Is Fresh Blood better than Old Blood ?
1667 – Jean Baptiste Denis
Early 1800’s
First successful human-human transfusion
1900 – Karl Landsteiner
Won the 1930 Nobel
Peace Prize
Isolated the A, B, &
O blood types.
Type AB blood was
identified two years
later.
Recruit
Transfuse blood
Screen Donor
Pretransfusion Testing
Collect & Prepare
Infections/disease tests
Monitor & evaluate
Medical Decision to transfuse
Blood Safety
Transfusion Safety
Transfusion Safety in the Hospital
Transfusion
Sept 2003
P latelet Units T rans fus ed
300
273
Units T rans fus ed
250
200
164
167
150
100
95
50
0
2004
2005
2006
2007
Cost of Platelet Transfusions
$140,000
$131,040
$120,000
$100,000
$80,000
$45,600
$60,000
$40,000
$20,000
$85,440 reduced cost
$2004
2005
2006
2007
Red Blood Cells
Problems with stored pRBC’s
1. Reduced ability of Hgb to release bound
oxygen at tissue level (2,3 DPG)
2,3 DPG levels become
undetectable after two weeks of
storage. Levels are restored
within 72 hours after transfusion
Does red blood cell storage affect clinical outcome? When in doubt, do the experiment.
Transfusion Vol 49 July 2009
Problems with stored pRBC’s
1. Reduced ability of Hgb to release bound
oxygen at tissue level (2,3 DPG).
2. Reduced RBC deformability = potential to
block capillary beds
RBC squeezing through a
capillary bed
Problems with stored pRBC’s
1. Reduced ability of Hgb to release bound
oxygen at tissue level (2,3 DPG)..
2. Reduced RBC deformability = potential to
block capillary beds
3. Storage lesion (age dependent defect) =
potential to block capillary beds
MoreIsKnownAbout theRisksof
BloodTransfusionThanthe
Benefits!
Problems with stored pRBC’s
1. Reduced ability of Hgb to release bound
oxygen at tissue level (2,3 DPG)
2. Reduced RBC deformability = potential to
block capillary beds
3. Storage lesion (age dependent defect) =
potential to block capillary beds
4. Activation of recipients immune system
Transfusions & Infection
Each unit of blood increases the risk of a
nosocomial infection by up to 50%!
Transfusion increases the risk of postoperative infections after cardiovascular surgery J Am Coll Surg
2006 Jan;202
An alternative scoring system to predict risk for surgical site infection complicaating coronary artery
bypass graft surgery Infect Control Hosp Epidemiol 2007 Oct;
Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal
surgery; a prospective study Transfusion Feb 2003
Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill
patient Crit Care Med 2002 Vol 30 #10
Transfusion Practice and Blood Stream Infections in Critically Ill Patients Chest 2005:127
Blood transfusions correlate with infections in trauma patients in a dose-dependant manner Am Surg
2002:68
838 ICU patients randomi
zed into one of the following strategies:
1.Restrictive (transfusion for Hgb < 7g/dl)
2.Liberal (transfusion for Hgb < 10 g/dl)
TRICC Trial Results
Complication
Restrictive Incidence
Liberal Incidence
All Cardiac morbidities
13.2%
21%
Myocardial Infarction
0.7%
2.9%
ARDS
7.7%
11.4%
Pulmonary Edema
5.3%
10.7%
30 day Mortality
18.7%
23.3%
A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care – Hebert et al
New England Journal of Medicine 1999
Blood Transfusion Morbidity
Study of 12,000 CAB patients at Cleveland Clinic
Post-Op Complication
Non-Transfused patients
Transfused patients
New onset of renal failure
requiring dialysis
0%
1.81%
Post-op ventilator support
> 72 hours
.44%
9.14%
Serious post-op infection
.24%
5.03%
.05%
3.03%
.37%
2.41%
(includes sepsis and mediastinitis)
Cardiac Morbidity
(Includes Low Cardiac Index (< 1.8), high
dose inotropic support > 4 hrs, post-op
MI with IABP or VAD)
Neurologic Morbidity
Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass
grafting – Koch, et al. ,Critical Care Medicine 2006
Blood Transfusion Morbidity
Study of 12,000 CAB patients at Cleveland Clinic
“Transfusion is the single factor most
reliably associated with increased
postoperative morbid events. Each unit
of red cells transfused is associated with
incrementally increased risk for adverse
outcome.”
Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass
grafting – Koch, et al. ,Critical Care Medicine 2006
How low can we go?
10/30 Rule*
First proposed in 1942 and based on
studies that defined “peak” oxygen
delivery in animals
*Keep Hgb at 10gm and Hct at 30%
10/30 Rule*
*Keep Hgb at 10gm and Hct at 30%
How low can we go?
• In animal studies, ECG ST segment changes
are observed once Hgb falls below 5 g/dL
• Both human and animal studies have
demonstrated that Hgb’s < 3 g/dL are
“maximally life-threatening.”
Time course and etiology of death in patients with severe anemia
Transfusion Vol 49 July 2009
Is Fresh Blood better than Old Blood ?
6,000 patients – 20,000 units of blood
Compared “newer blood” (14 days or less of
storage to “older blood” (>14 days of storage)
HIGHER RATES OF:
1. Mortality
2. Prolonged ventilation
3. Renal Failure
4. Sepsis
Duration of Red-Cell Storage and Complications after Cardiac Surgery
2008
The New England Journal of Medicine
FDA Requirements
1.Hemolysis must be no
greater than 1% at the end
of storage, and
2.RBC recovery rates must be
greater than 75% one day
after transfusion
Does the storage duration of blood products affect outcomes in critically ill patients
Spinella et al, Transfusion August 2011
Altered parameters in Stored RBC
Biochemical
Metabolic
Biomechanical
Oxidative
SNO-Hb ↓
RBC Storage Lesions
Tatsuro Yoshida PhD
Presentation to AABB
Byproducts of Stored RBC’s
1.Released heme and iron from ruptured cells
2.Shed microvesicles
3.Loss of lipid and protein products from
damaged RBC’s
4.Activated RBC adhesins
Properties of stored red blood cells: understanding immune and vascular reactivity Spinella et.al
Transfusion 2011
FDA Requirements
Membrane fragments (lipids) shed from
almost all cell types. They have been
implicated in immune suppression.
Byproducts of Stored RBC’s
“All of these materials and activities are normal
parts of the RBC life cycle, but they are
concentrated in space and time by the RBC
storage and transfusion process.”
Properties of stored red blood cells: understanding immune and vascular reactivity Spinella et.al
Transfusion 2011
“TWO-INSULT” Model
Insult # 1 = Patient’s underlying inflammatory
condition which “primes” the patient’s
immune cells
Insult # 2 = Full-on inflammatory activation
triggered by a potential second insult, such as
an allogeneic blood transfusion
Properties of stored red blood cells: understanding immune and vascular reactivity Spinella et.al
Transfusion 2011
Age of Blood Evaluation (ABLE) Trial
1.Canadian multicenter, randomized, controlled
trial in the resuscitation of critically ill patients
2.Opened in 2008 – Anticipated end 2013
3.2,500 patients
4.Outcome measurements = 90 day mortality,
MODS, infections, length of stay,
Red Cell Storage Duration Study (RECESS)
1.NHLBI multicenter, randomized, controlled trial
in cardiac surgery patients. Comparing blood
stored <10 and >21 days.
2.Opened in 2010 – Anticipated end 2013
3.1,800 patients
4.Outcome measurements = 90 day mortality,
MODS, major cardiac events, ventilation time,
renal function, liver function.
Age of Blood in Children in Pediatric
Intensive Care Units (ABC - PICU)
1.Randomizing children to either a) blood less
than 7 days old, or b) standard – issue RBC’s.
2.Opened in 2010 – Anticipated end 2013
3.1,500 patients
4.Outcome measurements = 28 day MODS, major
cardiac events, ventilation time, renal function,
liver function.
So what
do we do
with all
of this?
Byproducts of Stored RBC’s
1.Released heme and iron from ruptured cells
2.Shed microvesicles
3.Loss of lipid and protein products from
damaged RBC’s
4.Activated RBC adhesins
Properties of stored red blood cells: understanding immune and vascular reactivity Spinella et.al
Transfusion 2011
Transfusion. 2005 Aug;45(8):1295-301.
Extracellular potassium concentrations in red blood cell
suspensions after irradiation and washing.
Weiskopf RB, Schnapp S, Rouine-Rapp K, Bostrom A, Toy P.
J Trauma. 2006 Apr;60(4):851-8.
Pulmonary endothelial permeability is increased by fluid
from packed red blood cell units but not by fluid from
clinically-available washed units.
Rao RS, Howard CA, Teague TK.
Transfus Apher Sci. 2008 Apr;38(2):141-7. Epub 2008 Mar 17.
Stored packed red blood cells contain a procoagulant
phospholipid reducible by leukodepletion filters and
washing.
Cardo LJ, Hmel P, Wilder D.
Transfus Med. 2007 Apr;17(2):89-95.
Processing of stored packed red blood cells using
autotransfusion devices decreases potassium and
microaggregates: a prospective, randomized, single-blinded
in vitro study.
Westphal-Varghese B, Erren M, Westphal M, Van Aken H,
Ertmer C, Lange M, Booke M.
Anesth Analg. 2002 Aug;95(2):324-5, table of contents.
Intraoperative washing of long-stored packed red blood
cells by using an autotransfusion device prevents
hyperkalemia.
Knichwitz G, Zahl M, Van Aken H, Semjonow A, Booke M.
ASAIO J. 2007 Nov-Dec;53(6):680-3.
The effect of preprocessing stored red blood cells on
neonates undergoing corrective cardiac surgery.
Liu J, Ji B, Feng Z, Zhao J, Li C, Li B, Long C.
“Washing is associated with the loss of 10%
to 20% of the red cells.”
Blood Transfusion Therapy – A Physicians Handbook AABB 2005
REGULATORY ISSUES
1 Write a procedure
2. Get it signed by your doctors
3. Pick a QC marker
4. Measure (validate) what you are
doing
5. Record your results.
So what does this mean?
So what does this mean?
1.Understand that transfusions may
lead to worse outcomes.
So what does this mean?
1.Understand that transfusions may
lead to worse outcomes.
2. It is reasonable to infer that older
stored blood may lead to worse
outcomes!
So what does this mean?
1.Understand that transfusions may
lead to worse outcomes.
2. It is reasonable to infer that older
stored blood may lead to worse
outcomes!
3. Washing older stored blood may
reduce morbidity.