakdown in relation to bleeding risk in HFRS.
时间窗: Baseline and 3-7 days later
Lysis 30 (LY30): Percent lysis 30 minutes after Maximum Amplitude (MA) is finalised. The LY30 measurement is based on the reduction of the tracing area that occurs between the time that MA is measured until 30 minutes after the MA is finalised. Measured as a percentage (%). Measured according to standardised assay on the TEG 6s haemostasis analyser.
Change in Percentage Inhibition (% Inhibition) on thromboelastography from admission to follow-up (3-7 days), evaluating the effect of antithrombotic pathways on clot formation in HFRS.
时间窗: Baseline and 3-7 days later
Percentage Inhibition (% Inhibition): Indicates the reduction in platelet contribution to overall clot strength. Measured as a percentage (%). Measured according to standardised assay on the TEG 6s haemostasis analyser.
Change in Percentage Aggregation (% Aggregation) on thromboelastography from admission to follow-up (3-7 days), assessing platelet function and its role in haemostatic dysfunction in HFRS.
时间窗: Baseline and 3-7 days later
Percentage Aggregation (% Aggregation): Indicates the percent of platelets not inhibited, determined by comparing the uninhibited platelet contribution to the baseline platelet contribution. Measured as a percentage (%). Measured according to standardised assay on the TEG 6s haemostasis analyser.
次要结局
- Change in platelet count over the course of illness, assessing thrombocytopenia and its role in haemostatic dysfunction in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in prothrombin time (PT) over the course of illness, evaluating coagulation factor activity and clotting dysfunction in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in activated partial thromboplastin time (APTT) over the course of illness, assessing abnormalities in the intrinsic clotting pathway in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in fibrinogen levels over the course of illness, investigating fibrinogen consumption and clot formation abnormalities in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in D-dimer levels over the course of illness, evaluating fibrinolysis and its association with haemorrhagic complications in HFRS(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in aspartate aminotransferase (AST) over the course of illness, assessing liver involvement and potential contributions to haemostatic dysfunction in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in alanine aminotransferase (ALT) over the course of illness, evaluating liver injury and its association with disease severity in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in haemoglobin levels over the course of illness, assessing anaemia and its potential link to bleeding severity in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in white cell count (WCC) over the course of illness, evaluating immune response and its association with disease severity in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in blood film findings over the course of illness, identifying morphological changes in blood cells associated with HFRS severity.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in creatinine levels over the course of illness, evaluating renal impairment and disease progression in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Change in urea levels over the course of illness, assessing kidney dysfunction and its relationship to HFRS severity.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Day of illness at hospital presentation, assessing timing of medical intervention in relation to disease progression.(Baseline (at admission))
- Frequency of symptoms at presentation and throughout hospitalisation, characterising the clinical course and severity of HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Maximum level of clinical care required during hospitalisation, assessing disease severity and need for intensive care in HFRS patients.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Survival outcome, evaluating overall mortality and predictors of fatal HFRS cases.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Host RNA genomic analysis and its association with disease severity and haemostatic dysfunction(Baseline (at admission))
- Frequency of blood product use during hospitalisation, assessing transfusion requirements as a marker of haemorrhagic severity in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Frequency of acute renal replacement therapy use during hospitalisation, evaluating the need for dialysis as an indicator of severe renal dysfunction in HFRS.(Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days)
- Viral RNA genomic analysis and its association with disease severity and haemostatic dysfunction(Baseline (at admission))
- Validation of a severity score for predicting risk of death from HFRS in European patients(Baseline (at admission))