Micronized purified flavonoid fraction for the treatment of chronic venous insufficiency, with a focus on postthrombotic syndrome: A narrative review

Abstract

Introduction: Postthrombotic syndrome (PTS) is a form of secondary chronic venous insufficiency (CVI) that occurs after deep vein thrombosis (DVT). Effective treatments for PTS are lacking. Micronized purified flavonoid fraction (MPFF) is a venoactive drug used in the treatment of CVI.

Objective: To determine whether MPFF is a good candidate to explore as a therapeutic agent for PTS.

Methods: We performed a narrative review in which we identified 14 systematic reviews, 33 randomized controlled trials, and 19 observational studies that discussed the use of MPFF in CVI, as well as studies that reported on the mechanistic action of MPFF in relation to the pathophysiology of PTS.

Results: MPFF targets a number of pathophysiologic components of PTS. Based on animal models and human studies investigating objective vascular and lymphatic measures, MPFF promotes venous recanalization after DVT, decreases venous remodeling and reflux, inhibits inflammatory processes, improves venous tone and stasis, improves lymphatic circulation, improves capillary hyperpermeability, and decreases tissue hypoxia. Furthermore, MPFF shows promise in improving clinical manifestations, quality of life, and objective venous parameters of CVI. Studies suggest good patient acceptability and tolerability with the use of MPFF in CVI.

Conclusion: MPFF is a good candidate to explore as a potential therapy for PTS. Confirmatory high-quality studies are still needed to reinforce the evidence supporting the use of MPFF in CVI. Double-blind randomized controlled trials with clinical endpoints are needed to assess the clinical efficacy of MPFF in the treatment of PTS.

Keywords: diosmin; flavonoids; hesperidin; postthrombotic syndrome; venous insufficiency; venous thrombosis.

FIGURE 1

Flow diagram of study selection. CDSR: Cochrane Database of Systematic Reviews; CENTRAL: Central Register of Controlled Trials; DARE: Database of Abstracts of Reviews of Effects; EMBASE: Excerpta Medica Database; NHS EED: National Health Service Economic Evaluation Database

FIGURE 2

The pathophysiology of the postthrombotic syndrome (PTS) and the mechanism of action of micronized purified flavonoid fraction. The pathogenesis of PTS begins with venous obstruction and valvular reflux resulting from acute, then residual venous thrombosis. Inflammation can delay thrombus resolution, worsening both obstruction and reflux. As a consequence of persistent venous occlusion and reflux, venous hypertension results. Venous hypertension leads to tissue hypoperfusion and hyperpermeability, which together cause the clinical manifestations of PTS. MPFF improves venous recanalization following DVT and decreases venous reflux, acting on two key steps in the establishment of venous hypertension leading to PTS: venous obstruction and valvular reflux. MPFF has anti‐inflammatory effects, which may prevent further obstruction and reflux resulting from inflammatory responses following deep vein thrombosis. MPFF increases venous tone, decreases venous stasis, and improves lymphatic circulation, further relieving venous hypertension. Finally, MPFF acts on the deleterious outcomes of venous hypertension: it decreases tissue hypoxia and capillary hyperpermeability. MPFF: micronized purified flavonoid fraction