Volunteer safer than replacement donor blood: a myth revealed by evidence

Authors


  • 4D-S28-01

J.-P. Allain, Cambridge Blood Centre, Long Road, Cambridge CB2 2PT, Cambridge, UK
E-mail: jpa1000@cam.ac.uk

Abstract

The dogma that volunteer non-remunerated blood donors (VNRD) are safer has been a cornerstone of world transfusion, including developing countries, for WHO and other major transfusion organizations although the data supporting this dogma has never been convincing. It was supported by data collected without regard for the basic rule of epidemiology, which is to compare what is comparable. In this case, first-time and repeat VNRD were amalgamated, and genuine replacement/family donors (R/F) were mixed with paid donors. In sub-Saharan Africa (SSA), VNRD and R/F donors have a median age of < 20 and around 30, respectively. In VNRD, the proportion of females is considerably higher than in R/F donors further distorting the comparisons. In epidemiological terms, only first-time VNRD can be validly compared to R/F donors.

When such valid approach is taken, as published by three SSA countries (Cameroon, Ghana and Guinea), no significant difference in the prevalence of anti-HIV and HBsAg is apparent. In each study, first-time VNRD > 20 years of age have higher prevalence of HBsAg and sometimes of anti-HIV than R/F donors. These confirmed preliminary data strongly suggest that first-time VNRD and R/F donors are epidemiologically undistinguishable and equally safe for viral infections.

This collective data should directly impact three critical factors: the cost of blood, the availability of blood and the efforts put in recruiting repeat donors. R/F blood costs 2–5 times less than VNRD blood, and collecting R/F blood should no longer be discouraged. VNRD-only policy not only costs more but also limits blood availability for acute anaemia, potentially endangering patients’ lives. Collecting R/F blood as a legitimate supplement to VNRD blood may help reaching 10 units/1000 inhabitants, a level considered adequate for developing countries’ blood supply.

Only repeat donation significantly improves blood viral safety. As a result, not only first-time VNRD but also R/F donors should be actively encouraged to repeat donation. Evidence should take precedence over a moribund myth.

Introduction

On 22-01-2010, WHO declared: ‘Recognising that achieving self-sufficiency, unless special circumstances preclude it, in the supply of safe blood components based on voluntary, non-remunerated blood donation, and the security of that supply are important national goals to prevent blood shortages and meet the transfusion requirements of the patient population’. Following World Donor Day 2009, in Melbourne, Australia, WHO’s selected consultants issued a declaration on 100% voluntary non-remunerated donation of blood and blood components: ‘Recognizing that evidence shows that regular voluntary, non-remunerated blood donors are the cornerstone of safe and sustainable national supplies of blood and blood products which are sufficient to meet the transfusion requirements of the patient population’. ‘Believing that family replacement and paid donation can compromise the establishment of sustainable blood collection from voluntary non-remunerated blood donors’.

The above statements and the persistence of WHO and other major players in the blood transfusion field in disseminating to the world that only volunteer non-remunerated blood donors (VNRD) were acceptable because they are safer, and the only way to achieve self-sufficiency for patient transfusion is a dogma that has served as the cornerstone of blood services globally irrespective of cultural or economic capabilities. This dogma, however, is not supported by convincing data, and this article will demonstrate that it is not only unsupported by evidence but also potentially harmful to the poorest countries of the world.

Definitions

According to the council of Europe, ‘donation is considered voluntary and non-remunerated if the person gives blood […] of his/her own free will and receives no payment for it, either in the form of cash, or in kind which could be considered a substitute for money. This would include time off work other than reasonably needed for the donation and travel. Small tokens, refreshments and reimbursements of direct travel costs are compatible with voluntary, non-remunerated donation.’

Replacement donors, also called family donors (R/F donors), are individuals who are generally relatives or friends of hospitalized patients who require blood transfusion. Such donors can be motivated by altruism directed to a person instead of anonymous but also by strong incentives such as replacement being conditional to the patient being transfused or the cost of transfusion supported by families being substantially reduced. Nevertheless, donations are given by free will, and no small tokens are received as inducement.

According to the US Federal regulation, ‘paid’ donors are persons ‘who receive monetary payment for a blood donation’. In developed countries, such payment is given by commercial organizations usually collecting plasma, while in developing countries payment tends to be made to strangers by the family of a patient to substitute for unavailable ‘replacement’ donors within the family circle.

Reading between the lines

The numerous reports published in the last 20 years comparing data that was pooled across groups of VNRD with R/F donors indicated a significant difference in assay reactivity or confirmed prevalence of viral markers between the two groups. Most reports focused on HIV infections, some on anti-HCV and most did not find a difference for HBsAg. These reports taken at face value appeared to indicate a higher level of viral safety in the volunteer donor group. However, when examining the data and the epidemiologic features of SSA, several biases seriously challenging the data interpretation become clear.

  • 1 VNRD and R/F donors are of different age groups. In SSA, volunteers are essentially recruited in secondary schools, and the median age is below 20, in the case of our own study in Ghana 18 years [2]. The median age of R/F donors is older by at least 10 years (31 in Ghana) (Fig. 1). In SSA, the age range 30–39 is the highest risk group for HIV infection and the younger adults < 20 have significantly lower anti-HIV prevalence, irrespective of gender.
  • 2 In most published articles, VNRD are taken as a single group, while it is in fact made of two distinct groups: first-time donors and repeat donors. In this respect, the lower prevalence of viral markers in repeat donors is strongly supported by evidence because they have already been tested at least once, and only had a short period of time between two donations to acquire incident infections. It is also a fact in most reports from SSA that VNRD being for a large part in secondary school for 2–3 years, few repeat donation and the rate of repeat donors range between 20% and 70% in the leading blood centres but much lower nationwide [3]. Such mixture of native and prescreened donors artificially decreases marker prevalence in favour of VNRD. The potential confusion in assessing epidemiologic data between VNRD and R/F donors is illustrated in Table 1 [4]. Taken at face value, on the top lines of the table, VNRD have a clear safety advantage. However, when VNRD are stratified between first-time and repeat donors, the prevalence of anti-HIV is not significantly lower in first-time VNRD than in R/F donors, but HBsAg prevalence is significantly higher [4].
  • 3 There is a difference in gender distribution between VNRD and R/F donors. VNRD being recruited in girls’ as well as in boys’ schools and other education institutions, the proportion of female donors is relatively high (20–40%). R/F donors in contrast are overwhelmingly males (> 90%) [2,3,5]. Some viral infections, particularly hepatitis viruses tend to be of higher prevalence in men. As a result, as indicated for age, comparisons should be adjusted for gender.
Figure 1.

 Age distribution of replacement and volunteer donors in Ghana [2].

Table 1.   Reporting viral prevalence in blood donors in Mali [4]
Type of donorsN donorsNumber (%)
Conf anti-HIVHBsAgConf anti-HCV
  1. VNRD, volunteer non-remunerated blood donors.

R/F17 449550 (3·2)2521 (14·4)583 (3·3)
VNRD8094110 (1·4)1027 (12·7)248 (3·1)
1st time VNRD491198 (2·0)824 (16·8)223 (4·5)
Repeat VNRD318312 (0·4)203 (6·4)25 (0·8)

It has been consistently assumed and, in the past as well as recent reports probably justified, that R/F donors also consist of two different populations: genuine R/F donors procuring blood for relatives or friends and paid donors whom families recruit when blood is needed, and no replacement donor is available. As indicated later, most countries relying on R/F donors have banned paid donors although they remain present in some countries. The availability of electronic record keeping provides an easy way of identifying paid donors who appear as ‘repeat’ replacement donors [6].

Volunteer/replacement donor ratio: validity of existing data

The extent of replacement donation and percentage of volunteer donations in SSA is a topic of controversy when contrasting official data such as those provided by governments to WHO for global statistics with those collected from the field. The discrepancies can be considerable. As reported by Bates and Hassall [7], ‘in 2002, < 40% of blood donations in Africa were VNRD, rising to 58% in 2006 and 73% in 2007. At a recent congress of the African Association of Blood Transfusion in Nairobi, WHO reported that their target of 80% VNRD in Africa by 2012 has almost been achieved. Information from the WHO Africa regional office indicates however that only 17 of 41 countries had < 50% VNRD and in 38 of the 46 countries that provided data, 77·9% of blood was from VNRD with 50% from repeat donors [8,9]. At the Nairobi congress, 12 out of 46 countries in WHO’s Africa region including Ghana and Malawi were reported to have 100% voluntary donors. In the field, 50% of the blood in Ghana is collected from replacement donors, and repeat donors are no more than 25% of the 50% volunteer blood collected.

Analysis of the replacement donation system

To provide reliable data from the field, a short questionnaire was sent to heads of blood centres in 16 countries from SSA [8], the Mediterranean basin [4], Asia [3] and America [1]. In 11 of these countries, blood replacement is a condition for the patient being transfused, although in two countries this happened only when blood was out of stock and blood was transfused irrespective of replacement in life-threatening emergencies.

What makes replacement donors donate? In seven countries, the blood transfusion given to the patient was free of charge, irrespective of replacement being given or not. In four countries, transfusion was free of charge in the public sector and fully charged in the private sector or in the public sector when not covered by a national health insurance scheme. In five countries, replaced blood was discounted by 10–90% of the full charge. In each type of system, the incentive for donating was more the clinical need of a transfusion than the financial benefit. In 13/16 countries, not replacing the blood transfused was not penalized although in the other three countries, there was decreased priority when the bloodstock was low. In 13 countries that answered the question regarding the availability of paid donors in lieu of family donor indicated that they were banned and not available. Four countries indicated that there were paid donors available, and in two cases that the cost of their blood was up to 10 times the standard blood unit cost. As a result, it appears that the recommendations by WHO and other organizations to eliminate paid donors have been largely implemented.

Viral marker prevalence in first-time VNRD and R/F donors

In 2009, an article was published in Transfusion reporting the prevalence of viral markers in first-time VNRD and R/F donors tested in 2008 at a regional blood centre in Kumasi, Ghana [10]. Donors were stratified according to both age and gender. As previously published [2], the median age of volunteers was 18 and of replacement donors 32. VNRD were 35% women and > 90% of R/F donors were men. As shown in Table 2, there was no significant difference in the prevalence of either anti-HIV or HBsAg between the two groups of donors. Volunteers < 20 years of age had lower anti-HIV prevalence than R/F donors in the same age category, although this was not significant. In contrast, volunteers > 20 years of age had significantly higher prevalence of both anti-HIV and HBsAg than their R/F counterparts (Table 3).

Table 2.   Prevalence of anti-HIV and HBsAg in first-time volunteers and replacement donors from three sub-Saharan African countries [6,10,11]
CountryType of donorsN donorsConfirmed HIVHBsAg
  1. VNRD, volunteer non-remunerated blood donors.

CameroonFirst-time VNRD27211 (4·0)49 (18·0)
R/F donors3053114 (3·7)233 (7·6)
GhanaFirst-time VNRD664069 (1·0)919 (13·8)
R/F donors436050 (1·1)649 (14·8)
GuineaFirst-time VNRD178426 (1·5)259 (14·5)
R/F donors895642 (0·5)1142 (12·8)
Table 3.   Impact of age in comparing viral marker prevalence [10]
Donor groupAge group (%)
< 2020–2930–39≥ 40
First-time volunteer4685 (70·6)1423 (21·4)345 (5·2)187 (2·8)
 Anti-HIV28 (0·6)27 (1·9)11 (3·2)3 (1·6)
 HBsAg523 (11·2)277 (19·5)92 (26·7)27 (13·8)
Replacement274 (6·3)1879 (43·1)1440 (33·0)767 (17·6)
 Anti-HIV3 (1·1)25 (1·3)10 (0·7)11 (1·4)
 HBsAg31 (11·3)329 (17·5)208 (14·4)81 (10·6)

This initial publication triggered two other SSA blood centres, in Cameroon and Guinea, respectively, to undertake the same type of epidemiologic analysis [6,11]. As shown in Table 2, both studies clearly confirmed the data from Ghana. This set of data from three countries strongly suggests that, at least in West and Central Africa, no epidemiologic difference for anti-HIV, HBsAg and, most likely, anti-HCV prevalence exists between VNRD and R/F donors. Additional data needs to be collected in Eastern Africa to enable generalization of the important conclusion that both first-time VNRD and R/F donors are epidemiologically indistinguishable and that the latter do not carry any more viral risk than the former. With the safety element removed, the question remains: what is the justification for eradicating replacement donors and keeping only volunteer donors as the foundation of blood collection in SSA? Three major elements come in this discussion: cost, supply and safety through repeat donation.

Is VNRD blood affordable?

The main reasons for the persistence and dominance of R/F donors in SSA are as follows: (1) Blood transfusion services are mostly small units established within hospitals [12]. As a result, they are in direct contact with patients and their families coming to visit, making the recruitment of R/F donors easy. In contrast, centralized blood transfusion services established in large cities in the last decade tend to be located separately from hospitals in large units not directly in contact with patients’ families [13]. (2) Collecting blood from R/F donors is considerably cheaper than from VNRD because it does not require funding for advertisement, mobile units, vehicles, staff and compensation to donors [7,10]. As shown in Table 4, the cost of volunteer blood is 2–5 times higher than R/F blood [13]. Therefore, in countries with very limited resources, R/F blood is considerably more appealing, in line with the general restriction of health expenditures [14]. This phenomenon is clearly visible in SSA where virtually all centralized blood systems have been established with massive external funding. Once established, these systems away from patients are dependent on VNRD blood donations, and the sustainability of the additional costs is questionable once external funding dries out. In addition, in many areas of SSA, blood cost is covered directly by families, and while a cost of $10–20 is generally affordable, a cost of $50–100 is not affordable unless either fully or in part subsidized by governments [15]. (3) Culturally, most of SSA societies are organized around closely knit small communities in which family and friends support for patients is integrated into the culture, nurturing R/F donation.

Table 4.   Blood unit costs in sub-Saharan African countries according to system and type of donors [13]
CountrySystem%VNRD$/unit
  1. *Cost reduced by predonation screening with rapid tests [15]. VNRD, volunteer non-remunerated blood donors.

Cote d’IvoireCentralized10043
MalawiCentralized10056 (recurrent costs)
UgandaCentralized10054
ZimbabweCentralized10056–90
NamibiaCentralized100100 (including NAT)
MalawiHospital-based016
TanzaniaHospital-based< 1015
Ghana VNRDHospital-based7526*
R/F  14

How to ensure the blood supply?

It is well known that the majority of developing countries with low Human Development Index, including most countries in SSA, experience blood shortages despite a blood usage directed almost exclusively towards emergency transfusion for paediatrics, particularly primary malarial infection, obstetrics for peri-partum haemorrhage, surgery and severe anaemia occurring in haematology/oncology, particularly congenital anaemia (Fig. 2). It has been estimated, but not formally determined, that the level of blood required to cover these indications is at least 10 units/1000 inhabitants, preferably between 10 and 20 units [7,16]. As shown in Fig. 3, out of 16 SSA countries, all but two have a blood supply below 5 units/1000, indicating a chronic shortage of blood for emergency situations, meaning that some patients die for lack of blood. When stratifying the blood supply in countries collecting blood only from VNRD or mostly from R/F doors or by a mixture of both, it remains below 5 U/1000 irrespective of the system in place. More concerning is the fact that, except for Botswana, countries supported by the PEPFAR programme have not massively passed the 5 u/1000 bar. In a country like Burkina Faso where the recommendations of WHO have been implemented to nearly 100% VNRD, supply remains at 4 u/1000, and persistent blood shortages are acknowledged [17]. Although not in SSA, Trinidad and Tobago is relying almost exclusively on replacement blood and yet can make 12 u/1000 available to patients. This example suggests that sufficient supply is achievable on R/F donors alone and that, despite significant external support, other countries strictly relying on VNRD for blood stocks cannot provide sufficient supply. In view of the strongly suggestive data presented above, it appears logical from a safety point of view and advantageous economically, to collect both VNRD and R/F blood to reach the 10 or more units/1000 required clinically. This strategy has been used in Kumasi, Ghana over the last 10 years during which time considerable effort has been put into the active recruitment of volunteers not only in schools but also in places of worship and in partnership with FM radio stations [18]. Blood continues to be collected from R/F donors to meet the 10 u/1000 target, in particular during school recesses at Christmas, Easter and summer holidays during which times R/F donors are actively recruited [18]. As a result, the percentage of volunteer blood donations steadily increased from 35% in 2000 to 80% in 2009, complemented by replacement donations, maintaining the blood supply at > 10 u/1000 for the past 3 years [19]. Relying strictly on VNRD blood not only increases the cost of blood to a level exceeding local resources but also may contribute to maintaining unnecessary blood shortage. Mixing the two types of blood donors that has now been proven to no longer be detrimental to blood safety has considerable potential to help avoiding blood shortages. However, as repeat donation is the true key to blood safety, the issue of potential for repeat donation needs to be considered.

Figure 2.

 Distribution of blood supply in the world [16].

Figure 3.

 Blood supply in developing countries according to blood collection systems.

The solution: VNRD and R/F donors repeat donation

As first-time donors, it appears that VNRD and R/F donors are epidemiologically indistinguishable [6,10,11]. With repeat donation being the key to blood safety, the issue becomes: how to make these donors repeat donation? Contrary to many developed countries where > 80% donors are ‘regular’, this percentage ranges between 25% and 70% in leading SSA blood centres and between 0% and 30% in most countries. Several reasons explain this low level. First, inducing repeat donations in VNRD is costly because it requires substantial additional expenses as detailed earlier. Secondly, secondary school or university students stay in their respective institutions for limited periods of time ranging between 2 and 4 years. In such circumstances, even well-established programmes such as Club 25 have been of limited implementation and success [19,20]. Therefore, the vast majority of donors remain first-time donors. Funding and dedication to improve the situation are required although programmes such as partnership with FM radios developed in Kumasi, Ghana created a pool of spontaneous repeat donors through a conducive and festive environment to blood donation [18]. At present, no reported programme intending to recruit R/F donors for repeat donation has been reported. This might be a challenge for blood services to consider addressing.

Conclusion

This brief review of the widely used and referred to dogma that ‘only VNRD blood is providing safe blood in developing, resource poor areas’ is incorrect and not supported by the published evidence. It should be replaced by a statement such as: ‘blood collected from donors whether related or unrelated to patients in need of transfusion is equally safe with regard to viral infections. Only repeating donation provides added blood safety. Repeat donation should be promoted and taken as the primary objective of blood and blood component suppliers’. Restricting blood collection from genuine relatives or friends of patients in need of blood transfusion in the hospital environment is not justified and would contribute to an unjustified increase in the cost of blood and would result in worsening of blood shortages for resource poor populations and health services. Encouraging blood donation from patient-related and unrelated volunteer, non-remunerated blood donors is the most effective strategy to meet the clinical needs of blood in SSA. Despite the substantial additional cost, it is recognized that patient-unrelated blood donors are more susceptible to becoming repeat donors, thereby improving blood safety. However, exploring strategies to retain R/F donors for repeat donation remains one important objective for hospital-based blood services.

Acknowledgements

I thank the collaborators in Algeria, Burkina Faso, Cameroon, Egypt, Ghana, Guinea, India, Indonesia, Mali, Mauritania, Nigeria, Sri Lanka, Sudan, Togo, Trinidad & Tobago, Tunisia and Turkey involved in the survey for answering the questionnaire.

Disclosures

None.

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