Blood Donation And Relief From Migraine Pain
Overview
Migraine is a common neurological disorder characterized by headaches. Given the difficulty in finding effective treatments, many migraine sufferers turn to alternative methods, including blood donation, which is speculated to offer relief.
This study used logistic, Poisson, and Cox regression to analyze the relationship between migraine and blood donation activities within two cohorts: Danish blood donors from the Scandinavian Donations and Transfusions Database (SCANDAT-DK, with over 1 million participants) and the Danish Blood Donor Study (approximately 100,000 participants).
Analysis of the SCANDAT-DK data revealed no significant association between migraine and the likelihood of becoming a blood donor in males (odds ratio [OR] Males = 0.95, 95% Confidence Interval: 0.86–1.04). In females, there was a slightly reduced likelihood (OR Females = 0.88, 95% CI: 0.83–0.93). Blood donation did not decrease migraine incidence (standardized incidence ratio [SIR] Males = 0.94, 95% CI: 0.83–1.06; SIR Females = 1.04, 95% CI: 0.99–1.10). Donors with migraines had longer intervals between donations (hazard ratio [HR] Males = 0.87, 95% CI: 0.85–0.91; HR Females = 0.80, 95% CI: 0.78–0.82) and a higher risk of discontinuing donation (OR Males = 1.23, 95% CI: 1.14–1.32; OR Females = 1.28, 95% CI: 1.22–1.33). These findings were confirmed using self-reported migraine data in the DBDS cohort. A genetic predisposition to migraine was linked to longer donation intervals in females (HR Females = 0.98, 95% CI: 0.97–0.99), but this was not observed in males.
The results do not support the idea that blood donation is an effective treatment for migraine. Future studies should explore the biological mechanisms by which blood donation might affect migraine.
Introduction
Migraine is a widespread neurological condition marked by recurring, intense, and often incapacitating headaches known as migraine attacks. It ranks as the second leading cause of disability globally among adults, with approximately 1 billion individuals experiencing migraines annually. Consequently, advancing effective prevention and treatment methods for migraines is crucial for a significant segment of the population.
Traditional migraine treatments include a combination of non-pharmacologic and pharmacologic approaches. Pharmacologic treatments are further divided into prophylactic and acute therapies, aimed at reducing the frequency and severity of migraines and alleviating the attacks as they occur, respectively. Despite the variety of strategies and medications available, their effectiveness varies considerably among individuals. In Denmark, treatments are often administered through trial-and-error, leading to lengthy waiting lists for specialized care. As a result, many migraine sufferers turn to alternative, and sometimes unverified, treatments to find relief.
In this context, blood donation, and to a lesser extent, bloodletting, have emerged as alternative treatments explored by migraine sufferers. During the recruitment for the Danish Blood Donor Study (DBDS), it was noted that headache prevention and relief were significant incentives for many blood donors. Many donors had been advised by their general practitioners to consider blood donation as a potential remedy for their migraines.
The biological plausibility of a connection between blood donation and migraine relief exists, as relief could theoretically be mediated through mechanisms such as reduced hematocrit levels, lower blood pressure, or changes in plasma volume. However, evidence supporting a relationship between blood donation and migraine or headache relief is limited. In a previous cross-sectional survey of 6073 DBDS participants, 10% of male and 17% of female donors reported headache relief following blood donation. In contrast, a Dutch survey of 23,064 blood donors found that only about 1% reported headache relief.
The differing results of these studies are difficult to explain but may be influenced by participation, recall, and other biases common in self-reported outcomes, sample size limitations, and inconsistencies in outcome definitions between studies. To address these issues, nationwide data on blood donation and anti-migraine medication prescriptions (specifically triptans) were utilized to assess the association in a comprehensive cohort study in Denmark. This was complemented by investigations into the relationships between self-reported migraines, ascertained via a validated questionnaire, genetic predisposition to migraines, and subsequent blood donation activity. The objective was to determine whether migraines influence the likelihood of becoming or continuing as a blood donor and if blood donation affects the risk of developing migraines.
Method
A comprehensive nationwide blood donation history was sourced from the Danish section of the Scandinavian Donations and Transfusions Database (SCANDAT-DK). This database encompasses all available electronic records on blood donors, donations, transfusions, and recipients in Denmark and Sweden. Regularly updated, it includes vital donor information such as sex, date of birth, blood group, donation dates, and unique Personal Identification Numbers (PIN).
Utilizing SCANDAT-DK’s extensive data since 2003 and Denmark’s minimum blood donation age of 17, a cohort of all Danish individuals born from 1987 onwards was assembled, ensuring a complete donation history for each participant. Every individual in Denmark is registered with a unique PIN at birth via the Civil Registration System (CRS), facilitating extensive linkage between health and population records. Information on blood donations was obtained through SCANDAT-DK linkage, while pregnancy data was retrieved from the Danish Medical Birth Register, and triptan prescription data from the Danish Prescription Register. It is notable that triptans in Denmark are available only by prescription and not used off-label.
Also read; Maternal Migraines And Associated Pediatric Cancers
Additionally, similar analyses were performed using self-reported migraine data from the Danish Blood Donor Study (DBDS) Genomic Cohort, an ongoing cohort study initiated in 2010 with about 160,000 participants, of whom 100,148 have been genotyped. DBDS recruits blood donors using Denmark’s blood bank infrastructure and includes self-reported migraine information collected via electronic surveys.
For the population cohort, the date of the first filled prescription for triptans was used as a proxy for migraine onset, with medications classified under specific Anatomical Therapeutic Chemical (ATC) codes. Among DBDS participants, migraine diagnoses were established using a validated questionnaire based on the International Classification of Headache Disorders, third edition (ICHD-3). This questionnaire, administered between 2015 and 2018, assessed migraine diagnosis criteria, subtypes, attack frequency and duration, and associated symptoms, forming the Danish Migraine Population Cohort (DaMP).
Using the DBDS Genomic Cohort, polygenic risk scores (PRS) for migraines were calculated based on recent genome-wide association study (GWAS) meta-analysis data, excluding Danish ancestry to avoid biases. PRS were computed using LDpred2, accounting for linkage disequilibrium. The association between high PRS (top decile) and donor lapse risk was examined through Cox regression, with similar follow-up conditions and exclusions.
The SCANDAT-DK project was registered according to EU GDPR and Danish regulations, not requiring individual consent for register-based studies. The DBDS cohort study received approval from Danish Ethical Committees and the Danish Data Protection Agency. Data access is regulated by Danish authorities, with applications for data access described on the Danish Health Data Authority’s website.
There was no involvement of patients or the public in the research design, outcome measures selection, or results interpretation and presentation. Direct dissemination of results to participants is unfeasible due to cohort size and study duration.
Statistical Analysis
This study examines the epidemiology of migraines by sex and performs separate statistical analyses for females and males. Utilizing the SCANDAT-DK cohort, researchers investigated the association between migraines and the likelihood of becoming a blood donor. They compared the prevalence of triptan usage among first-time donors to never-donors, matched by sex, birth date, and residential region, presenting odds ratios (ORs) with 95% confidence intervals (CIs) derived from conditional logistic regression.
The study explored the relationship between blood donation and the risk of incident triptan prescriptions. Triptan-naïve donors were monitored from their first donation until the first triptan prescription, pregnancy, emigration, loss to follow-up, death, or the end of the study on October 31, 2019. The observed number of first triptan prescriptions among donors was compared with expected counts, adjusted for age, sex, and time period-specific rates among non-donors, using Poisson regression and Byar’s formula for 95% CIs.
Further analysis using Cox regression examined the link between triptan usage and two outcomes: the time between consecutive donations and the probability of donor lapse (defined as a gap in donation exceeding two years). Triptan exposure was treated as a time-dependent variable, and analyses were adjusted for age, period, and region of residence, and stratified by prior donations.
Similar analyses were performed on the DBDS cohort, focusing on self-reported migraines and triptan use. Participants were tracked from questionnaire completion or DBDS inclusion until death, emigration, pregnancy, subsequent donation, donor lapse, or study end on July 29, 2022. Adjustments were made for age, period, and region, and participants with a history of donor lapse were excluded.
Result
The study analyzed data from over a million individuals, including first-time blood donors, to investigate the prevalence and incidence of migraine, as well as its association with donation behavior. At the time of first donation, there was no significant difference in migraine prevalence between donors and non-donors. Incidence rates of migraine among donors were comparable to those in the general population. However, prior use of triptans, a migraine medication, was linked to longer donation intervals and increased risk of lapsing among both male and female donors. Additionally, questionnaire-based migraine diagnosis and history of triptan use were associated with similar patterns. Genetic predisposition to migraine showed mixed results, with some associations observed in females but not in males. These findings suggest a complex interplay between migraine, medication history, and donation behavior among blood donors.
Conclusion
In this study, researchers examined the relationship between blood donation and migraine among over 100,000 first-time blood donors using Danish register data. They found no significant association between blood donation and migraine treatment with triptans, nor did they observe a reduction in migraine incidence due to blood donation. Even when considering genetic predisposition to migraines, donation behavior remained unchanged. The study suggests that while historical practices like bloodletting imply migraine relief, current evidence does not support this. Additionally, the study highlights the influence of deferral practices after analgesic use on donor behavior and acknowledges variations in such practices globally. Despite limitations, including the inability to assess immediate effects of endorphin release post-donation, the study provides valuable insights into the relationship between blood donation and migraine. It concludes that further research is needed to explore potential biological or mechanistic effects of blood donation on migraine relief, emphasizing the importance of investigating distinct migraine subtypes and immediate effects of blood donation on migraine symptoms.
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