Comparison of the Proteome in ICU Patients in Search for TRALI Biomarkers: A Case-control Study Using Both Retrospective and Prospective Samples

NCT06444750 | Not Yet Recruiting

• 1 other identifier: CURIE
• Study Type: observational
• Target: 210
• Locations: 0 countries
• Sites: N/A

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 depending on the characteristics of the studied population. 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 exact pathophysiology of TRALI. Consequently, no biomarkers are yet known to detect TRALI. This study aims to identify TRALI biomarkers, gain insight in cellular pathways underlying TRALI development and the role of neutrophils and regulatory T cells, which could enhance transfusion safety.

Conditions

Transfusion-Related Acute Lung Injury; ARDS, Human

Keywords

Transfusion-Related Acute Lung Injury; Proteomics; Intensive Care Unit; Critical Ill patients

Outcome Measures

Primary Outcomes (1)

• Biomarkers for TRALI

  The primary endpoint of this study is to identify TRALI-specific biomarkers by comparing plasma proteomic profiles between the following groups: TRALI patients, indirect ARDS patients (with and without transfusion), pneumonia patients (with and without transfusion), and healthy volunteers. To isolate the impact of transfusion on the proteome and differentiate it from TRALI-specific changes, we will also analyze proteomic profiles before and after transfusion in relevant groups. This approach aims to increase the specificity and sensitivity of identified protein biomarkers for accurate TRALI diagnosis and facilitate the development of novel diagnostic assays

  From admission to the end of data collection (30 days)

Secondary Outcomes (2)

• Characterizing the TRALI proteome

  From admission to the end of data collection (30 days)

• Investigating Neutrophil and Treg responses

  From admission to the end of data collection (30 days)

Study Arms (6)

ICU patients who receive a transfusion without lung injury

Purpose: This group is critical for comparing the baseline effects of blood transfusion on the proteome in critically ill patients who do not develop lung injury Following transfusion, providing a control to differentiate between transfusion-related changes in the blood composition and the specific lung injury observed in TRALI. Understanding these changes will help identify biomarkers and mechanisms exclusive to TRALI. Research question: How do transfusion-related proteomic changes manifest in ICU patients who do not develop lung injury after transfusion, and how does this baseline differ from the proteomics of TRALI patients?

Other: Blood sample collection

ICU patients who receive a transfusion and have indirect ARDS

Purpose: By excluding patients with ARDS due to a pulmonary cause, this group isolates systemic, non-pulmonary factors that trigger lung injury from local pulmonary responses. Comparing this with TRALI helps us pinpoint unique biomarkers and understand the role of plasma proteins and various cellular-pathways dealing with systemic inflammation with concomitant lung injury. Research question: What distinct proteomic profiles and cellular pathways in non-pulmonary ARDS are observed in comparison with TRALI?

Other: Blood sample collection

ICU patients who receive a transfusion and have infectious pneumonia

Purpose: Since both TRALI and pneumonia involve lung injury, understanding the differences in these responses will provide insight into the mechanisms responsible for lung inflammation in TRALI, distinguishing it from the lung inflammation caused by local pulmonary infection. Research question: Can we differentiate between the immune and proteomic responses in localized infectious lung injury and transfusion-induced TRALI, exposing how the immune system reacts to an infection versus a transfusion event?

Other: Blood sample collection

ICU patients without transfusion and with indirect ARDS

Purpose: This group allows us to characterize the proteomic and immunological responses of ARDS independent of transfusion events. This comparison with TRALI aids in the identification of changes solely due to transfusion-induced acute lung injury. Research question: What are the unique blood signatures in indirect ARDS patients when transfusion factors are removed from the equation?

Other: Blood sample collection

Patients without transfusion and with infectious pneumonia

Purpose: Including this group clarifies the distinction between changes driven by infection and those unique to transfusion. By subtracting the effects of infectious responses, we can confirm that biomarkers are related specifically to TRALI. ABR 86798 CURIE study Version 5,April, 2025 16 of 35 Research question: How do the inflammatory cell and protein responses to localized lung infections compare to those induced by TRALI, ensuring biomarkers identified are specific to transfusion-related injury?

Other: Blood sample collection

Healthy volunteers

Purpose: The inclusion of healthy volunteers in this study is crucial. They provide a baseline of normal physiological and immunological steady-state composition of the blood, allowing us to identify biomarkers specific to TRALI and the other patient subgroups by accounting for baseline variability. This group serves as a valuable control for confounding factors such as critical illness (for which ICU admission), or pre-existing lung injury or concomitant systemic inflammation including the lung (ARDS), which might otherwise obscure the identification of TRALI-specific changes. This enhances data analysis and provides clarity in distinguishing potentially unique pathophysiologic mechanisms in TRALI. Research question: What baseline levels of protein, immune, and cellular profiles in healthy individuals differ from those in ICU patients undergoing transfusion, particular in terms of neutrophil activity, Treg function, and overall inflammation

Other: Blood sample collection

Interventions

Blood sample collection OTHER

Blood samples of 30 mL will be collected at admission. For the groups that receive a blood transfusion an extra 30 mL blood sample will be collected.

Also known as: Blood draw

Healthy volunteers; ICU patients who receive a transfusion and have indirect ARDS; ICU patients who receive a transfusion and have infectious pneumonia; ICU patients who receive a transfusion without lung injury; ICU patients without transfusion and with indirect ARDS; Patients without transfusion and with infectious pneumonia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Samples from twenty TRALI patients are already available at Sanquin Blood Bank. These samples have been collected within 24 hours after TRALI onset. The only clinical data available for these samples is sex and age. This is our study group. As control we will include ICU patients in University Medical Center (UMC): * Patients without lung injury receiving a blood transfusion; * Patients with indirect ARDS receiving a blood transfusion; * Patients with pneumonia receiving a blood transfusion; * Patients with indirect ARDS, who do not receive a blood transfusion; * Patients with pneumonia who do not receive a blood transfusion; * Healthy volunteers recruited through Sanquin's donor system

You may qualify if:

• Patients on the ICU:
• Without lung injury who received a red blood cell (RBC) or platelet transfusion (PLT).
• With indirect ARDS with and without a blood transfusion (RBC or PLT);
• With pneumonia, with and without a blood transfusion (RBC or PLT).

You may not qualify if:

• "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 hemorrhage.
• Patients with ARDS due to multiple transfusions.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

MeSH Terms

Conditions

Transfusion-Related Acute Lung Injury; Respiratory Distress Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Acute Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Transfusion Reaction; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Alexander Vlaar, Professor

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isabella Viegen, Bsc

CONTACT

+31 20 566 3311; i.viegen@amsterdamumc.nl

Anna-Linda Peters, MD/PhD

CONTACT

+31 20-566 9111; a.l.peters@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 30 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of department of Intensive Care Medicine

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 6, 2024
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: September 4, 2025

Record last verified: 2025-08