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| Restless legs syndrome in frequent blood donors and its relationship with ferritin levels and red cell indices |
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Davood U Bava1, Gita Negi1, Ravi Gupta2, Sushant Kumar Meinia1, Ranjan Mukharjee1, Aswin K Mohan1
1 Department of Transfusion Medicine, AIIMS, Rishikesh, Uttarakhand, India
2 Department of Psychiatry, AIIMS, Rishikesh, Uttarakhand, India
Click here for correspondence address and email
| Date of Submission | 14-Dec-2021 |
| Date of Decision | 29-Jan-2022 |
| Date of Acceptance | 06-Feb-2022 |
| Date of Web Publication | 26-Sep-2022 |
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 Abstract | | |
INTRODUCTION: Restless legs syndrome (RLS) is characterized by an urge to move the legs or arms, associated with uncomfortable sensations. Frequent blood donation is one of the known risk factors for RLS. Earlier studies have shown that the prevalence of RLS varies between 4% and 18% among blood donors. The present study was done to assess the prevalence of RLS among repeat blood donors and to find out its correlates in Indian population.
MATERIALS AND METHODS: This study was done for a period of 1 year from April 2019 to March 2020. Two hundred donors who fulfilled the definition of “regular donor” by National AIDS Control Organization were enrolled by convenient sampling. Responses to the Hindi version of CHRLS questionnaire for RLS were noted, and history of number of previous blood donations was taken. Estimation of red cell indices and serum ferritin levels was also done.
RESULTS: Two hundred donors were selected for analysis. Out of which, 198 donors were males (99%). RLS was reported in only four donors (2%) and all of them were males. This was comparable to population prevalence of RLS reported in this region.
CONCLUSION: The prevalence of RLS among repeat blood donors in Indian population was comparable to the general population. Our findings could be reassuring for the frequent donors. Inclusion of basic questions on symptoms of RLS in the donor screening questionnaire can be useful in detecting impending iron deficiency, though its impact on a big scale is doubtful. Keywords: Donor adverse events, iron deficiency in donors, restless legs syndrome, serum ferritin
How to cite this URL:
Bava DU, Negi G, Gupta R, Meinia SK, Mukharjee R, Mohan AK. Restless legs syndrome in frequent blood donors and its relationship with ferritin levels and red cell indices. Asian J Transfus Sci [Epub ahead of print] [cited 2023 Mar 24]. Available from: https://www.ajts.org/preprintarticle.asp?id=356876 |
| Introduction | |  |
Restless legs syndrome (RLS)/restless limbs syndrome (also known as “Willis-Ekbom's syndrome”) is characterized by an urge to move the legs or arms, associated with uncomfortable sensations typically described as creeping, crawling, tingling, burning, or itching. Frequent movements of legs relieve these uncomfortable sensations and urges. Symptoms are worse at rest and in evenings and nights relieved only temporarily by movements.[1],[2] These can delay sleep onset, can cause awakening from sleep, daytime tiredness, and fatigue.[1] The prevalence of RLS is estimated to be 2.2%–7.9% in the general population, across studies.[3] Pregnancy, renal failure, rheumatoid arthritis, peripheral vascular disease, peripheral neuropathy, iron-deficiency anemia, reduced body iron stores, and frequent blood donations are some of the known risk factors for RLS.[2],[4] Whereas a fairly large amount of literature is available for these associations, association of RLS with blood donation is relatively less investigated. Earlier studies have shown that the prevalence of RLS varies between 4% and 18% among blood donors.[5],[6],[8],[9],[10],[11]
Frequent blood donations increase chances for iron deficiency and subsequent anemia since after each donation, the body loses approximately 200–250 mg of iron.[12] Despite these facts, phlebotomy guidelines followed by blood banks do not mandate assessment of body iron stores, rather only hemoglobin (Hb) concentration is assessed routinely.[13],[14],[15] Although guidelines also cap the number of donations in a calendar year, at least theoretically, a number of iron depleted donors might get ignored and may be taken up for donation again. This would result in further depleting iron stores leading to iron deficiency with or without anemia. Serum ferritin is a good marker of body iron stores, and serum ferritin concentration below 50 μg/L has been linked to increased severity of RLS symptoms.[4]
Assessment of blood donation among patients with RLS showed that patients with RLS donate blood more frequently.[16] On the other hand, assessment of RLS among healthy blood donors also showed that frequent blood donation is a risk factor for developing RLS, though with conflicting results.[5],[6],[7],[8] Thus, results of the study differ depending upon which population was included in the study.
In addition to differences in population, as explained above, most of the former studies had heterogeneity with regard to important risk factors for RLS, namely age, gender, family history of RLS, and iron therapy after blood donation.[5],[6],[7],[8],[9],[10],[11] In India, the prevalence of RLS in the general population is lesser compared to European countries and the United States despite having higher prevalence of iron deficiency, perhaps due to difference in genetic vulnerability to RLS.[17] Thus, data obtained from western studies that explored an association between RLS and blood donation cannot be extrapolated to Indian population. Considering these factors, the present study was planned to assess the prevalence of RLS among repeat blood donors and to find out its correlates, for example., age, gender, frequency of donation, time since last donation, serum ferritin levels, and various red cell indices.
| Materials and Methods | | |
This study was conducted during a period of 1 year spanning between April 2019 and March 2020 after obtaining approval from the Institutional Ethics Committee. Two hundred donors who fulfilled the definition of “regular donor” by National AIDS Control Organization (NACO)[13] were enrolled for the study by convenient sampling. Subjects were included if they had donated whole blood at least three times during lifetime, and a minimum of one donation within last year. However, donors for apheresis collections and those who turned up for a second time during the study period were excluded from the study. Written informed consent was taken from all the donors who met the donor selection criteria laid by Directorate General of Health Services, Government of India,[14] NACO guidelines[13] and Drugs and Cosmetic Act[15] and agreed to participate in the study.
Demographic data including age, sex, and occupation were also collected along with the responses to the Hindi version of CHRLS questionnaire.[18],[19] History of number of previous blood donations including total years donated, number of donations in the last 2 years, number of donations >2 years, <5 years ago, number of donations >5 years, <10 years ago, number of donations >10 years ago, and time since last donation in months was also taken.
Hb levels screening for eligibility for donation was measured using HemoCue Hb 301 (HemoCue India, New Delhi) for capillary Hb.
Estimation of red cell indices
Two–three ml whole blood samples was collected from antecubital vein both in ethylenediaminetetraacetic acid and plain vials according to the WHO guidelines for best phlebotomy practices.[20] Complete blood count was done on Sysmex XP-100 (Sysmex India Pvt. Ltd, Mumbai) three-part hematology analyzer on the day of sample collection. The parameters assessed for the study were Hb, hematocrit, mean corpuscular volume, mean corpuscular Hb, mean corpuscular Hb concentration, and red cell distribution width.
Estimation of serum ferritin
Plain vial samples were centrifuged at 3000 r. p. m for 3 min, and about 1–1.5 ml of serum was collected in aliquots. Samples were stored in the freezer at − 40°C for estimation as a single batch. Serum ferritin was assessed by ADVIA Centaur Enhanced Chemiluminescence Immuno System (Siemens Healthineers India, Mumbai) which is a chemiluminometric two-site sandwich immunoassay where a goat anti-ferritin antibody labeled with acridinium ester and a mouse anti-ferritin antibody covalently linked to paramagnetic particles are used.
Donors were divided into various groups according to different parameters collected, and results were recorded. RLS-positive patients were advised to go to psychiatry outpatient department for further treatment while those with normal iron stores or those not having RLS were motivated for further donations.
Statistical analysis
Analysis was done using the Statistical Package for Social Sciences (SPSS) v. 24.0 (IBM India). Descriptive statistics was calculated. Categorical variables were compared using Chi-square test, whereas independent sample t-test was used to compare continuous variables. N-1 Chi-square test was used to compare population prevalence of RLS with prevalence in the present study.
| Results | | |
Two hundred and ten donors were enrolled for the study. Two hundred donors were selected for analysis after removing the outliers. Out of which, 198 donors were males (99%). RLS was reported in only four donors (2%) and all of them were males. This was comparable to population prevalence of RLS reported in this region (P = 0.66, 95% confidence interval for difference-2.5–1.9).[21] There were no donations in the RLS-present group in 6–10 years back and >10 years back categories, hence no comparison was possible. The mean last donation in months was 7.8 in the RLS-absent group while it was much recent, 6 months in case of RLS-present category. None of these differences were statistically significant, may be due to the smaller number of RLS positive cases. [Table 1] shows the comparison of subjects with and without RLS.
| Discussion | | |
This study showed that the prevalence of RLS among blood donors was comparable to the prevalence in the general population. Second, subjects with RLS had greater numbers of donations in the past 2 years, and lastly, patients with RLS had lower serum ferritin. Frequency of RLS in this study of blood donors was lesser than previous studies that showed prevalence ranging between 4% and 18%.[5],[6],[7],[8],[9],[10],[11]
Higher prevalence in previous studies of blood donors could be ascribed to multiple factors, for example., greater age of subjects,[5],[6],[7],[9] inclusion of female subjects percentage,[5],[6],[7],[8],[9],[10],[11],[17] the absence of exclusion criteria,[5],[8],[9],[10],[11] and greater population prevalence in the geographical area where the study was conducted.[5],[6],[7],[8],[9],[10],[11] In the present study, subjects were younger and women comprised only 2% of the sample. In addition, robust exclusion criteria were followed to rule out RLS mimics and population prevalence of RLS in India is lesser (2.2%–2.5%) compared to western population.[3],[19],[21]
The present study reported that the prevalence of RLS among donors was comparable to population prevalence.[19],[21] Similar results have been reported by a number of previous studies.[8],[11],[17] On the contrary, some of the studies have reported that the prevalence of RLS was higher among blood donors compared to general population.[5],[7],[9],[10] These studies differed with regard to selection of study population as latter studies included repeat donors and deferred donors, whereas former studies had first-time donors only. However, the frequency of blood donation was not found to correlate with prevalence of RLS in a number of previous studies except one.[5],[8],[9],[10],[11] Results of the present study also confirm findings of previous studies and show that frequency of blood donations was unrelated to frequency of RLS [Table 1].
This study showed that the serum ferritin levels lesser than 40 ng/ml were associated with RLS. Association between RLS and low serum ferritin is well known and has been reported in blood donors as well.[5],[17] Similarly, Birgegård et al.[6] showed that replenishment of iron stores by administration of intravenous iron improve RLS. However, in contrast to the abovementioned studies, Bryant et al.[7] and Pedrazzini et al.[11] could not find anything significant between iron status and RLS.
Association between RLS and red blood cell (RBC) indices was reported in only one study, and similar to the present study, none of the RBC indices were found to be associated with RLS.[17] These factors suggest that RLS is a multifactorial disease where environmental factors such as iron deficiency act as precipitant only, rather than the causative factor.[4] However, available evidences also suggest that improvement in iron stores can provide relief to a significant number of subjects having RLS.[6]
The present study was also not devoid of limitations. What we followed was convenient sampling and consisted of a negligible number of female donors. Strict criteria for the selection of donors also led to this gender bias. First-time donors, nondonors, donors who got rejected for low Hb, etc., could act as controls and our study was not controlled. Prospective studies with controls from general population after systematically randomizing sample on the basis of age, sex, and other confounders are warranted to elicit more causal relationship if any, between RLS and blood donations.
| Conclusion | | |
The prevalence of RLS among repeat blood donors in Indian population was comparable to the general population. Our findings could be reassuring for the frequent donors. However, the presence of RLS can be a pointer to the subclinical iron-deficient erythropoiesis which warrants the assessment of iron stores, serum ferritin levels to the least. Therefore, inclusion of basic questions on symptoms of RLS in the donor screening questionnaire can be useful in detecting impending iron deficiency, though its impact is not on a big scale.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Walters AS. Toward a better definition of the restless legs syndrome. The International restless legs syndrome study group. Mov Disord 1995;10:634-42.  |
| 2. | Allen RP. Restless leg syndrome/Willis-Ekbom disease pathophysiology. Sleep Med Clin 2015;10:207-14. |
| 3. | Ohayon MM, O'Hara R, Vitiello MV. Epidemiology of restless legs syndrome: A synthesis of the literature. Sleep Med Rev 2012;16:283-95. |
| 4. | Allen RP, Earley CJ. The role of iron in restless legs syndrome. Mov Disord 2007;22 Suppl 18:S440-8. |
| 5. | Ulfberg J, Nyström B. Restless legs syndrome in blood donors. Sleep Med 2004;5:115-8. |
| 6. | Birgegård G, Schneider K, Ulfberg J. High incidence of iron depletion and Restless Leg Syndrome (RLS) in regular blood donors: Intravenous iron sucrose substitution more effective than oral iron. Vox Sang 2010;99:354-61. |
| 7. | Bryant BJ, Yau YY, Arceo SM, Hopkins JA, Leitman SF. Ascertainment of iron deficiency and depletion in blood donors through screening questions for pica and restless legs syndrome. Transfusion 2013;53:1637-44. |
| 8. | Arunthari V, Kaplan J, Fredrickson PA, Lin SC, Castillo PR, Heckman MG. Prevalence of restless legs syndrome in blood donors. Mov Disord 2010;25:1451-5. |
| 9. | Spencer BR, Kleinman S, Wright DJ, Glynn SA, Rye DB, Kiss JE, et al. Restless legs syndrome, pica, and iron status in blood donors. Transfusion 2013;53:1645-52. |
| 10. | Burchell BJ, Allen RP, Miller JK, Hening WA, Earley CJ. RLS and blood donation. Sleep Med 2009;10:844-9. |
| 11. | Pedrazzini B, Waldvogel S, Vaucher P, Cornuz J, Heinzer R, Tissot JD, et al. Prevalence of restless legs syndrome in female blood donors 1 week after blood donation. Vox Sang 2014;107:44-9. |
| 12. | Deneys V. (2013). Prevention of anaemia in blood donors: Iron or not iron? Blood Transfusion 2013;11:9-12. |
| 13. | National AIDS Control Organization. Standards for Blood Banks & Blood Transfusion Services. New Delhi. Ministry Health Family Welfare; 2007. p. 1-101. |
| 14. | Saran RK, Bhasin R, Chatterjee K, Ramalingan V, Swamy N, editors. Transfusion Medicine Technical Manual. 2 nd ed. New Delhi: Directorate General of Health Services, Ministry of Health and family Welfare. Government of India; 2003. p. 305-40. |
| 15. | |
| 16. | Silber MH, Richardson JW. Multiple blood donations associated with iron deficiency in patients with restless legs syndrome. Mayo Clin Proc 2003;78:52-4. |
| 17. | Singh A, Chaudhary R, Sonker A, Pandey HC. Importance of donor history of restless leg syndrome and pica to asses iron deficiency. Transfus Apher Sci 2016;54:259-61. |
| 18. | Allen RP, Burchell BJ, MacDonald B, Hening WA, Earley CJ. Validation of the self-completed Cambridge-Hopkins questionnaire (CH-RLSq) for ascertainment of restless legs syndrome (RLS) in a population survey. Sleep Med 2009;10:1097-100. |
| 19. | Gupta R, Allan RP, Pundeer A, Das S, Dhyani M, Goel D. Hindi translation and validation of Cambridge-Hopkins Diagnostic Questionnaire for RLS (CHRLSq). Ann Indian Acad Neurol 2015;18:303-8. [ PUBMED] [Full text] |
| 20. | |
| 21. | Rangarajan S, Rangarajan S, D'Souza GA. Restless legs syndrome in an Indian urban population. Sleep Med 2007;9:88-93. |
Correspondence Address:
Gita Negi,
Department of Transfusion Medicine, AIIMS Rishikesh, Virbhadra Road Shivaji Nagar, Near Barrage, Sturida Colony, Rishikesh - 249 203, Uttarakhand
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/ajts.ajts_181_21
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