Micronized purified flavonoid fraction in the treatment of hemorrhoidal disease
Publication: Journal of Comparative Effectiveness Research
Abstract
Hemorrhoidal disease (HD) is common in adults. Treatment is largely conservative, although more invasive procedures may be required. Venoactive drugs such as micronized purified flavonoid fraction (MPFF) are widely used, but a recent and comprehensive review of supporting evidence is lacking. In acute HD, MPFF can reduce HD symptoms such as bleeding, pain, anal discomfort, anal discharge and pruritus. In patients undergoing surgery, postoperative adjunct MPFF consistently reduces pain, bleeding duration and use of analgesia. MPFF treatment is appropriate and effective both as a first-line conservative treatment and as a postoperative adjunct treatment. MPFF reduces the duration of hospital stay following surgery, facilitating a return to normal activity and improving quality of life. MPFF may also prevent HD recurrence.
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References
Papers of special note have been highlighted as: • of interest; •• of considerable interest
1.
Haas PA, Haas GP, Schmaltz S, Fox TA Jr. The prevalence of hemorrhoids. Dis. Colon Rectum 26(7), 435–439 (1983).
2.
Johanson JF, Sonnenberg A. The prevalence of hemorrhoids and chronic constipation. An epidemiologic study. Gastroenterology 98(2), 380–386 (1990).
3.
Riss S, Weiser FA, Schwameis K et al. The prevalence of hemorrhoids in adults. Int. J. Colorectal Dis. 27(2), 215–220 (2012).
4.
Kakkos SK, Nicolaides AN. Efficacy of micronized purified flavonoid fraction (Daflon®) on improving individual symptoms, signs and quality of life in patients with chronic venous disease: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials. Int. Angiol. 37(2), 143–154 (2018).
•• Systematic review and meta-analysis investigating the effectiveness of micronized purified flavonoid fraction (MPFF) in patients with chronic venous diseases of the lower extremities.
5.
Aziz Z, Huin WK, Badrul Hisham MD, Tang WL, Yaacob S. Efficacy and tolerability of micronized purified flavonoid fractions (MPFF) for haemorrhoids: a systematic review and meta-analysis. Complement. Ther. Med. 39, 49–55 (2018).
• Systematic review of ten randomized controlled trials examining the effects of MPFF in 1164 patients with hemorrhoids.
6.
Cospite M. Double-blind, placebo-controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute hemorrhoids. Angiology 45(6 Pt 2), 566–573 (1994).
7.
Cospite M. Double blind placebo controlled evaluation of clinical activity and safety of Daflon 500 mg in the treatment of acute haemorrhoids. Phlebology 9(Suppl. 1), 40–43 (1994).
8.
De Souza MDC, Cyrino FZ, De Carvalho JJ, Blanc-Guillemaud V, Bouskela E. Protective effects of micronized purified flavonoid fraction (MPFF) on a novel experimental model of chronic venous hypertension. Eur. J. Vasc. Endovasc. Surg. 55(5), 694–702 (2018).
9.
Paysant J, Sansilvestri-Morel P, Bouskela E, Verbeuren TJ. Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation. Int. Angiol. 27(1), 81–85 (2008).
10.
Nicolaides A, Kakkos S, Baekgaard N et al. Management of chronic venous disorders of the lower limbs. Guidelines according to scientific evidence. Part I. Int. Angiol. 37(3), 181–254 (2018).
11.
Sheikh P, Lohsiriwat V, Shelygin Y. Micronized purified flavonoid fraction in hemorrhoid disease: a systematic review and meta-analysis. Adv. Ther. 37(6), 2792–2812 (2020).
• The most recent systematic review and meta-analysis investigating the efficacy of MPFF on symptomatic hemorrhoids.
12.
Abramowitz L, Godeberge P, Staumont G, Soudan D. Clinical practice guidelines for the treatment of hemorrhoid disease. Gastroenterol. Clin. Biol. 25(6–7), 674–702 (2001).
13.
Agarwal N, Singh K, Sheikh P, Mittal K, Mathai V, Kumar A. Executive summary - The Association of Colon & Rectal Surgeons of India (ACRSI) practice guidelines for the management of haemorrhoids-2016. Indian J. Surg. 79(1), 58–61 (2017).
•• Updated practice guideline for managing hemorrhoids from the Association of Colon and Rectal Surgeons of India.
14.
Davis BR, Lee-Kong SA, Migaly J, Feingold DL, Steele SR. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of hemorrhoids. Dis. Colon Rectum 61(3), 284–292 (2018).
•• The latest recommendations for managing hemorrhoids from the American Society of Colon and Rectal Surgeons.
15.
Madoff RD, Fleshman JW. American Gastroenterological Association technical review on the diagnosis and treatment of hemorrhoids. Gastroenterology 126(5), 1463–1473 (2004).
16.
Shelygin YA, Frolov SA, Titov AY et al. The Russian Association of Coloproctology clinical guidelines for the diagnosis and treatment of hemorrhoids. Koloproktologia 18(1), 7–38 (2019).
•• Clinical guideline for managing hemorrhoids from the Russian Association of Coloproctology.
17.
Aigner F, Gruber H, Conrad F et al. Revised morphology and hemodynamics of the anorectal vascular plexus: impact on the course of hemorrhoidal disease. Int. J. Colorectal Dis. 24(1), 105–113 (2009).
18.
Lohsiriwat V. Hemorrhoids: from basic pathophysiology to clinical management. World J. Gastroenterol. 18(17), 2009–2017 (2012).
•• Comprehensive review describing the fundamental pathophysiology, clinical management and treatment outcomes of hemorrhoids.
19.
Laurence AE, Murray AJ. Histopathology of prolapsed and thrombosed hemorrhoids. Dis. Colon Rectum 5, 56–61 (1962).
20.
Morgado PJ, Suarez JA, Gomez LG, Morgado PJ Jr. Histoclinical basis for a new classification of hemorrhoidal disease. Dis. Colon Rectum 31(6), 474–480 (1988).
21.
Loder PB, Kamm MA, Nicholls RJ, Phillips RK. Haemorrhoids: pathology, pathophysiology and aetiology. Br. J. Surg. 81(7), 946–954 (1994).
22.
Johanson JF, Sonnenberg A. Constipation is not a risk factor for hemorrhoids: a case-control study of potential etiological agents. Am. J. Gastroenterol. 89(11), 1981–1986 (1994).
23.
Lee JH, Kim HE, Kang JH, Shin JY, Song YM. Factors associated with hemorrhoids in Korean adults: Korean national health and nutrition examination survey. Korean J. Fam. Med. 35(5), 227–236 (2014).
24.
Hyams L, Philpot J. An epidemiological investigation of hemorrhoids. Am. J. Proctol. 21(3), 177–193 (1970).
25.
Peery AF, Sandler RS, Galanko JA et al. Risk factors for hemorrhoids on screening colonoscopy. PLoS ONE 10(9), e0139100 (2015).
26.
Pigot F, Siproudhis L, Allaert FA. Risk factors associated with hemorrhoidal symptoms in specialized consultation. Gastroenterol. Clin. Biol. 29(12), 1270–1274 (2005).
27.
Poskus T, Buzinskienė D, Drasutiene G et al. Haemorrhoids and anal fissures during pregnancy and after childbirth: a prospective cohort study. BJOG 121(13), 1666–1671 (2014).
28.
Johanson JF. Association of hemorrhoidal disease with diarrheal disorders: potential pathogenic relationship? Dis. Colon Rectum 40(2), 215–219 (1997).
29.
Katsenis K. Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr. Vasc. Pharmacol. 3(1), 1–9 (2005).
30.
Lyseng-Williamson KA, Perry CM. Micronised purified flavonoid fraction: a review of its use in chronic venous insufficiency, venous ulcers and haemorrhoids. Drugs 63(1), 71–100 (2003).
31.
Mansilha A, Sousa J. Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy. Int. J. Mol. Sci. 19(6), 1669 (2018).
32.
Friesenecker B, Tsai AG, Allegra C, Intaglietta M. Oral administration of purified micronized flavonoid fraction suppresses leukocyte adhesion in ischemia-reperfusion injury: in vivo observations in the hamster skin fold. Int. J. Microcirc. Clin. Exp. 14(1–2), 50–55 (1994).
33.
Korthuis RJ, Gute DC. Postischemic leukocyte/endothelial cell interactions and microvascular barrier dysfunction in skeletal muscle: cellular mechanisms and effect of Daflon 500 mg. Int. J. Microcirc. Clin. Exp. 17(Suppl. 1), 11–17 (1997).
34.
Pascarella L, Lulic D, Penn AH et al. Mechanisms in experimental venous valve failure and their modification by Daflon 500 mg. Eur. J. Vasc. Endovasc. Surg. 35(1), 102–110 (2008).
35.
Takase S, Lerond L, Bergan JJ, Schmid-Schonbein GW. The inflammatory reaction during venous hypertension in the rat. Microcirculation 7(1), 41–52 (2000).
36.
Damon M, Flandre O, Michel F, Perdrix L, Labrid C, Crastes De Paulet A. Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat. Study of prostaglandin E2 and F2 alpha and thromboxane B2 release and histological changes. Arzneimittelforschung 37(10), 1149–1153 (1987).
37.
Lonchampt M, Guardiola B, Sicot N, Bertrand M, Perdrix L, Duhault J. Protective effect of a purified flavonoid fraction against reactive oxygen radicals. In vivo and in vitro study. Arzneimittelforschung 39(8), 882–885 (1989).
38.
Bouskela E, Donyo KA. Effects of oral administration of purified micronized flavonoid fraction on increased microvascular permeability induced by various agents and on ischemia/reperfusion in the hamster cheek pouch. Angiology 48(5), 391–399 (1997).
39.
Cotonat A, Cotonat J. Lymphagogue and pulsatile activities of Daflon 500 mg on canine thoracic lymph duct. Int. Angiol. 8(Suppl. 4), 15–18 (1989).
40.
Mchale NG, Hollywood MA. Control of lymphatic pumping: interest of Daflon 500 mg. Phlebology 9, 23–25 (1994).
41.
Behar A, Lagrue G, Cohen-Boulakia F, Baillet J. Study of capillary filtration by double labelling I131-albumin and Tc99m red cells. Application to the pharmacodynamic activity of Daflon 500 mg. Int. Angiol. 7(Suppl. 2), 35–38 (1988).
42.
Galley P, Thiollet M. A double-blind, placebo-controlled trial of a new veno-active flavonoid fraction (S 5682) in the treatment of symptomatic capillary fragility. Int. Angiol. 12(1), 69–72 (1993).
43.
Bleday R, Pena JP, Rothenberger DA, Goldberg SM, Buls JG. Symptomatic hemorrhoids: current incidence and complications of operative therapy. Dis. Colon Rectum 35(5), 477–481 (1992).
44.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339, b2535 (2009).
45.
Godeberge P. Daflon 500 mg is significantly more effective than placebo in the treatment of haemorrhoids. Phlebology 7(Suppl. 2), 61–63 (1992).
46.
Godeberge P. Daflon 500 mg in the treatment of hemorrhoidal disease: a demonstrated efficacy in comparison with placebo. Angiology 45(6 Pt 2), 574–578 (1994).
47.
Vajrabukka T, Rojanasakul A, Vathanophas V et al. Therapeutic activity of Daflon 500 mg® in acute episodes of hemorrhoids. Chula Med. J. 38(2), 77–83 (1994).
48.
Panpimanmas S, Sithipongsri S, Sukdanon C, Manmee C. Experimental comparative study of the efficacy and side effects of Cissus quadrangularis L. (Vitaceae) to Daflon (Servier) and placebo in the treatment of acute hemorrhoids. J. Med. Assoc. Thai. 93(12), 1360–1367 (2010).
49.
Jiang ZM, Cao JD. The impact of micronized purified flavonoid fraction on the treatment of acute haemorrhoidal episodes. Curr. Med. Res. Opin. 22(6), 1141–1147 (2006).
50.
Shelygin Y, Krivokapic Z, Frolov SA et al. Clinical acceptability study of micronized purified flavonoid fraction 1000 mg tablets versus 500 mg tablets in patients suffering acute hemorrhoidal disease. Curr. Med. Res. Opin. 32(11), 1821–1826 (2016).
51.
Misra MC, Parshad R. Randomized clinical trial of micronized flavonoids in the early control of bleeding from acute internal haemorrhoids. Br. J. Surg. 87(7), 868–872 (2000).
52.
Mokhtare M, Pakravan R, Rafieemanesh M et al. The efficacy of adding Daflon to the conventional treatment on the improvement of symptoms and health related quality of life in patients with acute hemorrhoids: a randomized clinical trial. EC Gastroenterol. Dig. System 6(11), 44–51 (2019).
53.
Thanapongsathorn W, Vajrabukka T. Clinical trial of oral diosmin (Daflon) in the treatment of hemorrhoids. Dis. Colon Rectum 35(11), 1085–1088 (1992).
54.
Ho YH, Foo CL, Seow-Choen F, Goh HS. Prospective randomized controlled trial of a micronized flavonidic fraction to reduce bleeding after haemorrhoidectomy. Br. J. Surg. 82(8), 1034–1035 (1995).
55.
Lee HW, Lee WY, Chun HK. Clinical effects of Venitol® on complications after hemorrhoidectomy: prospective randomized and placebo-controlled trial. J. Korean Soc. Coloproctol. 14(4), 761–766 (1998).
56.
Colak T, Akca T, Dirlik M, Kanik A, Dag A, Aydin S. Micronized flavonoids in pain control after hemorrhoidectomy: a prospective randomized controlled study. Surg. Today 33(11), 828–832 (2003).
57.
La Torre F, Nicolai AP. Clinical use of micronized purified flavonoid fraction for treatment of symptoms after hemorrhoidectomy: results of a randomized, controlled, clinical trial. Dis. Colon Rectum 47(5), 704–710 (2004).
58.
Mlakar B. Flavonoids reduce bleeding after closed haemorrhoidectomy - prospective randomized controlled trial. Eur. Surg. 40(1), 34–36 (2008).
59.
Mlakar B, Kosorok P. Flavonoids to reduce bleeding and pain after stapled hemorrhoidopexy: a randomized controlled trial. Wien Klin. Wochenschr. 117(15–16), 558–560 (2005).
60.
Shelygin YA, Blagodarny LA, Kostarev IV. The efficacy of Detralex in the prevention of complications after hemorrhoid sclerotherapy (in Russian). Koloproctologiya 1(11), 16–20 (2005).
61.
Dimitroulopoulos D, Tsamakidis K, Xinopoulos D, Karaitianos I, Fotopoulou A, Paraskevas E. Prospective, randomized, controlled, observer-blinded trial of combined infrared photocoagulation and micronized purified flavonoid fraction versus each alone for the treatment of hemorrhoidal disease. Clin. Ther. 27(6), 746–754 (2005).
62.
Ho YH, Tan M, Seow-Choen F. Micronized purified flavonidic fraction compared favorably with rubber band ligation and fiber alone in the management of bleeding hemorrhoids: randomized controlled trial. Dis. Colon Rectum 43(1), 66–69 (2000).
63.
Alonso-Coello P, Zhou Q, Martinez-Zapata MJ et al. Meta-analysis of flavonoids for the treatment of haemorrhoids. Br. J. Surg. 93(8), 909–920 (2006).
64.
Perera N, Liolitsa D, Iype S et al. Phlebotonics for haemorrhoids. Cochrane Database Syst. Rev. (8), CD004322 (2012).
65.
Meyer OC. Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease. Angiology 45(6 Pt 2), 579–584 (1994).
66.
Buckshee K, Takkar D, Aggarwal N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int. J. Gynaecol. Obstet. 57(2), 145–151 (1997).
67.
Scheyer M, Antonietti E, Rollinger G, Lancee S, Pokorny H. Hemorrhoidal artery ligation (HAL) and rectoanal repair (RAR): retrospective analysis of 408 patients in a single center. Tech. Coloproctol. 19(1), 5–9 (2015).
68.
Plapler H, Hage R, Duarte J et al. A new method for hemorrhoid surgery: intrahemorrhoidal diode laser, does it work? Photomed. Laser Surg. 27(5), 819–823 (2009).
69.
Lim DR, Cho DH, Lee JH, Moon JH. Comparison of a hemorrhoidectomy with ultrasonic scalpel versus a conventional hemorrhoidectomy. Ann. Coloproctol. 32(3), 111–116 (2016).
70.
Hoyuela C, Carvajal F, Juvany M et al. HAL-RAR (Doppler guided haemorrhoid artery ligation with recto-anal repair) is a safe and effective procedure for haemorrhoids. Results of a prospective study after two-years follow-up. Int. J. Surg. 28, 39–44 (2016).
71.
Faucheron JL, Trilling B, Reche F. HAL-RAR® procedure: a safe operation for hemorrhoids. J. Visc. Surg. 152(2), 143–144 (2015).
72.
Giamundo P, Salfi R, Geraci M, Tibaldi L, Murru L, Valente M. The hemorrhoid laser procedure technique vs rubber band ligation: a randomized trial comparing 2 mini-invasive treatments for second- and third-degree hemorrhoids. Dis. Colon Rectum 54(6), 693–698 (2011).
73.
De Nardi P, Tamburini AM, Gazzetta PG, Lemma M, Pascariello A, Asteria CR. Hemorrhoid laser procedure for second- and third-degree hemorrhoids: results from a multicenter prospective study. Tech. Coloproctol. 20(7), 455–459 (2016).
74.
Bilgin Y, Hot S, Soykan Barlas İ, Akan A, Eryavuz Y. Short- and long-term results of harmonic scalpel hemorrhoidectomy versus stapler hemorrhoidopexy in treatment of hemorrhoidal disease. Asian J. Surg. 38(4), 214–219 (2015).
75.
Bakhtiar N, Moosa FA, Jaleel F, Qureshi NA, Jawaid M. Comparison of hemorrhoidectomy by LigaSure with conventional Milligan Morgan’s hemorrhoidectomy. Pak. J. Med. Sci. 32(3), 657–661 (2016).
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© 2021 Philippe Godeberge. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
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Micronized purified flavonoid fraction in the treatment of hemorrhoidal disease. (2021) Journal of Comparative Effectiveness Research. DOI: 10.2217/cer-2021-0038
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