Abstract
Background
In Brazil little is known about adverse reactions during donation and the donor characteristics that may be associated with such events. Donors are offered snacks and fluids prior to donating and are required to consume a light meal after donation. For these reasons the frequency of reactions may be different than those observed in other countries.
Methods
A cross-sectional study was conducted of eligible whole blood donors at three large blood centers located in Brazil between July 2007 and December 2009. Vasovagal reactions (VVRs) along with donor demographic and biometric data were collected. Reactions were defined as any presyncopal or syncopal event during the donation process. Multivariable logistic regression was performed to identify predictors of VVRs.
Results
Of 724,861 donor presentations, 16,129 (2.2%) VVRs were recorded. Rates varied substantially between the three centers: 53, 290 and 381 per 10,000 donations in Recife, São Paulo and Belo Horizonte, respectively. Although the reaction rates varied, the donor characteristics associated with VVRs were similar [younger age (18–29), replacement donors, first time donors, low estimated blood volume (EBV)]. In multivariable analysis controlling for differences between the donor populations in each city younger age, first-time donor status and lower EBV were the factors most associated with reactions.
Conclusion
Factors associated with VVRs in other locations are also evident in Brazil. The difference in VVR rates between the three centers might be due to different procedures for identifying and reporting the reactions. Potential interventions to reduce the risk of reactions in Brazil should be considered.
Introduction
Blood donation is recognized as an extremely safe procedure1,2; however vasovagal (presyncopal and syncopal) reactions during or after donation increase the potential for donor injury. The prevalence of the vasovagal reactions (VVRs) varies by country1–8, and by many other factors such as age, gender, donation history (first-time vs repeat), body mass index (BMI), estimated blood volume of donors,1,2 and type of donation, (i.e., allogeneic or autologous whole blood donation, plamaspheresis, plateletpheresis and multi-component donations4 including double red cell collections9). Fortunately, the majority of adverse events are minor in severity,8,10 but occasionally vasovagal reactions of higher severity occur.11
In Brazil, a country with a population of about 190 million,12 the total annual allogeneic blood collection is approximately 3 million units, or 21 blood donations per 1000 inhabitants.13 Specific procedures are defined for donor recruitment, deferral criteria, laboratory tests, proper handling, and related component preparation procedures. The regulations are similar to those in place in the U.S.14 and Europe15, and internationally accepted procedures and guidelines are used as reference in the development of Brazilian regulatory and practice guidelines.16 In Brazil little is known about VVRs associated with blood donation, including the rates, severity and characteristics of blood donors who have adverse reactions, and variability of the VVRs between blood centers. We report on the rates and risk factors for vasovagal reactions in Brazil.
Materials and Methods
Overall study design
The NHLBI International REDS-II study in Brazil started in 2007, and is comprised of three major public blood banks. Two of them are in the Southeast (Fundação Pro-Sangue, São Paulo and Fundação Hemominas, Belo Horizonte, Minas Gerais)17 while the third is in Northeastern (Fundação Hemope, Recife, Pernambuco). This study is a retrospective cross-sectional study of all allogeneic donors who donated blood between July 2007 and December 2009 at the three REDS-II International blood sites in Brazil.
Measures
Data originate from standard procedures in place to capture information over the course of blood donation. In accord with Federal guidelines, it is mandatory to check vital signs before donation18. Each blood donor must meet acceptability criteria before being subjected to phlebotomy. These criteria include age between 18 and 65 years, minimum weight 50 kg (110 lbs) and being in good general health. The acceptable vital signs at each center are provided (Table 1) are generally similar throughout Brazil. A questionnaire concerning the medical history is completed for every potential blood donor by a physician in Recife and Belo Horizonte, and by a trained nurse in São Paulo.
Table 1.
Criteria for blood donation at each REDS-II Brazil blood center
| Recife | Belo Horizonte | Sao Paulo | |
|---|---|---|---|
| Age | 18 ≤ Age ≤ 65 | 18 ≤ Age ≤ 65 | 18 ≤ Age ≤ 65 |
| Weight | ≥50 Kg or 110 lbs | ≥50 Kg or 110 lbs | ≥50 Kg or 110 lbs |
| Pulse | 60 ≤ Pulse ≤ 100 bpm | 60 ≤ Pulse ≤ 100 bpm | 60 ≤ Pulse ≤ 100 bpm |
| Blood Pressure (BP) | |||
| Hypertension | 100 ≤ BP ≤ 160 mmHg | 100 ≤ BP ≤ 180 mmHg | 100 ≤ BP ≤ 180 mmHg |
| Hypotension | 60 ≤ BP ≤ 100 mmHg | 60 ≤ BP ≤ 90 mmHg | 60 ≤ BP ≤ 90 mmHg |
| Hemactocrit (Ht) or Hemoglobin (Hb) | |||
| Male | Hb: ≤13 g/dL | Hb: ≤13 g/dL 39 ≤ Ht ≤ 55 |
39 ≤ Ht ≤ 54 |
| Female | Hb: ≤12.5 g/dL | Hb: ≤12.5 g/dL 38 ≤ Ht ≤ 54 |
38 ≤ Ht ≤ 50 |
| Collection Volume | 450mL | 450mL** | 450mL* |
Sao Paulo:
- Males >=50kg = 450 mL
- Females >=50 to <=57 kg= 400mL
- Females >=57 kg= 450 mL.
Belo Horizonte:
- Males >=50kg = 450 mL
- Females >=50 to <=55 kg= 410mL
- Females >55 kg= 450 mL.
The Federal guidelines also recommend that no blood should be collected from candidates who are fasting and the blood center should offer a small snack before donation. After the donation, it is obligatory to supply adequate oral hydration and light meal or snacks. There are small differences in the donor intake procedures at the blood centers. In São Paulo and Recife the prospective blood donor goes to the registration, then vital signs and anemia testing, and if the blood donor is approved he/she goes to the donation area. In Belo Horizonte following acceptance for donation, donors go to the snack area and then to the donation area. Restrictions are also in place indicating that no blood should be collected from candidates who ate large meal, rich in fatty foods or consumed alcohol within 4 (four) hours before donation. Of note, there is no height restriction for blood donation in Brazil, and weight is usually self-reported.
A trained technician performs the phlebotomy in a separate room in the blood bank while the donor is in a semi-supine position. The total volume of blood to be collected should not exceed 8 mL / kg for women and 9 mL / kg for men. The allowed donation volume is 450 mL ± 50 mL, which may be increased by 30 mL to perform laboratory tests required by law and technical internal guidelines. Table 1 shows the criteria for blood donation at each REDS II Brazil blood center. After the blood collection, the blood donor remains seated for about 10 minutes and if she/he feels well, a light meal and refreshments are served at the canteen under attention of a trained technician for 15 minutes or more.
Only allogeneic whole blood donations were included in this analysis. Whole blood donation represents 98% of all of the donations in the REDS-II Brazil dataset. Estimated body blood volume (EBV) was calculated based on Nadler’s and colleagues formula19 based on sex, height, and weight. Of note, height and weight are self-reported in all 3 blood centers. VVRs are reported on non-standardized forms; however all forms capture specific symptoms of the reaction, monitoring of vital signs, and medical interventions received. Vasovagal adverse reactions were classified into three categories of severity: Mild grade for presyncopal vasovagal reactions such as pallor, sweating, anxiety; Moderate grade, for hypotension, vomiting, and transient loss of consciousness; and Severe grade for loss of consciousness associated other signs and symptoms such as recurrent vomiting, prolonged pulse and/or blood pressure recovery times, incontinence and convulsions, among others signs and symptoms. Only VVRs that occurred during or immediately after blood donation, while the blood donors still were at the blood center premises are included in this analysis. Needle-related injuries were excluded.
Statistical analysis
Unadjusted rates of reaction were calculated as the proportion of reactions out of all whole blood donation attempts overall and according to blood center and also donor demographic and biometric characteristics. Reaction rates and rates by severity category are expressed per 10,000 donations. Multivariable logistic regression analysis was performed to identify the predictors of vasovagal reactions associated with whole blood donation. All reactions were grouped into a single indicator variable for logistic regression analysis. Due to co-linearity between estimated blood volume and BMI and separately between systolic and diastolic blood pressure, the logistic regression included only one of each pair. The decision of which to include was based on clinical considerations, since statistically the effects were indistinguishable. Results are reported as adjusted odds ratios (AORs) with associated 95% Confidence Intervals (95% CIs). The p-values shown in Table 4 test common odds ratio or center-specific odds ratio for each characteristic in the model. Analyses were conducted using SAS/STAT version 9.2 (SAS Institute Inc., Cary, NC) and Excel version 2010 (Microsoft Inc., Redmond, WA).
Table 4.
Odds ratio from multivariable logistic regression analysis showing predictors of reaction in blood donors in Brazil*
| Characteristic | OR (95% C.I.) | ||
|---|---|---|---|
| Blood Center† | p<0.0001 | ||
| Recife | 0.21 (0.20 – 0.22) | ||
| Belo Horizonte | 1.38 (1.32 – 1.45) | ||
| Sao Paulo | 1.0 | ||
| Sex | Recife‡ | Belo Horizonte | Sao Paulo |
| p<0.0001 | p<0.0001 | p<0.0001 | |
| Female | 1.36 (1.17, 1.60) | 1.49 (1.36, 1.62) | 0.86 (0.79, 0.92) |
| Male | 1.0 | 1.0 | 1.0 |
| EBV | p<0.0001 | p<0.0001 | p<0.0001 |
| <3500 | 2.61 (1.98 – 3.44) | 1.77 (1.48 – 1.98) | 2.12 (1.92 – 2.35) |
| 3500–3999 | 1.83 (1.45 – 2.31) | 1.56 (1.38 – 1.76) | 1.89 (1.74 – 2.06) |
| 4000–4499 | 1.78 (1.48 – 2.13) | 1.34 (1.20 – 1.50) | 1.61 (1.50 – 1.74) |
| 4500–4999 | 1.36 (1.16 – 1.61) | 1.27 (1.15 – 1.41) | 1.29 (1.21 – 1.36) |
| ≥ 5000 | 1.0 | 1.0 | 1.0 |
| Hematocrit | p=0.0002 | p<0.0001 | |
| 38–39 | — | 0.77 (0.69 – 0.85) | 0.69 (0.63 – 0.75) |
| 40–41 | — | 0.85 (0.77 – 0.94) | 0.81 (0.75 – 0.87) |
| 42–43 | — | 0.87 (0.79 – 0.96) | 0.80 (0.75 – 0.86) |
| 44–45 | — | 0.90 (0.82 – 0.98) | 0.93 (0.87 – 0.98) |
| ≥ 46 | — | 1.0 | 1.0 |
| Age (in years) | p<0.0001 | ||
| 18–20 | 3.08 (2.89 – 3.28) | ||
| 21–24 | 2.80 (2.64 – 2.97) | ||
| 25–29 | 2.27 (2.14 – 2.41) | ||
| 30–40 | 1.70 (1.61– 1.80) | ||
| 41–65 | 1.0 | ||
| Donor Type | p<0.0001 | ||
| Community | 1.0 | ||
| Replacement | 1.09 (1.05 – 1.13) | ||
| Donation History | p<0.0001 | ||
| First Time | 2.49 (2.41 – 2.58) | ||
| Repeat | 1.0 | ||
| Race/Ethnicity | p<0.0001 | ||
| Black | 0.51 (0.48 – 0.54) | ||
| Mixed | 0.73 (0.70 – 0.76) | ||
| White | 1.0 | ||
| Asian | 0.75 (0.65 – 0.87) | ||
| Indigenous | 0.81 (0.64 – 1.03) | ||
| Pulse | p<0.0001 | ||
| < 65 | 0.77 (0.72 – 0.83) | ||
| 65–90 | 0.85 (0.81 – 0.89) | ||
| > 90 | 1.0 | ||
| Diastolic BP | p<0.0001 | ||
| < 60 | 1.11 (1.00 – 1.23) | ||
| 60–100 | 1.17 (1.09 – 1.26) | ||
| > 100 | 1.0 |
P-values for testing common odds ratios and for center-specific odds ratios (Sex, EBV, and Hematocrit) of each characteristic are shown in table
Average center difference
Quantitative Hematocrit data are unknown for over 99% of the records at Recife blood center
Results
A total of 724,861 allogeneic whole blood donations were attempted from July 2007 to December 2009 at the three centers, with 331,316 (45%) in São Paulo, 258,109 (36%) in Recife, and 135,436 (18.5%) in Belo Horizonte; 16,129 blood donors (2.2 %) experienced VVRs (Table 2). Nearly 95 percent of VVR’s where classified as mild, while 4.6% were moderate and 0.9% severe. Fifty-four percent of donors with reactions were male and 46% were female. Overall, the age group of 18 to 29 years old represented 42% of blood donors yet these young experienced contributed 64% of VVRs.
Table 2.
Reaction rate by demographic characteristics
| Characteristic | No Reactionsn (%) | Reactionsn (%) | Rate of Reaction(per 10,000 donations) |
|---|---|---|---|
| Reaction Grade | |||
| Mild | — | 15,239 (94.5) | 210 |
| Moderate | — | 745 (4.6) | 10 |
| Severe | — | 145 (0.9) | 2 |
| Overall | 708,732 (100.0) | 16,129 (100.0) | 222 |
| Sex | |||
| Female | 212,812 (30.0) | 7,466 (46.3) | 339 |
| Male | 495,920 (70.0) | 8,663 (53.7) | 172 |
| Age (in years) | |||
| 18–20 | 59,282 (8.4) | 2,887 (17.9) | 464 |
| 21–24 | 99,642 (14.1) | 3,793 (23.5) | 367 |
| 25–29 | 138,077 (19.5) | 3,703 (23.0) | 261 |
| 30–40 | 229,513 (32.4) | 3,946 (24.5) | 169 |
| 41–65 | 182,079 (25.7) | 1,800 (11.1) | 98 |
| Missing | 139 (0.0) | 0 (0.0) | — |
| Donor Type | |||
| Community | 455,505 (64.3) | 10,092 (62.6) | 217 |
| Replacement | 253,227 (35.7) | 6,037 (37.4) | 233 |
| Donation History | |||
| First Time | 223,405 (31.5) | 9,996 (62.0) | 428 |
| Repeat | 485,327 (68.5) | 6,133 (38.0) | 125 |
| Race/Ethnicity | |||
| Black | 74,054 (10.4) | 1,142 (7.1) | 152 |
| Mixed | 297,053 (41.9) | 5,299 (32.8) | 175 |
| White | 274,620 (38.7) | 8,059 (50.0) | 285 |
| Asian | 7,160 (1.0) | 202 (1.2) | 274 |
| Indigenous | 2,034 (0.3) | 70 (0.4) | 333 |
| Missing | 53,811 (7.6) | 1,357 (8.4) | — |
| EBV | |||
| < 3500 | 30,780 (4.3) | 1,474 (9.1) | 457 |
| 3500–3999 | 80,164 (11.3) | 3,117 (19.3) | 374 |
| 4000–4499 | 101,218 (14.3) | 2,834 (17.6) | 272 |
| 4500–4999 | 154,046 (21.7) | 3,201 (19.8) | 204 |
| ≥ 5000 | 231,606 (32.7) | 3,543 (22.0) | 150 |
| Missing | 110,918 (15.6) | 1,960 (12.2) | — |
| BMI | |||
| Underweight | 4,355 (0.6) | 221 (1.4) | 483 |
| Normal | 263,008 (37.1) | 8,264 (51.2) | 305 |
| Overweight | 233,043 (32.9) | 4,299 (26.6) | 181 |
| Obese | 77,962 (11.0) | 1,140 (7.1) | 144 |
| Severe Obese | 19,446 (2.7) | 245 (1.5) | 125 |
| Missing | 110,918 (15.7) | 1,960 (12.2) | — |
| Pulse | |||
| < 65 | 62,001 (8.8) | 1,614 (10.0) | 254 |
| 65–90 | 479,472 (67.6) | 9,993 (62.0) | 204 |
| > 90 | 66,552 (9.4) | 2,262 (14.0) | 329 |
| Missing | 100,707 (14.2) | 2,260 (14.0) | — |
| Diastolic BP | |||
| < 60 | 24,858 (3.5) | 808 (5.0) | 315 |
| 60–100 | 534,884 (75.5) | 12,144 (75.3) | 222 |
| > 100 | 56,190 (7.9) | 921 (5.7) | 161 |
| Missing | 92,800 (13.1) | 2,256 (14.0) | — |
| Systolic BP | |||
| < 100 | 781 (0.1) | 41 (0.2) | 499 |
| 100–160 | 546,536 (77.1) | 12,526 (77.7) | 224 |
| > 160 | 68,889 (9.7) | 1,315 (8.2) | 188 |
| Missing | 92,526 (13.1) | 2,247 (13.9) | — |
| Blood Center | |||
| Recife | 256,752 (36.2) | 1,357 (8.4) | 53 |
| Belo Horizonte | 130,283 (18.4) | 5,153 (32.0) | 381 |
| Sao Paulo | 321,697 (45.4) | 9,619 (59.6) | 290 |
| Hematocrit* | |||
| 38–39 | 55,638 (12.4) | 1,989 (13.7) | 345 |
| 40–41 | 77,003 (17.2) | 2,706 (18.7) | 340 |
| 42–43 | 86,854 (19.4) | 2,691 (18.6) | 301 |
| 44–45 | 88,444 (19.8) | 2,681 (18.5) | 294 |
| ≥ 46 | 138,969 (31.1) | 4,424 (30.5) | 309 |
Quantitative Hematocrit data are unknown for over 95% of the records at Recife blood center
Seventy per cent of donors were male and 30% were female. However, only 54% of donors with reactions were male, while 46% were female. Therefore, females were more likely to experience VVRs with 339 reactions per 10,000 presentations compared to 172 reactions per 10,000 for males (Table 2), yielding a crude OR of 2.0 (95% CI 1.9, 2.1).
Replacement donors (who gave blood for their friends or relatives) had slightly higher rates of VVRs compared to community donors (233 and 217 per 10,000, respectively). High VVR rates were evident in first-time donors (428 per 10.000), donors aged 18 to 20 years (464 per 10.000), and donors with lower EBV (457 per 10,000) or underweight BMI (483 per 10,000). High Pulse (> 90 bpm) and low pulse (<65 bpm) were positively associated with the vasovagal reaction (329 per 10,000 and 254 per 10,000 vs 204 per 10,000 for those with pulse 65–90 bpm). Reaction rates were higher for donors with lower blood pressures (whether diastolic or systolic).
Importantly, the rates of vasovagal reaction varied among the centers: Belo Horizonte had the highest rates of VVRs (381 per 10,000) followed by São Paulo (290 per 10,000) and Recife (53 per 100,000) (Table 3). Reaction rates according to demographic characteristics at each center also demonstrated notable differences (Table 3). For example, reactions rates by race/ethnicity categories are highly variable. In Belo Horizonte donors with self-reported Asian race had reaction rates of 574 per 10,000 whereas the rate observed in Asian donors in Recife was 9 per 10,000. The rate in Belo Horizonte was the highest for any race/ethnicity category, while it was the lowest for any category in Recife.
Table 3.
Reaction rate by blood center and demographic characteristics
| Characteristic | Recife(per 10,000 donations) | Belo Horizonte(per 10,000 donations) | Sao Paulo(per 10,000 donations) |
|---|---|---|---|
| Reaction Grade | |||
| Mild | 48 | 355 | 277 |
| Moderate | 1 | 23 | 12 |
| Severe | 4 | 2 | 1 |
| Overall | 53 | 380 | 290 |
| Sex | |||
| Female | 100 | 550 | 348 |
| Male | 42 | 285 | 256 |
| Age (in years) | |||
| 18–20 | 104 | 743 | 661 |
| 21–24 | 80 | 576 | 491 |
| 25–29 | 67 | 408 | 336 |
| 30–40 | 39 | 278 | 224 |
| 41–65 | 27 | 186 | 126 |
| Donor Type | |||
| Community | 44 | 350 | 272 |
| Replacement | 61 | 402 | 387 |
| Donation History | |||
| First Time | 110 | 630 | 554 |
| Repeat | 29 | 222 | 167 |
| Race/Ethnicity | |||
| Black | 34 | 235 | 174 |
| Mixed | 51 | 354 | 240 |
| White | 57 | 437 | 344 |
| Asian | 9 | 574 | 294 |
| Indigenous | 178 | 429 | 286 |
| EBV | |||
| < 3500 | 183 | 709 | 459 |
| 3500–3999 | 113 | 614 | 384 |
| 4000–4499 | 79 | 416 | 330 |
| 4500–4999 | 50 | 326 | 276 |
| ≥ 5000 | 34 | 242 | 213 |
| BMI | |||
| Underweight | 198 | 541 | 562 |
| Normal | 81 | 450 | 365 |
| Overweight | 43 | 321 | 237 |
| Obese | 38 | 293 | 199 |
| Sever Obese | 34 | 253 | 169 |
| Pulse | |||
| < 65 | 73 | 364 | 248 |
| 65–90 | 55 | 415 | 281 |
| > 90 | 57 | 478 | 356 |
| Diastolic BP | |||
| < 60 | 94 | 502 | 336 |
| 60–100 | 54 | 403 | 302 |
| > 100 | 34 | 261 | 196 |
| Systolic BP | |||
| < 100 | 0 | 640 | 574 |
| 100–160 | 56 | 410 | 304 |
| > 160 | 30 | 294 | 219 |
| Hematocrit * | |||
| 38–39 | — | 458 | 290 |
| 40–41 | — | 428 | 304 |
| 42–43 | — | 371 | 273 |
| 44–45 | — | 327 | 282 |
| ≥ 46 | — | 337 | 299 |
Quantitative Hematocrit data are unknown for over 95% of the records at Recife blood center
Multivariable logistic regression analysis confirmed that VVRs in Brazil are highly associated with specific donor characteristics (Table 4). Independent predictors of VVRs include younger age, with donors 18–20 and donors 21–24 years of age having odds of reactions approximately 3-fold higher than for donors aged 41 to 65 [AOR=3.08, 95% CI 2.89 – 3.28, and AOR=2.80, 95% CI 2.64 – 2.97, respectively]. First-time blood donors also had higher odds of reactions compared to repeat donors [AOR=2.49, 95% CI 2.41–2.58]. Lower EBVs were associated with higher odds of reactions across the 3 blood centers. When compared to donors with EBVs ≥5000mL, donors with EBV <3500mL were 1.8 to 2.6 times more likely to have a VVR depending on the center, and other categories of EBV were also associated with the risk of reactions. Race/ethnicities other than white had significantly lower odds of reactions. Analysis of the odds of VVRs by center showed that donors in Recife had a lower odds of donors having documented reactions [AOR=0.21, 95% CI 0.20–0.22] compared to Sao Paulo, but Belo Horizonte was not significantly different than Sao Paulo. An unexpected finding was the association between increasing hematocrit level and the odds of VVRs in São Paulo and in Belo Horizonte [AOR = 0.69 (95% CI 0.63 – 0.75) in Sao Paulo, and AOR = 0.77 (95% CI 0.69 – 0.85) in Belo Horizonte] for donors with hematocrit values between 38 and 39 when compared to donors with hematocrits of 46 or higher. We could not evaluate this relationship in Recife because hematocrit/hemoglobin values were not available in the analysis dataset.
Discussion
The aims of this study were to assess the frequency of and factors associated with VVRs in allogeneic whole blood donors in Brazil. The frequency of donation-related adverse events has not previously been reported in the peer reviewed literature for Brazil. This is the largest and first multicenter study to assess risk factors for donor adverse reactions. Results of our analysis show that 2.3% of all whole blood donations were complicated by a documented VVR, which is higher than rates reported in the general donor population in Italy,3–5 India,20,21 Greece,6 and Denmark,22 but similar to findings from the USA.1,23–25
Our study shows that young age, low EBV, and first-time blood donor status are the major factors associated with increased reaction rates, consistent with previous studies2,5,10,20,23. Like other authors24,26,27 we found a low incidence of serious reactions, and no evidence of severe events such as myocardium infarction or thrombophlebitis, which represent truly rare adverse complications of blood donation. Many studies have observed that first-time 1,2,9,23,25,28,29 donors were more likely to experience VVRs. We confirmed that replacement blood donors presented a slightly higher likelihood of adverse reaction, consistent with the finding of others.5,6 Synergistic psychological mechanisms might be driving these findings. A first-time donation is associated with anxiety in inexperienced donors relative to repeat donors who are familiar with the donation process.30 Moreover, donations from replacement donors may include an extra layer of anxiety due to desire to provide blood for a friend or relative in need of transfusion,6 whereas community donors come to donate blood to help anonymously individuals with no specific emotional connection with the recipient other than “helping society”31.
Unadjusted analyses indicated a higher rate of VVRs among females, as reported in other studies1,9,20,26,29. However, after adjusting for other risk factors, female gender was not a significant predictor of VVRs in our multivariable analysis. Of note, we used Nadler’s gender-specific formulas to calculate EBV which may have inherently controlled for any potential gender effect. However, there are also other factors related to differences in the allowed collection volume between males and females that may be relevant. Brazilian blood bank regulations18 limit the donation amount to 450 mL ± 50 mL, which may be increased by 30 mL to perform laboratory tests. Combining the minimum weight requirement of 50 kg (110 lbs) for blood donation and blood volume requirement results in an allowed maximum blood loss per donation of 430 mL for a 50 kg female and 480 mL for a 50 kg male donor, representing 18% and 14% smaller draw volumes, respectively, than the allowed in the USA14. The standards in Brazil are similar to the 450 mL standard volume collected in Europe15,32. Given these factors we expected the we might find VVR rates similar to those in Europe, but our study shows that the Brazilian rate of VVRs is higher when compared to reports from Europe.3,5,32
Our study has demonstrated an unexpected (and unreported) effect related to increasing hematocrit and higher likelihood of adverse reactions. One hypothesis that might explain this finding relates to whole blood viscosity (WBV)33. It has been shown that hematocrit is one of the principal determinants of WBV. Hematocrit has the greatest effect on WBV during high velocity blood flow; for instance a 10% increase in hematocrit typically increases viscosity at high shear rates (arterial flow) by about 20%34. Whole blood viscosity is also a key determinant of the overall work load on the heart and perfusion of tissues. In addition, there is also a relationship between WBV and blood pressure. If WBV increases then total peripheral resistance will increase, thereby reducing blood flow. Conversely, when WBV decreases, blood flow and perfusion will increase35. These physiological considerations might explain the relationship between higher hematocrit and adverse reaction events. High hematocrit may act to further restrict blood flow during vasovagal events. Further studies to evaluate the relationship between hematocrit and VVRs in blood donors are needed.
This study has several limitations. First, we lacked records regarding the onset time of VVRs, and had limited access to some other data such as information on the occurrence of delayed reactions and the lack of hematocrit/hemoglobin data for one of the centers. Consequently we could not examine all types of VVRs or factors associated with reactions that occurred after leaving the blood center. Second, weight and height were self-reported leading to the possibility of under- and over-estimation of each value. Third, although moderate and severe reactions are relatively uncommon compared to mild reactions, establishing a clear distinction between the reaction severities is difficult since the classification is a subjective decision by blood center staff. Furthermore, adverse events are not recorded on standardized reporting forms across the three blood centers. Different forms and different center practices regarding the classification of signs and symptoms of VVRs may have been substantial contributors to differences in reaction rates across blood centers. For these reasons we did not conduct analyses that sought determine if specific demographic characteristics may be associated with different reaction severities.
Evidence of remarkable differences in VVR rates at different blood centers is not unique to Brazil. Analyses conducted in the USA have reported similar large differences by center.1,2,36,37 There are considerable regional demographic and cultural differences between the Southeastern and Northeastern parts of Brazil38,39. Demographics and blood center procedures may contribute to the difference seen between VVR rates observed at the REDS-II Brazil centers. Additional explanations include the possibility that VVRs may not have been recorded in Recife due to differences in standard operating procedures. Developing consistent reporting practices using common definitions across the Brazilian blood bank network would be the first step to understand the differences in adverse reactions by center are significant as reported here.
Offering fluids and light snacks before starting the phlebotomy has been proposed as a method to decrease the development of VVRs among blood donors40,41, Yet, the provision of snacks and fluids before donation as means of reducing VVRs does is not consistent with our findings, since VVRs are higher in Belo Horizonte despite the fact that the Belo Horizonte blood center requires that donors have fluids and a light snack before donation whereas this is only a recommendation given to donors in Sao Paulo and Recife. This finding suggests that other variables such as emotional or psychological factors in association with the percentage of blood volume drawn may play an important role in the prevalence of vasovagal reaction. It has been already described that donors who present adverse reactions tend to be hypochondriac, depressed, overly concerned with their bodily functions, and are more prone to feelings of uselessness and pessimism42,43. This psychological aspect might explain why phlebotomist skills are related to lower donor reaction rate, for instance, lower rates were observed when more attention was given to the donors and more talkative nurses had lower rates of blood donors reactions44 Syncope and presyncope are also related to blood/injury phobia, i.e, the fear can be triggered by seeing blood, by sustaining an injury, or by receiving an injection or some other invasive medical procedure45–49. .In summary, the interaction between psychosocial characteristics and biophysical characteristics and the impact of these factors mechanistically on vasovagal and other reactions hase not been completely elucidated42,43.
Our results show that the risk factors for VVRs among the Brazilian blood donors population are similar to those observed in other countries2–4,6,7,32, even though blood donor eligibility and donation procedures are not the same. Overall, the Brazilian blood donor population is younger than the blood donor population in the USA50,51 and Europe52 and the highest rates of reaction VVRs were found within younger age donors. Efforts to reduce the risk of VVRs in donors in Brazil is important as part of donor vigilance and also may be increasingly important as blood centers in Brazil seek to convert young, first-time donors into long-term repeat blood donors.
The Retrovirus Epidemiology Donor Study - II (REDS-II), International Component (Brazil) is the responsibility of the following persons: Blood Centers: Fundação Pró-Sangue/Hemocentro São Paulo (São Paulo) - Ester C. Sabino, Cesar de Almeida Neto, Alfredo Mendrone Jr., Ligia Capuani and Nanci Salles; Hemominas (Belo Horizonte, Minas Gerais) - Anna Bárbara de Freitas Carneiro-Proietti, Fernando Augusto Proietti, Claudia Di Lorenzo Oliveira and Carolina Miranda; Fundação Hemope (Recife, Pernambuco) - Divaldo de Almeida Sampaio, Silvana Ayres Carneiro Leão and Maria Inês Lopes. Data Warehouse: University of São Paulo (São Paulo) - João Eduardo Ferreira, Márcio Oikawa and Pedro Losco Takecian.
US Investigators: Blood Systems Research Institute and University of California San Francisco - M.P. Busch, E.L. Murphy, B. Custer and T. Gonçalez; Coordinating Center: Westat, Inc - J. Schulman, M. King and K. Kavounis; National Heart, Lung, and Blood Institute, NIH - S.A. Glynn.
Footnotes
Conflict of interest: none
References
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