The Effect Of Blood Donor Characteristics On Transfusion Outcomes

The Effect Of Blood Donor Characteristics On Transfusion Outcomes

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Description: Understand how blood donor characteristics may be related to adverse events after RBC transfusion; Present a framework to study the blood donor-recipient continuum; Present results from a Canadian transfusion cohort study using large data Effect of donor age and sex on RBC transfusion survival. Lack of evidence of efficacy in anemic patients despite good physiological rationale.

 
Author: Michael Chasse MD PhD FRCPC  | Visits: 383 | Page Views: 673
Domain:  Medicine Category: Therapy 
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Contents:
The effect of blood donor
characteristics on transfusion
outcomes
Michaël Chassé, MD, PhD, FRCPC
Intensivist, Centre Hospitalier de l’Université de Montréal
Clinical Assistant Professor, Department of Medicine,
University of Montréal

Funding

Objectives
• Understand how blood donor characteristics may be
related to adverse events after RBC transfusion;
• Present a framework to study the blood donor-recipient
continuum;
• Present results from a Canadian transfusion cohort study
using large data
– Effect of donor age and sex on RBC transfusion survival

Why study blood… again?
After all… has been in use for a long time now!

Bibliotheque de la Faculte de Medecine, Paris, France

Why study blood
• Highly used therapy
– Most common medical intervention
– More than 100 million RBC transfusions a year
worldwide

Pfuntner A, Wier LM, Stocks C. Most Frequent Procedures Performed in US Hospitals, 2011: Statistical Brief #165. Rockville, MD: Agency for Health Care
Policy and Research; 2006-2013. Healthcare Cost and Utilization Project Statistical Briefs.
World Health Organization. 10 Facts on blood transfusion. http://www.who.int/features/factfiles/blood_transfusion/en/.

Why study blood
• Costly
– In 2012 in Canada, for
transfusable products
• 850 million dollars
• Excludes
– Cost to transfuse the
product (hospital, nurse,
etc.)
– Cost associated with
complications

Canadian Blood Services 2012 Annual Report. Ottawa: 2012
Rapport annuel 2012-2013 d’Héma-Québec. Québec: 2012.
TRANSFUSION 2004;44:1479-1486.

Lack of evidence of efficacy in anemic patients despite
good physiological rationale

Lack of evidence of efficacy in anemic patients despite
good physiological rationale

• Mortality

Lack of evidence of efficacy in anemic patients despite
good physiological rationale

• Infections

Lack of evidence of efficacy in anemic patients despite
good physiological rationale

• ARDS

Why?
• Are there harms that offset potential benefits?
– Transfusion reactions?
• Lethal ones are rare…

– Transfusion associated/related infections?
– Transfusion associated circulatory overload?
– Transfusion related acute lung injury?

Why
• Transfusion Related Immunomodulation





Increased risk of infection
Accelerated cancer growth
Organ dysfunction
Cause unknown, but persist even with leukoreduced
products

Targets for the study of transfusion
Donor

Manufacture

Storage

Administration

• Appropriate selection
• Appropriate supply

• Transformation (buffy coat, leukoreduction, preservatives…)
• Screening (infections)

• Duration
• Technology…

• Correct indication
• Correct dose
• To the good patient…

Study the donor

Bibliotheque de la Faculte de Medecine, Paris, France

Why study the donor
• “Proven” efficacy for infectious disease
BLOOD, 9 APRIL 2009 VOLUME 113, NUMBER 15

Transfusion Medicine, 1996, 6, 1–10

Why study the donor
• Age of donor
– Aging affects
• Erythropoiesis
• Increased DNA damage
• Modified cellular function
– Oncogenicity

• Change in cell membrane
• Increased amount of cytokines in blood
– TNF-α

– Age has been shown to affect outcome in organ transplantation
• Stem cell: RR 1.10, 95% CI 1.06-1.14 per decade
– Memory T-cells (more memory = more GVHD)

Why study donor
• Sex
– Different enzymatic activity in
RBC between sex
• Effect of sex-mismatched
transfusions?

– Blood composition
• Anti-neutrophils and others

Vox Sanguinis (2011) 101, 221–229

Methods


Design: Retrospective longitudinal cohort study (quasi-randomized!)



Population:
– Any patient
– At least one allogenic RBC transfusion
– In the included centers (
)

The Ottawa Hospital – General Campus, The Ottawa Hospital – Civic Campus, The University of Ottawa Heart Institute, and The Ottawa Hospital –

Riverside Campus



Source of data
– Canadian Blood Services (Donor data)
– The Ottawa Hospital DataWarehouse (transfusion data, culture results, lab results)
– ICES (Registered Person Database, Ontario Cancer Registry, CIHI-DAD)

The framework
Canadian Blood
Services

Donor

Hospital Datawarehouse

Data analysis

Patient

Institute of clinical
evaluative sciences
of Ontario

Proposed Framework



Timeframe


October 2006 to
December 2013

Analysis plan
• Main analysis
– Extended cox model






Multiple transfusions
Over time
From multiple donors
Each unit having different characteristics
Adjustment for confounding

– Main exposures: Donor Age, Donor sex
– Main outcome: Survival

Analysis

F
2009

X

M F

F M

2011

2010

ID

Start

End

Cum M

Cum F Total

Cov1

Censor

1

0

30

0

1

1

A

0

1

30

40

0

2

2

A

0

1

40

100

1

2

3

A

1

2

0

20

1

0

1

B

0

2

20

75

1

1

2

B

0

















Confounding

Main results

Interpretation
• Reduced survival after RBC transfusion from:
– Female donors
– Young donors

• Deserves confirmation:
– ARR 6.2% per year; 95% CI 5.4% to 7.0% at mean 6 transfusions
– Number Needed to Treat (NNT): 16

Limitations
• Not evidence that young age or donor sex is causal in the survival
pathway of transfusion recipients
– Exact mechanisms unknown
– Anything that is associated with donor age or donor sex could be responsible for
the observed change in survival

• Risk of unmeasured confounders
– But likely limited (quasi-random allocation, blinding…)

• Effect not homogeneous across subgroups
• Dose-response relationship but effect not linear

Next steps
• Additional exposures





Blood group (ongoing) ?
Manufacture (ongoing) ?
Novel infections?
Donor biomarkers?

• Additional linkages?
– Potential for mechanistic
studies?
• Linkage with biobanks?

• Additional outcomes





Cancer (ongoing) ?
Infections (ongoing) ?
MI (ongoing) ?
Renal failure (ongoing)

Confirmatory trial

Conclusion
• Donor characteristics probably affect transfusion
outcome
– Including long-term

• Donor sex and donor age seem to be important
factors

• Confirmatory studies ongoing

Acknowledgements


Scientists













Dean Fergusson
Jason Acker
Alan Tinmouth
Lauralyn McIntyre
Shane English
Alan Forster
Carl van Walraven
Kumanan Wilson
Greg Knoll
Tim Ramsay
Monica Taljaard
Nadine Shehata



Research assistant






Administrative support





Jodi Peters
Irwin Schweitzer

The Ottawa Hospital Data
Warehouse





Robin Ducharme
Diana Wolfe
Pauline Quach

Deanna Rothwell
Jocelyn Tufts

ICES


Meltum Gulsum Tuna