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Comparison of the Proteome in ICU Patients in Search for TRALI Biomarkers

Not yet recruiting
Conditions
Transfusion-Related Acute Lung Injury
ARDS, Human
Interventions
Other: Blood sample collection
Registration Number
NCT06444750
Lead Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Brief Summary

Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusions. After a transfusion, TRALI develops in 0.08-15% of cases. The incidence of TRALI is 50-100 times higher in critically ill patients compared to the general hospital population. No biomarkers are yet known to detect TRALI. This study will compare blood samples of TRALI patients with blood samples of intensive care patients in order to find possible biomarkers for TRALI.

Detailed Description

Background of the study:

Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusions. After a transfusion, TRALI develops in 0.08-15% of cases. Due to preventive measures the incidence has decreased. However, the incidence of TRALI is 50-100 times higher in critically ill patients compared to the general hospital population. Since the absolute incidence of respiratory transfusion complications is low and TRALI is under-diagnosed and -reported, to this date is has not been possible to elucidate the pathophysiology of TRALI. Consequently, no biomarkers are yet known to detect TRALI. This study aims to gain insight in cellular pathways underlying TRALI development which could enhance transfusion safety.

Objective of the study:

* To investigate the proteome in TRALI patients and thus gain knowledge on TRALI pathophysiology. This knowledge can be used to investigate preventive measures and therapy for TRALI.

* To identify biomarkers specific for TRALI, thus aiding in future diagnostics of TRALI.

Study design:

Case-control study. Samples available from known TRALI patients stored at Sanquin Blood Bank will be compared to samples from intensive care patients with acute respiratory distress syndrome (ARDS) or pneumonia.

The investigator will screen ICU patients for eligibility for one of our groups and ask for informed consent. After obtaining informed consent, patients depending on whether they need a transfusion. After admission and informed consent the investigator will collect remaining blood samples from the clinical laboratory within 24 hours of arrival.

Additionally, extra blood samples (40mL) will be drawn from patients within 24 hours of arrival.

For Group 1 (patients who receive a transfusion but do not have lung injury), Group 2 (patients who receive a transfusion and have ARDS), and Group 3 (patients who receive a transfusion with local lung injury) a second tube blood sample (30mL) will be drawn 12 hours after the first transfusion. The investigator will collect two samples for this group to analyze the effect of transfusion on the proteome

Study population:

Adult intensive care patient who are admitted with:

- pneumonia, indirect lung injury or no pulmonary injury Healthy volunteers.

Primary study parameters/outcome of the study:

The main aim of this research is to use proteomics to study protein profiles and identify biomarkers that correlate with TRALI.

Secundary study parameters/outcome of the study (if applicable):

The secondary outcomes of this research will be CD34 cultured neutrophils and T cell subsets. Furthermore, the effect of transfusion on the patient's proteome will be studied.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
210
Inclusion Criteria

Patients on the ICU:

  • Without lung injury who received a red blood cell or platelet transfusion.
  • Non-lung infection induced ARDS with and without a blood transfusion;
  • Pneumonia, without a blood transfusion.
Exclusion Criteria
  • Patients with "objection to registration of data for scientific use" as noted in the patient file.
  • Patients in whom it is impossible to obtain blood samples.
  • Patients with massive haemorrhage.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
ICU patients with pneumonia with transfusionBlood sample collectionICU patients who receive a transfusion and have infectious lung injury (locally). This will give an overview of the proteome of patients with local lung injury.
ICU patients without lung injury with transfusionBlood sample collectionICU patients who receive a transfusion and without lung injury. This will give an overview of the proteome of critical ill patients who received a transfusion but without lung injury. This way specific proteome changes caused by transfusion can be identified
ICU patients with ARDS (indirect) with transfusionBlood sample collectionICU patients who receive a transfusion and have ARDS caused by indirect lung injury (e.g. pancreatitis, trauma, non-pulmonary sepsis). This will give an overview of the proteome of critical ill patients who receive a transfusion and have lung injury not caused by TRALI.
ICU patients with pneumonia without transfusionBlood sample collectionICU patients without transfusion and with infectious pneumonia. This will give an overview of proteins involved in local lung injury.
Healthy volunteersBlood sample collectionHealthy volunteers.
ICU patients with ARDS (indirect) without transfusionBlood sample collectionICU patients without transfusion and with ARDS caused by indirect lung injury. This will give an overview of the proteome of ICU patients with a systemic cause of lung injury. Proteins that are specifically involved in a systemic reaction can be identified.
Primary Outcome Measures
NameTimeMethod
Biomarkers for TRALIWithin 24 hours of ICU admission

Use proteomics (OLINK) to study protein profiles and identify biomarkers. This will be measured in Normalized Protein eXpression (NPX) units biomarkers that correlate with TRALI.

Secondary Outcome Measures
NameTimeMethod
CD34 cultured neutrophilsWithin 24 hours of ICU admission

Measurement of CD34 cultured neutrophils. Neutrophil subsets will be checked for 20 markers in an antibody panel. This will be measured with flow cytometry.

T cell subsetswithin 24 hours of ICU admission

Measurement of T cell subsets. This will be measured with flow cytometry.

Patient's proteomewithin 24 hours of ICU admission

Effect of transfusion of patient's proteome in npx units

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