Transfusion Associated Dyspnea Profiling

Study Overview
=================
Brief 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.

Detailed 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.

Official Title
-----------------
Transfusion-Associated Dyspnea: Prospective Observational and Laboratory Assessment

Conditions
-----------------
Transfusion Reaction

Intervention / Treatment
-----------------
* Diagnostic Test: TADPOL battery (deep clinicolaboratory profile)


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases: CRTR (cardiorespiratory transfusion reaction)<br>Respiratory/cardiovascular disturbances after transfusion (>/=2 of respiratory distress, pulmonary edema, cardiovascular system changes, fluid shifts, cardiac strain indicators), with or without accompanying (or pre-existing) fever | Diagnostic Test: TADPOL battery (deep clinicolaboratory profile)<br>* profile dimensions: hemolytic allergic cardiorenal inflammatory leukoagglutinating exploratory bioarchive<br>|
| Controls: HRFTR (high risk febrile transfusion reactions)<br>Post-transfusion fevers requiring laboratory investigation (Tmax>/=39C, or lesser deflections if accompanied by chills/rigors), without respiratory features (hypoxia or dyspnea) | Diagnostic Test: TADPOL battery (deep clinicolaboratory profile)<br>* profile dimensions: hemolytic allergic cardiorenal inflammatory leukoagglutinating exploratory bioarchive<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COMPLEXITY | Determine the frequency of multi-domain disturbances (ie- overlap) in cardiorespiratory transfusion reaction referrals | 2 years | 
| PATHOGENESIS FOOTPRINTING | Statistically characterize concordance of established and potential criteria in TRALI, TACO, allergic bronchospasm, and TAD | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TACO (transfusion associated circulatory overload), TRALI (transfusion related acute lung injury), Allergic Reaction, FNHTR (febrile non-hemolytic transfusion reaction), TAD (transfusion associated dyspnea)