Clinical Advantages of Phlebotomy: An Umbrella Review of Meta-Analyses
Abstract
Background: Phlebotomy has been used as a non-pharmacological treatment for different types of diseases, regarding the philosophy of humors in traditional medicines, such as Persian Medicine. However, according to the narrow-approved indications for phlebotomy in Western Medicine, we aimed to systematically summarize high-level of evidence on safety and efficacy of phlebotomy in treatment of human diseases.
Methods: In this umbrella review, to identify meta-analysis studies of clinical trials on phlebotomy, four electronic databases, including PubMed, web of science, Scopus, and Cochran library were searched until Jun 18, 2022 with relevant keywords for ‘phlebotomy’ and ‘meta-analysis’ according to PRISMA guidelines and PICO questions. After excluding irrelevant studies, data on subject characteristics, method of intervention, and adverse events were extracted. To evaluate the quality of the methodology of the systematic reviews, AMSTAR2 scale was utilized.
Results: From 327 identified studies, 7 full texts met the inclusion criteria, consisting of 56 clinical trials on 5648 subjects. These meta-analysis studies reported effects of phlebotomy on hypertension, acute gouty arthritis, skin disease (chronic urticaria and porphyria), and liver diseases (non-alcoholic fatty liver disease, chronic hepatitis C, and liver surgery). Our results showed significant improvements in different outcomes, while the most common adverse event was hematoma.
Conclusion: The level of evidence on the efficacy and safety of phlebotomy in some specific health conditions was substantial; however, to investigate the efficacy and safety of phlebotomy in management of other health problems more clinical studies with high sample sizes are needed.
1. Xia YB, Cheng J Fau, Tong L, et al (2012). [Comparative study of bloodletting therapy between traditional Chinese medicine and Tibetan medicine]. Zhongguo Zhen Jiu, 32(5):464.
2. Schneeberg NG (2002). A twenty-first century perspective on the ancient art of bloodletting. Trans Stud Coll Physicians Phila, 24:157-85.
3. Parapia LA (2008). History of bloodletting by phlebotomy. Br J Haematol, 143 (4):490-495.
4. Yao Q, Zhang X, Mu Y, et al (2019). Bloodletting Therapy for Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis. Biomed Res Int, 2019:8650398.
5. DePalma RG, Hayes VW, Zacharski LR (2007). Bloodletting: Past and Present. J Am Coll Surg, 205(1):132-44.
6. Denic S, Agarwal MM (2007). Nutritional iron deficiency: an evolutionary perspective. Nutrition, 23 (7-8):603-614.
7. Kim KH, Oh KY (2016). Clinical applications of therapeutic phlebotomy. J Blood Med, 7:139-144.
8. FA FAS (1998). Effect of Phlebotomy on Plasma Glucose and Insulin Concentrations. Diabetes Care, 21 (12):2190.
9. Guillygomarc'h A, Mendler MH, Moirand R, et al (2001). Venesection therapy of insulin resistance-associated hepatic iron overload. J Hepatol, 35 (3):344-349.
10. Xiong XJ, Wang PQ, Li SJ (2019). Blood-Letting Therapy for Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Chin J Integr Med, 25 (2):139-146.
11. Jeitler M, Roth S, Steckhan N, et al (2022). Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial. J Integr Complement Med, 28 (6):530-539.
12. Amini MH, Esmaeili SS, Barzi DM, Fesharaki MG (2018). The effect of FASD (blood-letting) in the treatment of sciatica: a randomized clinical trial study. Ann Med Health Sci Res, 8:391-396.
13. Chelavi LH, Ilkhani R, Azadvari M, et al (2021). The effect of phlebotomy (Fasd) on carpal tunnel syndrome; a randomized clinical trial. Oncology and Radiotherapy, 15(5): 8-12.
14. Li SH, Hu WS, Wu QF, Sun JG (2022). The efficacy of bloodletting therapy in patients with acute gouty arthritis: A systematic review and meta-analysis. Complement Ther Clin Pract, 46: 101503.
15. Khan SA, Rehman S, Jamil SS (2012). Safety and Efficacy of Fasd (Blood Letting through Venesection) in the Cases of Osteoarthrosis – A Randomized Controlled Study. Hippocratic J. Unani Med, 7(2):1-140.
16. Adams LA, Crawford DH, Stuart K, et al (2015). The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective, randomized, controlled trial. Hepatology, 61 (5):1555-1564.
17. Valenti L, Moscatiello S, Vanni E, et al (2010). Venesection for non-alcoholic fatty liver disease unresponsive to lifestyle counselling—a propensity score-adjusted observational study. QJM, 104 (2):141-149.
18. Liu C, Lei B, Zheng J (2008). Randomized control study on the treatment of 26 cases of acne conglobata with encircling acupuncture combined with venesection and cupping. Zhen Ci Yan Jiu, 33 (6):406-408.
19. Vaghebin R, Khalili M, Amiresmaili S, et al (2022). Saphenous vein phlebotomy alleviates neuroinflammatory response and oxidative stress following traumatic brain injury. Interdisciplinary Neurosurgery, 30:101626.
20. T. U (2014). Decade in review—hypertension: the past decade in hypertension—facts, hopes, and hypes. Nat Rev Cardiol, 11:633-635.
21. James PA, Oparil S, Carter BL, et al (2014). 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA, 311 (5):507-520.
22. Mancia G, Fagard R Fau, Narkiewicz K, et al (2013). 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press, 22(4):193-278.
23. Chow CK, Teo Kk Fau, Rangarajan S, et al S (2013). Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA, 310(9):959-68.
24. Guo F, He D Fau, Zhang W, et al (2012). Trends in prevalence, awareness, management, and control of hypertension among United States adults, 1999 to 2010. J Am Coll Cardiol, 60(7):599-606.
25. Bauchner H, Fontanarosa PB, Golub RM (2014). Updated Guidelines for Management of High Blood Pressure: Recommendations, Review, and Responsibility. JAMA, 311 (5):477-478.
26. Shea BJ, Reeves BC, Wells G, et al (2017). AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 358:j4008.
27. Desai TK, Jamil LH, Balasubramaniam M, et al (2008). Phlebotomy improves therapeutic response to interferon in patients with chronic hepatitis C: A meta-analysis of six prospective randomized controlled trials. Dig Dis Sci, 53(3):815-22.
28. Park L, Gilbert R, Baker L, et al (2020). The safety and efficacy of hypovolemic phlebotomy on blood loss and transfusion in liver surgery: a systematic review and meta-analysis. HPB (Oxford), 22 (3):340-350.
29. Salameh H, Sarairah H, Rizwan M, et al (2018). Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis. Br J Dermatol, 179 (6):1351-1357.
30. Jaruvongvanich V, Riangwiwat T, Sanguankeo A, et al (2016). Outcome of phlebotomy for treating nonalcoholic fatty liver disease: A systematic review and meta-analysis. Saudi J Gastroenterol, 22 (6):407-414.
31. Ma B, Chen X, Liang Y, et al (2020). Efficacy of bloodletting therapy in patients with chronic idiopathic urticaria: a randomized control trial. Evid Based Complement Alternat Med, 2020:6598708.
32. Cumpston M, Li T, Page MJ, et al (2019). Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev, 10(10):ED000142.
33. Picardi A, Abeni D (2001). Stressful life events and skin diseases: disentangling evidence from myth. Psychother Psychosom, 70 (3):118-136.
34. Theoharides TC, Singh KL, Boucher W, et al (1998). Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology, 139 (1):403-413.
35. Ma H, Kui Y, Li Y, et al (2013). Bloodletting therapy combined with paroxetine hydrochloride for generalized anxiety disorder: A randomized controlled trial. 2013 IEEE International Conference on Bioinformatics and Biomedicine, IEEE, pp. 174-176.
36. Badminton MN, Elder GH (2002). Management of acute and cutaneous porphyrias. Int J Clin Pract, 56 (4):272-278.
37. Shah A, Bhatt H. Porphyria Cutanea Tarda. 2023 Apr 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.
38. Rocchi E, Gibertini P, Cassanelli M, et al (1986). Serum ferritin in the assessment of liver iron overload and iron removal therapy in porphyria cutanea tarda. J Lab Clin Med, 107 (1):36-42.
39. Easterbrook M (1999). An ophthalmological view on the efficacy and safety of chloroquine versus hydroxychloroquine. J Rheumatol, 26 (9):1866-1868.
40. Zubair A (2014). Therapeutic phlebotomy. Clin Liver Dis (Hoboken), 4 (5):102-106.
41. Trasolini R, Cox B, Galts C, et al (2022). Elevated serum ferritin in non-alcoholic fatty liver disease is not predictive of fibrosis. Can Liver J, 5 (2):152-159.
42. Rekman J, Wherrett C, Bennett S, et al (2017). Safety and feasibility of phlebotomy with controlled hypovolemia to minimize blood loss in liver resections. Surgery, 161 (3):650-657.
43. Yang J, Jiao L (2012). Discussions on history of the bloodletting therapy overseas. Zhongguo Zhen Jiu, 32 (6):553-557.
44. Jiang H, Qiu L-L, Li YY, et al (2020). Efficacy and mechanism of fire needling bloodletting for lower extremity varicose veins. Zhongguo Zhen Jiu, 40 (9):953-956.
45. Holsworth RE, Jr, Cho YI, et al (2014). Cardiovascular benefits of phlebotomy: relationship to changes in hemorheological variables. Perfusion, 29 (2):102-16.
46. Kuchel GA, Avorn J, Reed MJ, et al (1992). Cardiovascular responses to phlebotomy and sitting in middle-aged and elderly subjects. Arch Intern Med, 152 (2):366-370.
2. Schneeberg NG (2002). A twenty-first century perspective on the ancient art of bloodletting. Trans Stud Coll Physicians Phila, 24:157-85.
3. Parapia LA (2008). History of bloodletting by phlebotomy. Br J Haematol, 143 (4):490-495.
4. Yao Q, Zhang X, Mu Y, et al (2019). Bloodletting Therapy for Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis. Biomed Res Int, 2019:8650398.
5. DePalma RG, Hayes VW, Zacharski LR (2007). Bloodletting: Past and Present. J Am Coll Surg, 205(1):132-44.
6. Denic S, Agarwal MM (2007). Nutritional iron deficiency: an evolutionary perspective. Nutrition, 23 (7-8):603-614.
7. Kim KH, Oh KY (2016). Clinical applications of therapeutic phlebotomy. J Blood Med, 7:139-144.
8. FA FAS (1998). Effect of Phlebotomy on Plasma Glucose and Insulin Concentrations. Diabetes Care, 21 (12):2190.
9. Guillygomarc'h A, Mendler MH, Moirand R, et al (2001). Venesection therapy of insulin resistance-associated hepatic iron overload. J Hepatol, 35 (3):344-349.
10. Xiong XJ, Wang PQ, Li SJ (2019). Blood-Letting Therapy for Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Chin J Integr Med, 25 (2):139-146.
11. Jeitler M, Roth S, Steckhan N, et al (2022). Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial. J Integr Complement Med, 28 (6):530-539.
12. Amini MH, Esmaeili SS, Barzi DM, Fesharaki MG (2018). The effect of FASD (blood-letting) in the treatment of sciatica: a randomized clinical trial study. Ann Med Health Sci Res, 8:391-396.
13. Chelavi LH, Ilkhani R, Azadvari M, et al (2021). The effect of phlebotomy (Fasd) on carpal tunnel syndrome; a randomized clinical trial. Oncology and Radiotherapy, 15(5): 8-12.
14. Li SH, Hu WS, Wu QF, Sun JG (2022). The efficacy of bloodletting therapy in patients with acute gouty arthritis: A systematic review and meta-analysis. Complement Ther Clin Pract, 46: 101503.
15. Khan SA, Rehman S, Jamil SS (2012). Safety and Efficacy of Fasd (Blood Letting through Venesection) in the Cases of Osteoarthrosis – A Randomized Controlled Study. Hippocratic J. Unani Med, 7(2):1-140.
16. Adams LA, Crawford DH, Stuart K, et al (2015). The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective, randomized, controlled trial. Hepatology, 61 (5):1555-1564.
17. Valenti L, Moscatiello S, Vanni E, et al (2010). Venesection for non-alcoholic fatty liver disease unresponsive to lifestyle counselling—a propensity score-adjusted observational study. QJM, 104 (2):141-149.
18. Liu C, Lei B, Zheng J (2008). Randomized control study on the treatment of 26 cases of acne conglobata with encircling acupuncture combined with venesection and cupping. Zhen Ci Yan Jiu, 33 (6):406-408.
19. Vaghebin R, Khalili M, Amiresmaili S, et al (2022). Saphenous vein phlebotomy alleviates neuroinflammatory response and oxidative stress following traumatic brain injury. Interdisciplinary Neurosurgery, 30:101626.
20. T. U (2014). Decade in review—hypertension: the past decade in hypertension—facts, hopes, and hypes. Nat Rev Cardiol, 11:633-635.
21. James PA, Oparil S, Carter BL, et al (2014). 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA, 311 (5):507-520.
22. Mancia G, Fagard R Fau, Narkiewicz K, et al (2013). 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press, 22(4):193-278.
23. Chow CK, Teo Kk Fau, Rangarajan S, et al S (2013). Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA, 310(9):959-68.
24. Guo F, He D Fau, Zhang W, et al (2012). Trends in prevalence, awareness, management, and control of hypertension among United States adults, 1999 to 2010. J Am Coll Cardiol, 60(7):599-606.
25. Bauchner H, Fontanarosa PB, Golub RM (2014). Updated Guidelines for Management of High Blood Pressure: Recommendations, Review, and Responsibility. JAMA, 311 (5):477-478.
26. Shea BJ, Reeves BC, Wells G, et al (2017). AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ, 358:j4008.
27. Desai TK, Jamil LH, Balasubramaniam M, et al (2008). Phlebotomy improves therapeutic response to interferon in patients with chronic hepatitis C: A meta-analysis of six prospective randomized controlled trials. Dig Dis Sci, 53(3):815-22.
28. Park L, Gilbert R, Baker L, et al (2020). The safety and efficacy of hypovolemic phlebotomy on blood loss and transfusion in liver surgery: a systematic review and meta-analysis. HPB (Oxford), 22 (3):340-350.
29. Salameh H, Sarairah H, Rizwan M, et al (2018). Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis. Br J Dermatol, 179 (6):1351-1357.
30. Jaruvongvanich V, Riangwiwat T, Sanguankeo A, et al (2016). Outcome of phlebotomy for treating nonalcoholic fatty liver disease: A systematic review and meta-analysis. Saudi J Gastroenterol, 22 (6):407-414.
31. Ma B, Chen X, Liang Y, et al (2020). Efficacy of bloodletting therapy in patients with chronic idiopathic urticaria: a randomized control trial. Evid Based Complement Alternat Med, 2020:6598708.
32. Cumpston M, Li T, Page MJ, et al (2019). Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev, 10(10):ED000142.
33. Picardi A, Abeni D (2001). Stressful life events and skin diseases: disentangling evidence from myth. Psychother Psychosom, 70 (3):118-136.
34. Theoharides TC, Singh KL, Boucher W, et al (1998). Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology, 139 (1):403-413.
35. Ma H, Kui Y, Li Y, et al (2013). Bloodletting therapy combined with paroxetine hydrochloride for generalized anxiety disorder: A randomized controlled trial. 2013 IEEE International Conference on Bioinformatics and Biomedicine, IEEE, pp. 174-176.
36. Badminton MN, Elder GH (2002). Management of acute and cutaneous porphyrias. Int J Clin Pract, 56 (4):272-278.
37. Shah A, Bhatt H. Porphyria Cutanea Tarda. 2023 Apr 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.
38. Rocchi E, Gibertini P, Cassanelli M, et al (1986). Serum ferritin in the assessment of liver iron overload and iron removal therapy in porphyria cutanea tarda. J Lab Clin Med, 107 (1):36-42.
39. Easterbrook M (1999). An ophthalmological view on the efficacy and safety of chloroquine versus hydroxychloroquine. J Rheumatol, 26 (9):1866-1868.
40. Zubair A (2014). Therapeutic phlebotomy. Clin Liver Dis (Hoboken), 4 (5):102-106.
41. Trasolini R, Cox B, Galts C, et al (2022). Elevated serum ferritin in non-alcoholic fatty liver disease is not predictive of fibrosis. Can Liver J, 5 (2):152-159.
42. Rekman J, Wherrett C, Bennett S, et al (2017). Safety and feasibility of phlebotomy with controlled hypovolemia to minimize blood loss in liver resections. Surgery, 161 (3):650-657.
43. Yang J, Jiao L (2012). Discussions on history of the bloodletting therapy overseas. Zhongguo Zhen Jiu, 32 (6):553-557.
44. Jiang H, Qiu L-L, Li YY, et al (2020). Efficacy and mechanism of fire needling bloodletting for lower extremity varicose veins. Zhongguo Zhen Jiu, 40 (9):953-956.
45. Holsworth RE, Jr, Cho YI, et al (2014). Cardiovascular benefits of phlebotomy: relationship to changes in hemorheological variables. Perfusion, 29 (2):102-16.
46. Kuchel GA, Avorn J, Reed MJ, et al (1992). Cardiovascular responses to phlebotomy and sitting in middle-aged and elderly subjects. Arch Intern Med, 152 (2):366-370.
| Files | ||
| Issue | Vol 53 No 12 (2024) | |
| Section | Review Article(s) | |
| Keywords | ||
| Phlebotomy Persian medicine Bloodletting Traditional medicine Meta-analysis | ||
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How to Cite
1.
Khatami S, Rahimzade M, Lavari N, Jadidi T, Adel-Mehraban MS. Clinical Advantages of Phlebotomy: An Umbrella Review of Meta-Analyses. Iran J Public Health. 2024;53(12):2683-2693.
