ISBT Science Series (2014) 9, 228–233

STATE OF THE ART 3C-S15-02 © 2014 International Society of Blood Transfusion

Donor vigilance: a global update

J. C. Wiersum-Osselton,1,2,3 T. Marijt-van der Kreek,1,3 A. G. Bokhorst1,2,3 & W. L. A. M. de Kort1,3
1
Sanquin Blood Supply, Amsterdam, The Netherlands
2
TRIP National hemovigilance and biovigilance office, The Hague, The Netherlands
3
Member, International Society for Blood Transfusion, Haemovigilance Working Party, Amsterdam, The Netherlands

Background Without blood donations and the availability of blood transfusion,

many important therapeutic advances could not have been achieved. Donor hae-
movigilance is the systematic monitoring of adverse reactions and incidents in
the whole chain of blood donor care, with a view to improving quality and safety
for blood donors.
Method This ‘global update’ draws on work by the International Haemovigilance Net-
work and International Society for Blood Transfusion haemovigilance working party,
experience in the Netherlands, as well as a PubMed search using terms blood donor and
adverse reaction. Results are discussed for vasovagal reactions, needle-related compli-
cations,long-termmorbidity,donorironstatusandfrequentapheresis.
Results and Discussion The occurrence of vasovagal reactions is associated with
young, female donors, smaller estimated blood volume, first-time donor status.
A reduction in vasovagal reactions has been documented with use of a water
drink before donation, muscle tensing, social distraction and lower collection vol-
ume for donors with small estimated blood volume. Needle injury is relatively fre-
quent as a cause in cases of long-term morbidity; needle injury is associated with
traumatic phlebotomy, and in some cases, nerve damage is documented. Repeated
whole blood donations lead to reduction in body iron stores and in some cases
anaemia. Some blood services adjust donation intervals to avoid or reduce this,
while others have or are considering a policy of iron replacement therapy. Fewer
studies on acute complications in plasma and other types of apheresis have been
published. Preliminary studies of bone density and protein levels in non-commer-
cial frequent plasma donors have not substantiated any specific hazard despite the-
oretical concerns of calcium or protein depletion. International collaboration in
strengthening donor vigilance definitions and data analysis may in future increase
potential for study of risk factors and measures to improve donor care worldwide.
Conclusion Donor vigilance is gaining international interest and has increased
knowledge of risk factors for vasovagal reactions associated with blood donation.
There remains a need of research and of developing preventive measures, includ-
ing prevention and treatment of needle injury as well as possible long-term
effects of frequent donation.
Key words: adverse reaction, apheresis, blood donor, iron deficiency, needle
injury, vasovagal reaction, whole blood donation

Correspondence: Johanna C. Wiersum-Osselton, TRIP National
hemovigilance and biovigilance office, The Hague, the Netherlands.
E-mail: j.wiersum@tripnet.nl
Introduction
Without blood donors and their willingness to donate
whole blood or blood components, the blood transfusions
and many important therapeutic advances would not
have been achieved. We owe all donors high standards of

228

medical care and all possible measures to prevent adverse
consequences of donation and minimise their impact
when they do occur. Donor haemovigilance is the system-
atic monitoring of adverse reactions and incidents in the
whole chain of blood donor care, with a view to improv-
ing quality and safety for blood donors. Donor haemovig-
ilance includes all activities which contribute to
improving the health outcomes for blood donors as well
as the safety and effectiveness of blood donation for pur-
poses of medical treatment of patients [1].
Although the term ‘donor haemovigilance’ was not
introduced till approximately 2009, publications reporting
the occurrence and incidence of complications sporadi-
cally appeared well before 1980 [2]. Since 1980, there has
been an exponential rise in the number of publications in
this domain. Until about 2000, the great majority of arti-
cles came from North America but since then important
contributions have been made in all continents.
Recording the occurrence of complications of blood
donation – including complications of collection of blood
components by apheresis – is relevant at different levels:
(1) Care for the individual donor (medical dossier). More-
over, meticulous recording of problems at collection
is essential to enable donors to justly receive (insur-
ance) compensation for injury.
(2) Information available next time to trigger extra care
at the next donation in order to reduce likelihood of
recurrence.
(3) At the organisational level: know what the rate of
reactions is.
(4) Analyse risk factors, implement and evaluate preven-
tive measures, compare between departments and
organisations for purposes of learning and improving.
This ‘global update’ draws on work by the International
Haemovigilance Network and International Society for
Blood Transfusion haemovigilance working party, experi-
ence in The Netherlands, as well as a PubMed search
using terms blood donor and adverse reaction. Results are
discussed for vasovagal reactions, needle-related compli-
cations, long-term morbidity, donor iron status and fre-
quent apheresis.
Definitions and international data
comparison
Capturing national data on complications of blood
donation has lagged behind vigilance regarding adverse
reactions and adverse events affecting the recipients of
blood transfusions. The European Commission in its
guidance on the mandatory reporting of aggregate data
on serious transfusion reactions and serious adverse
events in the transfusion chain has encouraged reporting
of serious donor adverse reactions on a voluntary basis
Ó 2014 International Society of Blood Transfusion, ISBT Science Series (2014) 9, 228–233
Donor vigilance 229
[3]. In the USA, deaths associated in time with blood
donation (including plasmapheresis and other automated
donations) as well as those in transfusion recipients are
subject to mandatory reporting to the FDA, which
publishes the findings annually [4].
For the purposes of comparing figures between
countries and blood collection organisations, agreement
is necessary on the types of complications of blood
donation to be collected. To this end, from 2006, the
International Haemovigilance Network (then still the
European Haemovigilance Network) in collaboration with
the International Society for Blood Transfusion (ISBT)
working party on haemovigilance developed a standard
list of definitions for the main types of donation compli-
cation [5]. In 2013, the ISBT HV working party launched
a revision of the existent definitions (which date from
2008) to align with the new insights so that data capture
will better support organisations in their efforts to adopt
and monitor the effects of preventive measures as well as
enabling organisations to compare their data. Donor reac-
tions are included in the ‘ISTARE’ International Surveil-
lance Database for Adverse Reactions and Events which is
owned and hosted by the International Haemovigilance
Network, into which haemovigilance systems can (anony-
mously) enter their aggregate data and compare their
own with other countries’ data [5].
Vasovagal reactions
In recent years, studies from different countries have
analysed the incidence and risk factors for donors feeling
weak and dizzy or actually fainting during or following a
whole blood donation or component donation by aphere-
sis. The term ‘vasovagal reaction’ is used for this constel-
lation of symptoms, although strict diagnostic criteria to
confirm increased parasympathetic (vagal nerve) activity
are generally not formally applied. Reported rates of
vasovagal reactions vary considerably depending on the
donor population, but lie in the range of 0
4–1% or
higher if reporting includes mild to moderate reactions
[6–10].
Knowledge of risk factors opens possibilities for target-
ing groups of higher-risk donors for preventive measures.
Authors concur in finding higher incidences among
female, younger and first-time as well as inexperienced
donors. Rates are also higher among donors with smaller
estimated blood volume (this estimation is based on
donor gender, weight and height), anxious donors and
those with a lower predonation blood pressure [8, 9, 11,
12]. Less investigated and not yet explained, a higher pre-
donation haemoglobin level has been shown by two
groups to be independently associated with vasovagal
reactions [13, 14]. Associations have also been described
230 J. C. Wiersum-Osselton et al.
with increased predonation heart rate [8] and with
increasing duration of phlebotomy [15, 16].
Several types of preventive measure have been evalu-
ated and found successful in reducing the incidence of
vasovagal reactions (Table 1): predonation hydration,
deferral or reduced collection volume for smaller donors,
muscle tension or leg crossing, social support and specific
donor information. The first three measures effectively
reduce the percentage of a donor’s blood volume which is
donated. Using combined interventions in a large-scale
study among younger donors, Tomasulo et al. [17] found
an encouraging aggregate reduction of 24% of reactions.
Nevertheless, much work remains to achieve clarity about
the possible types of intervention and practical parame-
ters and which donors to target in different settings.
Needle injury
Needle-related complications include haematoma, arterial
puncture and painful arm, which may result from nerve
irritation through a haematoma or from direct injury to a
nerve or other structure. It is recognised that arm symp-
toms from needle-related complications may take several
weeks or longer to resolve, and these complications are
over-represented among reported cases where there is
long-term morbidity following a blood donation [24].
There is an association between traumatic venepuncture
and the occurrence of nerve injury [25].
Whole blood donations and donor iron status
Repeated blood donation (primarily whole blood dona-
tion, but repeated apheresis also carries this risk, [26])
tends to deplete donor iron reserves and may lead to hae-
moglobin levels below the donation threshold or frank
iron deficiency anaemia [27, 28]. It is not known whether
the state of iron-deficient erythropoiesis has any adverse
consequences in an adult non-anaemic asymptomatic
donor. There are different approaches to address the prob-
Table 1 Measures to reduce vasovagal reactions (VVR)
Measure Authors (selected)
Hydration Newman [18]
Muscle tensing Ditto [19]
Kowalsky[20]
Ditto [21]
Social support Hanson [22]
Deferral (or reduced collection volume) Eder [23]
for small body weight/EBV donors
Combination: deferral below EBV 3
5 l, Tomasulo [17]
water drink and muscle tensing
Ó 2014 International Society of Blood Transfusion, ISBT Science Series (2014) 9, 228–233
lem or iron depletion. The interdonation interval may be
increased through deferrals or pre-emptively [29] – how-
ever, this leads to loss of donations and reduced donor
retention. Blood service-based programmes of iron
replacement have been found effective in reducing hae-
moglobin deferrals and retaining donors [30, 31]; in Can-
ada, blood donors are informed of the risk of iron
depletion and encouraged to discuss iron supplementation
with their general practitioners [32]. It is clear that predo-
nation Hb determination – or an alternative method such
as the copper sulphate solution or haematocrit – does not
detect donors with depleted iron stores. Further work is
necessary to evaluate possible methods for monitoring
donors for iron depletion – these include determination of
serum ferritin and zinc protoporphyrin. A recent small
randomised, placebo-controlled trial of iron supplementa-
tion in iron-depleted non-anaemic female donors
increased ferritin and haemoglobin levels but failed to
demonstrate clinical benefit [33]. So far, haemovigilance
systems have not adopted definitions for reporting iron
depletion or for monitoring and benchmarking between
blood establishments.
Effect of complications of blood donation on
donor return
Studies are consistent in reporting reduced return follow-
ing donor reactions although the methods of measuring
donor return vary, as do the baseline return rates. For
instance, France et al. reported return rates of 42% for
first-time donors and 70% for repeat donors overall;
return by the novice donors was halved in donors with
higher scores on the Blood Donor Reactions Inventory
[34]. Newman (in 2006) reported a reduced blood donor
return following complications, rising to an 85%
reduction among donors who suffered from vasovagal
reactions combined with painful arm and fatigue [35]. In
the Netherlands, with overall return rates (subsequent
donation within a year) of 75–80% and 85–90% among
Remarks
500 ml water drink; 21% reduction in VVR (high school donors)
Less prefaint reactions (Blood Donor Reactions Inventory, BDRI)
Female donors: attenuated decrease of cerebral oxygenation
Possible support for increased return in subgroup of male donors
Inexperienced donors (0–2 previous donations); lower scores on BDRI
VVR 20% reduced in 16–18 years donors after introducing requirement
of >3
5 l EBV
Aggregate VVR reduction of 24% of VVR (17- to 22-year-old donors)

first-time donors and repeat donors, respectively, return
was reduced more strongly following vasovagal reactions
(first-time donor return rate approximately 55%) than
venepuncture-related problems (no reduction if collection
was completed [14]). A Dutch questionnaire study
noted a greater stopping risk among male than among
female donors following a (self-reported) vasovagal
reaction [36].
Apheresis
Fewer studies have described the incidence of apheresis
complications than those focusing on whole blood dona-
tion. Broadly, there are higher rates of needle-related
complications and lower rates of vasovagal reactions.
Besides procedure-related and physiological explanations,
differences in donor demographics have an effect, and
there is undoubtedly selective retention of donors, partic-
ularly in plasmapheresis programmes. Specific apheresis-
related complications are citrate toxicity, as well as some
extremely rare hazards such as the risk of air embolism.
Theoretical long-term risks such as the possibility of
protein depletion from frequent plasma donation [37] or
osteoporosis from calcium depletion by the citrate [38]
have only recently received attention and are not (yet)
included in lists for reporting and surveillance. The
monitoring of acute and longer-term safety of donors
who have been treated with growth factors for the dona-
tion of peripheral blood stem cells or granulocytes
constitutes a special area which lies beyond the scope of
this article.
Discussion
Through donor vigilance and the increased attention to
complications of blood donation, it is now possible for blood
operators to provide evidence-based information describing
the possible complications, stating the incidences which are
low but not negligible and giving practical tips on how to
reduce their occurrence. This enables potential blood donors
totakeinformeddecisionsaboutdonationandtoadoptbehav-
iours which will minimise inconvenience or harm from their
donation. Practical measures to avoid adverse reactions to
blood donation are not new – ever since blood drives started,
staff and volunteers have followed procedures to minimise
complications. However, the recent increases in knowledge
offer new opportunities to reduce acute complications of
donationaswellastherarelonger-termharms.
Some donors claim that they feel fitter after donating
blood. The question has been asked whether there might
be a physical health benefit from donation. Despite
reports of a reduction in cardiovascular disease in blood
donors and the suggestion that this might be a favourable
Ó 2014 International Society of Blood Transfusion, ISBT Science Series (2014) 9, 228–233
Donor vigilance 231
consequence of lower body iron stores, to date, the asso-
ciation has not been confirmed. A ‘healthy donor effect’
looks a more likely explanation. Meanwhile, the (mostly
non-serious) complications of blood donation are at least
as common as minor physiological adverse reactions in
the recipients of blood transfusion. There is an ethical as
well as professional and regulatory onus on those
involved in blood collection to follow state-of-the-art
recommendations and procedures for donor care and
safety.
The results of donor haemovigilance have so far have
come from single or collaborating blood operators within
single countries. Use of common definitions will enable
haemovigilance systems to examine differences between
donor (and recipient) haemovigilance findings from dif-
ferent countries. International collaboration is indispens-
able for the study of extremely rare complications.
Looking for explanations for differences in rates will
require data on of donor demographics and epidemiology,
blood collection procedures (e.g. volume drawn), compo-
nent production and specifications, laboratory methods
etc. Such study will be challenging but has the potential
to contribute to the objective of using haemovigilance
data as a starting point for improving safety for donors
and throughout the transfusion chain.
Conclusions
International surveillance definitions for complications of
blood donation and for non-infectious hazards are avail-
able on the websites of the ISBT and IHN. It is important
to be clear about which cases are to be counted in inter-
national comparisons or surveillance so that people can
as far as possible map their cases to the international list.
As systems do this progressively better, it will become
possible to analyse the differences to gain further under-
standing and potentially discover new ways of improving
safety.
Acknowledgements
The authors wish to acknowledge the important contribu-
tion of Jan Jørgensen to putting complications of blood
donation and donor haemovigilance on the map interna-
tionally.
Author contributions
All the authors are involved with supervising and Dutch
data collection on complications of blood donation and
analysing the results. JCW-O drafted the manuscript; the
coauthors reviewed and critically commented on the
manuscript and agree to its submission.
232 J. C. Wiersum-Osselton et al.
Disclosure
None of the authors have any financial conflicts to
disclose.
References
1 Wiersum-Osselton JC, de Kort W, Marijt-van der Kreek T,
et al.: Chapter 4: Setting up or consolidating a system for
donor haemovigilance at the level of a blood establishment; in
De Vries RRP, Faber JC (eds): Haemovigilance: An Effective
Tool for Improving Transfusion Safety, 2012, pp. 21–35. ISBN
978-0-470-65527-6.
2 Boynton MH, Taylor S: Complications arising in donors in a
mass blood procurement project. Am J Med Sci 1945;
209:421–436
3 European Commission: Common approach for definition of
reportable serious adverse events and reactions as laid down
in the Blood Directive 2002/98/EC and Commission Directive
2005/61/EC; version 3 (2012) SANCO/D4/IS.
4 FDA. Fatalities Reported to FDA Following Blood Collection
and Transfusion, Annual Summary for Fiscal Year 2011.
Available at; http://www.fda.gov/downloads/BiologicsBlood-
Vaccines/SafetyAvailability/ReportaProblem/TransfusionDon
ationFatalities/UCM300764.pdf [Last accessed 10-11-2013].
5 ISBT working party on haemovigilance. Standard for Surveil-
lance of Complications Related to Blood Donation; http://
www.isbtweb.org/fileadmin/user_upload/WP_on_Haemovigi-
lance/ISBT_StandardSurveillanceDOCO_2008__3_.pdf Also avai
lable at http://www.ihn-org.com/wp-content/uploads/2011/06
/ISBT-StandardSurveillance-DOCO-2008.pdf. [last accessed
10-11-2013].
6 ISTARE. See; http://www.ihn-org.com/haemovigilance-data-
bases/istare-2/ [last accessed 10-11-2013].
7 Newman BH, Pichette S, Pichette D, et al.: Adverse effects in
blood donors after whole-blood donation: a study of 1000
blood donors interviewed 3 weeks after whole-blood dona-
tion. Transfusion 2003; 43:598–603
8 Wiltbank TB, Giordano GF, Kamel H, et al.: Faint and pre-
faint reactions in whole-blood donors: an analysis of predo-
nation measurements and their predictive value. Transfusion
2008; 48:1799–1808
9 Eder AF, Dy BA, Kennedy JM, et al.: The American Red Cross
donor hemovigilance program: complications of blood dona-
tion reported in 2006. Transfusion 2008; 48:1809–1819
10 Rebibo D, Danic B: Haemovigilance donors: methods and results
[ArticleinFrench].TransfusClinBiol2007;14:142–146
11 Trouern-Trend JJ, Cable RG, Badon SJ, et al.: A case-con-
trolled multicenter study of vasovagal reactions in blood
donors: influence of sex, age, donation status, weight, blood
pressure, and pulse. Transfusion 1999; 39:316–320
12 France CR, France JL, Kowalsky JM, et al.: Transfusion 2012;
52:375–380
13 Bravo M, Kamel H, Custer B, et al. Poster/Oral communica-
tion, Montreal, April 2012.
14 Wiersum-Osselton JC, Marijt-van der Kreek T, Brand A, et al.:
Risk factors for complications in donors at first and repeat
Ó 2014 International Society of Blood Transfusion, ISBT Science Series (2014) 9, 228–233
whole blood donation: a cohort study with assessment of the
impact on donor return. Blood Transfus 2013; 3:1–9. doi: 10.
2450/2013.0262-12 [Epub ahead of print].
15 Newman B, Siegfried B, Buchanan BA: Are vasovagal
reaction rates in blood donors related to the duration of the
phlebotomy? (Letter) Transfusion 2008; 48:568–569
16 Newman B, Siegfried B: Phlebotomy duration and vasovagal
reaction rates in 5.4 million donations (Abstract). Transfusion
2013; 53(Suppl):110A
17 Tomasulo P, Kamel H, Bravo M, et al.: Interventions to
reduce the vasovagal reaction rate in young whole blood
donors. Transfusion 2011; 51:1511–1521
18 Newman B, Tommolino E, Andreozzi C, et al.: The effect of a
473-mL (16-oz) water drink on vasovagal donor reaction
rates in high-school students. Transfusion 2007; 47:1524–
1533
19 Ditto B, France CR, Albert M, et al.: Dismantling applied ten-
sion: mechanisms of a treatment to reduce blood donation-
related symptoms. Transfusion 2007; 47:2217–2222
20 Kowalsky JM, France JL, Wissel ME, et al.: Effect of applied
muscle tension on cerebral oxygenation in female blood
donors. Transfusion 2011; 51:1802–1808
21 Ditto B, Gilchrist PT, Holly CD, et al.: The effects of leg cross-
ing and applied tension on blood donor return. Vox Sang
2013; 105:299–304
22 Hanson SA, France CR: Social support attenuates presyncopal
reactions to blood donation. Transfusion 2009; 49:843–850
23 Eder AF, Dy BA, Kennedy JM, et al.: Improved safety for young
whole blood donors with new selection criteria for total esti-
mated blood volume. Transfusion 2011; 51:1522–1531
24 Sorensen BS, Johnsen SP, Jorgensen EJ: Complications
related to blood donation: a population-based study. Vox
Sang 2008; 94:132–137
25 Newman B: Arm complications after manual whole blood
donation and their impact. Transfus Med Rev 2013; 27:44–49
26 Page EA, Coppock JE, Harrison JF: Study of iron stores in
regular plateletpheresis donors. Transfus Med 2010; 20:22–29
27 Cable RG, Glynn SA, Kiss JE, et al.: Iron deficiency in blood
donors: analysis of enrollment data from the REDS-II donor
iron status evaluation (RISE) study. Transfusion 2011;
51:511–522
28 Spencer B: Blood donor iron status: are we bleeding them
dry? Curr Opin Hematol 2013; 20:533–539
29 Baart AM, de KW, Atsma F, et al.: Development and valida-
tion of a prediction model for low hemoglobin deferral in a
large cohort of whole blood donors. Transfusion 2012;
52:2559–2569
30 Pittori C, Buser A, Gasser UE, et al.: A pilot iron substitution
programme in female blood donors with iron deficiency with-
out anaemia. Vox Sang 2011; 100:303–311
31 Magnussen K, Bork N, Asmussen L: The effect of a standard-
ized protocol for iron supplementation to blood donors
low in hemoglobin concentration. Transfusion 2008; 48:749–
754
32 Goldman M, Uzicanin S, Scalia V, et al.: Iron deficiency in
Canadian blood donors. Transfusion 2013. doi: 10.1111/trf.
12380 [Epub ahead of print].

33 Waldvogel S, Pedrazzini B, Vaucher P, et al.: Clinical
evaluation of iron treatment efficiency among non-anemic but
iron-deficient female blood donors: a randomized controlled
trial. BMC Med 2012; 10:8. doi: 10.1186/1741-7015-10-8
34 France CR, France JL, Wissel ME, et al.: Donor anxiety, nee-
dle pain, and syncopal reactions combine to determine reten-
tion: a path analysis of two-year donor return data.
Transfusion 2013; 53:1992–2000
35 Newman BH, Newman DT, Ahmad R, et al.: The effect of
whole-blood donor adverse events on blood donor return
rates. Transfusion 2006; 46:1374–1379
Ó 2014 International Society of Blood Transfusion, ISBT Science Series (2014) 9, 228–233
Donor vigilance 233
36 Veldhuizen I, Atsma F, van DA, et al.: Adverse reactions,
psychological factors, and their effect on donor retention in
men and women. Transfusion 2012; 52:1871–1879
37 Laub R, Baurin S, Timmerman D, et al.: Specific protein con-
tent of pools of plasma for fractionation from different
sources: impact of frequency of donations. Vox Sang 2010;
99:220–231
38 Amrein K, Katschnig C, Sipurzynski S, et al.: Apheresis
affects bone and mineral metabolism. Bone 2010; 46:789–
795
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