Impact of Microcirculatory Disorders on the Symptoms of Chronic Venous Disease and Their Pharmacological Correction

Lobastov K.V.

doi:https://doi.org/10.17116/flebo20201401130

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Abstract:

The review is devoted to prevalence, pathogenesis and pharmacological correction of major specific venous symptoms. Incidence of subjective manifestations of chronic venous diseases (CVD) is 53—65% in general population and up to 80% in patients with confirmed disease. The most common symptoms are heaviness (36—81%), fatigue (33—72%), feeling of swelling (29—58%) and pain (15—70%). The most of symptoms are based on microcirculatory disorders (hypertension, inflammation, stasis, ischemia), which do not always correlate with hemodynamic disorders. However, these changes may be objectively confirmed by video microscopy, laser Doppler flowmetry, transcutaneous oximetry. Recent studies of microcirculation with orthogonal polarization spectral imaging demonstrate abnormalities in dermal capillaries (reduced functional density, enlargement) even in patients with CVD class C0s. More significant violations are observed along with progression of disease. Modern venoactive drugs can improve tissue perfusion and successfully relieve venospecific symptoms. Topical agents based on liposomal form of delivery are of particular interest because these agents increase bioavailability of drugs and their clinical effectiveness. Detragel is one of the drugs with liposomal delivery among the known ointments and gels for CVD management. Its effectiveness has been demonstrated in 12 clinical trials involving healthy volunteers, patients with chronic venous disease, diabetic angiopathy and superficial vein thrombosis. The use of this agent is associated with improved tissue perfusion, relief of venospecific symptoms, inflammation and reduced risk of adverse events after sclerotherapy. Thus, available data on the prevalence and pathogenesis of venospecific symptoms justify advisability of microcirculatory correction over macrohemodynamic measures in CVD patients.

Keywords:

chronic vein disease

microcirculation

pathogenesis

inflammation

local remedies

liposome

Authors:

Lobastov K.V.

Kafedra obshcheĭ khirurgii lechebnogo fakul'teta GOU VPO RGMU Roszdrava, Moskva

ORCID: 0000-0002-5358-7218

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References:

Davies AH. The Seriousness of Chronic Venous Disease: A Review of Real-World Evidence. Adv Ther. 2019;36(Suppl 1):5-12. https://doi.org/10.1007/s12325-019-0881-7
Rabe E, Guex JJ, Puskas A, Scuderi A, Quesada FF; VCP Coordinators. Epidemiology of chronic venous disorders in geographically diverse populations: results from the Vein Consult Program. Int Angiol. 2012;31(2):105-115.
Zolotukhin IA, Seliverstov EI, Shevtsov YN, Avakiants IP, Nikishkov AS, Tatarintsev AM, Kirienko AI. Prevalence and Risk Factors for Chronic Venous Disease in the General Russian Population. Eur J Vasc Endovasc Surg. 2017;54(6):752-758. https://doi.org/10.1016/j.ejvs.2017.08.033
Perrin M, Eklof B, Van Rij A, Labropoulos N, Vasquez M, Nicolaides A, Blattler W, Bouhassira D, Bouskela E, Carpentier P. Venous symptoms: the SYM Vein Consensus statement developed under the auspices of the European Venous Forum. International angiology: a journal of the International Union of Angiology. 2016;35(4):374.
Stoyko YuM, Kirienko AI, Zatevakhin II, Pokrovsky AV, Karpenko AA, Zolotukhin IA, Sapelkin SV, Ilyukhin EA, Gavrilov SG, Porembskaya OYa, Borsuk DA, Seliverstov EI, Alukhanyan OA, Andriyashkin AV, Andriyashkin VV, Barinov VE, Belentsov SM, Bogdanets LI, Bredikhin RA, Bukina OV, Burleva EP, Vakhitov MSh, Vinogradov LA, Volkov AYu, Golovanova OV, Guzhkov ON, Ivanov EV, Katelnitskaya OV, Katorkin SE, Kletskin AE, Koshevoy AP, Krylov AYu, Kudykin MN, Kuzovlev SP, Laberko LA, Larin SI, Lishov DE, Lobastov KV, Mazayshvili KV, Markin SM, Parikov MA, Pelevin AV, Potapov MP, Pryadko SI, Rapovka VG, Sabelnikov VV, Slavin DA, Sokolov AL, Soldatsky EYu, Sonkin IN, Starodubtsev VN, Subbotin YuG, Suchkov IA, Sushkov SA, Tolstikhin VYu, Fokin AA, Khitaryan AG, Khodkevich MB, Khorev NG, Tsukanov YuT, Chabbarov RG, Chernookov AN, Chechetka DYu, Shevela AI, Shimanko AI, Shonov OA, Yashkin MN, Bogachev VYu, Bubnova NA, Dibirov MD, Zhukov BN, Kalinin RE, Katelnitsky II, Plechev VV, Shaydakov EV, Shulutko AM. Diagnostics and Treatment of Chronic Venous Disease: Guidelines of Russian Phlebological Association. Phelbologiya. 2018(3):146-240. (In Russ.) https://doi.org/10.17116/flebo20187031146
Savelyev VS, Kirienko AI, Zolotukhin IA, Seliverstov EI. Prospective observational study SPECTRUM: register of patients with chronic venous diseases. Phlebologiya. 2012;6(1):4-9. (In Russ.)
Escudero Rodriguez JR, Fernandez Quesada F, Bellmunt Montoya S. Prevalence and clinical characteristics of chronic venous disease in patients seen in primary care in Spain: results of the international study Vein Consult Program. Cir Esp. 2014;92(8):539-546. https://doi.org/10.1016/j.ciresp.2013.09.013
Vuylsteke ME, Thomis S, Guillaume G, Modliszewski ML, Weides N, Staelens I. Epidemiological study on chronic venous disease in Belgium and Luxembourg: prevalence, risk factors, and symptomatology. Eur J Vasc Endovasc Surg. 2015;49(4):432-439. https://doi.org/10.1016/j.ejvs.2014.12.031
Klitfod L, Sillesen H, Jensen LP. Patients and physicians agree only partially in symptoms and clinical findings before and after treatment for varicose veins. Phlebology. 2018;33(2):115-121. https://doi.org/10.1177/0268355516686444
Taengsakul N, Saikaew T, Chaiaroon N, Urasuk T, Panoi A. Inflammatory Responses in Varicose Veins Surgery: Conven-tional Venous Stripping VS Endovenous Radiofrequency Abla-tion (EV-RFA). J Vasc Endovasc Therapy. 2019;4(1):9.
Dzieciuchowicz L, Espinosa G, Paramo JA. Haemostatic activation and inflammatory response after three methods of treatment of great saphenous vein incompetence. Phlebology. 2014;29(3):154-163. https://doi.org/10.1177/0268355512474445
Tisato V, Zauli G, Gianesini S, Menegatti E, Brunelli L, Manfredini R, Zamboni P, Secchiero P. Modulation of circulating cytokine-chemokine profile in patients affected by chronic venous insufficiency undergoing surgical hemodynamic correction. J Immunol Res. 2014;2014:473765. https://doi.org/10.1155/2014/473765
Jantet G. Chronic venous insufficiency: worldwide results of the RELIEF study. Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids. Angiology. 2002;53(3):245-256. https://doi.org/10.1177/000331970205300301
Ting AC, Cheng SW, Wu LL, Cheung GC. Clinical and hemodynamic outcomes in patients with chronic venous insufficiency after oral micronized flavonoid therapy. Vasc Surg. 2001;35(6):443-447. https://doi.org/10.1177/153857440103500604
Senra Barros B, Kakkos SK, De Maeseneer M, Nicolaides AN. Chronic venous disease: from symptoms to microcirculation. Int Angiol. 2019;38(3):211-218. https://doi.org/10.23736/S0392-9590.19.04116-6
Bergan JJ, Pascarella L, Schmid-Schönbein GW. Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension. Journal of vascular surgery. 2008;47(1):183-192. https://doi.org/10.1016/j.jvs.2007.09.028
Nicolaides A, Kakkos S, Baekgaard N, Comerota A, de Maeseneer M, Eklof B, Giannoukas AD, Lugli M, Maleti O, Myers K, Nelzen O, Partsch H, Perrin M. Management of chronic venous disorders of the lower limbs. Guidelines According to Scientific Evidence. Part I Int Angiol. 2018;37(3):181-254. https://doi.org/10.23736/S0392-9590.18.03999-8
Neglen P, Thrasher TL, Raju S. Venous outflow obstruction: An underestimated contributor to chronic venous disease. J Vasc Surg. 2003;38(5):879-885. https://doi.org/10.1016/s0741-5214(03)01020-6
Caggiati A, Phillips M, Lametschwandtner A, Allegra C. Valves in small veins and venules. Eur J Vasc Endovasc Surg. 2006;32(4):447-452. https://doi.org/10.1016/j.ejvs.2006.04.021
Vincent JR, Jones GT, Hill GB, van Rij AM. Failure of microvenous valves in small superficial veins is a key to the skin changes of venous insufficiency. J Vasc Surg. 2011;54(Suppl 6):S62-S69. https://doi.org/10.1016/j.jvs.2011.06.085
Govind D, Thomas KN, Hill BG, van Rij AM. Microvenous Reflux in the Skin of Limbs with Superficial Venous Incompetence. Ultrasound Med Biol. 2018;44(4):756-761. https://doi.org/10.1016/j.ultrasmedbio.2017.11.014
Junger M, Steins A, Hahn M, Hafner HM. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Microcirculation. 2000;7(6-2):3-12.
Franzeck UK, Bollinger A, Huch R, Huch A. Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous incompetence. Circulation. 1984;70(5):806-811. https://doi.org/10.1161/01.cir.70.5.806
Azizov GA, Kozlov VI. Chronic venous insufficiency of the lower limbs: microcirculatory features. Vestnik Rossijskogo universiteta druzhby narodov. Seriya: Meditsina. 2003;3:117-120. (In Russ.)
Lindert J, Werner J, Redlin M, Kuppe H, Habazettl H, Pries AR. OPS imaging of human microcirculation: a short technical report. J Vasc Res. 2002;39(4):368-372. https://doi.org/10.1159/000065549
Virgini-Magalhaes CE, Porto CL, Fernandes FF, Dorigo DM, Bottino DA, Bouskela E. Use of microcirculatory parameters to evaluate chronic venous insufficiency. J Vasc Surg. 2006;43(5):1037-1044. https://doi.org/10.1016/j.jvs.2005.12.065
Barkhatov IV. Assessment of the microcirculation system by laser Doppler flowmetry. Klinicheskaya meditsina. 2013;9(11):21-27. (In Russ.)
Kirienko AI, Zolotukhin IA, Yumin SM, Seliverstov EI. The effectiveness of specialized phlebological care in Russia: the results of the prospective observational study SPECTRUM. Phlebologiya. 2015;9(2):4-11. (In Russ.) https://doi.org/10.17116/flebo2015924-11
Baranski K, Chudek J. Factors affecting patients’ self-management in chronic venous disorders: a single-center study. Patient Prefer Adherence. 2016;10:1623-1629. https://doi.org/10.2147/PPA.S110773
Savelyev VS, Pokrovsky AV, Zatevakhin II, Kirienko AI, Alukhanyan OA, Andriyashkin AV, Andriyashkin VV, Barinov VE, Belentsov SM, Bogachev VYu, Bogdanets LI, Bredikhin RA, Bubnova NA, Bukina OV, Burleva EP, Vakhitov MSh, Volkov AS, Gavrilov SG, Golovanova OV, Guzhkov ON, Gumerov II, Dibirov MD, Doronin IV, Zhiruyev MS, Zhukov BN, Zolkin VN, Zoloev GK, Zolotukhin IA, Ivanov EV, Ignatyev IM, Ilyukhin EA, Karpenko AA, Katelnitsky II, Kletskin AE, Koshevoy AP, Krylov AYu, Kungurtsev VV, Kudykin MN, Kuzovlev SP, Laberko LA, Larin SI, Lobanov VN, Lobastov KV, Lutsenko MM, Mazayshvili KV, Maksimov SV, Mironov AV, Novikova YaV, Parikov MA, Pelevin AV, Plechev VV, Podyakov AYu, Pryadko SI, Rapovka VG, Rodoman GV, Ruzankin LE, Rybachkov VV, Sabelnikov VV, Sazhinov AP, Sapelkin SV, Seliverstov EI, Slavin DA, Sokolov AL, Stoyko YuM, Subbotin YuG, Tolstikhin VYu, Fokin AA, Khitaryan AG, Tsukanov AYu, Tsukanov YuT, Chabbarov RG, Chernookov AI, Chechetka DYu, Shaydakov EV, Shatalov AV, Shevela AI, Shimanko AI, Shulutko AM, Schultz AA. Diagnostics and Treatment of Chronic Venous Disease: Guidelines of Russian Phlebological Association. Phlebologiya. 2013;7(2):1-48. (In Russ.)
Banga AK. Transdermal and intradermal delivery of therapeutic agents: application of physical technologies. CRC Press; 2011.
Barel AO, Paye M, Maibach HI. Handbook of cosmetic science and technology. CRC Press; 2014.
Dragicevic N, Maibach HI. Percutaneous penetration enhancers chemical methods in penetration enhancement. Springer; 2016.
Sirtori CR. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Pharmacol Res. 2001;44(3):183-193. https://doi.org/10.1006/phrs.2001.0847
Belcaro G, Nicolaides AN, Geroulakos G, Cesarone MR, Incandela L, De Sanctis MT. Essaven gel – review of experimental and clinical data. Angiology. 2001;52(Suppl 3):S1-S4. https://doi.org/10.1177/0003319701052003s02
Belcaro G, Cesarone MR, Dugall M. Efficacy of topical treatment with aescin + essential phospholipids gel in a microcirculatory model of venous insufficiency. Angiology. 2004;55(Suppl 1):S15-S18. https://doi.org/10.1177/000331970405500604
Cesarone MR, Ricci A, Di Renzo A, Belcaro G, Dugall M. Efficacy of topical treatment with aescin + essential phospholipids gel on capillary fragility. Angiology. 2004;55(Suppl 1):S23-S25. https://doi.org/10.1177/000331970405500606
Belcaro G, Cesarone MR, Dugall M. Microcirculatory efficacy of topical treatment with aescin + essential phospholipids gel in venous insufficiency and hypertension: new clinical observations. Angiology. 2004;55(Suppl 1):S1-S5. https://doi.org/10.1177/000331970405500601
Ruffini I, Belcaro G, Cesarone MR, Dugall M. Efficacy of topical treatment with aescin + essential phospholipids gel in venous insufficiency and hypertension. Angiology. 2004;55(Suppl 1):S19-S21. https://doi.org/10.1177/000331970405500605
Cesarone MR, Belcaro G, Ippolito E, Ricci A, Ruffini M, Dugall M. Microcirculatory efficacy of topical treatment with aescin + essential phospholipids gel on transcutaneous PO2 in venous insufficiency. Angiology. 2004; 55(Suppl 1):S7-S10. https://doi.org/10.1177/000331970405500602
Ricci A, Ruffini I, Cesarone MR, Cornelli U, Corsi M, Belcaro G, Ippolito E, Dugall M. Variations in plasma free radicals with topical aescin + essential phospholipids gel in venous hypertension: new clinical data. Angiology. 2004;55(Suppl 1):S11-S14. https://doi.org/10.1177/000331970405500603
Incandela L, Belcaro G, Cesarone MR, De Sanctis MT, Griffin M. Microangiopathy and venous ulceration: topical treatment with Essaven gel — a placebo-controlled, randomized study. Angiology. 2001;52(Suppl 3):S17-S21. https://doi.org/10.1177/0003319701052003S05
Incandela L, Belcaro G, Cesarone MR, De Sanctis MT, Griffin M. Microvascular alterations in diabetic microangiopathy: topical treatment with Essaven gel — a placebo-controlled, randomized study. Angiology. 2001; 52(Suppl 3):S35-S41. https://doi.org/10.1177/0003319701052003S08
Bogachev VYu, Boldin BV, Turkin PYu. Modern therapy of chronic venous disorders of the lower limbs: transdermal phlebotropic medications in focus. RMZh. 2018;6:61-65 (In Russ.)
De Sanctis MT, Cesarone MR, Incandela L, Belcaro G, Griffin M. Treatment of superficial vein thrombosis with standardized application of Essaven gel — a placebo-controlled, randomized study. Angiology. 2001;52(Suppl 3): S57-S62. https://doi.org/10.1177/0003319701052003S11
Incandela L, De Sanctis MT, Cesarone MR, Ricci A, Errichi BM, Dugal M, Belcaro G, Griffin M. Treatment of superficial vein thrombosis: clinical evaluation of Essaven gel — a placebo-controlled, 8-week, randomized study. Angiology. 2001;52(Suppl 3):S69-S72. https://doi.org/10.1177/0003319701052003s13
Bogachev VYu, Boldin BV, Turkin PYu, Lobanov VN. Local drugs in treating and decreasing the incidence of adverse reactions after sclerotherapy of telangiectasia. Angiologiya i sosudistaya khirurgiya. 2019;25(4):102-106. (In Russ.) https://doi.org/10.33529/angio2019405