Donor hemovigilance: safety as the first priority of blood donor management

Authors


  • 5A-S33-03

R. J. Benjamin, Medical Office, American Red Cross Blood Services, 15601 Crabbs Branch Way, Rockville, MD 20 855, USA
E-mail: BenjaminR@USA.Redcross.Org

Abstract

Background  The American Red Cross instituted a donor hemovigilance program (HVP) in its 35 regional blood centres in 2003 to document adverse events occurring at the time of donation or reported later. The aims are to describe and quantitate rare events using standard definitions, define risk factors, design specific interventions and to assess outcomes. In the 1990s, most US blood centres converted to 500 ml whole blood (WB) collection bags to maximize blood collection. The AABB (formerly known as the American Association of Blood Banks) instituted a standard (#5.4.1.A) to permit a maximum blood loss of 10·5 ml/kg and minimum donor weight of 50 kg (110 lb), allowing 525 ml of blood to be removed from the smallest donors. In the last decade, the majority of States have enacted legislation to allow 16-year-old donors to donate with parental consent.

Methods  Standardized adverse event definitions and reporting were instituted in 2003, and adverse event data were collated and analysed at the National Medical Office. Standard database and statistical analytical methods were utilized. Estimated blood volume was calculated based on height, weight and gender, using the method of Nadler et al. Surgery 1962; 51:224–231.

Results  Analysis of HVP data from 2002 to 2006 highlighted that young, first time, female donors were at risk for vasovagal reactions, injuries related to falls and the need for outside medical care. Multivariate analysis revealed young age, low estimated blood volume (<3·5 l) (EBV) and first-time donation status as major independent risk factors. Calculation of EBV revealed that current AABB standards allow, and CFR limits do not prevent, 15–20% blood loss of EBV from short, low-weight female donors.

Interventions to reduce vasovagal reactions were piloted, starting in 2008, including: (i) a controlled environment through standardized work guidance, physical setup and staffing matrices; (ii) improved donor and parent educational material prior to donation; (iii) enhanced donor monitoring post donation; (iv) fluid intake encouraged within 30 minutes of donation; (v) distraction and muscle tension techniques; (vi) use of apheresis double red cell collection in eligible donors; (vii) enhanced post donation instructions to donors and patients; (viii) implementation of selective height and weight restrictions in donors <19 years old to avoid collection from donors with EBV <3·5 l.

Conclusions  A national HVP has highlighted the issue of vasovagal syncope-like reactions in young first-time donors with low EBV leading to multiple interventions designed to reduce risk. Outcomes are being assessed and monitored. Current AABB standards do not adequately protect young donors with low height/weight from excess blood loss in the United States.

Introduction

Blood centres have a primary obligation to protect the health of donors and to ensure an optimum experience, both as a moral imperative to ‘first do no harm’, but also to ensure that donors will return to give again. While most donations are uneventful, there are undeniable risks to donors due both to local damage at the needle site and systemic reactions, such as vasovagal syncope, falls and injury. Blood collecting agencies have long been aware of these risks and the standard methods of WB collection are in place in order to minimize harm to donors. Donors are required to be healthy on the day of donation and free from major cardiovascular or pulmonary disease. Vasovagal events are known to be more common in young first-time donors of low body weight. Thus, age (originally 18 years), weight (50 kg) and maximum blood loss (10·5 ml/kg) limits are defined. Based on the premise that a 50-kg individual has an approximate 3500 ml blood volume, the US standards allow the removal of 525 ml of blood from minimum weight donors [∼15% estimated blood volume (EBV)].

Since the 1990s, at least three changes have occurred in the US that impact on donor safety: first, most states enacted legislation to allow 17-year-old donors to donate without parental consent, and more recently this has been extended to 16-year-old donors in the majority of states, albeit with parental consent. Each year a larger proportion of donations are derived from donors of high school and college age; second, most blood collection agencies switched from using 450-ml collection bags to 500-ml bags in order to maximize plasma collection and to compensate for the RBC losses that occur with leukoreduction by filtration; third, the two largest blood collection agencies. Blood Systems Inc. (BSI) and the American Red Cross began to collect and collate donor injury data across their systems in the form of donor hemovigilance programs. These data now begin to shed light on decisions made in the past and call into question current practices. On a national and international scale, the AABB and ISBT (International Society for Blood Transfusion) have proposed separate but similar donor hemovigilance programs; however, the potential of these programs is not yet fully realized [1,2].

Donor hemovigilance programs

Donor hemovigilance programs provide standardized processes for recognizing, categorizing, reporting and collating information on adverse events related to the blood donation procedures. Their primary function is to quantify rare events so that blood centres can recognize sources of donor risk, design and implement specific interventions and assess the outcomes. A secondary and as yet unrealized goal is to provide benchmarks that allow other blood centres to compare results and identify and adopt best practices.

The American Red Cross Donor Hemovigilance Program (ARC HVP) was instituted in 2003, and is well described by Eder et al. [3]. This program uses a standard protocol and definitions of 15 different adverse event types, incorporating a severity grade (major/minor), and collects data on events that occur at the time of donation and those that are reported after the donor has left the donation site. While these reports include both WB and apheresis collections, focus on the WB donations utilizing multivariate analysis reveals that age, gender, first-time donation status and regional blood centre are independent risk factors for vasovagal-type reactions. These data highlight the difficulties in utilizing hemovigilance data for benchmarking purposes, as not only should comparisons between blood centres be risk-adjusted for donor demographics, but also consideration must be given for differences in identification, classification and reporting of injuries between centres.

Harm to young donors

The immediate concern that emerged from analysis of the ARC HVP data is the particular susceptibility of young donors to vasovagal reactions and syncope-related falls and injuries following WB donation. Eder et al. [4] document that 16- and 17-year-olds contributed 8% of donations to the American Red Cross in 2006, but recorded the highest rates of vasovagal and presyncope reactions (10·7%). Moreover, 16- and 17-year-old donors were 14-fold more likely than donors over 20 years old (OR 14·5, 95% CI 10·4–20·0) to suffer syncope-related falls and injuries, including lacerations, bruises, contusions, dental injuries and other injuries, including one broken jaw. Sixteen-year-old donors who suffered even a minor complication were significantly less likely to return to donate again than donors who had an uneventful donation (OR 0·40, 95% CI 0·36–0·44). Blood collection centres in the United States view high school blood donation as a critical strategy to maintain the donor base and encourage a new generation of blood donors. Indeed, high school aged donors are more likely to donate again in the following year than older donors, suggesting that a successful donation at a young age could encourage repeat donation [5].

Consequently, the AABB convened a workgroup to review the available published literature and develop strategies to improve safety for young donors [6]. While recognizing the importance of donor safety and the need to actively intervene to reduce adverse events in this susceptible population, the workgroup did not issue binding guidance, but outlined several recommendations to meet the primary objective to reduce the risk of adverse reactions and injuries among young donors. These recommendations included a focus on better predonation education of donors, parents and staff, controlled set-up and environment at blood drives to minimize psychological stress, the ingestion of water just before donation, distraction and muscle tension techniques during phlebotomy, the use of automated red cell collection for those donors who were eligible and better postdonation instructions to donors and parents to better manage adverse events, should they occur. The Task Force encouraged blood centres to evaluate the effectiveness of alternative eligibility criteria or collection procedures (e.g. defer donors with total blood volume <3500 ml; increase minimum weight requirement or decrease the volume of blood collected), recognizing that sufficient data was not yet available at the time to formulate a standard for the industry.

Are we collecting too much blood from young donors?

The analysis of vasovagal syncope events was further expanded by Wiltbank et al. [7], who analysed 422 231 WB donations donated at 16 blood centres, utilizing the BSI HVP. They noted that 17–18-year olds comprise 9·8% of their donations while they experience 27% of all reactions. These authors were able to include height, weight, estimated blood loss (EBV), body mass index (BMI), pulse and blood pressure into their analysis, along with standard donor demographics. Once again they identified young first-time female donors as being at particular risk. Remarkably, the strongest predictive indicator was the donors’ EBV. Using the Nadler et al. [8] formula for blood volume that incorporates height, weight and gender, these authors showed that in ∼5% of their donors, the calculated EBV was <3500 ml, suggesting that a standard 525 ml blood donation would exceed 15% of the donors EBV. Furthermore, a recent reanalysis of methods of determining EBV by Holme et al. [9] suggests that the Nadler formula overestimates blood volume, implying that a standard blood donation may approach 20% of the blood volume in short female donors with low weight. Acute blood loss of >15% is known to risk shock and cardiovascular collapse in normal volunteers. Not surprisingly, in a multivariate analysis, EBV <3500 ml was the strongest predictor of vasovagal type reactions (OR 2·9, 95% CI 2·6–3·0), with young age (17–18 years) (OR 2·8, 95% CI 2·2–2·6) and first-time donation status (OR 2·2, 95% CI 2·1–2·3) running close behind. Further analysis combining age and EBV suggested a synergistic adverse effect on risk of vasovagal reactions, with donors <23 years old with EBV <3500 ml at greatest risk, and with a decreasing risk as the donors EBV and age increase. Following these observations, BSI instituted new height and weight restrictions for all donors <23 years of age in order to ensure that not more than 15% of EBV is lost during WB donation. In the BSI system, this requires ∼1% of donors to be replaced and mostly affects female donors. The authors note that the European Commission recommends a maximum of 13% EBV blood loss for all donors, a restriction that would have significant impact on donor recruitment and defer donation by 25·5% of BSI donors and prevent 45·9% of donor reactions.

Rios et al. [10] performed a similar analysis of data collected at two Red Cross regional blood centres participating in the NHLBI–funded REDS II study. This analysis investigated 591 177 donations including 15 647 16-year olds, examining prefaint and systemic vasovagal reactions (SVR) separately. Nevertheless, the findings were remarkably consistent with the aforementioned report from BSI: 5·6% of donors were estimated to have EBV <3500 ml and these donors had the highest rates of both prefaint and SVR. Multivariate analysis revealed 16-year-old donors (OR 3·7, 95% CI 2·8–4·9), EBV <3·5 l (OR 3·3, 95% CI 2·6–4·2) and first-time donation status (OR 2·3, 95% CI 2·0–2·7) as the strongest predictors for SVR, with similar trends seen for prefaint reactions. The effects of decreasing age and low EBV were synergistic such that the effect of low EBV was most apparent in donors less than 23 years old. Rios et al. [10] argued that exclusion of low EBV (<3500 ml) donors less than 23 years old would defer 2·7% of current donors [almost all (99·9%) female donors] and would prevent 8·8.% of prefaint reactions and 11·0% of SVR’s. In this way, the most vulnerable donors might be protected without taxing the blood supply. A similar deferral of donors <23 years old with EBV of <4·0 l (to meet the European standard of <13% of EBV) would disqualify 9·7% of current donors while avoiding 31·9% of SVR’s and 26·7% of prefaints. Based on these data, the American Red Cross instituted an algorithm to prevent blood donors <19 years old (i.e. mostly high school donors) with EBV <3500 ml from donating WB. The impact of this change on donor deferral and adverse reaction rates is currently being assessed before considering expansion of the program to older donors.

The relationship between height, weight, gender and EBV

The data described by Wiltbank et al. and Rios et al. demonstrates that current AABB standards for maximum blood loss and minimum donor weight do not adequately protect young blood donors. Hemovigilance data clearly shows that young first-time WB donors with low EBV, most of whom are women, are at substantially greater risk for both prefaint and SVR’s, and also for syncope-related falls and injuries. Figure 1 shows the graphic relationship between EBV, weight, height and gender. For women <65 inches and men <60 inches in height there is a risk of excessive blood loss (>15% EBV) with standard WB donation. On the weight scale there is no clear cutoff that would protect the majority of female donors without unnecessarily deferring large numbers of donors, hence the need for the combination height and weight scale proposed by Wiltbank et al. [7] and also recently adopted by the American Red Cross.

Figure 1.

 Graph shows the relationship between height, weight and gender for donors with blood volumes of 3.5 l. The AABB minimum weight standard (110 lbs) is shown to emphasize the poor correlation between EBV and weight. Donation of 525 ml of whole blood (WB) from a donor of a given gender, whose height and weight fall below the diagonal line (i.e. the stippled area), will result in >15% blood loss.

While the two largest blood systems in the US have instituted more rigorous restrictions on young donors with respect to height and weight, the alternative approach of collecting smaller volumes of blood from donors with low EBV or at risk of vasovagal reactions because of first-time donation status, gender, young age etc. has not yet been addressed. In general, US Blood Centres are reticent to collect varying volumes of blood from donors because of the complexities of manufacturing of components that would result; however, in many European countries, 450-ml collections are standard and some countries purposefully collect 200-ml units from first-time donors.

Time to reconsider 500-ml WB collection volumes in the United States?

These considerations highlight the need for the United States to revisit its decision to move to 500-ml collection bags for all donors in the 1990s. These 500-ml collection bags contain sufficient anticoagulant (e.g. ∼70 ml citrate phosphate dextrose (CPD)) to store 450–550 ml of WB. Collections less than 450 ml are discarded as ‘quantity not sufficient’ or if >550 ml, are ‘overweight’. Blood collection facilities take great care to collect volumes within these limits in order to meet the manufacturers recommended volume limits. A second constraint, if a single volume of blood is to be collected from all donors, is the AABB limit of 10·5 ml/kg maximum blood loss from the smallest (50 kg) blood donor. To meet this limit, the total blood loss of all donors should not exceed 525 ml, including blood loss in testing samples (∼30–35 ml), tubing (8–12 ml) and diversion pouches (∼42 ml) (Fig. 2). Considering the maximum possible blood loss through these routes, the actual volume of blood collected in a 500-ml bag should comprise 450–485 ml, depending on the particular collection bag utilized (Fig. 2). Most blood centres therefore set their collection scales to collect 460–480 ml of WB. The question arises whether available collection scales are sufficiently accurate to collect blood within the required 20–35 ml range to meet the AABB standards? Mechanical scales in use by many centres are quoted by the manufacturers to have a precision [Coefficient of Variation (CV)] of 2%, implying a standard deviation (SD) of 10 ml for a mean 500-ml collection. If normally distributed, 95% of collections fall within ±3 SD, or ±30 ml of the mean, a 60-ml range. We therefore questioned whether mechanical trip scales could function within the precision constraint necessary to meet the AABB standards.

Figure 2.

 Volume constraints on blood collected in 500 -ml collection bags. The manufacturers allow 450–550 ml of whole blood collection in 500 -ml bags. The AABB standards restricts the maximum volume from the smallest donor to 525 ml minus any blood loss in the tubing (8–12 ml), diversion pouch (∼42 ml) and/or testing samples(30–35 ml), permitting ∼450–485 ml to be actually collected in the bag.

In order to test this question, we measured the weights of consecutive WB collections collected utilizing an automatic donor trip scale (Model 368; Highland Labs Inc., Holliston, MA, USA) set to collect 470 ml of WB, in three different regional blood centres each using different collection sets with or without diversion pouches. Figure 3 shows that the vast majority of collections fell within the 450–550 ml constraint of the collection sets. We then calculated the maximum possible blood loss in samples, tubing and diversion pouches. It can be seen in Fig. 3 that 56–74% of maximum possible collections exceeded 525 ml and the actual CV varied in practice from 2·1–2·3%. Investigation of each donor from whom >525 ml was collected revealed that the vast majority (99·5%) weighed more than 115 lbs and were therefore within the AABB standard of 10·5 ml/kg blood loss. Three donors were <115 lbs and had >525 ml withdrawn (>15% EBV), although no adverse events were noted.

Figure 3.

 Quality control measurements of volume of blood in the collection bag and maximum calculated blood loss, taking into account the maximum blood loss in tubing (8–12 ml), diversion pouch (42 ml) and testing samples (35 ml). 310–639 consecutive collections were weighed at the manufacturing site in three different regional blood centres utilizing different collection sets, one with a diversion pouch (Pall 129-92; Pall Corp, East Hills, NY, USA) and two without (Fenwal 4R3312E and 4R3307E; Fenwal Inc., Lake Zurich, IL, USA). Blood volumes were calculated, aligned numerically and normalized for the number of collections weighed from each Region (0–100% of collections).

These data highlight the fact that mechanical trip scales do not have the requisite precision to collect WB units within the constraints as described in Fig. 2 earlier, and may collect a total of more than 525 ml of blood from a donor near the 50 kg weight limit. There are a number of possible solutions that might prevent excessive blood loss from a low EBV donor, including setting a higher weight limit for donors collected in 500 ml collection sets (115 or 120 lbs); reducing the ‘wastage’ of blood in tubing, diversion pouches and sample tubes; or validating the use of electronic scales that have a higher precision and are able to meet the precision and accuracy requirements.

Conclusions

Over the last decade, the United States reduced the effective age of blood collection and increased blood drives in the high school setting. At the same time, blood centres moved to larger collection sets to maximize the amount of blood collected from each donor. The institution of national hemovigilance programs now highlights the increased incidence of adverse events in young donors that can be linked to the removal of excessive blood loss relative to the donors EBV, driven somewhat by the constraints of the use of 500 ml collection sets and the imprecision of current scale technology. Blood centres have an obligation to put in place measures to protect young donors. These now include more stringent criteria to prevent the loss of excess blood through restrictions based on EBV, the use of more precise scales and possibly the collection of a smaller volume of blood from young donors.

Disclosures

None.

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