Rates of Vaso-Vagal Reactions Among First Time Teenaged Whole Blood, Double Red Cell, and Plateletpheresis Donors

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1 138 Available online at Annals of Clinical & Laboratory Science, vol. 39, no. 2, 2009 Rates of Vaso-Vagal Reactions Among First Time Teenaged Whole Blood, Double Red Cell, and Plateletpheresis Donors Robert F. Reiss, Ruth Harkin, Marvin Lessig, and Julie Mascari New York Blood Center, New York, New York Abstract. Given the paucity of published data regarding reaction rates in younger teenaged donors, we evaluated the reaction rates in all of our first time teenaged donors after New York Blood Center lowered the minimum permissible age for blood donations from 17 to 16 yr in The overall rates of vaso-vagal reactions in donors aged 16 to 19, and those resulting in syncope, occurring in 72,769 consecutive first time whole blood, 3,822 double red cell, and 777 platelet apheresis donations were calculated. They were correlated with age and compared to those found in donors aged Separate rates were calculated by gender, age in yr, and donation type, and then compared to each other. The overall reaction rate among first time teenaged whole blood donors was 8.2% and was significantly greater than among plateletpheresis donors (4.0%; p <0.0002). The rate in female whole blood donors (10.0%) was significantly higher than in males (6.4%; p <0.0002). In male double red cell donors the overall reaction rate of 3.5% was significantly lower than that found in male whole blood donors (p <0.002). Among both male and female whole blood donors a significant correlation with decreasing donor age between 19 and 16 yr was found (r 2 = 0.981; p = 0.01) and (r 2 = 0.988; p = 0.006), respectively. We conclude that teenaged donors have increased reaction rates when compared to adults and the reaction rates increase with decreasing age. In addition, females have higher reaction rates than males. Finally, reaction rates associated with apheresis donations are significantly lower than those associated with whole blood donations. Keywords: vaso-vagal reactions, teenaged blood donors, blood donations, transfusion medicine Introduction While New York State had previously permitted 17-yr-old teenagers to donate blood without parental consent, in 2005 the state regulations were altered to also permit collection of blood from 16- yr-old donors with consent. Thereafter, the New York Blood Center (NYBC) undertook a vigorous campaign to recruit teenaged donors, with particular emphasis on 16- and 17-yr-old high school students. They were asked to donate whole blood (WB), double red cells by apheresis (DRBC), and platelets by apheresis (PA). While there are Address correspondence to Robert F. Reiss, M.D., New York Blood Center, 310 East 67th Street, New York, NY, 10065, USA; tel ; fax ; rreiss@ nybloodcenter.org. considerable data showing that younger donors have increased rates of vaso-vagal reactions when compared to older donors [1-3], until recently there has been a paucity of data related specifically to 16- and 17-yr-old donors, and the comparative rates of reactions between such youthful whole blood and apheresis donors. Recently, data collected by the American Red Cross Biomedical Services on very large numbers of teenaged donors indicate that the youngest donors have significantly increased rates of vaso-vagal reactions when compared to older youthful donors [4]. Similar data have been presented in preliminary form by others [5]. These findings validated the results of smaller studies that estimated reaction rates among 17-yr-old donors to be between 8.0 and 12.0% [6,7]. Most recently, in a large study of 422,231 first time and repeat whole /09/ $ by the Association of Clinical Scientists, Inc.

2 Vaso-vagal reactions in teenaged blood donors 139 blood donors, of which 17- and 18-yr-old teen-agers comprised approximately 10%, blood volume and other physiologic parameters and their relationships to donor reactions were analyzed. While the study confirmed an increased reaction rate among younger donors, the data suggested that in large part this was related to differences in size and related blood volume when compared to older donors [8]. Importantly however, this study also confirmed the findings of a smaller study that suggested that teenaged donors had increased reaction rates when compared to adult donors of equivalent weight [9]. In this communication, we report the overall rates of vaso-vagal reactions, as well as those characterized by syncope, among a large number of teenaged WB and apheresis donors during the years 2006 and 2007, and we compare these rates to those observed in 20- to 29-yr-old donors. Furthermore, we examine the relationship of age to the rate of reactions in 20- to 29-yr-old donors. Finally, we compare the reaction rates noted in teenaged WB blood donors to those found in teenaged apheresis donors. Materials and Methods All donors weighing 110 pounds, regardless of age or gender, were considered for WB and PA donation. Donor weights were not measured or recorded for such donations. Donors wishing to undergo DRBC donation were required to meet the weight and height requirements for male and female DRBC donors. Because of this, 98% of the teenaged double red donors were male, and therefore weighed at least 130 pounds. All donor reactions were entered into the PROGESA software system (MAK-SYSTEM, Paris, France) and then extracted to the NYBC BOSS TM system (Blood Operations Support Software, New York Blood Center, New York, NY) This latter system can produce reports that are able to categorize donors suffering reactions according to age, gender, first-time or repeat donation, donation type (WB, DRBC, or PA), and severity of reaction. Mild vaso-vagal reactions include those whose symptoms are limited to pallor, sweating, dizziness, nausea, and weakness. Moderate reactions include those characterized by syncope with or without convulsions. Severe reactions are defined as those associated with syncope and requiring referral to a health care facility because of prolonged recovery or injury from falls. Other types of reactions (eg, hematoma, allergic reactions) are recorded separately and were not considered in this analysis. The BOSS TM software system also records the total number of donors and donations divided according to the same demographic categories. The rates of total donor reactions and those characterized by syncope occurring between 1 January 2006 and 31 December 2007 among first time WB, DRBC, and PA donors were calculated separately for each type of donation. These data were stratified according to gender and teenaged donor age group (16-, 17-, 18-, and 19-yr-old). Similar data for first time 20- to 29-yr-old donors were also collected and stratified according to gender and yr of age. The reaction rates were then correlated with age for teenaged male and female WB, DRBC, and PA donors by calculating their Pearson productmoment correlation coefficients. In addition, the reaction rates of individual groups of donors separated on the basis of age, gender, and type of donation were compared to each other by calculating the z-ratios and associated 2-tailed probabilities for the difference of independent proportions. All calculations were performed utilizing VassarStats, an online web site for statistical computation [10]. Results A total of 72,769 first time, 16- to 19-yr-old teenaged WB donors donated during the study period. The overall reaction rate among these individuals was 8.2% and was approximately twice that noted among 777 teenaged PA donors who donated during the same time period (4.1%; p < ). It was also more than twice the rate noted in 3,822 teenaged DRBC donors, 98% of whom were male (3.5%; p <0.0002). The age and gender breakdowns, together with severity of reaction, are shown in Tables 1, 2, and 3 for WB, PA, and male DRBC donors, respectively. In 16- to 19-yr-old WB donors, the overall reaction rate of 8.2% was significantly higher than the reaction rate of 5.6% found in 44,203 WB donors aged (p <0.0002). Furthermore, among these donors the overall rate of reactions was highly correlated with decreasing age from 19 to 16 yr (r 2 = 0.992: p = ). This strong correlation was also noted independently for male (r 2 = 0.981; p = 0.01) and female (r 2 = 0.988; p = 0.006) teen-aged donors (Fig. 1). A similar tendency was seen between the rate of reactions associated with syncope and decreasing age in female donors, but it did not reach significance (r 2 = 0.826; p = 0.091). This association was not noted in teenaged male donors (r 2 = 0.502, p = 0.291). In this 16- to 19-yr- old group of WB donors, the rate of reactions associated with syncope of 0.81% was significantly higher than the 0.46% found in the 20- to 29-yrold group (p <0.002). While there was a significant

3 140 Annals of Clinical & Laboratory Science, vol. 39, no. 2, 2009 Table 1. Reaction rates in whole blood donors. Gender Age Donations All Reactions Syncope (yr) (%) (%) Female 16 10, , , , , , Male 16 8, , , , , , Fig. 1. Reaction rates (%) for whole blood donors shown according to age (yr) and gender. Table 2. Reaction rates in plateletpheresis donors. Gender Age Donations All Reactions Syncope (yr) (%) (%) Female Male Table 3. Reaction rates in double red cell donors. Gender Age Donations All Reactions Syncope (yr) (%) (%) Male difference in the overall reaction rate between 16- and 17-yr-olds (9.1 vs 8.3%; p = 0.004), there were also significant differences between 17- and 18-yrolds (8.3 vs 7.3%; p <0.0002) and between 19- and 20- to 29-yr-olds (6.7 vs 5.6%; p = ). The difference between 18- and 19-yr-olds did not reach significance (7.3 vs 6.7%; p = 0.103). A similar correlation between age and the overall reaction rate was seen among all WB donors in the 20- to 29-yr-old age group (r 2 = 0.712; p = 0.002). While this correlation among female donors in this age group remained high (r 2 = 0.682; p = 0.003), it did not reach significance among males (r 2 = 0.361; p = 0.066) (Fig. 1). There was little correlation between age and the rate of reactions associated with syncope in this age group (r 2 = 0.165; p = 0.244). In addition, the overall rate of reactions among female WB blood donors, aged (10.0%), was significantly higher than among male donors (6.4%; p <0.0002). Further, the rate of reactions associated with syncope among these female donors was 0.96%, and was significantly greater than that noted in male donors (0.65%; p <0.002). The difference between the overall reaction rate in teenaged PA donors (4.1%) and those in the 20- to 29-yr age bracket (3.6%) was small although highly significant (p <0.0002). Further, among teenaged PA donors, there was little correlation between age and incidence of reactions among either males (r 2 = 0.443; p = 0.334) or females (r 2 = 0.438; p = 0.338).

4 Vaso-vagal reactions in teenaged blood donors 141 Among 3,748 male teenaged DRBC donors, the overall reaction rate (3.5%) was significantly lower than the rate found in male whole blood donors (6.4%; p <0.002), and higher than the 2.3% noted among 2,668 male DRBC donors in the 20- to 29-yr-old age bracket (p = 0.007). Although there was a trend for increasing reaction rates with decreasing age from 19 to 16 yr, the correlation did not reach significance (r 2 = 0.670; p = 0.181). Discussion The rate of vaso-vagal reactions among WB donors cited in the older literature was between 3 and 5% [11-14]. More recently, lower reaction rates are reported. In a recent study of first time and repeat donors an overall rate of reactions of about 1.4% was reported. Importantly, among first time donors, who comprised approximately 25% of donors, the reaction rate was 2.75% while it was only 1.0% among repeat donors [8]. This confirmed prior studies that identified previous blood donation as being inversely related to the rate of donor reactions [13-16]. An increased rate in female donors has been identified in numerous studies [1,2,8,11,16]. In multiple studies it has been found that the rate of vaso-vagal reactions is related to decreasing age. Donors under the age of 30 yr have an increased rate of vaso-vagal reactions [1,8,17], while increasing age is associated with decreasing rates of reactions [2,3,11,14,15]. Among younger donors, and in particular teenaged high school students, still higher rates of reactions, which in one study reached 12.5%, have been documented [18]. Recent preliminary reports, involving very large numbers of donors, have emphasized the finding that the younger the donor, the higher the rate of reactions, with 16- and 17-yr-olds having the highest rates [4,5]. We have confirmed that first time teenaged WB donors have a rate of vaso-vagal reactions approximately twice that of young adults donating for the first time, and that teenaged female donors have consistently higher rates when compared to males. In addition, similar increases in reactions characterized by donor syncope were seen in the younger donors. Of note, some study results indicate that the difference in rates between 17-yrold male and female donors is not seen if the donors of both genders weighing less than 150 pounds are excluded [6]. Further examination of the relationship between body weight and reaction rates in both teenaged and adult donors also demonstrates that the reaction rate for teenaged donors increases disproportionately to weight when compared to adults [8,9]. While we have found a highly significant inverse correlation between rate of reactions and age, we were unable to delineate an age plateau that separates those teenagers with a high rate of reactions from those found in young adults and that might suggest a minimal permissible age for WB donation by teenagers (Fig. 1). Thus, it is important to identify modalities that can reduce the high number of reactions in 16- to 19-yr-old donors. We have demonstrated that the reaction rates among teenaged PA donors are lower than among whole blood donors and are only slightly higher than the rates found in older donors. These findings differ from a study in Japan in which a higher incidence of reactions was found in female PA donations, when compared to female WB donations [19]. A reduced incidence of reactions associated with automated red cell donations has been reported [20]. The reduced rate of reactions in these teenaged male donors, when compared to teenaged male WB donors in our population, tends to confirm the conclusions of this report, although we did not control for the weight requirement of 130 pounds required to undergo DRC collection. Our experience with apheresis donations suggests potential ways to reduce the rates of reactions in WB donors. Foremost among the differences between the two donation modalities are the replacement of blood volume lost with crystalloid solutions and the increased donorphlebotomist interaction that occurs during apheresis donations. While it has been proposed that the state of hydration [21], and time since eating [2,11,17,21] are not associated with reaction frequency, an early study found an association of vaso-vagal reactions with lack of recent food intake [12]. Psychological factors have been implicated in the causation of donor reactions [14,22] and a recent study demonstrated that the interaction between donor and phlebotomist influences the rate of reactions [23].

5 142 Annals of Clinical & Laboratory Science, vol. 39, no. 2, 2009 While lack of pre-donation hydration may not be related to an increased reaction rate, it has been demonstrated that consumption of liquid shortly before phlebotomy can reduce the incidence of vaso-vagal reactions in younger donors by 21%. This effect was most pronounced in first time donors and was hypothesized to be due to gastric dilation rather than replacement of fluid lost with the phlebotomy [18]. Recently, pre-donation hydration and nutrition supplementation of high school donors has been shown to effectively decrease the rate of reactions [24]. Other interventions that have been reported to reduce the incidence of vaso-vagal reactions include muscle tensing exercises [25], distraction techniques [26], decreasing the volume of whole blood donation, and increasing the minimum permissible donor weight or estimated blood volume for whole blood donation [8]. The decreased reaction rates noted with apheresis procedures in this study support the suggestion that eligible teenaged WB donors be redirected toward automated DRBC collections, with fluid replacement [4] or PA collections. While it is true that the morbidity associated with a vaso-vagal reaction itself is limited, minimizing the number of such reactions is important for 3 reasons. First, donors who suffer reactions with syncope are at an increased risk for injury from associated falls. The magnitude of this risk has been quantified to be 10-15% [27]. Second, the occurrence of such reactions negatively impacts the success of further individual recruitment efforts. It has been shown that donors who suffer such reactions are less likely to return for repeat donation [28,29]. Finally, the request to run repeat blood drives in those high schools where high reactions rates had occurred during prior blood collection activities has met with increased resistance on the part of school administrators (Purvis, R. personal communication, 2008). While our observations reported in this paper, together with the reported experiences of others, have prompted NYBC to implement multiple changes to our policies regarding teenaged blood donors, including increased fluid intake prior to donation and muscle tensing exercises, and to consider increased diversion of eligible teenaged WB donors to DRBC and PA procedures, there is a need for further research directed to decreasing reaction rates in blood donors, and teenaged donors in particular. In conclusion, the reaction rate among 16- to 19-yr-old WB donors is significantly increased with respect to donors in the 20- to 29-yr-old age group. The rate among female WB donors is significantly higher than in male donors. Most striking is the marked correlation of increased donor reactions with decreasing age of teenaged WB donors that according to some studies may be disproportionate to their lesser weights. The rate of reactions is significantly greater among first time WB donors than among first time DRBC and PA apheresis donors. Modalities that can be implemented to reduce the reaction rate among teenaged donors are crucial to their protection from possible injuries resulting from syncope occurring in the course of these reactions, and maintaining their future participation in blood donation programs. Future research should be directed to defining the relative effectiveness of these possible interventions. Acknowledgements The authors thank Jay Valinsky, Ph.D., and James Louie, M.D., for their critical reviews of this manuscript. References 1. Callahan R, Edelman EB, Smith, MS, Smith JJ. Study of the incidence and characteristics of blood donor reactors. Transfusion 1963;3: Tomasulo P, Anderson AJ, Paluso MB, Gutschenritter A, Aster RH. A study of criteria for blood donor deferral. Transfusion 1980;20: Kasprisin DO, Glynn SH, Taylor F, Miller KA. Moderate and severe reactions in blood donors. Transfusion 1992; 32: Eder AF, Hillyer CD, Dy BA, Notari EP, Newman BH, Benjamin RJ. Adverse Reactions to allogeneic whole blood donation by 16- and 17-year-olds. JAMA 2008; 299: Harkin R, Lessig M, Reiss R. Reaction incidence among teen-aged first time and repeat whole blood and apheresis donors. Transfusion 2007;47(suppl):107A. 6. Newman BH. Vasovagal reactions in high school students: findings relative to race, risk factor synergism, female sex, and non-high school participants. Transfusion 2002;42:

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