To evaluate the effect of different interventions on Vasovagal Reaction (VVRs) in voluntary whole blood donors

INTRODUCTION

India, the most populous country in the world, has an estimated clinical demand of 14·6 million whole blood units.  Approximately 36.3 donations per 1,000 eligible populations, will address whole blood and component requirement. Analyzing this massive demand of blood, the supply available is 93 percent, that is, 33.8 donations, leaving a supply gap of 2.5 donations per 1,000 eligible persons which is around one million units 1. Bridging this gap requires a dual approach of mobilizing new donors through increased blood donation awareness and strengthening the existing donor pool. The goal being a sufficient supply of safe blood through Voluntary Von-Remunerated Blood Donation VNRBD.

One of the key challenges in retaining the repeated blood donors is the unpleasant experience from previous donations particularly having Vaso-Vagal Reactions VVRs.

As per Standard for Surveillance of Complications Related to Blood Donation published in 2014 by International Society for Blood Transfusion ISBT slash Associate for the Advancement Blood and Biotherapies AABB slash International Hemovigilance Network IHN, VVR is defined as: a general feeling of discomfort and weakness with anxiety, dizziness and nausea, which may progress to loss of consciousness or faint. It is the most common acute complication related to blood donation 2.

Vasovagal reactions are divided in two main subgroups

Without Loss Of Consciousness LOC the donor does not faint

With LOC the donor faints for a period of time.

 Optional subdivision for donors with LOC

LOC less than 60 seconds without other signs and symptoms

LOC more than or equal to 60 seconds or with complications of convulsive movements urinary or fecal incontinence

 Optional subdivision

With injury - Injury caused by falls or accidents in donors with a vasovagal reaction

Without injury

 Optional subdivision

Location of reaction

On collection facility, that is, in area within which staff can observe the donor and be responsible for the care of donors with complications - Symptoms occurred before donor has left the donation site

Outside collection facility- Symptoms occurred after donor has left the donation site.

Since these VVRs include symptoms ranging from mild to moderate like anxiety, sweating, dizziness to severe ones like loss of consciousness, seizures, and occasional bladder or bowel incontinence, such experiences not only deter repeat donors as they have decreased intentions for future donations but can also discourage First Time Donors FTDs from donating, impacting the overall blood collection 3, 4.

Various studies have identified multiple physiological and psychological factors contributing to VVRs including young age, low body weight or BMI, low pre-donation blood pressure, female gender, needle phobia, and anxiety 5-10.

A Severity Grading Tool of Blood Donor Adverse Events is designed to be used with the Standard for Surveillance of Complications Related to Blood Donation published in 2014 by ISBT slash AABB slash IHN 11.

Grade 1 No outside medical care OMC

Grade 2   1.    OMC, no hospitalization, or                  2.    Activities of daily living ADL less than 2 weeks                 3.    Sutures of lacerations or                 4.   IV hydration

Grade 3 1.    Hospitalization

2.    ADL more than 2 weeks

               3. Fractures, medically confirmed concussion, dental injury requiring dental procedure, example, cap or crown, dental implant, bridge, tooth extraction, denturesGrade 4 Immediate medical intervention to prevent death

Grade 5 Death

Outside Medical Care OMCdonor is evaluated and or treated by Emergency Medical Response EMR, Health Care Professional HCP, urgent care, hospital emergency room ER without admission to the hospital. Please note that if EMR is called, which is, an ambulance and the donor is evaluated but not transported, then it is still considered OMC.

Activities of Daily Living ADLInclude everyday household chores, doing necessary business, shopping, going to work or school, or getting around for other purposes. ADL are impacted if the donor

a.    Needs the help of other persons with bathing or showering, dressing, eating, getting in or out of bed or chairs, using the toilet, and getting around the home called, Self-care ADL.

b. Cannot work, attend school or manage routine personal/family activities because of the Donor Adverse Event called, Instrumental ADL.

 Two interventions have helped mitigate these donor adverse reactions are pre-donation water loading 12, 13 and applied muscle tension 14, 15. First, water ingestion enhances cardiovascular changes by increasing peripheral vascular resistance and sympathetic activation which leads to increased blood pressure 16. Second, rhythmic Applied Muscle Tension (AMT) exercises increase the venous return and sympathetic excitation, thereby optimizing cerebral oxygenation 17. There are three pumps in the lower limb which get activated during plantarflexion and dorsiflexion:

a) The foot pump, located in the lateral plantar veins.

b) The leg pump, located in the soleus muscle.

c) The gastrocnemial pump, acting at the popliteal level above the knee. The venous valves play a key role allowing, during muscle contraction, the unidirectional venous flow to the heart 18.

Several Applied Muscle Tension variations have been documented in various literature

Repeated 5 second intervals of lower body isometric muscle tension exercises of legs and abdomen while crossing their legs and maintaining steady breathing at three strategic high risk time points that is when the needle is inserted when the needle is removed and when getting up from the donation chair of approximately 100 sec of Applied Muscle Tension at each time point 19 Female donors were instructed to cross their legs and tense their thighs buttocks and stomach muscles for 5 seconds and then rest for 5 seconds beginning when the needle was inserted and continuing until just before they left the donation cot 20 Five cycles of Applied Muscle Tension exercises were performed for a period of 100 seconds In one cycle 20 seconds of Applied Muscle Tension exercise the donor lay down on a couch and raised his or her both legs to approximately 1 foot and squeezed the abdominal and lower limb muscles along with ankle movement in up and down direction for 5 seconds In the next 5 seconds the donor had to be in the knee to chest position and perform ankle movement and muscle squeezing The final 10 seconds of the cycle was for relaxation After completion of the Applied Muscle Tension procedure blood was collected within 15 to 30 min 21 Donors were told to tense the major muscle groups of their arms and legs at 5 seconds intervals while breathing steadily and given some hints such as trying to imagine the tension produced by squeezing a tennis ball 22  As a tertiary oncology center, 85 percent of the blood supply is via the outdoor donation camps. Frequency of ADRs in Whole Blood Donors is 1.5 percent out of which VVRs account to 96 percent. Our institutional blood donation protocol includes a structured approach to donor screening and care.

Donors complete a medical questionnaire, undergo hemoglobin and blood pressure checks, and consume approximately 200ml of water before proceeding with donation. Blood collection volume is determined based on donor weight as per the institutional Standard Operating Procedures SOP. A total of 350ml of blood is collected from all female donors and those weighing less than 60kg and for all those weighing more than 60 kg, 450ml of blood is collected. Post-donation, donors rest briefly, receive refreshments, and are monitored for adverse reactions. These ADRs are managed as per SOP with followups conducted the next day via telephone.

Currently, as stated, the donors must consume 200ml of plain water after which they go for blood donation. The interventions chosen for the study are first, Oral Rehydration Solution ORS wherein a packet of ORS will be dissolved in 1 liter of water and 200ml of that solution will be given to the donor; second, AMT wherein the donor shall be asked to do repeated rhythmic plantarflexion and dorsiflexion during the donation period and third a combination of ORS and AMT.  We have decided the plantar flexion technique for AMT considering the feasibility in outdoor donation camps as it will be easier for the donors to perform without any hesitation.

So, in this study these different interventions will be tested for our better understanding of their efficacy in reducing the occurrence of VVRs and compare the results with the current practice considering consumption of plain water as a control.

By implementing these evidence-based strategies, donor safety and retention can be enhanced, ultimately improving blood supply sustainability

AIMS AND OBJECTIVES

Primary objectiveTo evaluate the effect of different interventions namely a)    Plain water b)    Oral Rehydration Solution ORS, c)    Plain water  plus Applied Muscle Tension AMT and d)    ORS plus AMT  on Vasovagal Reaction VVRs in whole blood donors.

Secondary objectivea)    Compare the effect of the intervention or combination of interventions on VVRs whole blood donors. b)    Analysis of all VVRs in terms of their categorization and management.

STUDY DESIGN AND METHOD

TARGET POPULATION:

All adult individuals eligible for whole blood donation in outdoor blood donation camps.

INCLUSION CRITERIA:

Eligible donors who are consenting to participate in the study.

EXCLUSION CRITERIA:

Donors with previous history of VVRs.

 MATERIALS AND METHODS:

The study will be a prospective, interventional, randomized, open label study carried out by the Department of Transfusion Medicine at Tata Memorial Hospital, Parel. This trial shall be conducted at outdoor blood donation camps. For this study there shall be 4 groups wherein the study participants shall be randomly assigned, namely:  a)    Group I:     Control- plain water b)    Group II:    Oral Rehydration Solution c)    Group III:   Plain water plus Applied Muscle Tension  d)    Group IV:  Oral Rehydration Salts plus Applied Muscle Tension

QUADRI- ARM INTERVENTIONAL STUDY

CATEGORY I: control of plain water: 200ml of plain water within 5 to 30 minutes prior to donation

CATEGORY II: Oral Rehydration Solution: 200ml of ORS 5 to 30 minutes prior to donation

CATEGORY III: Plain Water plus Applied Muscle Tension: 200ml of plain water 5 to 30 minutes prior to donation and plantar flexion throughout the duration of blood donation

CATEGORY IV: Oral Rehydration Salts plus Applied Muscle Tension : 200ml of ORS 5 to 30 minutes prior to donation and plantar flexion throughout the duration of blood donation

All the eligible whole blood donors will be explained by the medical doctor about the study and those interested shall be given donor information sheet and informed written consent for the study will be procured from them.

SAMPLE SIZE: A total of 6136 blood donors will be enrolled and divided into 4 groups for the study.

RANDOMIZATION: Randomization will be conducted at the time of donor enrollment to ensure real-time allocation without delays. A permuted block randomization method, using variable block sizes of 4 and 8, will be employed to maintain balance across treatment groups. Donors will be randomized in a 1 to 1 to 1 to 1 ratio across the four study arms

6136 total whole blood donors:

Category I: Plain water:  1534 donors: 450ml 767 donors, 350ml 767 donors

Category II: ORS:  1534 donors: 450ml 767 donors, 350ml 767 donors

Category III: Plain water plus AMT: 1534 donors: 450ml 767 donors, 350ml 767 donors

Category IV: ORS plus AMT: 1534 donors: 450ml 767 donors, 350ml 767 donors

As per the study, the blood donors will be given instructions by the medical doctor before sending them for whole blood donation.

a)    Group I, Donors will be instructed to consume 200ml of plain water and then head for donation after 5 minutes and within 30 minutes of water consumption. A standard measuring cup will be used to measure 200ml.

b)    Group II, Donors enrolled in this arm will be instructed to consume 200ml of ORS and then head for donation after 5 minutes and within 30 minutes of ORS consumption. ORS is prepared and used as per manufacturing instructions.

c)    Group III, After consuming 200ml of plain water, the donors will then head for donation after 5 minutes and within 30 minutes of plain water consumption. They shall be instructed to perform repeated rhythmic plantar flexion every 2 to 3 seconds throughout the donation period which shall be constantly monitored by the staff present at the donation site.

d)    Group IV, Donors will be instructed to consume 200ml of ORS and then head for donation after 5 minutes and within 30 minutes of ORS consumption. They then shall perform repeated rhythmic plantar flexion every 2 to 3 seconds throughout the donation period which shall be constantly monitored by the staff present at the donation site.

FLOW OF STUDY:

Donor registration followed by Donor screening. Eligible donors explained about the study and written informed consent is taken followed by randomization. All the donors will be given plain water and ORS based on the category they are randomized to and will be directed towards the donation area. While donating blood, the donors required to do AMT shall be asked to do ankle movements, that is plantar flexion. All the donors will be monitored pf ant kind of VVRs. Once donation is complete, they shall be directed to refreshment area. Once the donor is done with refreshments and is feeling well, he or she can leave the site of donation.

All the study donors will be monitored for VVRs. In case of any occurrence, the VVRs shall be documented for the symptoms, the vitals of blood pressure and pulse rate at the time of reaction and the appropriate management as per SOP. After assessing the donor vitals and ensuring that the donor is fit to leave the camp site, the donor is then free to leave.

PARAMETERS TO BE ASSESSED:

1.    Age

2.    Gender

3.    Weight

4.    Total blood volume

5.    Type of donation: first time/ repeat

6.    Pre donation blood pressure

7.    Volume of blood collected

8.    Total duration of blood collection

9.    Type of intervention

10. Any occurrence of VVR: Yes or No

11. Symptoms of VVR

a)    Generalized weakness

b)    Anxiety

c)    Dizziness

d)    Nausea

e)    Vomiting

f)      Pallor of skin and lips

g)    Convulsions

h)    Loss of bowel or bladder control

i)      Cyanosis

j)      Sweating

k)    Loss of consciousness of less than 60sec or more than 60sec)

l)      Any other adverse donor event

12. Time of VVR: during donation or after donation

13. Donation completed: Yes or No

14. Grade of VVR:

a)    Grade 1

b)    Grade 2

c)    Grade 3

d)    Grade 4

e)    Grade 5

15. Management of VVR

DEFINITION OF VASOVAGAL REACTION:

As per Standard for Surveillance of Complications Related to Blood Donation published in 2014 by International Society for Blood Transfusion ISBT slash Associate for the Advancement Blood and Biotherapies AABB slash International Hemovigilance Network IHN:

A vasovagal reaction is a general feeling of discomfort and weakness with anxiety, dizziness and nausea, which may progress to loss of consciousness or faint. It is the most common acute complication related to blood donation

Vasovagal reactions are divided in two main subgroups:

Without Loss Of Consciousness LOC - the donor does not faint

With LOC - the donor faints for a period of time.

 CALCULATIONS:

Total blood volume equals to weight multiplied by blood volume (millilitre per kilogram of body weight) (23)

Males have blood volume 70ml per kg

Females have blood volume 65ml per kg

STATISTICAL ANALYSIS

The overall comparison among all four groups will first be tested using a Chi-square test for independence. The proportion of VVRs in each group will be reported with 95 percent confidence intervals. Logistic regression analysis will also be employed to adjust for potential confounding variables such as age, sex, first-time donor status, and odds ratio with 95 percent C.I. will be reported. All analyses will be performed using Statistical Package for the Social Sciences SPSS statistical software and a p-value of less than 0.05 will be considered statistically significant.

POTENTIAL IMPACT OF THE STUDY

Being a tertiary care Oncology Center, there is a huge requirement of blood and blood components for the patients. The annual whole blood collection exceeds 26000 units, more than 84 percent of which is through the blood collection drives conducted regularly to ensure sufficient inventory in the blood center. Frequency of ADRs in Whole Blood Donors is 1.5 percent out of which VVRs account to 96 percent. Even though many of donors are the usual highly motivated regular donors, the incidence of VVRs can demotivate them and reduce their intention of donation in the future. Conducting this study will give us some insight on the effectivity of various measures that can be taken to prevent VVRs. By incorporating such methods into our SOP, the interventions can be standardized. This will inevitably improve the donor experience; helping in better recruitment and retention of whole blood donors ensuring uninterrupted supply of blood for patients’ needs.

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