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Characterising the Loss of Haemostasis in Haemorrhagic Fever With Renal Syndrome

ConditionHaemorrhagic Fever With Renal Syndrome
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorLiverpool School of Tropical Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients aged 18 or older, including pregnant women

Laboratory-confirmed HFRS (serology and/or RT-PCR)

Willing and able to provide informed consent

Disqualifiers

Patients under 18 years of age

Co-infections with other pathogens

Pre-existing coagulation disorders

Use of anticoagulant medication

Trial population

Patients will be recruited from the University Medical Centre Ljubljana. Suspected cases of HFRS will be identified based on a clinical case definition of presence of fever and one of the following: acute kidney injury (AKI), thrombocytopenia, bleeding, or epidemiological risk. Cases will be confirmed for inclusion in the study following laboratory confirmation of hantavirus infection using serological methods for antibody detection or reverse transcription polymerase chain reaction (RT-PCR) to detect hantavirus genetic material in the blood.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Blood draw for thromboelastography - admission

    Procedure/Surgery

    Two blood samples will be collected at admission for thromboelastography using the TEG 6s platform (Haemonetics®). One sample will be collected in a citrated blood tube for global haemostasis assessment, and one sample will be collected in a heparinised tube for platelet function analysis.

  • Blood draw for thromboelastography - follow-up

    Procedure/Surgery

    Two blood samples will be collected 3 - 7 days after initial thromboelastography for follow-up analysis using the TEG 6s platform (Haemonetics®). One sample will be collected in a citrated blood tube for global haemostasis assessment, and one sample will be collected in a heparinised tube for platelet function analysis.

  • Blood draw for transcriptomic analysis

    Procedure/Surgery

    One blood sample will be collected at admission for transcriptomic analysis. Blood sample will be collected into a PAXgene® RNA tube and analysed using nanopore sequencing to characterise the viral and host transcriptome.

  • Data collection - clinical/demographic/epidemiological data

    Other intervention

    Routine clinical/demographic/epidemiological data will be collected at admission and throughout hospitalisation. This will relate to clinical presentation (day of illness at presentation, presenting symptoms); demographics and epidemiology (age, gender, site of infection); clinical course during hospitalisation (maximum level of care, dialysis use, blood product use, survival outcome).

  • Data collection - routine laboratory parameters

    Other intervention

    Data on routine laboratory parameters will be collected throughout hospitalisation. These will relate to laboratory clotting parameters (platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer); liver function tests (aspartate aminotransferase, alanine aminotransferase); laboratory haematology parameters (haemoglobin, white cell count, blood film); laboratory biochemistry parameters (urea, creatinine); viral load.

  • Severity score calculation

    Other intervention

    A severity score will be assigned to each patient based on clinical and laboratory data at admission according to a pre-defined scoring system.

Treatment groups

62 Participants
are divided into 2 treatment groups
Group A: Non-haemorrhagic cases6 interventions
Group B: Haemorrhagic cases6 interventions

Trial outcomes

Primary outcomes

1

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.

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.

Time frame
Baseline and 3-7 days later
2

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.

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.

Time frame
Baseline and 3-7 days later
3

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.

Alpha Angle (α-Angle): The speed of clot strengthening. Measured in degrees (°). Measured according to standardised assay on the TEG 6s haemostasis analyser.

Time frame
Baseline and 3-7 days later
4

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.

Maximum Amplitude (MA): The ultimate strength of the clot. Measured in millimetres (mm). Measured according to standardised assay on the TEG 6s haemostasis analyser.

Time frame
Baseline and 3-7 days later

Secondary outcomes

1

Change in platelet count over the course of illness, assessing thrombocytopenia and its role in haemostatic dysfunction in HFRS.

Platelet count measures the number of platelets in the blood, which are essential for clot formation. Measured as ×10⁹/L. Change over the course of illness, measured in days.

Time frame
Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days
2

Change in prothrombin time (PT) over the course of illness, evaluating coagulation factor activity and clotting dysfunction in HFRS.

Prothrombin time (PT) measures the time taken for blood to clot via the extrinsic pathway. Measured in seconds (s). Change over the course of illness, measured in days.

Time frame
Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days
3

Change in activated partial thromboplastin time (APTT) over the course of illness, assessing abnormalities in the intrinsic clotting pathway in HFRS.

Activated partial thromboplastin time (APTT) assesses the intrinsic clotting pathway and measures time to clot formation. Measured in seconds (s). Change over the course of illness, measured in days.

Time frame
Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days
4

Change in fibrinogen levels over the course of illness, investigating fibrinogen consumption and clot formation abnormalities in HFRS.

Fibrinogen is part of clotting assessment and is a key protein involved in clot formation, converted into fibrin to stabilise clots. Measured in g/L. Change over the course of illness, measured in days.

Time frame
Baseline (day 1) and daily thereafter through hospitalisation, up to 21 days

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Liverpool School of Tropical Medicine

Lead sponsor

Institute of microbiology and immunology, Slovenia

Collaborator

Source ClinicalTrials.gov

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