preoperative blood transfusions for sickle cell disease (review)

Preoperative blood transfusions for sickle cell disease (Review)

Hirst C, Williamson L

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library

2010, Issue 2

http://www.thecochranelibrary.com

Preoperative blood transfusions for sickle cell disease (Review)

Copyright 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

15DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 1 Perioperative mortality. . 16

Analysis 1.2. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 2 Serious complications related to

sickle cell disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Analysis 1.3. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 3 Postoperative Infection. . 17

Analysis 1.4. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 4 Life-threatening surgical

complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Analysis 1.5. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 5 Transfusion related

complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Analysis 1.6. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 6 Blood counts. . . . . . 19

Analysis 1.7. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 7 Volume of blood

transfusion/venesected. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Analysis 2.2. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 2 Serious complications related

to sickle cell disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Analysis 2.3. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 3 Postoperative Infection. 20

Analysis 2.5. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 5 Transfusion related

complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

21WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

21HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

22CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

22DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

22SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

23INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iPreoperative blood transfusions for sickle cell disease (Review)


[Intervention Review]

Preoperative blood transfusions for sickle cell disease

Ceri Hirst1, Lorna Williamson2

1AstraZeneca, Alderley Park, UK. 2National Blood Service, East Anglia Centre, Cambridge, UK

Contact address: Ceri Hirst, AstraZeneca, Parklands (90HW2Q1), Alderley Park, Cheshire, SK10 4TG, UK.

[email protected]. [email protected].

Editorial group: Cochrane Cystic Fibrosis and Genetic Disorders Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 2, 2010.

Review content assessed as up-to-date: 14 December 2009.

Citation: Hirst C, Williamson L. Preoperative blood transfusions for sickle cell disease. Cochrane Database of Systematic Reviews 2001,

Issue 3. Art. No.: CD003149. DOI: 10.1002/14651858.CD003149.


A B S T R A C T

Background

Sickle cell disease is one of the most common inherited diseases in the world, and can cause haemolytic anaemia, vaso-occlusive crises

and dysfunction in virtually any organ system in the body. Surgical procedures are often required. Blood transfusion regimens can be

used preoperatively in an attempt to increase transport of oxygen around the body and dilute the sickled red blood cells, thus reducing

the risk of vaso-occlusion.

Objectives

To assess the relative risks and benefits of preoperative blood transfusion regimens in people with sickle cell disease undergoing surgery

of any type in any setting.

Search strategy

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from

comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.

Date of the most recent search: 15 December 2009.

Selection criteria

All randomised or quasi-randomised controlled studies comparing preoperative blood transfusion regimens to different regimens or no

transfusion in people with sickle cell disease undergoing surgery.

Data collection and analysis

Both authors independently assessed study quality and extracted data.

Main results

The searches identified three studies, of which two, involving a total of 920 participants, were eligible for inclusion in the review. The

first study compared an aggressive transfusion regimen (decreasing sickle haemoglobin to less than 30%) to a conservative transfusion

regimen (increasing haemoglobin to 10 g/dl) in 604 elective operations in people with sickle cell disease. The conservative regimen was

found to be as effective as the aggressive regimen in preventing perioperative complications, and was associated with fewer transfusion-

related adverse events. The second study compared a preoperative transfusion group to a group receiving standard care, and did not

show an advantage to preoperative transfusion.

1Preoperative blood transfusions for sickle cell disease (Review)


Authors conclusions

While in general, conservative therapy appears to be as effective as aggressive therapy in preparation for surgery in people with sickle

cell disease, further research is needed to examine the optimal regimen for different surgical types, and to address whether preoperative

transfusion is needed in all surgical situations.

P L A I N L A N G U A G E S U M M A R Y

Blood transfusions for people with sickle cell disease before they undergo surgery

Once they have given up their oxygen, red blood cells in people with sickle cell disease become shaped like crescents. These cells can block

blood vessels, which causes problems throughout the body. People with sickle cell disease often need surgery, but this can increase the

number of sickle-shaped cells in the blood. Blood transfusions before an operation can help dilute the sickled red blood cells and increase

the level of oxygen in the blood. This reduces the risk of blood vessels becoming blocked causing further damage. Blood transfusions can

be full or partial. They can be linked to adverse events such as the development of antibodies to foreign red blood cells, iron overload,

infection rates after surgery and length of stay in hospital. Two studies with 920 people are included in the review. One study compared

full transfusion to partial transfusion. This showed no difference between the two treatments in preventing complications immediately

after surgery, but partial transfusion was linked to fewer adverse events. The second study compared transfusion to standard care and

did not show an advantage in transfusion. Both studies reported a range of complications related to transfusion. However, many details

of study design were not recorded in the published papers and statistical analysis indicated a lack of certainty in the findings. There is

not enough evidence to recommend blood transfusions before surgery for people with sickle cell disease as standard practice. A large

study should look at the best use of this treatment and consider different risk groups.

B A C K G R O U N D

Description of the condition

Sickle cell disease is a genetic haemoglobin disorder, which can

cause severe pain crises and dysfunction of virtually every organ

system in the body, ultimately causing premature death. Popula-

tions originating from sub-Saharan Africa, the Middle East and

parts of the Mediterranean are predominantly affected, but pop-

ulation movement has made this a worldwide problem. Approxi-

mately 10,000 people in the UK and one in sixty people in West

Africa now suffer from the disease (Davies 1997; Hickman 1999).

Despite vastly improved care services for people with sickle cell

disease, the average life expectancy for men and women with ho-

mozygous disease (SS) is still only 42 years and 48 years, respec-

tively (Platt 1994). There are many different types of sickle cell

disease, but the defining disease, homozygous sickle cell disease

(SS), is caused by the inheritance from both parents of an abnor-

mal gene for a haemoglobin chain. Variations with similar symp-

toms arise when one sickle gene is inherited along with another ab-

normal beta chain haemoglobin gene (Serjeant 1992), most com-

monly haemoglobin SC disease (SC) and sickle beta thalassaemia

(S Thal).

In sickle cell disease, the oxygenated red blood cells appear nor-

mal, but, once they have transported and given up their oxygen,

the haemoglobin molecules associate as crystals and distort the

red blood cells, giving the appearance of sickle-shaped cells. Blood

transfusions are undertaken in many people to maintain the oxy-

gen-carrying potential of blood and, in some situations, to dilute

the circulating sickle cells, thus reducing the risk of vaso-occlusive

episodes and anaemia (Serjeant 1992).

Surgical interventions are relatively common in people with sickle

cell disease, treating problems associated with persistent or acute

organ dysfunction. For example haemolytic anaemia causes in-

creased bilirubin levels and a high incidence of gallstones and

therefore cholecystectomy is frequently needed (Haberkern1997).

Hypersplenism and splenic sequestration and infarction may be

treated with splenectomy. Orthopaedic complications resulting

from avascular necrosis, bone infection and musculoskeletal mal-

formations may require joint replacement, drainage or surgical

correction (Vichinsky 1999). Ear, nose and throat (ENT) opera-



tions account for approximately one-fifth of surgical procedures

in this population (Waldron 1999). Surgical trauma, however, can

increase sickling and anaemia, and this may be exacerbated by res-

piratory depression associated with anaesthesia. Surgery in people

with sickle cell disease is associated with postoperative complica-

tions with frequencies ranging from 7% to 32% (Serjeant 1992).

Description of the intervention

Blood transfusions are frequently used in preparation for surgery.

Several regimens are used in current clinical practice. These in-

clude top-up transfusion (conservative), in which normal red cells

are given to dilute the sickle cells; and partial or full exchange

transfusion (aggressive), in which the individuals own blood is

removed and replaced. This can be done either immediately or up

to 14 days prior to surgery, although in preparation for elective

surgery it is usually undertaken at least 24 hours before the oper-

ation to maximise the oxygen transport capacity of the transfused

blood. Various practises are used, but with no consensus over the

bestmethod or the necessity of transfusion in specific surgical cases

(Bischoff 1988; Buchanan 1995; Fullerton 1981).

Why it is important to do this review

As well as the direct and indirect financial cost of blood transfu-

sions, they can adversely affect the individual, causing hypervis-

cous blood (precipitating vaso-occlusion), alloimmunisation (de-

velopment of antibodies to foreign red blood cells), haemolytic

transfusion reactions and infection from blood products. Red cell

transfusions can also contribute to iron overload andmay affect the

postoperative infection rate and inpatient stay (Vichinsky 1990).

These adverse costs and events are particularly relevant in the de-

veloping world where resources and equipment are limited and

the infection risks of transfused blood can be higher than in devel-

oped countries (Ohene-Frempong 1999). We aimed to examine

the available evidence for the relative risks and benefits of preop-

erative blood transfusion regimens.

O B J E C T I V E S

To determine whether there is evidence that preoperative blood

transfusion in people with sickle cell disease undergoing surgery:

1. reduces mortality;

2. reduces complications directly related to the surgical

procedure, such as local infection and bleeding;

3. reduces serious perioperative complications related to sickle

cell disease, including pain, acute sickle chest syndrome and the

postoperative frequency and severity of infections;

4. is associated with severe adverse events (as reported in the

included studies).

If transfusion had been shown to be beneficial, with minimal ad-

verse events, we would have compared the effectiveness of differ-

ent transfusion regimens (e.g. top-up versus exchange, timing of

the treatment) within and between studies.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All those randomised or quasi-randomised studies in which pre-

operative blood transfusion regimens are compared to either no

transfusionor a different transfusion regimen, in peoplewith sickle

cell disease undergoing either elective or emergency surgery. Stud-

ies for people undergoing elective and emergency surgery would

have been analysed separately.

Studies in which quasi-randomised methods, such as alternation,

are used would have been included if there were sufficient evidence

that the treatment and control groups were similar at baseline.

If there had been sufficient numbers of studies using quasi-ran-

domisation methods, then this group would have been analysed

separately.

Studies should include sufficient information regarding the clin-

ical setting, as factors relating to the availability of trained staff,

adequate surgical and anaesthetic equipment, safe blood and a

sanitary environment may have a profound effect on outcome.

Types of participants

People with homozygous sickle cell disease (SS), sickle beta tha-

lassaemia (S0 and S+) and sickle haemoglobin C disease (SC)

(proven by electrophoresis and sickle solubility test, with family

studies or DNA tests as appropriate) of all ages and both sexes

undergoing surgery of any type in any setting.

Types of interventions

Preoperative blood transfusion regimens compared to no transfu-

sion or alternative preoperative transfusion regimens (e.g. top-up

compared with partial or full exchange).

Types of outcome measures

Primary outcomes



1. Perioperative mortality

2. Serious complications related to sickle cell disease e.g. acute

chest syndrome, cerebrovascular accident, painful crisis

3. Postoperative infection (site, organism and severity)

Secondary outcomes

1. Life-threatening surgical complications, including a fall in

haemoglobin greater than 2 g/dl

2. Recognised and reported transfusion-related complications,

including alloimmunisation, infection from blood products,

procedural complications and transfusion reactions

3. Recovery period (intensive care unit and inpatient stay)

4. Quality of life (mobility, ability to work or attend school,

self-reliance)

5. Measures of organ damage (postoperative difference from

baseline) for example creatinine (kidney function), liver function

tests, lung function tests

6. Haemoglobin level and haemoglobin S percentage (pre-

transfusion, post-transfusion and post-operative)

7. Volume of red cells infused and, where known, volume of

blood venesected, with haematocrit

Search methods for identification of studies

Electronic searches

Relevant studies were identified

from the Groups Haemoglobinopathies Trials Register using the

terms: sickle cell AND blood transfusion AND preoperative.

The Haemoglobinopathies Trials Register is compiled from elec-

tronic searches of the Cochrane Central Register of Controlled

Trials (Clinical Trials) (updated each new issue of The Cochrane

Library) and quarterly searches of MEDLINE. Unpublished work

is identified by searching the abstract books of five major con-

ferences: the European Haematology Association conference; the

American Society of Hematology conference; the British Soci-

ety for Haematology Annual Scientific Meeting; the Caribbean

Health Research Council Meetings; and the National Sickle Cell

Disease Program Annual Meeting. For full details of all search-

ing activities for the register, please see the relevant section of the

Cystic Fibrosis and Genetic Disorders Group Module.

Date of the most recent search of the Groups

Haemoglobinopathies Trials Register: 15 December 2009.

Searching other resources

The bibliographic references of all retrieved literature were re-

viewed for additional reports of studies.

Data collection and analysis

Selection of studies

Two authors (CH and LW) independently selected the studies. If

disagreement arose on the suitability of a study for inclusion in

the review, we reached a consensus by discussion.

Data extraction and management

Two authors (CH and LW) independently extracted data using

standard data acquisition forms.

If the data had been available, outcome data, with the exception of

transfusion related complications, would have been grouped into

those measured during surgery and at 3 hours, 24 hours, 1 week

and 1 month after surgery.

Assessment of risk of bias in included studies

In order to assess the risk of bias in the included studies, we as-

sessed their methodological quality based on a method described

by Schulz (Schulz 1995). We categorised the following dimen-

sions of methodological quality as adequate, unclear or inadequate

and related these to a low, unclear or high risk of bias: allocation

concealment; and generation of the randomisation sequence. We

categorised RCTs according to whether double blinding had been

reported or not and estimated that the risk of bias would increase

when fewer people were blinded to the intervention. If disagree-

ment arose on the assessment of quality of an included trial, we

reached a consensus by discussion.

Measures of treatment effect

We recorded dichotomous outcomes (e.g. life or death), as present

or absent, whilst we recorded continuous data such as blood counts

and organ function tests (creatinine, etc) as either mean change

from baseline for each group or mean post-treatment values and

standard deviation for each group. We aimed to calculate a pooled

estimate of the treatment effect for each outcome across studies,

(for binary outcomes the odds of an outcome among treatment

allocated participants to the corresponding odds among controls).

Dealing with missing data

We would have sought full reports from authors if studies had

been published in abstract form, presented atmeetings or reported

to the co-authors. Where information was missing or unclear, we

would have contacted the primary investigator.

In order to allow an intention-to-treat analysis, irrespective of later

exclusion (regardless of cause) or loss to follow up, data were col-

lected by allocated treatment groups.



Assessment of heterogeneity

Heterogeneity between studies would have been tested for using

a standard chi-squared test and the I2 statistic (Higgins 2003).

The I2 statistic describes the percentage of the variability in effect

estimates that is due to heterogeneity rather than chance and its

values lie between 0% and 100%. A simplified categorization of

heterogeneity that we plan to use is of low (I2 value of 25%),

moderate (I2 value of 50%), and high (I2 value of 75%) (Higgins

2003).

Data synthesis

We based overall estimates on the fixed-effect model. If further

trials are included in the future, and if there is significant hetero-

geneity identified, we plan to use the random-effects model.

Subgroup analysis and investigation of heterogeneity

If heterogeneity between studies had been found, we would have

undertaken examination of subgroups to help to explain the rea-

sons for this. Subgroup analysis of type of surgery, severity of dis-

ease and participant age were performed where possible.

Sensitivity analysis

If heterogeneity between studies had been found, sensitivity anal-

ysis based on themethodological quality of the studies would have

been performed, including and excluding quasi-randomised stud-

ies.

R E S U L T S

Description of studies

See:Characteristics of included studies; Characteristics of excluded

studies.

Results of the search

Three studies were identified through literature searches (Al-

Jaouni 2006; Vichinsky 1995; Wali 2003).

Included studies

Two studies, including 920 participants, met the predefined in-

clusion criteria (Al-Jaouni 2006; Vichinsky 1995).

In the Vichinsky study, 551 participants who underwent a total

of 604 elective operations were included (Vichinsky 1995). The

surgical procedure was randomised into two groups for preopera-

tive transfusion: aggressive, designed to decrease the haemoglobin

S level to less than 30% (Group 1); and conservative, which was

designed to increase the haemoglobin level to 10 g/dl (Group 2).

Bloodwas fromSS negative donors, and participants with a history

of allergic reactions to transfusion received leuco-depleted blood.

In Group 1, 57% of participants received exchange transfusions

and 30% had repeated transfusions. In contrast, 77% of partici-

pants in Group 2 received a single transfusion.

Participant characteristics were similar in both groups (Table 1) (

Vichinsky 1995). Fifty-four per cent in Group 1 were males, com-

pared to 48% in Group 2. Age distribution was also balanced for

the age groups 0 years to 9 years, 10 years to 19 years and over 20

years. All participants were followed up for 30 days. Data regard-

ing risk factors for complications, participant history and surgical

risk category, defined according to a previously established system

(Cohen 1988), were also recorded. More participants in Group 1

had a history of cardiac disease, smoking or central nervous system

disease, although only the latter was statistically significant (P =

0.049). Surgical procedures were defined as low risk (e.g. inguinal

hernia repair), medium risk (e.g. intra-abdominal procedures), or

high-risk (e.g. intracranial procedures). The distribution was sim-

ilar between groups, although only one participant, who had re-

ceived the aggressive transfusion regimen, underwent a high-risk

procedure during the study.

Table 1. Patient characteristics - Vichinsky 1995

Characteristic Group 1 % of patient Group 2 % of patient

Male 54 48

Age 0-9 40 40

Age 10-19 35 36

Age >20 25 24



Table 1. Patient characteristics - Vichinsky 1995 (Continued)

Anaesthetic risk score

2 47 48

3 51 51

4 2 1

Screening findings

Oxygen saturation 4 12 13

Previous transfusions

0 23 25

1-10 53 54

>10 24 21

Alloimmunization 19 13



Table 1. Patient characteristics - Vichinsky 1995 (Continued)

Reaction 7 5

Complications were recorded and classified as minor (brief

temperature elevations and mild wound infections), serious (com-

plications requiring prolonged hospitalisations), or life threaten-

ing. Specifically defined complications included alloimmunisa-

tion, painful crisis, acute chest syndrome, neurological events, re-

nal complications and fever or infection. Data regarding transfu-

sion-related complications were also collected. Results were pre-

sented as a percentage of each group of operations. Further pub-

lications based on subsets of data from this study, and also in-

cluding non-randomised data, are discussed in more detail below

(Vichinsky 1995).

In the Al-Jaouni study, 369 participants were enrolled in two Saudi

Arabian hospitals between January 1996 and June 2001 (Al-Jaouni

2006). Participants were randomised to receive either preopera-

tive transfusion (simple or partial exchange transfusion) or no pre-

operative transfusion. In both groups, transfusions were allowed

during surgery to compensate for blood loss. Baseline character-

istics of patients were similar between groups, in terms of partici-

pant age, sickle cell disease type, gender and surgery type. Median

participant age was 16 years (range: 1 year to 35 years). Surgi-

cal procedures included adenoidectomy, tonsillectomy, total hip

arthroplasty, cholecystectomy, splenectomy, and obstetric and gy-

naecological surgeries. Participants were hydrated and oxygenated

perioperatively. Data were collected on complications in the in-

traoperative and postoperative periods (timing not specified).

Excluded studies

One study was ineligible because it did not use a randomised study

design (Wali 2003).

Risk of bias in included studies

Allocation

Both studies were described as randomised but neither gave any

details of the method, hence we judged them to have an unclear

risk of bias. Likewise, neither study reported on concealment of

allocation and were also judged to have an unclear risk of bias for

this criteria (Al-Jaouni 2006; Vichinsky 1995).

Blinding

Neither study reported on double blinding and we therefore

judged both to have an unclear risk of bias (Al-Jaouni 2006;

Vichinsky 1995). We consider that double blinding would not

have been possible for either clinicians or participants in these

studies due to the nature of the treatment under investigation;

however, it would be possible for outcome assessors to be blinded

to treatment group, but neither study reported on this.

Incomplete outcome data

Neither study stated whether an intention-to-treat analysis was

used (Al-Jaouni 2006; Vichinsky 1995).

In the Vichinsky study, of the original data collected on 692 sur-

gical procedures, which had been randomly allocated, 88 were

subsequently excluded due to cancellation of the surgery, diagnos-

tic error or refusal of the individual to participate in the study (

Vichinsky 1995). This represents 12.7% of the study population.

Forty-two were from Group 1 and 46 from Group 2. While it is

stated that the participant characteristics of this group were sim-

ilar in both groups, and that the age range was representative of

the whole sample, the fairly limited information of participant

characteristics provided in the paper, and the high exclusion rate,

detracts somewhat from the study.

We judged both studies to have an unclear risk of bias (Al-Jaouni

2006: Vichinsky 1995).

Effects of interventions

Aggressive versus conservative blood transfusions

One study evaluated this comparison (Vichinsky 1995).

Primary outcomes


Two participants died in the Vichinsky study, odds ratio (OR)

4.95 (95% confidence interval (CI) 0.24 to 103.49). Both men

had received aggressive transfusion therapy prior to splenectomy

and hip replacement operations. Both had a history of pulmonary



disease and developed respiratory failure after surgical complica-

tionswhich progressed tomulti-organ failure anddeath (Vichinsky

1995).

2. Serious complications related to sickle cell disease

The following complications were reported (Vichinsky 1995):

a. acute chest syndrome: 11% aggressive, 10% conservative, OR

1.10 (95% CI 0.65 to 1.86);

b. painful crisis: 5% aggressive, 7% conservative, OR 0.69 (95%

CI 0.35 to 1.37);

c. neurological event: 1% aggressive, 1% conservative, OR 0.99

(95% CI 0.20 to 4.96);

d. renal complication: 1% aggressive, less than 1% conservative,

OR 3.00 (95% CI 0.31 to 29.00);

e. miscellaneous: 6% aggressive, 5% conservative, OR 1.20 (95%

CI 0.60 to 2.44).

Therefore, it can be seen that serious complications were no more

prevalent in the conservative transfusion group than the aggressive

transfusion group. Only the sickle pain rate appears to be raised,

but this is not statistically significant (P = 0.09) (Vichinsky 1995).

3. Postoperative infection

Vichinsky reported that both aggressive and conservative regimen

groups had a perioperative infection rate of 7% (Vichinsky 1995).

However, post-operatively 7%of participants in the aggressive reg-

imen group had infections, 2% higher, although not significantly

different in statistical terms, OR 1.49 (95%CI 0.76 to 2.94), than

that of the conservative group (5%).

Secondary outcomes

1. Life-threatening surgical complications

Vichinsky reported that miscellaneous intra-operative complica-

tions occurred in 19% of participants receiving aggressive transfu-

sion therapy, and 20% of those in the conservative therapy group,

OR 0.85 (95% CI 0.57 to 1.28) (Vichinsky 1995).

2. Transfusion-related complications

In the Vichinsky study, alloimmunisation occurred in 10% of par-

ticipants in the aggressive transfusion group, but only 5% in the

conservative group, OR 2.34 (95% CI 1.22 to 4.49) (Vichinsky

1995). Haemolysis, delayed or immediate, was seen in 6% of par-

ticipants in the aggressive group and 1% in the conservative group,

OR 4.97 (95% CI 1.67 to 14.78). Only four participants suffered

allergic or anaphylactic reactions, three in the conservative group

(1%) and one in the aggressive group (less than 1%). Other trans-

fusion-related complications included fever (four in each group)

and fluid overload resulting in respiratory distress (three partici-

pants, all in the aggressive group).

3. Recovery period

The average inpatient stay in both groups was eight days (

Vichinsky 1995).

4. Quality of life

This was not recorded as an outcome measure in the Vichinsky

study (Vichinsky 1995).

5. Measures of organ damage

This was not recorded as an outcome measure in the Vichinsky

study (Vichinsky 1995). However, renal complications were seen

in 1% of participants who received aggressive transfusion therapy

and less than 1% of those who received conservative therapy, and

neurological events occurred in 1% of participants in both groups.

6. Haemoglobin level and haemoglobin S percentage (pre-

transfusion, post-transfusion and post-operative)

The average haemoglobin levels were similar in both groups before

and after transfusion: 8 g and 7.9 g at the time of enrolment,

11 g and 10.6 g prior to surgery (Vichinsky 1995). The average

preoperative sickle haemoglobin (HbS) was 31% in group 1 and

59% in Group 2. White blood cell counts were not recorded in

the study (Vichinsky 1995).

7. Volume of blood transfused, and where known venesected

On average the participants in Group 1 received 5 units of blood,

compared to 2.5units inGroup2.The volume of blood venesected

was not recorded as an outcome measure in this study (Vichinsky

1995).

Preoperative blood transfusion versus no transfusion

One study evaluated this comparison (Al-Jaouni 2006).

Primary outcomes


Deaths were not specifically reported in the Al-Jaouni study; how-

ever the report states that there were no major intra- or post-op-

erative complications in either group (Al-Jaouni 2006).



2. Serious complications related to sickle cell disease

In the Al-Jaouni study, there were more painful crises, OR 1.62

(95% CI 0.38 to 6.88); neurological complications (unspecified),

OR 8.85 (95%CI 0.47 to 165.63); and respiratory complications,

OR 1.36 (95% CI 0.42 to 4.37) in the transfusion group than in

the no transfusion group, although differenceswere not statistically

significant (Al-Jaouni 2006).

3. Postoperative infection

There was no difference in incidence of perioperative infection be-

tween groups, OR 0.96 (95% CI 0.19 to 4.83) (Al-Jaouni 2006).

Secondary outcomes

1. Life-threatening surgical complications

This outcome was not reported in the included study (Al-Jaouni

2006).

2. Transfusion-related complications

In the Al-Jaouni study, there were five cases of circulatory over-

load or heart failure in the transfusion group, but none in the no

transfusion group, OR 10.88 (95%CI 0.60 to 198.20) (Al-Jaouni

2006). The wide confidence intervals around this non-significant

result indicate a lack of statistical power (due to low number of

cases).

None of the other secondary outcomes were reported in the Al-

Jaouni study (Al-Jaouni 2006).

D I S C U S S I O N

It is widely agreed that people with sickle cell disease should be

warm, well-hydrated and well-oxygenated for surgery in order to

avoid conditions that could lead to relative or regional hypoxia,

increased sickling and compromised oxygen delivery to tissues (

Serjeant 1992). However, use of various blood transfusion reg-

imens, while theoretically efficacious, has not been conclusively

shown to be beneficial, and has significant associated costs, both

economic and physical. This systematic review has highlighted a

lack of prospective randomised controlled studies of preoperative

blood transfusion for people with sickle cell disease.

The first study included in this review, by the Preoperative Trans-

fusion in Sickle Cell Disease Study Group (Vichinsky 1995), has

shown that, in general, conservative transfusion (Hb 10 g/dl) does

not carry an increased risk of perioperative complications over ag-

gressive transfusion (HbS less than 30%), and is associated with

fewer transfusion reactions. However, since concealment of allo-

cation, randomisation sequence generation, double blinding and

intention-to-treat analysis were not recorded in the published pa-

pers, this could depreciate the reliability of the findings. In ad-

dition, the wide confidence intervals for many of the outcomes

measured could indicate a lack of certainty in these findings, and

the implications for research should be viewed in light of these

relative limitations.

Subsets of these data have been included in several studies, which

also include non-randomised data, to ascertain the generalisability

for specific operations or participants groups. In addition, other,

non-randomised studies address the role of preoperative blood

transfusions in sickle cell disease. An increasing body of obser-

vational data suggests that preoperative blood transfusion may

reduce morbidity and mortality associated with surgery in peo-

ple with sickle cell disease (Bhattacharyya 1993; Fullerton 1981;

Halvorson 1997; Ware 1988). This is backed by findings from

the Cooperative Study of Sickle Cell Disease, the largest study

undertaken with sickle cell participants, which included 1079 sur-

gical procedures on 717 participants and spanned 10 years of clin-

ical practice in North America. However, many clinicians refute

these findings and practise successfully with minimal use of trans-

fusions (Bischoff 1988; Griffin 1993). In the latter study Griffin

found an overall complication rate of 26%, which rose to 52% for

major procedures such as cholecystectomy, but was only 5% for

minor operations such as herniorrhaphy and tympanostomy. This

data, though non-randomised, would support use of transfusions

in major, but not minor, surgical procedures.

In the first included study, 22.5% of participants underwent ton-

sillectomy, adenoidectomy or myringotomy (Vichinsky 1995). A

subgroup analysis, including these 118 randomised and a fur-

ther 47 non-randomised participants, was undertaken (Waldron

1999), and it was again concluded that a conservative regimen was

as effective as a more aggressive one in reducing adverse events.

Although the non-transfused group was small, the authors specu-

lated that while preoperative blood transfusions may be beneficial

in higher risk surgical procedures, the shorter duration of surgery,

decreased risk of blood loss and lack of airway involvement evident

in myringotomy may make transfusions unnecessary in these par-

ticipants. Similarly, a non-randomised comparison of sickle par-

ticipants undergoing myringotomy showed a higher overall com-

plication rate in transfused participants (43%) than those without

transfusion (13%) (Orringer 1995). However, with the more in-

vasive procedure of hip core decompression, non-transfused par-

ticipants had a significantly greater risk of postoperative compli-

cations.

Cholecystecomy is the most common surgical procedure required

by people with sickle cell disease. In a subset of 230 participants

from the Preoperative Transfusion in Sickle Cell Disease Study,

plus a non-randomised branch which included 37 non-transfused

and 97 transfused participants, it was suggested that preoperative



transfusion reduced sickle-related adverse events in participants

undergoing cholecystectomy (Haberkern 1997). Although the un-

transfused group had a higher incidence of perioperative pain and

acute chest problems, there was no increased morbidity overall,

and no adverse events and costs associated with transfusion. Be-

cause of the small number of participants in the non-transfused

group, the differences in participant characteristics and the par-

tially non-randomised study design, the results of this subset may

not be generalisable. However, smaller, non-randomised, studies

have also advocated the use of transfusions prior to cholecystec-

tomy (Bhattacharyya 1993; Ware 1988).

Orthopaedic surgery appears to carry a very high risk of compli-

cations (Vichinsky 1999), and this subset of the study group plus

non-randomised data showed 67% of participants suffered a se-

rious adverse event. Most common were excessive intra-operative

blood loss, sickle-related events and infection. There are no ran-

domised data available addressing the effectiveness of transfusion

in these cases.

There is also a lack of data regarding surgery in people with

haemoglobin sickle cell disease (HbSC). In a non-randomised

study by the same group, Neumayr recommended selective trans-

fusions prior to surgery, although with minor procedures such

as myringotomy he speculated that this may be unnecessary (

Neumayr 1998).

The second study, which included 369 participants in Saudi Ara-

bia, demonstrated no advantage, in terms of reduced sickle-re-

lated complications, perioperative infection and transfusion-re-

lated complications, for preoperative transfusion compared to no

preoperative transfusion, but these findings are limited by lack of

information on methodological quality and patient characteris-

tics (Al-Jaouni 2006). No major complications were reported in

either the transfusion or no-transfusion groups, but there were

significantly more complications overall in participants receiving

transfusion, and surgery was delayed in 24% of participants in

the transfusion group, compared to 0.6% in the no transfusion

group, due largely to the protocol need to fulfil the criteria of HbS

concentration of greater than 40% (Al-Jaouni 2006).

Preoperative transfusion has become almost routine for people

with sickle cell disease in North America. However, developing

countries often do not have the resources to support such an ex-

tensive programme. The potential risks associated with transfu-

sion therapy are increased in such settings due to a lack of trained

staff, modern equipment, sanitary conditions and clean, infection

free blood products (Ohene-Frempong 1999). Therefore, the risk-

benefit ratio will be different in developing countries to those in

the included study, and the results discussed in this reviewmay not

be generalisable to this setting. Transfusions are undertaken less

frequently in countries such as Jamaica than in North America,

and interestingly, observational studies from this setting do not

report significantly increased morbidity or mortality in operations

without transfusion (Homi 1979; Thame 1999). Whether this is

due to the setting or clinical differences is unclear, but such studies

imply overuse of preoperative transfusion in sickle cell disease.

With recent research demonstrating potential for several pharma-

cological therapies (Brugnara 2000; Charache 1995) and bone

marrow or stem cell transplants becoming increasingly feasible (

Davies 1996), the quality of life for people with sickle cell disease

is set to improve. Indeed, the demand for blood transfusions is

likely to decline with the introduction of alternative treatments,

less invasive surgical techniques, such as laparoscopic surgery, and

improved anaesthetic agents. However, more sound evidence in

the form of well-run, multi-centre, randomised controlled studies

is required to optimise the clinical management regimen for these

people.

A U T H O R S C O N C L U S I O N S

Implications for practice

While the first included study did not show evidence that aggres-

sive transfusion presents an advantage over conservative transfu-

sion for preoperative management of people with sickle cell dis-

ease, recommendations concerning the optimal use of the therapy

for subgroups of surgical and patient type cannot be made and

need further elucidation in randomised studies (Vichinsky 1995).

In addition, the second included study did not show an advantage

to preoperative transfusion over standard care, but these findings

are limited by lack ofmethodological data (Al-Jaouni 2006). There

is, therefore, insufficient reliable evidence to show that routine

preoperative transfusions compared to no transfusion is beneficial

for surgical procedures.

Implications for research

Information from a well-designed prospective randomised con-

trolled study of preoperative blood transfusion in people with

sickle cell disease is urgently required in order to make recommen-

dations for the optimal use of this therapy. The study should in-

clude transfused and non-transfused participants. Subgroup anal-

ysis for different surgical risk groups and participant risk factors

should also be done to provide guidance on the optimal preop-

erative management regimen for each individual with sickle cell

disease undergoing surgery. Without conclusive data of this type,

people with sickle cell disease may be undergoing unnecessary

treatment, suffering avoidable adverse events and incurring con-

siderable economic costs through inefficient use of the therapies

available.



R E F E R E N C E S

References to studies included in this review

Al-Jaouni 2006 {unpublished data only}

Al-Jaouni S, Al-Muhayawi S, Qari M, Nawas MA, Abdel-Razeq H.

The safety of avoiding transfusion preoperatively in patients with

sickle cell hemoglobinopathies [abstract]. Blood 2002;100(11 Pt 2

of 2):21b. Al-Jaouni S, Al-Muhayawi SM, Qari MH, Nawas MA, Al-

Mazrooa A. Randomized clinical trial to evaluate the safety of

avoiding pre-operative transfusion in sickle cell anemia. Bahrain

Medical Bulletin 2006;28(4):1647.

Vichinsky 1995 {published data only}

Haberkern CM, Neumayr L, Earles AN, Robertson S, Black D,

Orringer EP, et al.Cholecystectomy in sickle cell anaemia (SCA)

patients: report of 364 patients from the Preoperative Transfusion

Study [abstract]. Blood 1995;86(10, Suppl 1):142a.

Haberkern CM, Neumayr L, Earles AN, Robertson S, Black D,

Orringer EP, et al.Cholecystectomy in sickle cell anemia patients:

report of 364 patients from the Preoperative Transfusion Study

[abstract]. Proceedings of the 21st Annual Meeting of the National

Sickle Cell Disease Program. 1996:45.

Haberkern CM, Neumayr LD, Orringer EP, Earles AN, Robertson

SM, Black D, et al.Cholecystectomy in sickle cell anemia patients:

perioperative outcome of 364 cases from the National Preoperative

Transfusion Study. Preoperative Transfusion in Sickle Cell Disease

Study Group.. Blood 1997;89(5):153342.

Neumayr L, Koshy M, Haberkern C, Earles AN, Bellevue R,

Hassell K, et al.Surgery in patients with hemoglobin SC disease.

Preoperative Transfusion in Sickle Cell Disease Study Group.

American Journal of Hematology 1998;57(2):1018.

Orringer EP, Olivieri NF, Neumayr L, Haberkern C, Vichinsky EP.

Is preoperative transfusion always necessary in sickle cell anemia

(SCA)? [abstract]. Blood 1995;86 Suppl:300a.

Preoperative Transfusion Study Group. Preliminary report on

preoperative transfusion study in sickle cell disease [abstract].

Proceedings of the 14th Annual Meeting of the National Sickle Cell

Disease Program. 1989:63.

Vichinsky EP. High rates of complications in sickle cell anemia

(SCA) patients undergoing orthopedic surgery [abstract].

Proceedings of the 22nd Annual Meeting of the National Sickle

Cell Disease Program. 1997:125. Vichinsky EP, Haberkern CM, Neumayr L, Earles AN, Black D,

Koshy M, et al.A comparison of conservative and aggressive

transfusion regimes in the perioperative management of sickle cell

disease. New England Journal of Medicine 1995;333(4):20613.

Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J,

Koshy M, et al.The perioperative complication rate of orthopedic

surgery in sickle cell disease: report of the National Sickle Cell

Surgery Study Group. American Journal of Hematology 1999;62(3):

12938.

Waldron P, Pegelow C, Neumayr L, Haberkern C, Earles A,

Wesman R, et al.ENT surgery in sickle cell disease: perioperative

morbidity [abstract]. Proceedings of the 22nd Annual Meeting of

the National Sickle Cell Disease Program. 1997:124.


Wesman R, et al.Tonsillectomy, adenoidectomy and myringotomy

in sickle cell disease: perioperative morbidity. Journal of Pediatric

Hematology/Oncology 1999;21(2):12935.

References to studies excluded from this review

Wali 2003 {published data only}

Wali YA, al Okbi H, al Abri R. A comparison of two transfusion

regimens in the perioperative management of children with sickle

cell disease undergoing adenotonsillectomy. Pediatric Hematology

and Oncology 2003;20(1):713.

Additional references

Bhattacharyya 1993

Bhattacharyya N, Wayne AS, Kevy SV, Shamberger RC.

Perioperative management for cholecystectomy in sickle cell disease.

Journal of Pediatric Surgery 1993;28(1):725.

Bischoff 1988

Bischoff RJ, Williamson A, Dalali MJ, Rice JC, Kerstein MD.

Assessment of the use of transfusion therapy perioperatively in

patients with sickle cell hemoglobinopathies. Annals of Surgery

1988;207(4):4348.

Brugnara 2000

Brugnara C. Red cell dehydration in pathophysiology and

treatment of sickle cell disease. Web-site: Joint centre for sickle cell

and thalassaemic disorders, Harvard Medical School 2000.

Buchanan 1995

Buchanan GR, Rogers ZR. Conservative versus aggressive

transfusion regimens in sickle cell disease [letter]. New England

Journal of Medicine 1995;333(24):16412.

Charache 1995

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert

SV, et al.Effect of hydroxyurea on the frequency of painful crises in

sickle cell anemia. New England Journal of Medicine 1995;332(20):

131722.

Cohen 1988

Cohen MM, Duncan PG, Tate RB. Does anaesthesia contribute to

operative mortality?. Journal of the American Medical Association

1988;260(19):285963.

Davies 1996

Davies SC, Roberts IA. Bone marrow transplant for sickle cell

disease - an update. Archives of Disease in Childhood 1996;75(1):

36.

Davies 1997

Davies SC, Oni L. Management of patients with sickle cell disease.

British Medical Journal 1997;315(7109):65660.

Fullerton 1981

Fullerton MW, Philippart AI, Sarnaik S, Lusher JM. Preoperative

exchange transfusion in sickle cell anaemia. Journal of Pediatric

Surgery 1981;16(3):297300.

Griffin 1993

Griffin TC, Buchanan GR. Elective surgery in children with sickle

cell disease without preoperative blood transfusion. Journal of

Pediatric Surgery 1993;28(5):6815.



Haberkern 1997

Haberkern CM, Neumayr LD, Orringer EP, Earles AN, Robertson

SM, Black D, et al.Cholecystectomy in sickle cell anaemia patients:

perioperative outcome of 364 cases from the National Preoperative

Transfusion Study. Blood 1997;89(5):153342.

Halvorson 1997

Halvorson DJ, McKie V, McKie K, Ashmore PE, Porubsky ES.

Sickle cell disease and tonsillectomy: preoperative management and

postoperative complications. Archives in Otolaryngol Head and Neck

Surgery 1997;123(7):68992.

Hickman 1999

Hickman M, Modell B, Greengross P, Chapman C, Layton M,

Falconer S, et al.Mapping the prevalence of sickle cell and beta

thalassaemia in England: estimating and validating ethnic-specific

rates. British Journal of Haematology 1999;104(4):8607.

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring

inconsistency in meta-analyses. BMJ 2003;327(7414):55760.

Homi 1979

Homi J, Reynolds J, Skinner A, Hanna W, Serjeant G. General

anaesthesia in sickle cell disease. British Medical Journal 1979;1

(6178):15991601.

Neumayr 1998

Neumayr L, Koshy M, Haberkern C, Earles AN, Bellevue R,

Hassell, K, et al.Surgery in patients with hemoglobin SC disease.

American Journal of Hematology 1998;57:1018.

Ohene-Frempong 1999

Ohene-Frempong K. Sickle cell disease in the United States of

America and Africa [abstract]. Hematology 1999:64.

Orringer 1995

Orringer EP, Olivieri NF, Neumayr L, Haberkern C, Vichinsky EP.

Is preoperative transfusion always necessary in sickle cell anemia

(SCA)? [abstract]. Blood 1995;86 Suppl:300a.

Platt 1994

Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg

MH, et al.Mortality in sickle cell disease: life expectancy and risk

factors for early death. New England Journal of Medicine 1994;330

(23):163944.

Schulz 1995

Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence

of bias. Dimensions of methodological quality associated with

estimates of treatment effects in controlled trials. Journal of the

American Medical Association 1995;273(5):40812.

Serjeant 1992

Serjeant GR. Surgery and anaesthesia. Sickle Cell Disease. Oxford

Medical Publications, 1992:4558.

Thame 1999

Thame JR, Hambleton IR, Serjeant GR. Transfusion experience in

the Jamaican cohort study of sickle cell disease [abstract]. West

Indian Medical Journal 1999;48(Suppl 2):21.

Vichinsky 1990

Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin

B. Alloimmunization in sickle cell anaemia and transfusion of

racially unmatched blood. New England Journal of Medicine 1990;

322(23):161721.

Vichinsky 1999

Vichinsky EP, Neumayr LD, Haberkern C, Earles AN, Eckman J,

Koshy M, et al.The perioperative complication rate of orthopedic

surgery in sickle cell disease: report of the National Sickle Cell

Surgery Study Group. American Journal of Hematology 1999;62(3):

12938.

Waldron 1999


Wesman R, et al.Tonsillectomy, adenoidectomy and myringotomy

in sickle cell disease: perioperative morbidity. Journal of Pediatric

Hematology/Oncology 1999;21(2):12935.

Ware 1988

Ware R, Filston H, Schultz WH, Kinney TR. Elective

cholecystectomy in children with sickle hemoglobinopathies.

Successful outcome using a preoperative transfusion regimen.

Annals of Surgery 1988;208(1):1722. Indicates the major publication for the study



C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Al-Jaouni 2006

Methods Randomised controlled trial, method of randomisation not specified.

Participants 369 participants with sickle cell anaemia.

Interventions Preoperative simple or partial exchange transfusion versus no preoperative transfusion.

Outcomes Painful crises, neurological complications, respiratory complications, circulatory over-

load, infections, delay of surgery.

Notes

Risk of bias

Item Authors judgement Description

Adequate sequence generation? Unclear Not reported.

Allocation concealment? Unclear Not reported.

Blinding?

All outcomes

Unclear Double blinding not possible for partici-

pants and clinicians, not clear of outcome

assessors were blinded.

Incomplete outcome data addressed?

All outcomes

Unclear It was not stated whether an intention-to-

treat analysis was used.

Vichinsky 1995

Methods Randomised controlled trial, method of randomisation not specified.

Participants 551 participants with homozygous sickle cell disease confirmed by electrophoresis.

Interventions Aggressive (HbS < 30%) versus conservative (Hb > 10 g/dl) preoperative blood transfu-

sion.

Outcomes Death, miscellaneous intra-operative event, acute chest syndrome, fever or infection,

miscellaneous post-operative event, painful crisis, neurological event, renal complication.

Notes

Risk of bias



Vichinsky 1995 (Continued)

Item Authors judgement Description

Adequate sequence generation? Unclear Randomisation sequence generation was

not recorded.

Allocation concealment? Unclear Concealment of allocation was not

recorded.

Blinding?

All outcomes

Unclear Double blinding not possible for partici-

pants and clinicians, not clear of outcome

assessors were blinded.

Incomplete outcome data addressed?

All outcomes

Unclear It was not stated whether an intention-to-

treat analysis was used. Of the original data

collected on 692 randomly allocated surgi-

cal procedures, 88 (12.7% of study popu-

lation) were subsequently excluded due to

cancellation of the surgery, diagnostic error

or refusal of the individual to participate

in the study. 42 were from Group 1 and

46 from Group 2. While it is stated that

the participant characteristics of this group

were similar in both groups, and that the

age range was representative of the whole

sample, the fairly limited information of

participant characteristics provided in the

paper, and the high exclusion rate, detracts

somewhat from the study.

Hb: haemoglobin

HbS: sickle cell haemoglobin

Characteristics of excluded studies [ordered by study ID]

Wali 2003 Participants were not randomised to treatment groups.



D A T A A N D A N A L Y S E S

Comparison 1. Aggressive versus conservative blood transfusion

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Perioperative mortality 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected

2 Serious complications related to

sickle cell disease

1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected

2.1 Acute chest syndrome 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2.2 Painful crisis 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2.3 Neurological event 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2.4 Renal complication 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2.5 Miscellaneous 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

3 Postoperative Infection 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected

3.1 Perioperative 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

3.2 Postoperative 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

4 Life-threatening surgical

complications


5 Transfusion related

complications


5.1 Alloimmunisation 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

5.2 Haemolysis 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

5.3 Allergic or anaphylactic

reaction

1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

5.4 Miscellaneous 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

6 Blood counts 1 Mean Difference (IV, Fixed, 95% CI) Totals not selected

6.1 Pre-transfusion

haemoglobin

1 Mean Difference (IV, Fixed, 95% CI) Not estimable

6.2 Preoperative haemoglobin 1 Mean Difference (IV, Fixed, 95% CI) Not estimable

6.3 Preoperative haemoglobin

S percentage

1 Mean Difference (IV, Fixed, 95% CI) Not estimable

6.4 White blood cells 0 Mean Difference (IV, Fixed, 95% CI) Not estimable

7 Volume of blood transfusion/

venesected

1 604 Mean Difference (IV, Fixed, 95% CI) Not estimable



Comparison 2. Preoperative blood transfusion versus no transfusion

Outcome or subgroup titleNo. of

studies

No. of

participants Statistical method Effect size

1 Perioperative mortality 0 0 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2 Serious complications related to

sickle cell disease


2.1 Painful crises 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2.2 Neurological

complications

1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

2.3 Respiratory complications 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

3 Postoperative Infection 1 Odds Ratio (M-H, Fixed, 95% CI) Totals not selected

4 Life-threatening surgical

complications

0 0 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

5 Transfusion related

complications


5.1 Circulatory overload 1 Odds Ratio (M-H, Fixed, 95% CI) Not estimable

6 Blood counts 0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable

7 Volume of blood transfused/

venesected

0 0 Mean Difference (IV, Fixed, 95% CI) Not estimable

Analysis 1.1. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 1 Perioperative

mortality.

Review: Preoperative blood transfusions for sickle cell disease

Comparison: 1 Aggressive versus conservative blood transfusion

Outcome: 1 Perioperative mortality

Study or subgroup Aggressive Conservative Odds Ratio Odds Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Vichinsky 1995 2/278 0/273 4.95 [ 0.24, 103.49 ]

0.01 0.1 1 10 100

Favours aggressive Favours conservative



Analysis 1.2. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 2 Serious

complications related to sickle cell disease.



Outcome: 2 Serious complications related to sickle cell disease



1 Acute chest syndrome

Vichinsky 1995 33/303 30/301 1.10 [ 0.65, 1.86 ]

2 Painful crisis

Vichinsky 1995 15/303 21/301 0.69 [ 0.35, 1.37 ]

3 Neurological event

Vichinsky 1995 3/303 3/301 0.99 [ 0.20, 4.96 ]

4 Renal complication

Vichinsky 1995 3/303 1/301 3.00 [ 0.31, 29.00 ]

5 Miscellaneous

Vichinsky 1995 18/303 15/301 1.20 [ 0.60, 2.44 ]

0.1 0.2 0.5 1 2 5 10


Analysis 1.3. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 3 Postoperative

Infection.



Outcome: 3 Postoperative Infection



1 Perioperative

Vichinsky 1995 22/303 21/301 1.04 [ 0.56, 1.94 ]

2 Postoperative

Vichinsky 1995 22/303 15/301 1.49 [ 0.76, 2.94 ]

0.2 0.5 1 2 5




Analysis 1.4. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 4 Life-threatening

surgical complications.



Outcome: 4 Life-threatening surgical complications



Vichinsky 1995 53/303 60/301 0.85 [ 0.57, 1.28 ]

0.1 0.2 0.5 1 2 5 10


Analysis 1.5. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 5 Transfusion

related complications.



Outcome: 5 Transfusion related complications



1 Alloimmunisation

Vichinsky 1995 31/303 14/301 2.34 [ 1.22, 4.49 ]

2 Haemolysis

Vichinsky 1995 19/303 4/301 4.97 [ 1.67, 14.78 ]

3 Allergic or anaphylactic reaction

Vichinsky 1995 1/303 3/301 0.33 [ 0.03, 3.18 ]

4 Miscellaneous

Vichinsky 1995 10/303 4/301 2.53 [ 0.79, 8.17 ]

0.1 0.2 0.5 1 2 5 10




Analysis 1.6. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 6 Blood counts.



Outcome: 6 Blood counts

Study or subgroup Aggressive Conservative Mean Difference Mean Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

1 Pre-transfusion haemoglobin

Vichinsky 1995 303 8 (0) 301 7.9 (0) 0.0 [ 0.0, 0.0 ]

2 Preoperative haemoglobin

Vichinsky 1995 303 11 (0) 301 10.6 (0) 0.0 [ 0.0, 0.0 ]

3 Preoperative haemoglobin S percentage

Vichinsky 1995 303 31 (0) 301 59 (0) 0.0 [ 0.0, 0.0 ]

4 White blood cells

-10 -5 0 5 10


Analysis 1.7. Comparison 1 Aggressive versus conservative blood transfusion, Outcome 7 Volume of blood

transfusion/venesected.



Outcome: 7 Volume of blood transfusion/venesected

Study or subgroup Aggressive Conservative Mean Difference Mean Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Vichinsky 1995 303 5 (0) 301 2.5 (0) 0.0 [ 0.0, 0.0 ]

Total (95% CI) 303 301 0.0 [ 0.0, 0.0 ]

Heterogeneity: not applicable

Test for overall effect: Z = 0.0 (P < 0.00001)

-10 -5 0 5 10




Analysis 2.2. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 2 Serious

complications related to sickle cell disease.


Comparison: 2 Preoperative blood transfusion versus no transfusion

Outcome: 2 Serious complications related to sickle cell disease

Study or subgroup Transfusion No transfusion Odds Ratio Odds Ratio


1 Painful crises

Al-Jaouni 2006 5/188 3/181 1.62 [ 0.38, 6.88 ]

2 Neurological complications

Al-Jaouni 2006 4/188 0/181 8.85 [ 0.47, 165.63 ]

3 Respiratory complications

Al-Jaouni 2006 7/188 5/181 1.36 [ 0.42, 4.37 ]

0.01 0.1 1 10 100

Favours transfusion Favrs no transfusion

Analysis 2.3. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 3 Postoperative

Infection.



Outcome: 3 Postoperative Infection



Al-Jaouni 2006 3/188 3/181 0.96 [ 0.19, 4.83 ]

0.1 0.2 0.5 1 2 5 10




Analysis 2.5. Comparison 2 Preoperative blood transfusion versus no transfusion, Outcome 5 Transfusion




Outcome: 5 Transfusion related complications



1 Circulatory overload

Al-Jaouni 2006 5/188 0/181 10.88 [ 0.60, 198.20 ]

0.001 0.01 0.1 1 10 100 1000


WH A T S N E W

Last assessed as up-to-date: 14 December 2009.

15 December 2009 New search has been performed A search of the Groups Trials Register identified the full published paper to

an already included abstract (Al-Jaouni 2006).

H I S T O R Y

Protocol first published: Issue 3, 2001

Review first published: Issue 3, 2001

1 October 2008 Amended Converted to new review format.

1 August 2007 Amended The Synopsis has been replaced by a Plain language summary.

1 August 2007 New search has been performed The search of the Haemoglobinopathies Trials Register identified no new trials

eligible for inclusion in this review.

1 August 2006 New search has been performed The search of the Haemoglobinopathies Trials Register identified no new trials

eligible for inclusion in this review.

1 April 2005 New search has been performed The search of the Haemoglobinopathies Trials Register identified no new trials

eligible for inclusion in the review.

The lead author has changed her family name from Riddington to Hirst.



(Continued)

1 March 2004 New search has been performed The searches found two new trials. One trial was eligible for inclusion (Al-

Jaouni 2002), but the other was ineligible, as it did not use a randomised design

(Wali 2003).

The new data from the Al-Jaouni trial demonstrated no advantage in using

preoperative blood transfusion in 369peoplewith sickle cell disease undergoing

surgery in Saudi Arabia. There was no significant reduction in sickle related

events in the preoperative transfusion group, and an increase in transfusion


3 March 2003 New search has been performed The searches found no new trials eligible for inclusion.

1 February 2002 New search has been performed No further data to add, no substantive update.

C O N T R I B U T I O N S O F A U T H O R S

The review was conceived by the Cochrane Cystic Fibrosis and Genetic Disorders Group and designed by Dr Hirst (ne Riddington).

Dr Hirst and the Cochrane Cystic Fibrosis and Genetic Disorders Group conducted searches for relevant studies.

Dr Hirst and Dr Williamson screened, appraised and abstracted data for the review.

Dr Hirst sought additional information from authors where necessary.

Dr Hirst performed data entry and interpretation with advice from the Cochrane Cystic Fibrosis and Genetic Disorders Group.

Dr Hirst, with support from Dr Williamson, undertook subsequent updates of the review.

D E C L A R A T I O N S O F I N T E R E S T

Since completion of the review, Ceri Hirst has received funding from several pharmaceutical companies for contract research unrelated

to the review topic.

S O U R C E S O F S U P P O R T

Internal sources

No sources of support supplied



External sources

Research and Development - Research & Development Programme, UK.

I N D E X T E R M S

Medical Subject Headings (MeSH)

Anemia, Sickle Cell [surgery; therapy]; Blood Transfusion [methods]; Preoperative Care

MeSH check words

Humans



preoperative blood transfusions for sickle cell disease (review)

Documents

conservative blood transfusion

blood counts

national blood service

cochrane collaboration

cochrane review

analyses analysis

cochrane library2010

sickle cell diseaseceri