transfusion in palliative cancer patients: a review of the literature

17
Palliative Care Review Feature Editor: Vyjeyanthi S. Periyakoil Transfusion in Palliative Cancer Patients: A Review of the Literature Marı ´a Elena Uceda Torres, MD, 1 Juan Nicola ´ s Rodrı ´guez Rodrı ´guez, MD, PhD, 2 Jose ´ Luis Sa ´ nchez Ramos, MD, PhD, 3 and Francisco Alvarado Go ´ mez 4 Abstract Background: Transfusion is not an exceptional circumstance in palliative cancer patients (PCPs). This makes it necessary to confront not only medical aspects but also those of infrastructure and ethical issues. On some occasions, literature needs to be consulted to work out the best approach in a patient’s particular case. Our aim was to review the literature contained in PubMed and EMBASE so as to find out about the information available on transfusion in PCPs. Methods: A search for literature was carried out in databases PubMed and EMBASE, using ‘‘transfusion,’’ ‘‘cancer,’’ ‘‘end-of-life care,’’ ‘‘terminal care,’’ and ‘‘palliative care’’ as key words. Publications were classified according to the main topic discussed (clinical, infrastructure, and ethics) and the information included in each article critically assessed. Results: We found 334 articles but only 43 were considered valuable for the present study. Of these 43 articles, 21 deal with clinical topics while 12 deal with infrastructure and 10 with ethical issues. There is an absolute lack of randomized controlled trials or clinical guidelines. Trigger parameters for transfusion are not clearly established. Benefits of the procedure are shortly experienced and remain controversial. Home transfusions are encouraged, but this sole procedure has not been demonstrated to be cost effective. Different cultures, cases, and realities illustrate the diversity of the ethical management of transfusion in PCPs. Discussion: Although transfusion is certainly a common practice in PCPs, there is a relative lack of literature on this topic. Publications are unconnected and hardly any prospective studies have been performed. A large part of the little literature available only concerns descriptive and very general aspects of the issue. As transfusional products and financial and human resources are finite, it would be desirable to establish clear research lines on the different aspects considered (clinical, infrastructure, and ethical) that can help clinicians, nurses, patients, and carers to make a decision. Introduction T ransfusion is one of the treatments used to alleviate symptoms derived from cytopenias and coagulation disorders observed in cancer patients. Anemia is the most widely occurring cytopenia (50% of patients at some point during the evolution of their disease, 1 more in hematologic malignancies, and 70% of patients in the advanced period 2 ); but also platelets and coagulative factors can be affected. In the transfusion management of palliative cancer patients (PCPs), some particular aspects must be taken into account: the time and place of transfusion, trigger values for transfu- sion, the patient’s life expectancy, the patient’s and family’s willingness, the degree of improvement of the patient’s per- formance status with the transfusion, and the complications deriving from the procedure. At this moment, transfusion becomes one of the most dif- ficult problems doctors and nurses have to face. Curiously, any literature specifically concerning transfusion in palliative care is scarce. Moreover, only one previous review, restricted to red blood cell transfusion (RBC-T), clinical trials, and fo- cusing exclusively on clinical aspects, has been published very recently. 3 The aim of the present article is therefore to find out the information available regarding transfusion in PCPs, 1 U.G.C. Health Centre ‘‘Molino de la Vega,’’ Huelva, Spain. 2 U.G.C. Hematology, 4 Andalusian Public Health System Virtual Library, Hospital ‘‘Juan Ramo ´n Jime ´nez,’’ Huelva, Spain. 3 Nursing Department, University of Huelva, Huelva, Spain. Accepted September 2, 2013. JOURNAL OF PALLIATIVE MEDICINE Volume 17, Number 1, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2013.0387 88

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Page 1: Transfusion in Palliative Cancer Patients: A Review of the Literature

Palliative Care ReviewFeature Editor: Vyjeyanthi S. Periyakoil

Transfusion in Palliative Cancer Patients:A Review of the Literature

Marıa Elena Uceda Torres, MD,1 Juan Nicolas Rodrıguez Rodrıguez, MD, PhD,2

Jose Luis Sanchez Ramos, MD, PhD,3 and Francisco Alvarado Gomez4

Abstract

Background: Transfusion is not an exceptional circumstance in palliative cancer patients (PCPs). This makes itnecessary to confront not only medical aspects but also those of infrastructure and ethical issues. On someoccasions, literature needs to be consulted to work out the best approach in a patient’s particular case. Our aimwas to review the literature contained in PubMed and EMBASE so as to find out about the information availableon transfusion in PCPs.Methods: A search for literature was carried out in databases PubMed and EMBASE, using ‘‘transfusion,’’‘‘cancer,’’ ‘‘end-of-life care,’’ ‘‘terminal care,’’ and ‘‘palliative care’’ as key words. Publications were classifiedaccording to the main topic discussed (clinical, infrastructure, and ethics) and the information included in eacharticle critically assessed.Results: We found 334 articles but only 43 were considered valuable for the present study. Of these 43 articles, 21deal with clinical topics while 12 deal with infrastructure and 10 with ethical issues. There is an absolute lack ofrandomized controlled trials or clinical guidelines. Trigger parameters for transfusion are not clearly established.Benefits of the procedure are shortly experienced and remain controversial. Home transfusions are encouraged,but this sole procedure has not been demonstrated to be cost effective. Different cultures, cases, and realitiesillustrate the diversity of the ethical management of transfusion in PCPs.Discussion: Although transfusion is certainly a common practice in PCPs, there is a relative lack of literature onthis topic. Publications are unconnected and hardly any prospective studies have been performed. A large partof the little literature available only concerns descriptive and very general aspects of the issue. As transfusionalproducts and financial and human resources are finite, it would be desirable to establish clear research lines onthe different aspects considered (clinical, infrastructure, and ethical) that can help clinicians, nurses, patients, andcarers to make a decision.

Introduction

Transfusion is one of the treatments used to alleviatesymptoms derived from cytopenias and coagulation

disorders observed in cancer patients. Anemia is the mostwidely occurring cytopenia (50% of patients at some pointduring the evolution of their disease,1 more in hematologicmalignancies, and 70% of patients in the advanced period2);but also platelets and coagulative factors can be affected. Inthe transfusion management of palliative cancer patients(PCPs), some particular aspects must be taken into account:the time and place of transfusion, trigger values for transfu-

sion, the patient’s life expectancy, the patient’s and family’swillingness, the degree of improvement of the patient’s per-formance status with the transfusion, and the complicationsderiving from the procedure.

At this moment, transfusion becomes one of the most dif-ficult problems doctors and nurses have to face. Curiously,any literature specifically concerning transfusion in palliativecare is scarce. Moreover, only one previous review, restrictedto red blood cell transfusion (RBC-T), clinical trials, and fo-cusing exclusively on clinical aspects, has been published veryrecently.3 The aim of the present article is therefore to find outthe information available regarding transfusion in PCPs,

1U.G.C. Health Centre ‘‘Molino de la Vega,’’ Huelva, Spain.2U.G.C. Hematology, 4Andalusian Public Health System Virtual Library, Hospital ‘‘Juan Ramon Jimenez,’’ Huelva, Spain.3Nursing Department, University of Huelva, Huelva, Spain.Accepted September 2, 2013.

JOURNAL OF PALLIATIVE MEDICINEVolume 17, Number 1, 2014ª Mary Ann Liebert, Inc.DOI: 10.1089/jpm.2013.0387

88

Page 2: Transfusion in Palliative Cancer Patients: A Review of the Literature

which not only considers clinical but also infrastructure andethical aspects as well.

Methods

Search strategy

PubMed and EMBASE were chosen to be studied as theyare some of the most powerful and popular search engines formedical consultations. The period of investigation was 1946 to2011. The search in EMBASE was restricted to articles in-cluded exclusively in this database. Table 1 shows the searchstrategy followed and its results in both databases. Referencescontained in the articles finally selected were reviewed for thepossibility of finding additional papers of interest.

Selection criteria and process

A first selection was performed using the title and/or ab-stract idea of the article and using the following items (at leastone) as exclusion criteria:

1) Not in the English language.2) Pathologies other than cancer.3) Transfusion as a part of an active treatment (with or

without palliative intention).4) Nonpalliative patients.5) Others (radiology techniques, cancer evolution, and

miscellanea).

For those articles in which the title and/or abstract ideawere not available or were insufficient to clarify the content ofthe article, the article was read in its entirety to make thedecision regarding its content, following the same exclusioncriteria stated above.

Data extraction

To classify the purpose of the articles, the following aspectswere considered according to the central topic discussed bythe authors.

1) Clinical: product and incidence of transfusion; type ofpatient (pediatric or adult; solid or hematologic ma-lignancies); inpatient or home transfusion (outpa-

tients); parameters and triggers for decidingtransfusion; improvement of symptoms with the pro-cedure; transfusion as a prognostic factor for survival.

2) Infrastructure: possibility of home transfusion, infra-structure to perform it; and cost analysis.

3) Ethical.

Results and discussion have been outlined and carried outrespectively according to these three different aspects.

Results

Initially we found 157 articles in PubMed and 178 in EM-BASE for a final overall count of 334 articles (one redundantpublication was detected). Of these, 291 (87.1%) were ex-cluded, and only 43 (12.9%) were considered valuable for thereview. The main cause of exclusion was the consideration oftransfusion in the article as part of an active treatment. Those43 selected articles were grouped as follows.

Clinical (21 articles)

No clinical guidelines, reviews, or consensus conferenceshave been found. Only a position paper regarding platelettransfusion (Plt-T) in hematologic advanced malignanciescould be considered a certain guide to use. No clinical trialscomparing the efficacy of transfusion to placebo or other al-ternative treatments, e.g., erythropoietic stimulating agents(ESA) could be found either. Minimal or no references to freshfrozen plasma have been found in these articles. (See Table 2.)

RBC-T. The incidence of RBC-T in PCP is variable (5%–17.5%), being higher in hematologic malignancies, bleedingsolid tumors, inpatients, conventional care (general acute carehospitals), and in those admitted to oncology units. A mixtureof hemoglobin (Hb) levels (usually £ 8 g/dl) and clinical pa-rameters should be taken into account when deciding ontransfusion. Most patients are transfused only once during theperiod of study, and the mean of RBC units per patient is < 3.No frequent or important reactions related to these transfu-sions have been described. Six studies report the results ofRBC-T in terms of improving quality of life or feeling better.Approximately 60% of patients feel this benefit. This benefitdoes not seem to be related to age, pretransfusion Hb level,ECOG score, nor severity of pretransfusion symptoms relatedto anemia; and it seems to be higher in discharged patientsnow at home (78.6%). These benefits are observed early on(after two days), but are not sustained for any longer thanthree weeks later. One study focuses on RBC-T as a negativepredictor parameter for survival in solid tumors when per-formed in the last two weeks of life.

Plt-T. Plt-T is an increasingly valuable intervention inthese patients and is most frequently performed in hemato-logic patients. Most authors do not use these transfusions for aprophylactic purpose but rather for when a bleeding episodeoccurs. The frequency of Plt-T is slightly higher (1.6 per pa-tient) than the one for RBC-T. Reactions to these transfusionsare scarce as well.

Infrastructure (12 articles)

For most authors, transfusion at home is feasible andshould be a major objective in palliative care, because it helps

Table 1. Search Strategy and Results

Num. Query PubMed Embasea

#1 cancer 2,657,076 831,223#2 transfusion 119,539 63,384#3 end-of-life care 51,582 6,338#4 terminal care 41,775 6,190#5 palliative care 43,567 17,747#6 #3 OR #4 OR #5 83,893 21,897#7 #1 AND #2 AND #6 160 205#8 PubMed: #7 AND filters:

publication date from1/1/1950 to 12/31/2011Embase: #7 AND[ < 1966–2011]/py

157 178b

aEMBASE results reflect only those articles included exclusively inthis database.

bAfter crossover analysis, only one duplicated paper (both inEmbase) was detected.

py, publication year.

TRANSFUSION IN PALLIATIVE CANCER PATIENTS 89

Page 3: Transfusion in Palliative Cancer Patients: A Review of the Literature

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ien

ts(p

rob

ably

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eto

the

bet

ter

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form

ance

stat

us

of

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po

pu

lati

on

).T

ann

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erg

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nn

On

col

2004

;15:

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840.

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rvat

ion

al.

RB

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2p

atie

nts

.D

iver

seca

nce

rs.

Ou

tpat

ien

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on

tro

lo

fsy

mp

tom

sw

asac

hie

ved

for

am

ean

du

rati

on

of

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ter

each

tran

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n.

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ew

eek

afte

rtr

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usi

on

ther

ew

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cell

ent

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tro

lo

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mp

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sre

gar

din

gq

ual

ity

of

life

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dv

erse

reac

tio

ns

asso

ciat

edto

tran

sfu

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nw

ere

scar

ce.

Th

eyre

com

men

dd

esig

nin

gth

etr

eatm

ent

of

anem

iab

ased

on

anin

div

idu

alca

sean

aly

sis

by

the

med

ical

staf

fin

con

jun

ctio

nw

ith

the

pat

ien

t’s

pre

fere

nce

san

dv

alu

es.

(con

tin

ued

)

91

Page 5: Transfusion in Palliative Cancer Patients: A Review of the Literature

Ta

bl

e2.

(Co

nt

in

ue

d)

Au

thor

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efer

ence

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pe

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546.

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cip

ants

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iver

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ien

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tsp

ecifi

ed.

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ajo

rity

of

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tici

pan

tsag

reed

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ano

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ia/

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dic

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nsf

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sho

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tb

ew

ith

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dfr

om

term

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cer

pat

ien

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sho

uld

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nan

ind

ivid

ual

bas

is,

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nly

acco

rdin

gto

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ien

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clin

ical

stat

us.

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edia

trO

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l20

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Ob

serv

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late

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iver

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cers

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utp

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Hem

ato

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ign

anci

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.

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un

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ost

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um

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tw

hen

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ffer

edat

ho

me.

No

com

pli

cati

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ere

ob

serv

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Au

tho

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kth

atth

isse

rvic

ep

rov

ides

sup

po

rtto

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ien

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dre

lati

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and

that

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sfied

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hth

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e.M

any

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ne

con

sult

atio

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Inth

eec

on

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icst

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yp

erfo

rmed

by

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auth

ors

,th

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eatm

ent

mo

del

isec

on

om

ical

lysu

per

ior

toth

etr

adit

ion

alm

od

el(h

osp

ital

assi

stan

ce).

(con

tin

ued

)

92

Page 6: Transfusion in Palliative Cancer Patients: A Review of the Literature

Ta

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(Co

nt

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ue

d)

Au

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efer

ence

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e19

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han

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atie

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rep

ort

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rov

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ter

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tin

flu

ence

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qu

alit

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efit

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serv

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ot

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ien

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per

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ith

ino

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wee

kaf

ter

tran

sfu

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n.

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imp

rov

emen

tin

sig

ns

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cep

th

emat

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it),

sym

pto

ms,

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per

form

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us

was

ob

serv

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do

nly

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qu

alit

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dex

com

ple

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rate

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po

rted

feel

ing

mo

reu

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ost

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on

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he

ben

efit

of

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sfu

sio

nse

ems

tob

eo

nly

psy

cho

log

ical

for

pat

ien

ts.

(con

tin

ued

)

93

Page 7: Transfusion in Palliative Cancer Patients: A Review of the Literature

Ta

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(Co

nt

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sto

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ns

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ain

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2004

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(con

tin

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94

Page 8: Transfusion in Palliative Cancer Patients: A Review of the Literature

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evie

wo

nm

anag

emen

to

fca

rein

ped

iatr

icp

atie

nts

wit

had

van

ced

can

cer

(in

clu

din

gtr

ansf

usi

on

aso

ne

of

the

pro

ble

ms

totr

eat)

.

Min

imal

refe

ren

ceto

tran

sfu

sio

no

fre

db

loo

dce

lls

and

pla

tele

ts

Ped

iatr

icca

nce

rp

atie

nts

.In

-/o

utp

atie

nts

:n

ot

spec

ified

.V

ery

gen

eral

and

bri

efre

com

men

dat

ion

so

nth

eu

seo

fb

loo

dp

rod

uct

sin

the

trea

tmen

to

fb

leed

ing

.

Rip

amo

nti

C.

Su

pp

ort

Car

eC

ance

r19

99;7

:233

–243

.23

Rev

iew

on

man

agem

ent

of

dy

spn

eain

adv

ance

dca

nce

rp

atie

nts

(in

clu

din

gtr

ansf

usi

on

aso

ne

of

the

too

lsto

use

).

RB

CD

iver

seca

nce

rs.

In-/

ou

tpat

ien

ts:

no

tsp

ecifi

ed.

Rev

iew

on

the

use

fuln

ess

of

RB

Ctr

ansf

usi

on

sin

the

trea

tmen

to

fd

ysp

nea

.Id

eas

and

con

clu

sio

ns

are

ob

tain

edfr

om

oth

erar

ticl

esm

enti

on

edab

ov

e.

Las

sau

nie

re,

etal

.J

Pal

liat

Car

e19

96;1

2:38

–41.

24P

osi

tio

np

aper

.P

late

lets

Hem

ato

log

ical

pat

ien

ts.

In-/

ou

tpat

ien

ts:

no

tsp

ecifi

ed.

Rev

iew

on

pla

tele

tco

un

tsas

atr

igg

erfo

rtr

ansf

usi

on

(in

crea

sed

risk

of

ble

edin

gis

ob

serv

edw

ith

pla

tele

tco

un

tsu

nd

er20

x10

9/

l,an

des

pec

iall

yu

nd

er10

x10

9/

l).

Pro

ph

yla

ctic

pla

tele

ttr

ansf

usi

on

sar

en

ot

con

sid

ered

man

dat

ory

and

they

sho

uld

be

giv

ento

sto

pcl

inic

ally

sig

nifi

can

tb

leed

ing

.T

he

use

of

sin

gle

-do

no

rp

late

lets

isn

ot

reco

mm

end

ed,

and

po

ole

dra

nd

om

-do

no

rp

late

lets

are

pre

ferr

ed.

Ces

sati

on

of

pla

tele

ttr

ansf

usi

on

ssh

ou

ldb

eco

nte

mp

late

din

div

idu

ally

.

95

Page 9: Transfusion in Palliative Cancer Patients: A Review of the Literature

Ta

bl

e3.

Ar

tic

le

sF

oc

use

do

nT

ra

nsfu

sio

nin

Pa

ll

ia

tiv

eC

an

ce

rP

at

ie

nt

sw

it

hIn

fr

ast

ru

ct

ur

eA

sp

ec

ts

as

th

eC

en

tr

al

To

pic

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thor

sR

efer

ence

Ty

pe

ofst

ud

yT

ran

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sion

pro

du

ctT

yp

eof

pat

ien

tM

ain

fin

din

gs

Bia

nch

ini

E,

etal

.P

edia

trB

loo

dC

ance

r20

10;5

5:98

8.

43E

val

uat

ion

of

acti

vit

yo

fa

‘‘fo

ur

wh

eel

ho

spit

al.’’

Po

ster

abst

ract

.

RB

C,

pla

tele

tsP

edia

tric

can

cer

(hem

ato

log

ican

dn

on

hem

ato

log

ic)

pat

ien

tsn

ot

all

inp

alli

ativ

est

atu

s(1

8p

atie

nts

).O

utp

atie

nts

.

Tra

nsf

usi

on

sat

ho

me

are

feas

ible

,al

low

ing

anim

pro

vem

ent

of

the

qu

alit

yo

fli

feo

fp

atie

nts

(in

clu

din

gas

pec

tssu

chas

rela

tio

nsh

ipw

ith

rela

tiv

esan

dfr

ien

ds)

.

Ger

tzM

A.

Leu

kL

ym

ph

om

a20

09;5

0:31

3–31

4.

44O

pin

ion

arti

cle.

Pla

tele

tsH

emat

olo

gic

mal

ign

anci

es.

In-/

ou

tpat

ien

ts:

no

tsp

ecifi

ed.

Bri

efre

vie

wo

fp

late

let

lev

eltr

igg

erfo

rtr

ansf

usi

on

and

the

pro

ble

ma

term

inal

lyil

lth

rom

bo

cyto

pen

icp

atie

nt

rep

rese

nts

.A

refl

ecti

on

ism

ade

abo

ut

the

adv

anta

ges

of

pla

tele

ttr

ansf

usi

on

ath

om

eco

nsi

der

ing

the

pat

ien

t’s

hig

her

qu

alit

yo

fli

fean

dth

ere

du

ctio

no

fco

sts

com

par

edw

ith

clas

sica

lm

anag

emen

t.L

awlo

rP

,et

al.

Su

pp

ort

Car

eC

ance

r20

09;1

7:96

9.45

Ev

alu

atio

no

fth

erap

euti

cin

terv

enti

on

sin

ho

spic

e.P

ost

erab

stra

ct.

RB

CD

iver

seca

nce

rs.

Inp

atie

nts

.T

her

eis

asi

gn

ifica

nt

incr

ease

inth

era

tes

of

ther

apeu

tic

inte

rven

tio

ns

(in

clu

din

gtr

ansf

usi

on

s)in

pal

liat

ive

pat

ien

tsth

rou

gh

ou

tth

ed

ecad

e19

97–2

007.

Mac

Gra

thP

,et

al.

Su

pp

ort

Car

eC

ance

r20

09;1

7:52

7–53

7.

46In

terv

iew

of

hem

ato

log

ical

nu

rses

,p

alli

ativ

en

urs

es,

and

hem

ato

log

ists

totr

yto

dev

elo

pg

uid

elin

esfo

rb

est

pra

ctic

ein

clin

ical

and

sup

po

rtiv

eca

re.

Pla

tele

ts,

RB

CH

emat

olo

gic

alm

alig

nan

cies

.In

-/o

utp

atie

nts

:n

ot

spec

ified

.

Th

ere

isla

cko

fco

nse

nsu

sin

the

dif

fere

nt

clin

ical

per

son

nel

imp

lica

ted

inth

eca

reo

fh

emat

olo

gic

alp

atie

nts

abo

ut

the

atte

nti

on

toth

ese

pat

ien

tsin

the

case

of

cata

stro

ph

icb

leed

ing

.T

his

cou

ldm

ake

the

dis

char

ge

of

pat

ien

tsm

ore

dif

ficu

lt.

Th

ere

isg

reat

con

tro

ver

syre

gar

din

gth

eca

reo

fh

emat

olo

gic

alp

alli

ativ

ep

atie

nts

wit

ha

gre

atri

sko

fca

tast

rop

hic

ble

eds.

Fo

ra

gro

up

of

par

tici

pan

ts,

this

risk

isp

erce

ived

asan

imp

ort

ant

ob

stac

lefo

rd

yin

gat

ho

me;

ho

wev

erit

isn

ot

per

ceiv

edas

am

ajo

ro

bst

acle

tob

ein

gre

ferr

edto

pal

liat

ive

care

by

oth

ers.

Th

eu

seo

fb

loo

dp

rod

uct

sto

pre

ven

to

rle

ssen

the

ble

edin

gre

mai

ns

con

tro

ver

sial

asw

ell.

Ko

dam

aY

,et

al.

Jpn

JC

lin

On

col

2009

;39:

606–

611.

47R

etro

spec

tiv

e.R

evie

wo

fm

edic

alh

isto

ries

and

inte

rvie

wto

atte

nd

ing

ph

ysi

cian

s.

RB

C;

pla

tele

tsH

emat

olo

gic

mal

ign

anci

es(1

5p

atie

nts

).O

utp

atie

nts

.

Au

tho

rsco

nsi

der

that

for

man

yp

ract

itio

ner

s,tr

ansf

usi

on

sho

uld

be

con

du

cted

inm

edic

alin

stit

uti

on

s.H

om

eca

resh

ou

ldex

clu

de

pat

ien

tsw

ho

nee

dfr

equ

ent

tran

sfu

sio

ns

or

pla

tele

ttr

ansf

usi

on

s.

(con

tin

ued

)

96

Page 10: Transfusion in Palliative Cancer Patients: A Review of the Literature

Ta

bl

e3.

(Co

nt

in

ue

d)

Au

thor

sR

efer

ence

Ty

pe

ofst

ud

yT

ran

sfu

sion

pro

du

ctT

yp

eof

pat

ien

tM

ain

fin

din

gs

Mer

cad

ante

S,

etal

.P

alli

atM

ed20

08;2

2:76

0–76

7.48

Pro

spec

tiv

e.S

tud

yo

fcl

inic

alan

dfi

nan

cial

anal

ysi

so

fan

acu

tep

alli

ativ

eca

reu

nit

.

RB

CM

ain

lyso

lid

tum

ors

.In

pat

ien

ts.

Tra

nsf

usi

on

rate

sw

ere

rela

tiv

ely

hig

h(1

1.7%

)as

ap

oss

ible

refl

ecti

on

of

no

tco

nsi

der

ing

som

ep

atie

nts

form

ally

pal

liat

ive.

Au

tho

rsco

nsi

der

that

acu

tep

alli

ativ

eca

reu

nit

sar

eco

stef

fect

ive,

incl

ud

ing

tran

sfu

sio

ns

aso

ne

of

the

pro

ced

ure

sp

erfo

rmed

;b

ut

no

spec

ific

cost

stu

die

so

nth

isto

pic

hav

eb

een

per

form

ed.

Dev

lin

B,

etal

.C

om

mu

nit

yP

ract

2008

;81:

32–3

5.49

Ev

alu

atio

no

fd

om

icil

iary

blo

od

tran

sfu

sio

nse

rvic

e.T

elep

ho

ne

inte

rvie

ws

top

atie

nts

.

RB

CC

ance

ran

dn

on

can

cer

(16

pat

ien

ts).

Ou

tpat

ien

ts.

Au

tho

rsan

aly

zeth

eai

ms

and

use

fuln

ess

of

the

serv

ice,

avo

idin

gh

osp

ital

adm

issi

on

,co

mp

osi

tio

no

fth

est

aff

(in

clu

din

gd

iffe

ren

tn

urs

es,

hem

ov

igil

ance

coo

rdin

ato

r,an

dd

iffe

ren

tco

nsu

ltan

ts),

staf

ftr

ain

ing

,an

dre

sou

rce

con

sid

erat

ion

s.P

atie

nts

con

sid

erth

ese

rvic

eas

exce

llen

tan

dth

eyw

ou

ldre

com

men

dth

ed

om

icil

iary

blo

od

tran

sfu

sio

nto

oth

ers.

Fam

ilie

sal

sop

erce

ive

this

po

siti

ve

effe

ct.

Car

ton

iC

,et

al.

Hae

mat

olo

gic

a20

07;9

2:66

6–67

3.

50C

ost

anal

ysi

so

fa

do

mic

ilia

ryp

rog

ram

of

sup

po

rtiv

ean

dp

alli

ativ

eca

re.

RB

C;

pla

tele

tsH

emat

olo

gic

neo

pla

sms

(144

pat

ien

ts,

62%

inp

alli

ativ

esi

tuat

ion

).O

utp

atie

nts

.

Pat

ien

tsin

the

term

inal

ph

ase

of

thei

rd

isea

seh

ave

hig

her

cost

sre

late

dto

thei

rca

re(c

om

par

edto

oth

erp

has

eso

fth

ed

isea

se),

esp

ecia

lly

wh

ena

hig

her

nu

mb

ero

ftr

ansf

usi

on

s(>

4)ar

ere

qu

ired

.T

hes

eco

sts

can

be

exp

lain

edas

wel

lb

yth

eh

igh

ern

um

ber

of

med

ical

and

nu

rse

vis

its.

Sp

ecifi

cco

sts

of

tran

sfu

sio

nar

en

ot

anal

yze

d,

and

this

circ

um

stan

ceis

on

lyre

cog

niz

edas

anac

tiv

ity

that

incr

ease

sth

eco

sto

fth

ese

pat

ien

ts.

Mia

no

M,

etal

.H

aem

ato

log

ica

2002

;87;

637–

642.

51P

rosp

ecti

ve

stu

dy

on

the

feas

ibil

ity

of

ah

om

eca

rep

rog

ram

ina

ped

iatr

ich

emat

olo

gy

and

on

colo

gy

dep

artm

ent.

RB

C;

pla

tele

tsP

edia

tric

can

cer

and

hem

ato

log

ical

tum

ors

no

tal

lin

pal

liat

ive

stat

us

(ov

eral

l45

pat

ien

ts,

8o

fth

emp

alli

ativ

e).

Ou

tpat

ien

ts.

No

con

clu

sio

ns

can

be

dra

wn

spec

ifica

lly

abo

ut

tran

sfu

sio

ns.

Co

nsi

der

edo

ver

all,

the

pro

gra

mre

du

ced

day

so

fo

utp

atie

nt

clin

ican

din

pat

ien

tw

ard

ho

spit

aliz

atio

nti

me.

Mo

reo

ver

,th

ep

rog

ram

was

cost

effe

ctiv

e.

(con

tin

ued

)

97

Page 11: Transfusion in Palliative Cancer Patients: A Review of the Literature

Ta

bl

e3.

(Co

nt

in

ue

d)

Au

thor

sR

efer

ence

Ty

pe

ofst

ud

yT

ran

sfu

sion

pro

du

ctT

yp

eof

pat

ien

tM

ain

fin

din

gs

Cra

igJI

,et

al.

Tra

nsf

us

Med

1999

;9:3

1–36

.52

Pro

spec

tiv

est

ud

yo

nth

eef

fect

so

fd

edic

atin

ga

nu

rse

tom

anag

eth

ep

rov

isio

no

fb

loo

dp

rod

uct

ssu

pp

ort

inh

osp

ital

ou

tpat

ien

td

epar

tmen

tan

dh

om

eca

re(p

re-

and

po

stin

terv

enti

on

).C

ost

anal

ysi

s.Q

ues

tio

nn

aire

sto

pat

ien

tsto

mea

sure

thei

rsa

tisf

acti

on

wit

hth

ep

rog

ram

.

RB

C;

pla

tele

tsN

on

on

colo

gic

and

hem

ato

log

ical

tum

ors

no

tal

lin

pal

liat

ive

stat

us

(45

pat

ien

ts).

In-

and

ou

tpat

ien

ts.

Th

eo

ver

all

atte

nti

on

tim

eto

the

pat

ien

td

idn

ot

dif

fer

inh

om

eca

re,

bu

ta

sig

nifi

can

tre

du

ctio

nw

aso

bse

rved

inth

eh

osp

ital

ou

tpat

ien

td

epar

tmen

t.In

bo

thp

lace

sth

ew

aiti

ng

tim

efr

om

adm

issi

on

totr

ansf

usi

on

was

red

uce

dsi

gn

ifica

ntl

yan

dth

isw

ases

pec

iall

yap

pre

ciat

edb

yp

atie

nts

.H

om

eat

ten

tio

nre

du

ced

clin

icv

isit

s.A

nec

on

om

ican

aly

sis

(wit

hso

me

asp

ects

excl

ud

ed)

ism

ade

tok

no

wth

eco

sto

fth

isse

rvic

eat

ho

me.

Sp

etti

gu

eB

,et

al.

Nu

rsT

imes

1998

;94:

54–5

5.53

Cas

ere

po

rtd

escr

ibin

gth

efe

asib

ilit

yan

dp

roce

du

refo

rad

min

iste

rin

gh

om

etr

ansf

usi

on

s.

RB

CS

oli

dtu

mo

r.O

utp

atie

nt.

Tra

nsf

usi

on

ath

om

eis

feas

ible

wh

enan

adeq

uat

ein

fras

tru

ctu

reis

pro

vid

ed(m

ult

idis

cip

lin

ary

team

).

Vin

cig

uer

raV

,et

al.

Pro

gC

lin

Bio

lR

es19

86;2

16:1

55–1

64.

54C

om

par

ativ

eco

stan

aly

sis

of

ho

me

and

ho

spit

altr

eatm

ent.

RB

CN

ot

spec

ified

(218

pat

ien

ts,

174

ho

me

care

,an

d44

inst

itu

tio

nal

care

).In

-an

do

utp

atie

nts

.

Tra

nsf

usi

on

sat

ho

me

are

feas

ible

,w

ith

anad

equ

ate

infr

astr

uct

ure

.A

cost

anal

ysi

sre

vea

lsh

igh

erco

sts

inin

stit

uti

on

alca

reco

mp

ared

toh

om

eca

re.

Ho

wev

erth

isco

ncl

usi

on

can

no

tb

ecl

earl

yex

trap

ola

ted

totr

ansf

usi

on

on

ly,

asth

isac

tiv

ity

has

no

tb

een

stu

die

dsp

ecifi

call

y.

98

Page 12: Transfusion in Palliative Cancer Patients: A Review of the Literature

to improve the patient’s quality of life and reduces patients’and families’ anxiety. However, for others, this option is stillcontroversial, mainly regarding patients with a higher trans-fusion dependency and/or when Plt-T is needed due to theircomplexity, the amount of time these patients take up, or theinfrastructure necessary to perform this service. Also contro-versial are issues such as who should be involved in the de-cision to carry out transfusion (doctors and/or nurses;specialists, etc). (see Table 3.)

The cost analysis articles found do not focus exclusively ontransfusion but rather on patient care in general, transfusionbeing only a part of it. Only one article demonstrates thattransfusion needs of patients with hematologic malignanciessignificantly increase costs in domiciliary programs, regard-less of disease phase but mainly in advanced phases.

Ethical (10 articles)

The decision of transfusing at the end of life can vary ac-cording to patients’ and relatives’ preferences as well asphysicians’ opinions. However, there is a need to remark thatthe decision of whether to transfuse or not must be taken atthe bedside, individualizing every case, considering thepreferences of the patients and their families and with theiragreement. Only a minority of PCPs have written their owndirectives in advance, and transfusion is not considered aconsistent pattern in them. This generates many cases ofsurrogate decisions. When an agreement with the patient andtheir family’s preferences is not achieved, consultation withethics committees should be recommended. (See Table 4.)

Discussion

Transfusion is one of the treatments that can be used toalleviate symptoms derived from cytopenias or coagulationdisorders in PCPs. It is also one of the most striking dilemmasthat palliative care teams must confront, as it represents notonly a medical but also an ethical and structural problem.When confronting these situations, literature could be a greathelp. This is why we have tried to analyze in this descriptivework the information available about transfusions in PCPs,using two of the most representative and widely used searchengines (PubMed and EMBASE). We are aware that our re-view is limited by the relatively narrow terms of our literaturesearch and the restriction to English language only and tojournal articles included in both search engines.

The review undertaken reveals that publications regardingtransfusion in PCP, as contained in PubMed and EMBASE,are scarce and descriptive. Following are the topics treated bythe articles found and selected.

Clinical4–24

No clinical guidelines regarding this group of patients havebeen published. Only one position paper about Plt-T in he-matologic advanced malignancies24 was found. So, if clinicalguidelines are necessary, those concerning general popula-tion25–30 or cancer patients31–32 should be used. Furthermore,there is an almost total lack of clinical studies in pediatricpatients13 and regarding fresh frozen plasma transfusion.21

RBC-T. Contrary to all expectations, PCPs are rarelytransfused (incidence 5%–17.5%),20 and usually in less than

two sessions and most of them receive < 3 units.8,15 A higherproportion of transfusions has been observed in patients withhematological malignancies8 or bleeding solid tumors;8,15,16

those in conventional hospital care (versus hospices and homecare, in this decreasing frequency);10,19 those treated by on-cology units compared with palliative units;6 and inpatients15

(probably due to a better performance status in outpatients).10

The composition of the team attending the patient can alsoinfluence the incidence of transfusions.12 Almost 50% of pa-tients are transfused in their last five weeks of life,10 and 13.7%in their last week.9 An absence of improvement in symptomsrelated to anemia after transfusion has been associated with anearer proximity to death.15 Transfusion has been considereda negative predictor parameter for survival in solid tumorswhen practiced in the last 15 days of life.17 So the usefulness ofRBC-T in the last month of life should be considered withcaution.

PCPs have been demonstrated to be among the groups ofpatients prone to inappropriate transfusions when presetcriteria are used.33 So an Hb level ( £ 8 g/dl was the trigger inmost studies) must not be used as the only factor whenmaking a decision about whether or not to perform a trans-fusion; it should be considered in conjunction with clinicalaspects too. An individual analysis is desirable,20 especially,when the benefits of transfusion do not seem to correlate withthe pretransfusional Hb level.15 Another point for discussionis the objective of the transfusion. As the number of RBC unitstransfused is usually low, the alleviation of symptoms seemsto be the major goal of the procedure. However, some authorshave proposed that, as quality of life is a major objective, atransfusion of up to 12 g/dl in Hb levels should be per-formed.9

Focusing on the benefits of transfusion, this particularaspect remains unclear. Some difficulties should be con-sidered when evaluating this point:34–36 (1) symptoms re-lated to anemia are diverse and subjective (for patients,palliative staff, and between them); (2) the tools used tomeasure these symptoms (when described) are diverse andalso subjective and are not comparable with each other; and(3) no clinical trials comparing the efficacy of transfusionversus placebo or ESA have been performed. In those arti-cles in which an evaluation of the efficiency of transfusionhas been performed, it seems clear that a majority of patients(50% to 82%) benefit from transfusion.4,8,9,15,16 This effect isperceived from very early on (after two days),4,16 and ismaintained for up to almost three weeks (mean 18.5 days).11

This benefit does not seem to be related to age,8 pre-transfusion Hb level, ECOG score, nor severity of pre-transfusion symptoms related to anemia; and it appears tobe greater in patients discharged home (78.6%), probably asa reflection of their better performance status.15 However,these conclusions about a positive effect of transfusioncannot be generalized, with some authors reporting only apsychological benefit for the patient18 or even no benefit atall.10 A recently published review on RBC-T3 (with six pa-pers37–42 not included in the present review) included thesame databases we analysed, plus others (CINAHL, Web ofScience, ZETOC, and CENTRAL), and including random-ized controlled trials, before and after studies, and inter-rupted time series and the outcome of these transfusions inPCP; yet their conclusions do not differ from the conclusionsexpressed above.

TRANSFUSION IN PALLIATIVE CANCER PATIENTS 99

Page 13: Transfusion in Palliative Cancer Patients: A Review of the Literature

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Page 14: Transfusion in Palliative Cancer Patients: A Review of the Literature

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101

Page 15: Transfusion in Palliative Cancer Patients: A Review of the Literature

Finally, three additional aspects have to be considered:(1) The analytical investigation of the possible cause of anemiaseems to be rarely investigated.9 This could be interesting, as itis minimally disturbing for the patient, costs are low, and thefinding of deficiency anemia could be treated, avoidingtransfusions. (2) Risks and adverse reactions derived fromRBC-T seem to be so rare that these circumstances cannotbe an obstacle when in favor of a policy of home transfusions.(3) ESA cannot be routinely recommended except in thecontext of clinical trials due to the four to eight weeks’ delaybefore maximum benefit is achieved, possible side effects,their efficiency in only a few patients, and their cost.20

Plt-T. This is an ever increasing and valuable interventionin PCPs,5 especially in hematologic patients.7,13 The use of Plt-T for a prophylactic purpose is not recommended andshould be abandoned. However, its use to control significantclinical bleeding (when moderate to severe thrombocyto-penia occurs) could be mandatory.7,13 Two theoretical clin-ical aspects of Plt-T can be considered obstacles whenfacilitating this procedure at home:5 (1) the expected highfrequency of transfusion-related reactions and (2) the shortlifespan of platelets. Regarding the first, this circumstancehas not been observed,7,13,14 so the procedure cannot be ruledout just by considering this obstacle. Regarding the second,the short platelet lifespan makes a high number of transfu-sions necessary, and these can be very difficult to maintainand carry out if the patient lives far from his palliative teambase. A true recommendation in this aspect cannot be ex-pressed. However, its implementation is widely encouraged.

Infrastructure43–54

For most authors, home transfusions are desirable for thepatient and family’s comfort, as the displacement to hospitalsfor transfusion is disturbing.43,44,46,49,52–54 Moreover, it hasbeen published that 40% of unnecessary hospital admissionsare due to transfusions,55 so this is a potential way to reducehospitalization costs. While all authors consider this should bea priority, this service requires a very well organized infra-structure,49 which is time consuming and puts a strain onother resources (financial, transport, etc.), making it impos-sible in those places where the infrastructure is not organizednor guaranteed. However, some authors believe that homemanagement of patients with high transfusional needs couldbe very difficult and should be avoided.47 This latter extremeis still controversial even among the different members of thesanitary staff attending the patient.46

As most cost studies do not focus on transfusional activityalone but rather on the total cost of hospital or home care, it isdifficult to draw conclusions exclusively regarding transfusionalactivity. Demonstrating that home care of PCPs54 or that thedevelopment of acute palliative care units in hospitals48 are cost-effective measures does not necessarily mean that transfusioncosts in these circumstances are also lower. Only one articleabout hematological patients50 reflects that costs are increasedby transfusions in home programs, especially in terminal phases,due to the higher transfusional need of these patients and theincrease in the number of medical and nursing visits. In fact, thishigh need for transfusion may differentiate the costs and theorganizational model of home care for hematological patients(more complex) from that of patients with solid tumors.

Ethical56–65

Most of the articles found refer to American realities andthis must be taken into account, as other sociocultural envi-ronments can differ in their conclusions. Other cultures(Mediterranean and Far Eastern) are less represented.

Although transfusion in PCPs is recognized invariably as anethical problem, its frequency, however, does not seem to behigh and does not increase with the time of the patient’s ad-mission. Only the patient’s age being under 18 seems to be afactor that favors it.61 This could be a reflection of the tendencyfor more intensive treatment in younger patients and also thedifficulty that medical teams have to confront when surrogateddecisions are encountered. When making the decision totransfuse or not, pros (mainly improvement of quality of life)versus cons (mainly infrastructure and costs required) or risks(transfusion reactions) must be considered, not just from a teampoint of view, but also in conjunction with patients’ and rela-tives’ wishes and expectations.57,64 Cultural factors also influ-ence the physician’s decision to carry out transfusion in PCPs.Japanese physicians would recommend transfusion for PCPsregardless of the patient’s outlook and condition,63 whileFinnish doctors most often forgo this measure in these samepatients.59 So, a well-defined transfusion policy in every palli-ative care team is desirable to avoid differences in the man-agement of patients.62 This reduces problems with patientsand/or relatives and also within the team.

Only a minority of these patients have written down theirdirectives in advance and these rarely include transfusion.56

Surrogate decisions, sometimes even contrary to the patient’sbest interests, create another scenario for potential conflict.58

Some religious beliefs ( Jehovah’s Witnesses) are also prone tocreate ethical conflicts. This attitude can cause doctors to feelthat these patients are not receiving the best treatment avail-able.65 A fluid and profound communication with the patientsand their families is essential to avoid or reduce these prob-lems. In those cases in which the conflict has a difficult solu-tion, ethical committees should be consulted.60,64

In conclusion, with the limitations stated above in our study,the literature provided by PubMed and EMBASE regardingtransfusion in PCPs is scarce and unconnected between them,the level of evidence to make decisions based on it is very lowand no clear recommendations can be carried out. This pre-carious situation is reflected in the present article. When con-sulting literature on this topic, the use of more than one searchengine is desirable, although the number of relevant articlesdoes not increase substantially. Further clinical studies aredesirable to establish transfusion criteria or the objectives oftransfusion in this specific group of patients. In the same way,home transfusions seem to be preferable, but the infrastructureneeded to perform them is not widely agreed upon and aconsensus should be reached. Research should be done to re-veal whether this sole procedure is cost effective or not and inwhich patients. Finally, ethical studies focusing on transfusionas a specific point are also necessary. This would mainly be toidentify groups of people causing conflict, its incidence, itscauses, and the strategies needed to reach a solution. Thesestudies should be performed considering the different geo-graphical and social realities in which we live.

Author Disclosure Statement

No competing financial interests exist.

102 UCEDA TORRES ET AL.

Page 16: Transfusion in Palliative Cancer Patients: A Review of the Literature

Acknowledgments

The authors thank Dr. J. M. Nunez Olarte from the pallia-tive care unit of the Hospital ‘‘Gregorio Maranon’’ (Madrid,Spain) for his review of the manuscript.

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Address correspondence to:Juan Nicolas Rodrıguez Rodrıguez, MD, PhD

U.G.C./Servicio de HematologıaHospital ‘‘Juan Ramon Jimenez’’

21005 Huelva, Spain

E-mail: [email protected]

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