Transcript Leucodepletion of Blood & Blood Components

Selective Leuco-depletion of
Blood Products
Dr. Sangeeta Pathak
Sr. Consultant & Head-Blood Bank
Whether all cellular components should
have their white cells reduced in number
remains controversial*
*Vamvakas EC. White blood cell containing allogeneic blood transfusion, postoperative infection & mortality: A meta
analysis of observational “before & after” studies. Vox Sang 2004;86:111-19
Objective
In which circumstances would you
recommend/not recommend the use of
leucocyte depleted blood products?
– Able to answer the question regarding leucocyte
depleted blood products.
– Finances!
Definition
Leucocyte depleted blood
products must contain <0.5x109
leucocytes per unit red cells or
adult therapeutic dose of
platelets.
The Numbers!!!!
Keeping in view the variability of leukocyte numbers in the
component and the leuko-reduction method, the leukocyte
content in a blood component unit should be less than
5 × 106/unit after leuko-reduction (3 log reduction 99.9%) with a
minimum of 85% red cell recovery in 95% of the units tested, as
per the standards of the American Association of Blood Banks.
The European council guidelines are a little more stringent in
terms of residual leukocyte content and require it to be less
than 1 × 106/unit.
Leukoreduced blood components: Advantages and strategies for its implementation in developing
countries. R.R.Sharma, Neelam Marwah; Asian J Transfus Sci. 2010 January; 4(1): 3–8.
Current Scenario Worldwide…
In recent years BCT has witnessed opposing
trends in the area of Leuco-depletion
– Forced implementation
• National Blood Services:
– UK National Blood Service
– American Red Cross
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• Nearly all of Europe & Canada have implemented
leucocyte reduction in all cellular component - termed
Universal leucocyte reduction
• It has not been mandated by the FDA in the United
State & the most recent survey data indicate that –
– 72% of red cells
– 40% of whole derived platelet
– Nearly all apheresis platelet
are leucocyte reduced*.
*US Department of Health and Human Services. The 2007 National Blood Collection and Utilization Survey Report.
Washington, DC:DHHS, 2008
• Oct 2000, the University Health Consortium concluded
that the available evidence was insufficient to
recommend universal leucocyte reduction.
• In contrast, the US Blood Safety & Availability
Committee recommended in Jan 2001 that universal
leucocyte reduction be implemented as “soon as
feasible”.
• Adoption of universal leucocyte reduction remains a
hotly debated topic*.
*Vamvakas EC, Blajchman MA. Universal WBC reduction: The case for and against. Transfusion 2001;41:691 - 712
Indian Scenario!!!!
In developing
countries like India,
cost is the major
hurdle for use of
universal leucodepletion of blood
products and its usage
thus remains
controversial and
limited !!!
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Standards!!!
Leukoreduced blood components: Advantages and strategies for its implementation in developing
countries. R.R.Sharma, Neelam Marwah; Asian J Transfus Sci. 2010 January; 4(1): 3–8.
Practical aspects
• To achieve residual count less than specified,
process should be completed with in 48 hours form
collection of the donor unit.
• Quality should be assured by monitoring the
components for 100% compliance.
Transfusion-transmitted pathogen associated
primarily or solely with leucocyte
Pathogen
Leucocyte subtype
Viruses
Cytomegaloviruses
Mainly monocytes
possibly small
amount in
granulocyte
Human T-cell
leukemia viruses
I and II
T-Lymphocyte
Human Herpes Virus &
Epstein-Barr Virus
B-Lymphocytes
B-Lymphocytes
Bacteria
Yersinia enterocolitica
Prions
Leucocyte involvement
Granulocytes
Unknown
Transfusion Microbiology by John A.J.Barbara Marcela Contreras
Disadvantages??????
Little evidence suggests a serious clinical
disadvantage of leucocytes reduction.
Are they there???? If any???
Disadvantages:
• The Technology is Expensive
• There are three documented disadvantages.
1st Disadvantage!!!
•
Filtration results in a substantial loss of the
therapeutic blood element intended for Transfusion.
•
The VATS* found that patients randomly assigned to
the leucocytes reduction arm received a statistically
smaller mass of red cells.
•
It is unclear whether this actually results in additional
red cells transfusion.
*Collier AC, Kalish LA, Bush MP et al. Leucocytes reduced red cells transfusion in patients with anemia & HIV virus
infection. The Viral activation transfusion study – a randomized controlled trial. JAMA 2001;285:1592-601.
1st Disadvantage!!!
• This problem may be particularly important if
filtration is combined with other manipulations,
such as preparation of RBC’s by the buffy coat
removal technique, preparation of washed
platelet concentrates, or pathogen inactivation
techniques.
2nd Disadvantage!!!
• Bedside leucocytes reduction has been associated with
hypotensive reactions, especially among recipients
treated with ACE inhibitors*.
• As blood passes through negatively charged filters,
contact activation occurs.
• The activation, in turn, causes generation of short lived
vasoactive proteins such as bradykinin, leading to
hypotension.
*Cyr M, Eastland T, Blais C, et al. Bradykinin metabolism and hypotensive transfusion reactions. Transfusion 2001;41:136-50
2nd Disadvantage!!!
Takahashi et al.
Bradykinin increased from
37pg/mL
6794pg/mL
some filters
(if ACE inhibitor added)
(Associated with production of )
Bradykinin
(during filtration of)
platelet concentrate
36000pg/mL
(because ACE inhibitor also inhibits
the kininases responsible for the
breakdown of bradykinin.)
These reactions led to recommendations to use pre-storage leukocyte
reduced components to eliminate this complication.
2nd Disadvantage!!!
Recently, these reactions were reported in a patient
taking ACE inhibitor, despite the fact that the Blood
was pre-storage leucocyte reduced; an inherited
defect in kinin metabolism was suspected*.
1. Patient taking ACE inhibitor and
2. Patients with inherited deficiencies of kininases
more susceptible to the hypotensive effects of
administered bradykinin.
*Arnold DM, Molinaro G, Warkentin TE, et al. Hypotensive transfusions reactions can occur with blood products that are
leukoreduction before storage. Transfusion 2004;44:1361-6.
3rd Disadvantage!!!
Reports of allergic reactions characterized by
– acute conjunctivitis,
– Pain at the site of blood infusion*, or
– Sudden onset of pain and
– Hypertension**
have been observed in some patients undergoing
transfusion of LR blood.
*Podlosky LR, Boskov LK. Infusion site pain related to bedside leucoreduction filters(letter). Transfusion 1995;35:362
**Haley NR, Sledge LS, Gibble J, et al. an unusual transfusion reaction pattern to leucocyte reduced red cells.
Transfusion 2000;40(suppl):40s
3rd Disadvantage!!!
• Although these events appear to occur in a very small
proportion of patients who undergo transfusion.
• The study highlight that even low-frequency adverse
consequences attributed to leucocyte filtration will
affect growing numbers of patients as the technology
becomes more widely used.
Disadvantage – Cost!!!
The major argument against leucodepletion is the cost of white cell
removal.
Leucocyte depletion adds a significant cost to each transfusion
episode.
Buffy coat removal costs approximately $2 per unit whilst second
and third generation filters cost between $15-$60 per RCC or
platelet transfusion.
Thus leucodepletion must be shown to be cost effective.
This means that their influence on patient clinical outcome must be
shown to be of sufficient benefit to warrant the cost of treating
all eligible patients within defined categories.
Not useful in…
a) Fresh frozen plasma (FFP) and cryoprecipitate
transfusion - as these blood components are
prepared with least cellular contamination and hence
do not require leucodepletion.
b) Prevention of transfusion associated graft versus
host disease (TAGVHD) - Gamma irradiation is the
method of choice for prevention of TAGVHD.
c) Transfusion associated acute lung injury (TRALI) is due to the leucocyte antibodies present in donor
plasma and leucodepletion is not useful in prevention
of TRALI.
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Future Evaluation
The role of leucodepletion is a complex one and its
ultimate place in transfusion is yet to be determined.
Health care professionals now have a responsibility to
ensure that new modalities of treatment produce a
clearly definable benefit to the patients in whom they
are used.
Cost is but one factor that must be assessed, but it is
no longer appropriate to recommend new and
expensive techniques such as leucodepletion without
well documented evidence of its efficacy.
Future Evaluation
This approach has been recently affirmed by the Royal
College of Physicians of Edinburgh who held a consensus
conference on leucodepletion.
There is likely to be a considerable amount of
information published on this topic over the next few
years and the role of leucodepletion will need to be
regularly reassessed in the light of results from the
relevant clinical trials.
Study!!!
• Using an analytical decision model a costeffectiveness analysis was conducted in a Hospital in
Queensland in 2007.
• This study has concluded that cost effectiveness is
not an influential factor in policy decision regarding
quality and safety initiatives in the Australian Blood
sector.
• The same hospital implemented Universal
Leucodepletion in 2008.
• A prospective RCT of leucocyte reduction in a major academic
medical centre failed to demonstrate a difference in in-hospital
mortality, hospital length of stay, or other secondary outcomes*.
• Other RCTs in HIV-infected patients** and trauma patient ***
failed to show a benefit in patient outcomes.
• A “before & after” study of the effects of adopting universal
leucoreduction in Canada reported that the unadjusted hospital
mortality rates declined from 7.03% to 6.19% (p<0.04)****
*Dzik S, Anderson JK, O’Neill M, et al. A prospective, randomized clinical trail of universal WBC reduction. Transfusion
2002;42:1114-22.
**Collier AC, Kalish LA, Busch MP, et al. Leucocyte-reduced red blood cell transfusions in patients with anemia and human
immunodeficiency virus infection: The viral activation transfusion study-a randomized controlled trial. JAMA
2001;285:1592-601.
***Nathens AB, Nester TA, Rubenfeld GD, et al. The effcts of leucoreduced blood transfusion on risk following injury: A
randomized controlled trial. Shock 2006;26:342-7.
****Hebert PC, Fergusson D, Blajchman MA, et al. Clinical Outcomes following institution of the Canadian universal
leucoreduction program for red cells transfusions. JAMA 2003;289:1941-9
• There was no difference in serious nosocomial
infections, although post-transfusion fevers and
antibiotic use did decrease.
• A similar analysis of Canadian data in premature
neonates found no difference in primary outcomes:
nosocomial bacteremia and neonatal intensive care unit
mortality*. Improvement in some secondary clinical
outcomes were reported.
• These two studies must be interpreted with caution,
however, because of their retrospective design and
potential bias from confounders.
*Fergusson D, Hebert PC, Lee SK, et al. Clinical outcomes following institutions of universal leucoreduction of blood
transfusions for premature infants. JAMA 2003;289:19560-6
• When viewed in the context of the negative RCTs noted
above, adoption of universal leucocyte reduction cannot
be justified on the basis of available scientific
evidence.
Other considerations such as
• logistics,
• public policy,
• public perception and
• mechanisms for funding leucocyte reduction
all play a role in making a final decision regarding
adoption of universal leucocyte reduction.
Deterrents !!!
•
•
•
•
High cost to blood services and hospitals.
Increase space requirements.
Equipments to be purchased.
More staff to be recruited and trained.
Universal leucodepletion: Cost/Benefit Analysis; Marcela Contreras Gac Méd Méx Vol. 140, Suplemento No. 3, 2004
References!!!
• ROSSI’S – Principles of Transfusion Medicine IVth
Edition, Leucocytes-reduced blood components,
2009;16:242-3
• AABB Technical Manual – 16th Edition, Hemotherapy
Decisions and their Outcomes, 2008;20:576-6