Vasovagal reactions in blood donors - UQ eSpace

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Thijsen Amanda (Orcid ID: 0000-0002-3310-2703)

Vasovagal reactions in blood donors: risks, prevention, and management

Amanda Thijsen1 & Barbara Masser2, 3

Author Affiliations: 1 Clinical Services and Research, Australian Red Cross Blood Service, Sydney, New South Wales,

Australia 2 Clinical Services and Research, Australian Red Cross Blood Service, Brisbane, Queensland,

Australia 3 School of Psychology, The University of Queensland, St Lucia, Brisbane, Queensland, Australia Author responsible for correspondence and reprint requests: Amanda Thijsen, 17 O’Riordan Street, Alexandria NSW 2015, Australia Phone: +61 29234 2493, Email: athijsen@redcrossblood.org.au Sources of support: Australian governments fully fund the Australian Red Cross Blood Service for the provision of blood, blood products and services to the Australian community. Conflict of interest: The authors declare that they have no conflicts of interest relevant to the manuscript submitted to Transfusion Medicine. Word count: Abstract: 250 words | Main text: 5523 words Running title: Vasovagal reactions in blood donors

This is the author manuscript accepted for publication and has undergone full peer review buthas not been through the copyediting, typesetting, pagination and proofreading process, whichmay lead to differences between this version and the Version of Record. Please cite this articleas doi: 10.1111/tme.12488

ABSTRACT

This narrative review examines current research on risk factors, prevention methods, and

management strategies for vasovagal reactions (VVRs) that occur during or as a result of blood

donation. VVRs are important to Blood Collection Agencies (BCAs) as they negatively impact the

number of completed collections, perceptions of the safety of blood donation, and rates of donor

return. There has been significant progress in understanding and preventing VVRs in blood

donation in recent years, with a multitude of risk factors identified. This has resulted in many BCAs

implementing evidence-based strategies such as donor age and weight restrictions. However, the

profile of our most vulnerable donors and features of the donation setting that may protect these

donors from experiencing a VVR have not been identified. Further, an increased number of trials

of physiological and psychological prevention interventions to reduce both immediate and delayed

VVRs have been reported. However, a lack of methodological consistency in operationalizing

interventions to reduce or prevent VVRs means that it remains challenging for practitioners to

identify effective VVR prevention strategies. Further, research is still required to determine how to

successfully implement prevention and management strategies into standard operating

procedures within collection centres. Finally, research in the management and mitigation of the

effect of VVRs is currently only suggestive of what should be done to care for the donor who

reacts, and how to empower those donors to return. Collectively, research into these aspects of

VVRs will provide support to donors, BCAs, and improve the safety of blood donation.

Keywords: Blood donor, Vasovagal, Retention, Donor Adverse Events, Reaction

Introduction

Blood Collection Agencies (BCAs) rely on healthy volunteers for the provision of blood. Although

donating blood is safe and uncomplicated for most people, a small proportion of donors

experience adverse reactions either during or after the procedure. The most common adverse

event is a vasovagal reaction or vasovagal syncope (VVR). VVRs are thought to be triggered by

various physical (such as standing up after losing 500mL of blood) and psychological stimuli (e.g.,

pain, stress, fear) (Gilchrist et al. 2015). During a VVR, the donor experiences a drop in arterial

blood pressure and cerebral perfusion which reduces blood flow to the brain (Wieling et al. 2009).

This results in pre-syncopal symptoms (e.g., feeling lightheaded or dizzy) or vasovagal syncope

(i.e., loss of consciousness) which can be accompanied by mild seizures and/or incontinence (see

Table 1) (Wiersum-Osselton et al. 2013; Gilchrist and Ditto 2015). Vasovagal symptoms can last

several hours causing prolonged discomfort and, if the donor experiences syncope, can result in

fall-related injuries such as fractures and head injuries (Eder et al. 2008).

VVRs are more frequently recorded by BCAs in relation to whole blood (WB) donation than for

other forms of blood product donation (Crocco et al. 2009). Across a range of BCAs, the incidence

of pre-syncopal reactions for WB donations is 1.4 to 7.0%, and the incidence of vasovagal syncope

is 0.1 to 0.5% (Amrein et al. 2012). In apheresis-type donations, VVRs are more common in platelet

donations (0.68-0.81%) compared to plasma donations (0.16%) (Despotis et al. 1999; Crocco et al.

2009). Among WB donors, the largest number of VVRs occur at needle removal and when leaving

the donation chair (Tomasulo et al. 2010). A small proportion of reported VVRs (9-12%) are known

to occur after the donor has left the centre. However, the recorded number of off-site reactions

may be an underestimate as donors may fail to report these to BCAs (Kamel et al. 2010; Bravo et

al. 2011).

Whilst VVR incidence rates provide good insight into the timing and number of reactions

experienced, they do not provide information on the donors’ subjective experience of VVRs. BCA

rating systems and records rely on phlebotomists’ reports as trained observers, and this does not

always reflect what the donor feels they experience from donating blood (France et al. 2008a). To

capture donors’ subjective perceptions of VVR-type experiences, Meade and colleagues (1996)

developed the Blood Donation Reactions Inventory (BDRI) through which donors rate the severity

of the VVR-type symptoms they experience. BDRI scores significantly positively correlate with

phlebotomist ratings of VVRs (Meade et al. 1996), but with larger numbers of donors reporting

VVR symptoms than typically seen in official incidence rates. Between 14-38% of first-time WB

donors self-report vasovagal symptoms using the BDRI (Masser et al. 2013). Further, the BDRI

outperforms phlebotomist ratings in predicting donor return (France et al. 2004), suggesting

donors’ perceptions of the reactions they experience are a more important determinant of

subsequent behaviour than official incidence rates.

Regardless of how they are assessed, VVRs impact negatively on donor safety and future donation

behaviour. From an operational perspective, VVRs also have a negative impact on donor wait

times, the management of appointments, and the number of completed blood collections (France

et al. 2004; France et al. 2005; van Dongen et al. 2013). As a consequence of this, VVRs are

important to BCAs and are the focus of a significant body of donor research. In this narrative

review, we consider what is known from the literature with regard to risk factors for VVR and

prevention methods. Further, we will also consider how donors and staff manage these types of

reactions and how VVRs impact donor retention.

Risk factors for vasovagal reactions

A multitude of factors are linked with a heightened risk of experiencing a VVR during or after

blood donation. These can be broadly divided into three categories – donor characteristics that

are generally observable (e.g., gender, ethnicity), donor characteristics that may not be

immediately observable without additional questioning or assessment (e.g., prior night sleep

duration, fear of needles), and contextual features of the donation experience (e.g., wait time,

phlebotomist experience; see Table 2).

Generally observable donor characteristics

At the univariate level, an array of observable or easily calculable donor characteristics are

associated with an increased risk of experiencing a VVR. Age is frequently implicated, with younger

WB donors more likely to experience a VVR than older donors (Ogata et al. 1980; Tomita et al.

2002; France et al. 2005; Zervou et al. 2005; Eder et al. 2008; Ditto et al. 2012), as is first-time

donor status (vs. more experienced donors; Ogata et al. 1980; Kasprisin et al. 1992; Meade et al.

1996; Newman 2003; France et al. 2005; Zervou et al. 2005; Eder et al. 2008; France et al. 2013),

and gender, with women being more likely to experience a VVR than men (Ogata et al. 1980;

Tomita et al. 2002; France et al. 2005; Eder et al. 2008; Ditto et al. 2012; Takanashi et al. 2012;

Vossbeck-Elsebusch and Gerlach 2012; France et al. 2013). Other analyses report higher rates of

VVRs among White donors (vs. non-White donors; Newman 2002; France et al. 2005, but see also

Newman et al. 2003), lower BMI/weight (vs. higher BMI/weight; Ogata et al. 1980; Kasprisin et al.

1992; Newman 2003; France et al. 2013), and lower estimated blood volume (vs. higher, relative

to the proportion being collected; Tomita et al. 2002; France et al. 2013). Of all of these, age, first-

time donor status, and gender are routinely identified as risk factors, with many large-scale

analyses evidencing independent effects of these characteristics. This occurs even when the

shared variance between these univariate predictors is controlled for in multivariate analyses that

consider these factors (and others) in conjunction with each other. For example, in an analysis of

1,776,445 collections from BCAs in the US, Eder and colleagues (2008) showed that 16-17-year-old

donors were significantly more likely to experience an officially recorded VVR than 18-19-year-old

donors or donors aged over 20 years. Further, in the same analysis, donor status (first-time vs.

more experienced) and gender (being female vs. male) were also implicated as significant

independent predictors of VVRs. For other characteristics, the evidence base is either less

comprehensive or compelling (e.g., there are only a small number of studies that have considered

ethnicity as a predictor of VVRs, and conflicting results have emerged within these analyses; e.g.,

Newman 2002, France et al. 2005, in comparison to Newman et al. 2003). For example, Zervou

and colleagues (2005) found an association of lower body weight with officially recorded VVRs

only among male donors, whereas Tomita et al. (2002) found the association of circulating blood

volume and officially recorded VVRs stronger for older rather than younger female apheresis

donors with no association observed in male apheresis donors.

Donor characteristics that are unobservable without further questioning or assessment

Once observable donor characteristics are taken into account, other factors emerge as being

predictive of VVRs. These range from factors that can be assessed as part of a routine blood

donation (e.g., pre-donation blood pressure, pulse; Ogata et al. 1980; Kasprisin et al. 1992;

Takanashi et al. 2012) to lifestyle factors (e.g., prior night sleep duration [Takanashi et al. 2012],

prior food [Takanashi et al. 2012], and/or caffeine intake [Kasprisin et al. 1992; Meade et al.

1996)]). Further, donor characteristics, such as a history of fainting (Meade et al. 1996), along with

underlying or situationally induced (psychological) states (e.g., anxiety [Ditto and France 2006b],

anticipated anxiety [Olatunji et al. 2010; Viar et al. 2010], fear of blood and injury [Meade et al.

1996; Labus et al. 2000; Ditto et al. 2012], fear of blood draw [France et al. 2013], perceived blood

loss [Ditto et al. 2012], pain [Meade et al. 1996], anticipated pain [Olatunji et al. 2010], and

anticipated disgust [Olatunji et al. 2010; Viar et al. 2010]) have also been associated with

perceived VVR type symptoms. As with the observable donor characteristics analyses, many of the

analyses exploring the predictive value of these unobservable characteristics have taken a

multivariate approach. For example, Takanashi et al. (2012) compared the records of 4,924

Japanese donors who had experienced a VVR to a control group of 43,948 donors with no

donation-related complications. For both male and female donors, being a first-time donor, having

a pre-donation pulse of greater or equal to 90 beats per minute, a diastolic blood pressure of

equal to or below 70 mmHg, a sleep duration of 6 hours or less (compared to eight hours or more)

and having not eaten a meal in the last four hours were all independently significantly associated

with a greater risk of a VVR after adjusting for age, sex, BMI, pulse and systolic blood pressure.

When considering psychological states, anticipatory anxiety or fear of aspects of the phlebotomy

process appear to have a more consistent association with VVR, in comparison to other affective

reactions that have been examined (e.g., disgust) (Olatunji et al. 2010; Vossbeck-Elsebusch and

Gerlach 2012). While the studies focused on psychological states are smaller in scope and fewer in

number in comparison to the demographic analyses, anticipatory anxiety and/or fear are

consistent predictors of experiencing vasovagal sensations (Meade et al. 1996; Labus et al. 2000;

Ditto and France 2006b; Olatunji et al. 2010; Ditto et al. 2012; Gilchrist and Ditto 2015). While

theoretically anxiety may more accurately reflect the uncertainty that donors feel around whether

the outcome of donating will be good or bad (Chell et al. 2016), analyses using a single question to

assess fear of having blood taken show good predictive ability in identifying those most at risk of a

VVR. France and colleagues (2013) asked 1715 high school students aged 17-18 years waiting to

donate blood to self-report their fear of the blood draw on a simple 1 (no fear) to 4 scale and then

tracked their subsequent donation to assess whether they experienced a VVR or not. The VVR rate

of a control sample of 1692 donors who were not asked the fear question was also obtained.

Initial analyses indicated that asking the fear question did not cause an increase in the rate of

VVRs, as the rate of VVR did not differ between the question and control group for either first-

time or more experienced donors. Further, when fear of the blood draw was considered in a

multivariate analysis alongside other identified predictors of VVR (e.g., age, gender, donor status,

body mass, estimated blood volume, systolic blood pressure, diastolic blood pressure, pulse rate),

only self-reported fear of the blood draw, estimated blood volume, and gender of the donor

emerged as significant predictors of VVR. The rate of VVR was higher among those with greater

fear and lower estimated blood volume. In this analysis, contrary to other studies, once fear and

estimated blood volume were controlled for, male donors were at a greater risk of VVR than

female donors.

Contextual features

Alongside the characteristics that the donor brings to the donation setting, there are contextual

features that may influence a donor’s risk of experiencing a VVR. The association of these with

donors’ experiences of VVR has been considered in a small number of analyses. Ogata et al. (1980)

analysed the records of 10,547 Japanese donors and found that VVRs were more frequent in the

spring and least common in the summer. Further, reactions were more common with a relatively

inexperienced phlebotomist than a more experienced one. The importance of the phlebotomist in

the experience of VVRs was echoed in the results of Stewart et al. (2006) who documented a

reduction in VVR as a function of the phlebotomist’s social skills. Kaspirin et al. (1992) explored the

relationship of wait times to VVR and reported a positive correlation between the two. Donors

who waited more than 60 minutes from registration to the beginning of phlebotomy had a

frequency of reactions nearly four times that of those who waited 19 minutes or less. More recent

analyses suggest that the duration of the actual donation also has an impact. France et al. (2016),

in a further exploration of donor fear of the blood draw, found that the overall proportion of

officially recorded VVRs increased with increases in draw time. However, for all draw times, fear of

the blood draw remained the single best predictor of VVR. Considering the impact of the ‘social’

aspect of blood donation, Ditto and colleagues (2014) showed a positive association between

seeing another donor being treated for VVR symptoms and self-report of VVR symptoms using the

BDRI in non first-time blood donors. Further, observing a donor being treated for VVR was

associated with a slower rate of return in the following two years in first-time donors.

Whether an individual donor will experience a VVR or VVR symptoms cannot be determined when

that person presents to donate. VVR risk factors can be identified through large-scale BCA

database analyses and the inclusion of information reported by the donor, such as fear and

anxiety. Further, how that donor is treated once they are in the donation centre may also impact

on whether VVR symptoms result. Accepting that the evidence base for the predictive value of

subjectively reported risk factors (e.g., fear, anxiety, donor experience) is less comprehensive than

that for objectively measured risk factors, the analysis by France and colleagues (2013) provides an

interesting insight into the potential interplay between demographic features and psychological

characteristics of the donor. However, the fact remains that large-scale analyses using rigorous

methodologies that take into account both observable and unobservable characteristics of donors

and contextual features of the donation environment have not yet been conducted. Such large-

scale analyses would allow us to determine the profile of our most vulnerable donors and the

contextual features that may protect them from experiencing a VVR. In the absence of this,

strategies to prevent VVR are currently recommended for all donors.

Preventing vasovagal reactions

The potential underlying mechanisms of VVRs include the orthostatic effects on a hypovolemic

static state following a donation (i.e. the drop in blood pressure when getting out of the donation

chair), and the psychological stress associated with the procedure (e.g., sight of the needle or

phlebotomy-related pain) (Wieling et al. 2011a). Due to the complexity of the underlying

mechanisms of VVRs, current prevention strategies target either physiological or psychological

aspects of the reaction.

Physiological strategies

The effects of a variety of physiological prevention interventions on VVRs have been assessed

through a number of randomised controlled trials in blood donation settings. The primary

objective of these interventions is to prevent the sudden drop in blood pressure which causes the

donor to experience VVR symptoms. Within this intervention literature, the main focus has been

on the efficacy of two techniques – pre-donation water loading and applied muscle tension (AMT)

– enacted in centre to prevent VVRs.

Fisher and colleagues (2016) recently considered the results of five randomised controlled trials

exploring the effect of pre-donation water loading (ingesting 500mL of water within 30 minutes)

on VVRs. Overall, donors who water loaded prior to donation were observed by the phlebotomist

or researcher to have a significantly lower relative risk of experiencing a VVR in comparison to the

control groups, who mainly received no treatment. Specifically, the relative risk of being observed

to experience a VVR in donors who water loaded was 0.79 (95% CI, 0.70-0.89). However, three of

the five trials were assessed by Fisher and colleagues of having a high risk of selection bias due to

the methods of randomisation employed. When these trials were removed from the meta-

analysis, the effect of pre-donation water loading on VVRs was no longer significant, suggesting a

negligible decrease in relative risk of observed VVRs among those who water loaded in

comparison to those who did not. Where severity of reaction was assessed through ratings on the

BDRI, pre-donation water loading significantly reduced the severity of vasovagal symptoms self-

reported by donors in comparison to donors who had not water loaded (Hanson and France 2004;

France et al. 2010).

A recent study not included in the Fisher and colleagues (2016) meta-analysis reported

significantly lower odds of a phlebotomist-registered VVRs among those who drank 500mL of fluid

approximately 9 minutes before phlebotomy compared to those assigned to the ‘usual practice’

control arm (OR, 0.74; 95% CI, 0.55-0.99) (Morand et al. 2016). Drawing on research conducted in

non-blood donation settings that found beneficial effects of dietary sodium in increasing plasma

volume and orthostatic tolerance in dehydrated athletes (Wieling et al. 2011a), Morand and

colleagues (2016) also evaluated the impact of consuming 500mL of an isotonic drink before

phlebotomy. No differences were found in the rate of on-site reactions between those who

consumed water and those who consumed the isotonic drink. However, follow up calls to donors

revealed that consumption of the isotonic drink was related to significantly lower odds of

reporting having experienced a reaction offsite in 48 hours post donation than those in the ‘usual

practice’ control condition (OR, 0.62; 95% CI, 0.40-0.98). While such a reduction is highly desirable,

particularly as offsite reactions can result in the most severe injuries to donors (Newman and

Graves 2001), more research is needed to determine the efficacy of isotonic drinks in reducing

offsite VVRs. Further, more research is needed to determine the optimal method (e.g., timing and

volume of fluid to be consumed) and how effective water loading technique is in reducing

phlebotomist-registered VVRs.

In the same meta-analysis, Fisher and colleagues (2016) also considered the evidence for the

efficacy of AMT, another physiological intervention. AMT involves donors engaging in repeated

contraction of leg and abdomen muscles in order to increase blood pressure. Eight trials were

considered which compared AMT to no-treatment control conditions. In these, no significant

differences were observed in the relative risk of rate of chair reclines, heart rate, systolic blood

pressure, diastolic blood pressure, and registered VVRs by phlebotomists between the AMT

condition and the no-treatment control condition. AMT did, however, impact the severity of

donor’s self-reported vasovagal symptoms. In three trials, reporting log-transformed BDRI scores,

donors who used AMT reported significantly lower severity scores compared to those who did not

(Ditto et al. 2003a; Ditto and France 2006a; Ditto et al. 2007). However, significant variability in

the instructions used to prompt AMT was observed between the studies. For example, in one

study, participants were instructed to lift one leg at a time for 10 seconds (France et al. 2010)

whilst in another, participants were asked to engage in repeated, 5-second cycles of tensing the

major muscle groups in their arms and legs (Ditto et al. 2003b; Ditto et al. 2007). Two trials

evaluating the impact of combining both AMT and pre-donation water loading reported a

significantly lower relative risk of phlebotomist-registered VVRs and lower donor self-reported

symptom severity in donors who received the combined intervention compared to the no

treatment control group (France et al. 2010; Morand et al. 2016). However, again, the precise

instructions given to donors to prompt AMT differed greatly between the two studies making

comparison of the trials difficult. The absence of a standardised AMT instruction in the blood

donation context coupled with the variability observed in outcomes of trials of this technique

suggests a need for further research to determine the effectiveness of AMT as an intervention.

Further, research is also required to determine the efficacy of AMT in conjunction with pre-

donation water loading.

Along with pre-donation water loading and AMT, the efficacy of another physiological intervention

to increase donor blood pressure – the consumption of caffeine – has been evaluated. In a small

randomised trial with high risk donors (62 young females with a sensitivity to blood or injury

stimuli), 125 or 250 mg of caffeine administered prior to blood donation resulted in significantly

lower number of chair reclines, reduced self-reported VVR symptoms, and greater increases in

blood pressure in comparison to those in a no caffeine placebo control group (Sauer and France

1999). No significant differences were observed between the three groups in reduction of pre-

donation anxiety or increased heart rate. Unlike pre-donation water loading and AMT, the effect

of caffeine administration pre-donation has not been more broadly considered. As such, further

research is needed to determine if caffeine may provide benefit to blood donors in preventing

Psychological strategies

In comparison to the empirical literature focused on pre-donation water loading and AMT,

relatively few studies have considered the psychological aspects of donation and their relationship

to vasovagal symptoms. Where interventions have been evaluated, these have focused primarily

on emotion regulation to reduce stress or anxiety through providing distraction or social support

during the procedure. For example, Bonk and colleagues (2001) investigated the efficacy of audio-

visual distraction for first-time donors who were classified as having either a monitoring (attention

to the situation) or blunting (distraction, denial or reinterpretation of what is occurring) coping

style. Blunting donors who received distraction that matched their coping style had significantly

lower self-reported vasovagal symptoms than participants in the no-treatment control condition.

In terms of social support, Hanson and France (2009) conducted a small randomised controlled

trial with novice donors (n=65) to explore the effects of pairing donors with a research assistant

who had been trained to be supportive. Donors receiving this form of in situ social support self-

reported lower levels of vasovagal reactions and stronger intentions to donate again than those in

the control condition. Hanson and France (2009) suggested, drawing on the cardiovascular

reactivity literature, that the presence of a calming support person (or experienced phlebotomist;

Stewart et al. 2006) may reduce vasovagal symptoms through attenuating stress reactions.

In addition, trials of physiological interventions have provided some evidence of the beneficial

effects of anxiety and VVR reduction. Ditto and colleagues (2007) found that donors assigned to

their placebo control condition in which donors were asked to focus attention on their non-

donating arm while using upper-body muscle tension exercises reported less severe vasovagal

symptoms and less anxiety compared to donors in the business-as-usual condition. Further, Holly

and colleagues (2012) found in a randomised trial, that engaging in AMT in the waiting area

significantly reduced anxiety and self-reported vasovagal symptoms in donors compared to the

business-as-usual group. As these effects have emerged as artefacts of trials designed to assess

the efficacy of other interventions, the precise mechanism through which AMT exercises in the

waiting area reduced vasovagal symptoms remains unidentified. As such, further research is need

to determine precisely how physiological and psychological interventions can be effectively

implemented to reduce the stress and anxiety that (some) donors experience, and how these

interventions map through to reductions in the experience of vasovagal symptoms.

Although a large number of intervention studies have evaluated the impact of using physiological

and psychological methods to prevent VVRs and/or vasovagal symptoms, questions with regard to

the efficacy of these techniques still remain. Proposed methods of prevention have not been

standardised in evaluations (e.g., AMT) and outcomes have been inconsistently assessed, with

more techniques showing benefit in relation to self-reported vasovagal symptoms than

phlebotomist-registered reactions. However, the latter may not be a major concern given that

self-reported vasovagal symptoms are a stronger predictor of return behaviour (France et al.

2004). Further, what is not yet clear is the impact of VVR prevention techniques on reducing VVRs

in plasmapheresis and plateletpheresis donors. While rates of VVR are lower in apheresis donors

(Crocco et al. 2009), all published intervention trials have focused solely on WB donors. Finally,

little is known about how to successfully implement VVR prevention strategies in routine blood

collection practices and whether any documented beneficial effect on VVR reduction is maintained

outside the controlled environment of an efficacy trial.

Managing the impact of vasovagal reactions

Whilst there is a strong focus in transfusion medicine research on identifying risk factors for VVRs

and how to effectively prevent these reactions, comparatively little research has been conducted

on how to best manage the physiological and psychological impact of experiencing a VVR.

However, it is clear that once a donor begins to experience a VVR, both the donor and

phlebotomist play a key role in managing the donor’s reaction.

In blood collection centres, the primary response to VVRs among phlebotomists is to raise the

donor’s legs above their head (i.e. the Trendelenburg position) to increase central blood volume

and cardiac output. However, a formal evaluation of this technique by Wieling and colleagues

(2011b) suggested that it may only result in minimal increases in blood pressure. An alternative

management strategy is therefore to use physical manoeuvres (e.g., dynamic tension, lower-body

muscle tension) to increase the heart rate and blood pressure. These exercises more rapidly

resolve symptoms in those experiencing prolonged VVRs (Wieling et al. 2004; Wieling et al. 2011a;

Wieling et al. 2011b). Although, BCAs sometimes use these techniques to speed up recovery once

the donor is deemed fit to sit in an upright position, their use is not routine (Thijsen et al. 2016).

Phlebotomists often supplement these physical manoeuvres by providing the donor with cold

water, something to eat, or by placing a cool cloth on the donor’s forehead (Wieling et al. 2011b;

Thijsen et al. 2016). While these techniques are not documented to have a physiological impact

(Wieling et al. 2011b), for some donors the distraction or the perception that something is being

done to manage their reaction may be beneficial. Finally, the phlebotomist may provide social

support during the event and interactions with the attending phlebotomist can positively influence

the overall donation experience and increase future donation intentions (Stewart et al. 2006).

Donors rely on staff, as the perceived experts in the donation context, for the prevention and

management of all aspects of their donation experience including if a VVR results (Thijsen et al.

2016). It is therefore necessary to increase our evidence-base of what support phlebotomists

provide to donors and how to optimise this to manage the impact of VVRs.

In addition to the physical effects, VVRs have a psychological impact on the donor with some

experiencing stress, anxiety and/or discomfort as a result of their VVR symptoms (van Dongen et

al. 2013; Thijsen et al. 2016). In a study examining coping strategies and VVRs, Kaloupek and

colleagues (1985) found that those who experienced VVRs practised suppression strategies (that

is, trying to reduce tension by not thinking about the situation) more frequently during their

donation compared to those with no reaction. In a similar study, donors employing problem-

focused strategies during their donation reported lower levels of distress compared to those using

emotion-focused strategies (Kaloupek and Stoupakis 1985). Consistent with this, Gilchrist and

colleagues (2015) examined the role of perceived control in reducing vasovagal symptoms. In a

controlled research environment, those assigned to the intervention condition were able to

control the breaks they took from the stimulus-video. As a result of this, participants in this group

reported lower VVR symptoms compared to those in the control condition who had

predetermined breaks. While heightening donors’ perceptions of control has previously been

found to be useful in improving the donation experience of those approaching their donation

(France et al. 2008b), the current findings suggest that increasing donors’ perceptions of control

may also serve to mitigate the severity of their VVR experience.

Impact of VVR on donor return

Whilst VVRs have an immediate negative impact on the donor’s health and emotional wellbeing,

these reactions also have a longer-term negative impact for BCAs as they reduce donor return

rates. Research shows that, among WB donors, VVRs have the strongest deterrent effect of all

forms of phlebotomy trauma (Veldhuizen et al. 2012; Wiersum-Osselton et al. 2013), with even

the subjective experience of mild VVRs reducing return rates by 20% for first-time donors and by

33% for repeat donors (France et al. 2004). Rates of donor return after the experience of a VVR are

not constant across demographic categories. Specifically, even though male donors typically

experience fewer VVRs, they are less likely to return following a reaction compared to female

donors (van Dongen et al. 2013; Wiersum-Osselton et al. 2013). Due to its strong influence on

donor retention, it is important to increase our understanding of what factors associated with

VVRs impact on donor retention and why certain donors do not come back.

VVRs constitute a stressor for the donor (Hoogerwerf et al. 2015), potentially resulting in higher

levels of anxiety, irritation, fear, worry, tension, or anger. This emotional reaction to the

experience of a VVR has a negative impact on the donor’s donation experience and this, in turn,

may deter donors from returning to donate again (Gillespie and Hillyer 2002).

Another potential deterrent to continued blood donation is fear of a recurrent event. In a Dutch

study, the mean anxiety level of donors who experienced an adverse event (defined as fatigue,

VVR and subjective distress) increased from before to after their donation (van Dongen et al.

2013), suggesting that VVRs may continue to impact on donors beyond their initial donation.

Contrary to donor beliefs, the risk of a recurrent event in whole blood donation is not reliably

predicted by a prior reaction, with only 2% of all VVRs observed on return donation occurring in

donors with a prior reaction (Eder et al. 2012). It is therefore important to communicate this low

risk of VVRs to donors and provide education to them on prevention techniques to increase their

likelihood of returning to donate again.

Finally, VVRs can impact on a donor’s confidence in their ability to donate (i.e. self-efficacy).

Veldhuizen and colleagues (2012), using the Theory of Planned Behaviour (TPB) framework to

understand donor return, observed a negative association between experience of a VVR, donors’

self-efficacy, and feelings about blood donation. Such feelings may lead to donors’ self-deferring.

France and colleagues (2007) observed that among experienced donors, self-reported VVR scores

negatively impacted on attitudes to donation, with these in turn predicting (reduced) intention to

return. Thus, improving self-efficacy and attitudes to blood donation following a VVR may be

crucial components of improving donor retention.

Future directions for research

Although the experience of VVRs has a major impact on donors and the routine operations of

BCAs, this review highlights that much is still left to be done (see Table 3). Research is still needed

to identify precisely who is at risk of experiencing VVRs, and particularly to build the evidence base

for the impact of unobservable characteristics of the donor and contextual features of the

donation setting on risk of VVRs. Further, research still needs to identify what can be done to

prevent VVRs or mitigate the negative effects of VVRs on donors if they occur. To date, large-scale

analyses have not been conducted that allow us to determine the profile of our most vulnerable

donors, so that interventions can be strategically deployed. While a number of trials in a range of

countries have assessed the efficacy of pre-donation water loading and/or AMT in preventing

VVRs, inconsistencies in the methods employed means that the evidence-base demonstrating the

efficacy of either form of intervention remains weak. Further, the challenges involved in

implementing intervention strategies to donors who may not perceive that they need them (e.g.,

experienced donors) have yet to be addressed (Masser 2012). While other interventions targeting

the physiological mechanisms and psychological mechanisms of VVRs have been proposed (e.g.,

caffeine ingestion, isotonic drinks, distraction, social support etc.), the research showing support

for the efficacy of these approaches is limited to only a few studies. Replication attempts are

needed before these strategies can be integrated into routine operations to reduce rates of VVRs.

However, even with the identification of effective interventions, some donors will still experience

VVRs. Research in the management and mitigation of the effect of VVRs remains suggestive of

what can be done by phlebotomists to optimally care for donors experiencing a VVR and how

donors can be empowered to minimise the impact of a VVR on their psychological wellbeing. As

such, research is still needed on how to retain donors who have reacted. Potentially these latter

stages of the reacting donors’ experience provide the biggest opportunity for gains to be made by

BCAs in retaining donors in the panel. However, at present, precisely who to intervene with, how

to intervene, when to intervene, and how to retain donors who have experienced a VVR remain

among the great unknowns of optimal blood donor management.

Acknowledgements

We are grateful to Dr Anne van Dongen and Dr Tanya Davison for providing feedback on the

manuscript. Both authors drafted the manuscript and commented on the final draft.

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Table 1 Vasovagal symptoms by reaction severity

Reaction category Symptoms

Pre-syncopal (Mild) Light-headedness, pallor, dizziness, sweating, fatigue, blurred and fading vision, difficulty hearing, palpitations, nausea and/or vomiting

Syncope (Severe) Loss of consciousness

Table 2 Summary of findings of risk factors for vasovagal reactions in blood donation

Phlebotomy type Observable donor characteristics

Unobservable donor characteristics

Contextual factors

Whole blood Young age Low blood pressure Spring season First-time donors Elevated pulse Less experienced

phlebotomist Female Less sleep duration Lower phlebotomist

social skills White donors Greater time after

eating Longer wait time

Low BMI/ weight Less caffeine intake Longer bleed time Low EBV History of VVR Witnessing a VVR Greater anxiety Greater anticipated

anxiety

Greater fear of blood and injury

Greater fear of blood draw

Pain Anticipated pain Anticipated disgust Perceived blood loss Apheresis Young age Elevated pulse First-time donors Less sleep duration Female Greater time after

eating

Low BMI Low EBV

Table 3 Current knowledge and future directions for research on vasovagal reactions in donors

What is known about this topic

• Vasovagal reactions have a negative impact on donor health and on the daily operations of blood collection agencies (e.g., donor wait times, number of completed blood collections).

• Univariate predictors of VVRs have been identified (e.g., young age, low body weight) and have been used to place restrictions on who can donate.

• Water loading and applied muscle tension have been extensively evaluated as VVR prevention strategies. These techniques have been observed in some trials to reduce the incidence of self-reported and phlebotomist-registered reactions.

• VVRs are a strong deterrent to future blood donation behaviour.

What is new

• A comprehensive overview of the breadth of research on risk factors of VVRs for both whole blood and apheresis collections is given, and suggestions are made for multivariate analyses to increase our understanding of VVR predictors.

• An examination of the variability in design and methods between various VVR prevention interventions is provided and the complexities this provides in identifying which techniques to implement into routine blood collection practise and how to do this is discussed.

• The identification of a gap in our evidence base in knowing how to effectively manage VVRs to reduce the negative impact of VVRs on donor return rates.

What are the future key questions for future work on the topic?

• Which of our donors are most vulnerable to experiencing VVRs when individual and contextual features are considered together in multivariate analyses?

• When evaluated through RCTs using standardised methods, which physiological and psychological interventions – alone or together – reduce the risk of donors’ experiencing VVRs and/or reduce the severity of VVR symptoms?

• What is the optimal way to care for a donor who experiences VVR symptoms to promote their return to donate again? What are the mechanisms through which optimal donor care works?

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