ProtocolInternational Journal of Clinical Trials

Publication:
The transfusion-associated dyspnea prospective observation and laboratory assessment study: a protocol for investigating and disambiguating cardiopulmonary and high-grade febrile transfusion reactions in adults

Int J Clin Trials. 2023;10(1):56-65.DOI10.18203/2349-3259.ijct20230051

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Abstract

Background Cardiorespiratory transfusion reactions drive most transfusion-related morbidity and mortality. Transfusion-associated circulatory overload and transfusion-related acute lung injury have established causes, important impacts, mitigation options, and revised definitions, while non-conforming CRTRs fall into a category known as transfusion-associated dyspnea. Though procedures to investigate high-risk febrile transfusion reactions are typically rooted in detecting incompatibility or bacterial contamination, a common standard for examining CRTRs is lacking. CRTRs are further challenged by charting limitations, confounding (or enhanced susceptibility) by comorbidities, and/or overlapping insults. Deeper profiling of CRTRs could improve categorizations, reveal best-value diagnostics, and decipher the nature of (and/or minimize) reactions coded as TAD.

Methods The primary objective of this multi-center study is to reduce uncertainty in final conclusions drawn on CRTRs (cases), defined by dyspnea with objective disturbances and/or significant hemodynamic insults, with/without fever (±F). HRFTRs (controls) represent higher-grade F (T≥39°C or chills/rigors or lower-grade F (≥38°C by +Δ1°C) with non-respiratory effects). Patients (goal: 200) consent to additional sampling (≤24h post-TR) to identify contributing factors in case/control presentations, and in diagnostic groups (TRALI, TACO±F, TAD). Mechanistic axes of interest are cardiorenal, hemolytic, leukoagglutinating, biolipid, vasoactive, and inflammatory. Secondary goals include elucidation of real-life “insult-multiplicity” in CRTRs, tests of greatest yield, and distinguishing features in TRALI/TACO/TAD.

Conclusions A deep systematic CRTR probe may not only reduce diagnostic uncertainty but frame biomarker performance and pathologic signatures in definition-specific CRTRs. The re-classifiability or biology of TAD may be better understood. High-quality, mechanistic, true-to-quantity hemovigilance better exposes burdens and management options. Trial Registration: The trial is registered with ClinicalTrials.gov. with registry number NCT04267029.

Keywords

Affiliations

  1. Department of Anesthesiology and Pain Medicine, Division of Hematology, University of Toronto, Toronto, Canada; Department of Anesthesia and Pain Medicine, Hospital for Sick Children, Toronto, Canada; Department of Physics, Toronto Metropolitan University, Toronto, Canada
  2. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program, Division of Hematology, University of Toronto, Toronto, Canada; Laboratory Medicine Program, University Health Network, Toronto, Canada
  3. Laboratory Medicine and Pathobiology (Transfusion Medicine), at the University Health Network
  4. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program, Division of Hematology, University of Toronto, Toronto, Canada; Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Canada
  5. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada
  6. Department of Laboratory Medicine and Pathobiology, Division of Hematology, University of Toronto, Toronto, Canada; Laboratory Medicine Program, Benign Hematology/Blood Disorders Program, University Health Network, Toronto, Canada
  7. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program, Division of Hematology, University of Toronto, Toronto, Canada
  8. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada; Division of Medical Oncology and Hematology, Benign Hematology/Blood Disorders Program, University Health Network, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, Sinai Health, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, Canada
  9. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada Department of Laboratory Medicine, St Michael’s Hospital, Unity Health, Toronto, Canada
  10. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology, Division of Hematology, University of Toronto, Toronto, Canada; Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Canada; Platelet Immunology Laboratory, Diagnostic Services, Canadian Blood Services, Winnipeg, Canada
  11. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Precision Diagnostics and Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, Canada
  12. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology Division of Hematology, University of Toronto, Toronto, Canada; Laboratory Medicine Program, Benign Hematology/Blood Disorders Program, University Health Network, Toronto, Canada
  13. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada; Laboratory Medicine Program, 11Division of Medical Oncology and Hematology, Benign Hematology/Blood Disorders Program, University Health Network, Toronto, Canada
  14. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Pathology and Molecular Medicine, Queen’s University at Kingston Health Sciences Centre, Kingston, Canada
  15. Quality in Utilization, Education and Safety in Transfusion (QUEST) Research Program; Department of Laboratory Medicine and Pathobiology; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Canada; Laboratory Medicine Program; Division of Medical Oncology and Hematology, Benign Hematology/Blood Disorders Program, University Health Network, Toronto, Canada

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