Transfusion Associated Dyspnea Profiling

Transfusion Reaction Clinical Trial

— TADPOL  

Official title:

Transfusion-Associated Dyspnea: Prospective Observational and Laboratory Assessment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04267029
• Other study ID #: TADPOL_v0.7
• Status: Completed
• Start date: January 1, 2019
• Est. completion date: December 22, 2022

Study information

• Verified date: April 2023
• Source: Toronto Transfusion Medicine Collaborative
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Transfusion reactions are defined as harms occurring during or after blood transfusion, with new heart/lung stress (eg. troubled breathing) regarded as cardiorespiratory transfusion reactions (CRTRs). CRTRs are among the most important, as the leading cause of transfusion-related harm and death. Though there are distinct classifications for these events, real life cases often don't fall neatly into a given category, with outliers regarded as "transfusion associated dyspnea (TAD)". It is unknown what TAD is -- whether it has a unique root cause, is a milder version of other known CRTRs, or is a blend of events. The purpose of this study is to better understand TAD and CRTRs by profiling them through a detailed medical history and more intensive laboratory assessment. This review of CRTRs may improve the quality/validity of final conclusions reported in the health record and to hemovigilance bodies, and uncover the nature of TAD and/or minimize CRTRs defaulting to the TAD category. Our enhanced understanding will advance diagnostic, treatment, and prevention efforts.

Description:

"Transfusion-Associated Dyspnea: Prospective Observation and Laboratory Assessment" (TADPOL) aims to improve the diagnosis and characterization of cardiorespiratory transfusion reaction (CRTR) patients ("cases"), as compared with high risk febrile transfusion reaction (HRFTR) patients ("controls"), by applying a standardized and intensive clinicolaboratory profiling tool.

CRTR, in contrast with HRFTR, are more difficult to diagnose and manage. Patients are often sick with (or prone to) pathologies that resemble reactions (eg. congestive heart failure [CHF] vs transfusion associated circulatory overload [TACO]), and/or experience more than one transfusion-associated disturbance at a time.

CRTRs are also the most disruptive, distressing, and disposition-escalating events for patients at an individual level, and are disproportionately accountable for transfusion associated deaths at the collective level in national hemovigilance systems. The cardinal CRTRs range from TACO (most commonly) to allergic bronchospasm to transfusion related acute lung injury (TRALI).

Inaccurate classification may undercount certain phenomena (when criteria fail to be met by confounding conditions), and/or overcount others (when including all possibilities-of-relevance in hemovigilance).

These uncertainties beget gaps (or excesses) in patient care and in donor/product-associated decision-making.

HYPOTHESES: The TADPOL CRF and laboratory profiling effort will improve the yields of confident (more certain), accurate (better-grounded), and thorough (multi-event-sensitive) diagnoses in CRTR patients.

Most cases of TAD are likely to be re-classified as milder versions (or overlaps) of possible CRTR states (± the underlying condition), while the remainder may exhibit a signature resembling FNHTR (FTR controls).

Precise case-mapping should yield useful personalized information, while aggregated findings from each disturbance pathway - as they are distributed in each conventional reaction category - can validate the utility of markers being explored in reaction investigation algorithms.

The TADPOL bioarchive and anonymized dataset will also be assets for explorations of novel indicators and patterns.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: December 22, 2022
• Est. primary completion date: October 4, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Transfusion of blood products (components or derivatives) with an available pre-transfusion group & screen specimen

• Referred to the blood transfusion laboratory for review of a suspected acute transfusion reaction (occurring within 24 hours of completing transfusion), and either exhibiting a cardiorespiratory disturbance (CRTR: cases) or a high-risk febrile disturbance (HRFTR: controls)

Exclusion Criteria:

• Pregnant females

• Massive hemorrhage entailing >20 implicated products in the 24h period before the acute transfusion reaction's onset

• Previous enrolment in the same designation (ie- an individual with RTR will not re-enroll if having another RTR, but may re-enrol if having FTR)

• Expected to discharge home or die sooner than specimen acquisition

• Withdrawal of consent at any time

Related Conditions & MeSH terms

• Dyspnea
• Transfusion Reaction

Intervention

Diagnostic Test:
• TADPOL battery (deep clinicolaboratory profile)
profile dimensions: hemolytic allergic cardiorenal inflammatory leukoagglutinating exploratory bioarchive

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario

Sponsors (6)

Lead Sponsor	Collaborator
Toronto Transfusion Medicine Collaborative	Canadian Blood Services, MOUNT SINAI HOSPITAL, Sunnybrook Health Sciences Centre, Unity Health Toronto, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Callum JL, Cohen R, Cressman AM, Strauss R, Armali C, Lin Y, Pendergrast J, Lieberman L, Scales DC, Skeate R, Ross H, Cserti-Gazdewich C. Cardiac stress biomarkers after red blood cell transfusion in patients at risk for transfusion-associated circulatory overload: a prospective observational study. Transfusion. 2018 Sep;58(9):2139-2148. doi: 10.1111/trf.14820. — View Citation

Cohen R, Escorcia A, Tasmin F, Lima A, Lin Y, Lieberman L, Pendergrast J, Callum J, Cserti-Gazdewich C. Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions. Transfusion. 2017 Jul;57(7):1674-1683. doi: 10.1111/trf.14099. Epub 2017 Mar 28. — View Citation

McVey MJ, Cohen R, Arsenault V, Escorcia A, Tasmin F, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. Frequency and timing of all-cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances. Vox Sang. 2021 Sep;116(8):898-909. doi: 10.1111/vox.13086. Epub 2021 Feb 26. — View Citation

Parmar N, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. The association of fever with transfusion-associated circulatory overload. Vox Sang. 2017 Jan;112(1):70-78. doi: 10.1111/vox.12473. Epub 2016 Dec 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CERTAINTY	Improve certainty in final cardiorespiratory transfusion reaction event classifications (by reduction in the number of cases otherwise achieving no better than "possible" provisional conclusions), from the expected base ambiguity rate of 60%, down to 30%.	2 years
Secondary	COMPLEXITY	Determine the frequency of multi-domain disturbances (ie- "overlap") in cardiorespiratory transfusion reaction referrals	2 years
Secondary	PATHOGENESIS FOOTPRINTING	Statistically characterize concordance of established and potential criteria in TRALI, TACO, allergic bronchospasm, and TAD	2 years

External Links

•   TADPOL Protocol paper