Clinical Physiology of Circulation

ISSN 1814-6910 (Print)
ISSN 2410-9134 (Online)

 

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Issue's catalogue ➤ КФК. 2025; 22 (2): 115-198 ➤ Патогенетические аспекты хронической венозной недостаточности при трофических расстройствах и венозных язвах

Pathogenetic aspects of chronic venous insufficiency, trophic disorders and venous ulcers

Authors: Malinin A.A.1, Chomaeva A.A.2, Argunova S.Sh.3, Dzucev V.R.4

Company:
1 Bakoulev National Medical Research Center for Cardiovascular Surgery, Moscow, Russian Federation
2 Treatment and Rehabilitation Center, Cherkessk, Russian Federation
3 Karachay-Cherkess Republican Clinical Hospital, Cherkessk, Russian Federation
4 Republican Clinical Hospital, Vladikavkaz, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2025-22-2-150-161

UDC: 616-009.85:616.14-007.64

Link: Clinical Physiology of Blood Circulaiton. 2025; 22 (2): 150-161

Quote as: Malinin A.A., Chomaeva A.A., Argunova S.Sh., Dzucev V.R. Pathogenetic aspects of chronic venous insufficiency, trophic disorders and venous ulcers. Clinical Physiology of Сirculation. 2025; 22 (2): 150–161 (in Russ.). DOI: 10.24022/1814-6910-2025-22-2-150-161

Keywords:  pathogenesis chronic venous disease chronic venous insufficiency trophic venous ulcers causes of trophic disorders

Received / Accepted:  16.05.2025 / 30.05.2025

Full text:
Subscribe 🔒

Abstract

The review analyzes works devoted to the pathogenesis of CVI in the stage of trophic disorders, as well as trophic venous ulcers in patients with various etiologies of the disease.

The review is devoted to identifying various pathogenetic mechanisms for the development of severe CVI to improve the knowledge of outpatient and inpatient physicians to understand the challenges of treating this complex category of patients.

CVI in the stage of trophic disorders is a socio-economic problem that affects various aspects of life and quality of life, as well as the risk of disability. The presence of a trophic venous ulcer is associated with the need for ongoing treatment and dressings and the appointment of drug therapy. Risk factors for the development of trophic venous ulcers are of great importance for preventing their occurrence and initiating timely and sufficiently long-term treatment.

Knowledge of the pathophysiological processes of trophic venous ulcer development in various etiologies of CVI determines a treatment strategy that can improve its effectiveness. Understanding the various aspects of the pathogenesis of CVI will allow choosing the correct treatment tactics and reducing the number of relapses of trophic venous ulcers.

References

  1. Wilcox J.R., Carter M.J., Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA dermatol. 2013; 149 (9): 1050–1058.
  2. Lal B. K. Venous ulcers of the lower extremity: definition, epidemiology, and economic and social burdens. Semin. Vasc. Surg. 2015; 28 (1): 3–5.
  3. O’Donnell T.F. Venous ulcers of the lower extremity: etiology, risks, and predictive factors. Venous Ulcers. 2023; 41: 62–63.
  4. Чекмарева И.А., Паклина О.В., Абдувосидов Х.А. Морфологические изменения в зоне венозных трофических язв у людей пожилого и старческого возраста. Морфология. 2020; 157 (2–3): 234.
  5. Lyons O.T., Saha P., Smith A. Redox dysregulation in the pathogenesis of chronic venous ulceration. Free Radical Biology and Medicine. 2020; 149: 23–29.
  6. Aslam M.R., Muhammad Asif H., Ahmad K., Jabbar S., Hayee A., Sagheer M. S., Sharif A. Global impact and contributing factors in varicose vein disease development. SAGE Open Med. 2022; 10: 20503121221118992
  7. Низамов Ф.Х. Хроническая венозная недостаточность после COVID-19: коррекция отечного и болевого синдромов. Амбулаторная хирургия. 2021; 18 (2): 151–153. DOI: 10.21518/1995-1477-2021-18-2-151-153
  8. Богачёв В.Ю., Болдин Б.В., Туркин П.Ю., Дженина О.В., Саменков А.Ю. Современные показания к флеботропной терапии и ее продолжительность. Амбулаторная хирургия. 2021; 18 (1): 13–23. DOI: 10.21518/1995-1477-2021-18-1-13-23
  9. Blebea J. Venous hemodynamics and microcirculation in chronic venous insufficiency. Venous Ulcers. 2023; 19: 39–43.
  10. Rockson S.G. Lymphatic disorders in the pathogenesis of chronic venous insufficiency. Venous Ulcers. 2023; 519: 529–532.
  11. Gore M. Chronic venous insufficiency of lower extremity. Ind. J. Surg. 2021; 1–9.
  12. Korolova K. Determination of prognostic treatment criteria for hemodynamic surgery in patients with varicose veins of the lower extremities. Dan. Scient. J. 2020; 41 (1): 13–17.
  13. Rabe E., Regnier C., Goron F., Salmat G., Pannier F. The prevalence, disease characteristics and treatment of chronic venous disease: an international web-based survey. J. Comparative Effectiv. Research. 2020; 9 (17): 1205–1218.
  14. Machin M., Salim S., Tan M., Onida S., Davies A.H., Shalhoub J. Surgical and non-surgical approaches in the management of lower limb post- thrombotic syndrome. Expert Rev. Cardiovasc. Ther. 2021; 19 (3): 191–200.
  15. Fedusyak V.Ya. The current status of the etiopathogenesis of chronic venous insufficiency and the formation of trophic ulcer. Scient. Bull. Uzhhorod University. 2022; 66 (2): 29–33.
  16. Раджабов Д.Р. Некоторые аспекты этиопатогенеза и лечения острых тромбозов глубоких вен нижних конечностей. Здравоохранение Таджикистана. 2022; 2: 112–119. DOI: 10.52888/0514-2515-2022-353-2-113-120
  17. Терехов А.Г., Ишуткина Ю.В., Колева Е.Г. Современные представления о трофических язвах нижних конечностей. Innova. 2022; 1(26): 31–34.
  18. Стяжкина С.Н., Киршин А.А., Тихомирова Г.И., Шарафутдинов М.Р., Антропова З.А., Субботин А.В. и др. Особенности течения посттромбофлебитической болезни у больных с дисплазией соединительной ткани. Вестник современной клинической медицины. 2021; 14 (6): 76–81. DOI: 10.20969/VSKM.2021.14(6).76-81
  19. Finlayson K.J., Wu M.L., Edwards H.E. Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach: a longitudinal study. Int. J. Nurs. Stud. 2015; 52 (6): 1042–1051.
  20. Sun H.J., Wu Z.Y., Nie X.W., Bian J.S. Role of endothelial dysfunction in cardiovascular diseases: The link between inflammation and hydrogen sulfide. Front. Pharmacol. 2020; 10: 1568. DOI: 10.3389/fphar.2019.01568
  21. Шанаев И.Н. Современные представления о механизмах развития варикозной и посттромботической болезней. Кубанский научный медицинский вестник. 2020; 27 (1): 105–125. DOI: 10.25207/1608-6228-2020-27-1-105-125
  22. Пахомова Р.А., Бабаджанян А.М., Кочетова Л.В., Гуликян Г.Н. Микрофлора трофических язв венозной этиологии на фоне консервативного лечения. Современные проблемы науки и образования. 2019; 2: 161–163.
  23. Дубровщик О.И., Довнар И.С., Колешко С.В., Ясюк Л.С., Ясюк А.А. Трофические язвы венозного генеза: современные возможности лечения. Журнал Гродненского государственного медицинского университета. 2016; 2 (54): 107–111.
  24. Гривенко С.Г., Изосимов В.В., Умеров Э.Э. Возможные пути совершенствования комплексного лечения трофических язв венозной этиологии и оценки ее эффективности. Медицинский вестник Юга России. 2017; 8 (4): 36–46. DOI: 10.21886/2219-8075-2017-8-4-36-46
  25. Босевски М., Крстевски Г., Ди Микко П., Фидальго А., Лоринг М. Риск развития посттромбофлебитического синдрома после тромбоза глубоких вен нижних конечностей: локализация тромба или резидуальный тромбоз? Ангиология и сосудистая хирургия. 2021; 27 (2): 62–66.
  26. Henke P.K., Comerota A.J. An update on etiology, prevention, and therapy of postthrombotic syndrome. J. Vasc. Surg. Mosby Inc. 2011; 53: 500–509.
  27. Kahn S.R., Shrier I., Julian J.A., Ducruet T., Arsenault L., Miron M.J. et al. Determinants and time course of the post-thrombotic syndrome after acute deep venous thrombosis. Ann. Intern. Med. 2008; 149: 698–707.
  28. Lee A., Gu C.S., Vedantham S., Kearon C., Blostein M., Kahn S.R. Performance of two clinical scales to assess quality of life in patients with post-thrombotic syndrome. J.Vasc. Surg.: Venous and Lymphatic Disorders. 2021; 9 (5): 1257–1265.
  29. Fife C.E., Eckert K.A., Carter M.J. Publicly reported wound healing rates: The fantasy and the reality. Adv Wound Care (New Rochelle). 2018; 7: 77–94.
  30. Kahn S.R., Comerota A.J., Cushman M., Evans N.S., Ginsberg J.S., Goldenberg N.A. et al. The postthrom-botic syndrome: evidence-based prevention, diagnosis, and treatment strategies. Circulation. 2014; 130: 1636–1661.
  31. Bihari I., Guex J.J., Jawien A., Szolnoky G. Clinical perspectives and management of edema in chronic venous disease – what about ruscus? Medicines. 2022; 9 (8): 41.
  32. Benfor В., Peden E.K. A systematic review of management of superficial venous reflux in the setting of deep venous obstruction, J. Vasc. Surg.: Venous and Lymphatic Disorders. 2022; 10 (4): 945–954. DOI: 10.1016/j.jvsv.2021.12.087
  33. Порембская О.Я. Микроциркуляторные нарушения при хронических заболеваниях вен и основы их системной фармакологической коррекции. Флебология. 2021; 15 (2): 110–116.
  34. Лобастов К.В. Значение микроциркуляторных нарушений в развитии симптомов хронического заболевания вен и возможность их фармакологической коррекции. Флебология. 2020; 14 (1): 30–39.
  35. Labropoulos N. How does chronic venous disease progress from the first symptoms to the advanced stages? A review. Adv. Ther. 2019; 36: 13–19.
  36. Gujja K., Kayiti T., Sanina C., Wiley J.M. Chronic venous insufficiency. Intervent. Cardiol.: Principles and Practice. 2014; 3 (4): 593–605.
  37. Kolluri R., Bashir R., Matros T., Albers A., Fowler B.C., Frederick A. et al. Prevalence and predictors of elevated central venous pressure and obstructive sleep apnea in patients with lower extremity chronic venous disease. J. Vasc. Surg. Venous Lymphat. Disord. 2020; 8 (5): 775–782.
  38. Raffetto J.D., Ligi D., Maniscalco R., Khalil R.A., Mannello F. Why venous leg ulcers have difficulty healing: overview on pathophysiology, clinical consequences, and treatment. J. Clin. Med. 2020; 10 (1): 29–35.
  39. Головина В.И., Селиверстов Е.И., Ефремова О.И., Золотухин И.А. Роль цитокинов в патогенезе варикозной болезни. Флебология. 2021; 15 (2): 117–126.
  40. Gethin G., Vellinga A., Tawfick W., O’Loughlin A., McIntosh C., Mac Gilchrist C., Ivory J.D. The profile of patients with venous leg ulcers: a systematic review and global perspective. J. Tissue Viability. 2021; 30 (1): 78–88.
  41. Castro-Ferreira R., Cardoso R., Leite-Moreira A., Mansilha A. The role of endothelial dysfunction and inflammation in chronic venous disease. Ann. Vasc. Surg. 2018; 46: 380–393. DOI: 10.1016/j.avsg.2017.06.131
  42. Mansilha A., Sousa J. Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy. Int. J. Molecular Sci. 2018; 19 (6): 1669.
  43. Manolache N., Stoleriu G., Brănişteanu D.E., Robu S., Diaconu C., Costache D.O. New pathophysiological aspects in chronic venous disease. Roman. J. Military Med. 2022; 125 (4): 721–725.
  44. Markovic J.N. Fundamental physiologic concepts of venous hemodynamics and systemic venous return. JTAVR. 2020: 05 (2).
  45. Pappas P.J., You R., Rameshwar P., Gorti R., DeFo-uw D.O., Phillips C.K. et al. Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-beta1 gene expression and protein production. J. Vasc. Surg. 1999; 30: 1129–1145.
  46. Gastaldi G., Pannier F., Roztočil K., Lugli M., Mansilha A., Haller H., Van Rijn M.J. Chronic venous disease and diabetic microangiopathy: pathophysiology and commonalities. Int. Angiol. 2021; 40 (6): 457–469.
  47. Martinez-Zapata M.J., Vernooij R.W., Simancas-Racines D., Uriona Tuma S.M., Stein A.T., Moreno Carriles R.M.M. et al. Phlebotonics for venous insufficien-cy. Cochrane Database Syst. Rev. 2020; 3; 11. DOI: 10.1002/14651858.CD003229
  48. Carneiro J.A., Cardoso R.R., Duraes M.S., Guedes M.C.A., Santos F.L., da Costa F.M., Caldeira A.P. Frailty in the elderly: prevalence and associated factors. Rev. Bras. Enferm. 2017; 70 (4): 747–752. DOI: 10.1590/0034-7167-2016-0633
  49. Lal B.K., Saito S., Pappas P.J., Padberg F.T. Jr., Cerveira J.J., Hobson R.W. 2nd, Duran W.N. Altered proliferative responses of dermal fibroblasts to TGF-beta1 may contribute to chronic venous stasis ulcer. J. Vasc. Surg. 2003; 37 (6): 1285–1293. DOI: 10.1016/s0741-5214(02)75295-6
  50. Laurora G., Pizzicannella G., Cesarone M.R., Fisher C., Belcaro G., Nicolaides A.N. Skin flux and histology in venous hypertension. Vasc. Surg. 1993; 27 (2): 110–114.
  51. Ortega M.A., Fraile-Martínez O., García-Montero C., Álvarez-Mon M.A., Chaowen C., Ruiz-Grande F., Bujan J. Understanding chronic venous disease: a critical overview of its pathophysiology and medical management. J. Clin. Med. 2021; 10 (15): 3239.
  52. Cesarone M.R., Belcaro G., Rohdewald P., Pellegrini L., Ledda A., Vinciguerra G. et al. Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with pycnogenol: a prospective, controlled study. Phytomedicine. 2010; 17 (11): 835–839.
  53. Belcaro G., Cesarone M.R., Ledda A., Cacchio M., Ruffini I., Ricci A. et al. O-(beta-hydroxyethyl)-rutosides systemic and local treatment in chronic venous disease and microangiopathy: an independent prospective comparative study. Angiology. 2008; 59 (Suppl 1): 7S–13S.
  54. Partsch H. Compression heals leg ulcers due to abolishment of venous reflux. J. Wound. Care. 2019; 28 (7): 427. DOI: 10.12968/jowc.2019.28.7.427
  55. Prandoni P., Ageno W, Mumoli M, Zanatta N., Imberti D., Visona A. et al. Recanalization rate in patients with proximal vein thrombosis treated with the direct oral anticoagulants. Thromb. Res. 2017; 153: 97–100.
  56. Lattimer C.R., Rudolphi P.B., Recke A., Geroulakos G., Kalodiki E., Kahle B.K. Comparison of four haemodynamic tests that quantify superficial venous insufficiency. Eur. J. Vasc. Endovasc. Surg. 2019; 57 (4): 570–577.
  57. Levy J.H., Iba T., Gardiner E.E. Endothelial Injury in COVID-19 and Acute infections: putting the pieces of the puzzle together. Arterioscler. Thromb. Vasc. Biol. 2021; 41 (5): 1774–1776. DOI: 10.1161/ATVBAHA.121.316101
  58. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagee A. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395 (10234): 1417–1418. DOI: 10.1016/S0140-6736(20)30937-5
  59. Зудин А.М., Шаповал А.С. Сулодексид в терапии посттромботической болезни, осложнившейся развитием трофических дефектов нижних конечностей у пациентов, перенесших пневмонию. Атеротромбоз. 2021; 11 (1): 41–50. DOI: 10.21518/2307-1109-2021-11-1-41-50
  60. Frykberg R.G., Banks J. Challenges in the treatment of chronic wounds. Advances in Wound Care (New Rochelle). 2015; 4 (9): 560–582. DOI: 10.1089/wound.2015.0635
  61. Каторкин С.Е., Кушнарчук М.Ю., Мельников М.А., Жуков А.А., Кравцов П.Ф., Репин А.А. Хирургическая коррекция рефрактерных венозных трофических язв. Вестник медицинского института «Реавиз». Реабилитация, Врач и Здоровье. 2021; 1 (49): 38–46. DOI: 10.20340/vmi-rvz.2021.1.CLIN.3
  62. Горбачевский С.В., Рахмонов К.Х., Глушко Л.А., Дадабаев Г.М., Сабитов А.А. Успешный случай комплексной хирургической коррекции хронической тромбоэмболической легочной гипертензии у больного с крайне высоким операционным риском. Сердечно- сосудистые заболевания. Бюллетень НЦССХ им. А.Н. Бакулева РАМН. 2022; 23 (6): 651–657. DOI: 10.24022/1810-0694-2022-23-6-651-657
  63. Сабитов А.А., Черногривов И.Е., Сагымбаев Б.А., Хакимов М.М., Горбачевский С.В. Регресс легочной гипертензии после тромбэндартерэктомии у пациентки с длительным анамнезом хронической тромбоэмболической легочной гипертензии и высоким исходным легочным сосудистым сопротивлением. Сердечно-сосудистые заболевания. Бюллетень НЦССХ им. А.Н. Бакулева РАМН. 2024; 25 (4): 305–312. DOI: 10.24022/1810-0694-2024-25-4-305-312
****
  1. Wilcox J.R., Carter M.J., Covington S. Frequency of debridements and time to heal: a retrospective cohort study of 312 744 wounds. JAMA dermatol. 2013; 149 (9): 1050–1058.
  2. Lal B. K. Venous ulcers of the lower extremity: definition, epidemiology, and economic and social burdens. Semin. Vasc. Surg. 2015; 28 (1): 3–5.
  3. O’Donnell T.F. Venous ulcers of the lower extremity: etiology, risks, and predictive factors. Venous Ulcers. 2023; 41: 62–63.
  4. Chekmareva I.A., Paklina O.V., Abduvosidov H.A. Morphological changes in the zone of venous trophic ulcers in elderly and senile people. Morphology. 2020; 157 (2–3): 234 (in Russ.).
  5. Lyons O.T., Saha P., Smith A. Redox dysregulation in the pathogenesis of chronic venous ulceration. Free Radical Biology and Medicine. 2020; 149: 23–29.
  6. Aslam M.R., Muhammad Asif H., Ahmad K., Jabbar S., Hayee A., Sagheer M. S., Sharif A. Global impact and contributing factors in varicose vein disease development. SAGE Open Med. 2022; 10: 20503121221118992
  7. Nizamov F.Kh. Chronic venous insufficiency after COVID-19: correction of edema and pain syndromes. Outpatient Surgery. 2021; 18 (2): 151–153 (in Russ.). DOI: 10.21518/1995-1477-2021-18-2-151-153
  8. Bogachyov V.Yu., Boldin B.V., Turkin P.Yu., Dzhenina O.V., Samenkov A.Yu. Current indications for phlebotropic therapy and its duration. Outpatient Surgery. 2021; 18 (1): 13–23 (in Russ.). DOI: 10.21518/1995-1477-2021-18-1-13-23
  9. Blebea J. Venous hemodynamics and microcirculation in chronic venous insufficiency. Venous Ulcers. 2023; 19: 39–43.
  10. Rockson S.G. Lymphatic disorders in the pathogenesis of chronic venous insufficiency. Venous Ulcers. 2023; 519: 529–532.
  11. Gore M. Chronic venous insufficiency of lower extremity. Ind. J. Surg. 2021; 1–9.
  12. Korolova K. Determination of prognostic treatment criteria for hemodynamic surgery in patients with varicose veins of the lower extremities. Dan. Scient. J. 2020; 41 (1): 13–17.
  13. Rabe E., Regnier C., Goron F., Salmat G., Pannier F. The prevalence, disease characteristics and treatment of chronic venous disease: an international web-based survey. J. Comparative Effectiv. Research. 2020; 9 (17): 1205–1218.
  14. Machin M., Salim S., Tan M., Onida S., Davies A.H., Shalhoub J. Surgical and non-surgical approaches in the management of lower limb post- thrombotic syndrome. Expert Rev. Cardiovasc. Ther. 2021; 19 (3): 191–200.
  15. Fedusyak V.Ya. The current status of the etiopathogenesis of chronic venous insufficiency and the formation of trophic ulcer. Scient. Bull. Uzhhorod University. 2022; 66 (2): 29–33.
  16. Radzhabov D.R. Some aspects of the etiopathogenesis and treatment of acute deep vein thrombosis of the lower extremities. Tajikistan Healthcare. 2022; 2: 112–119 (in Russ.). DOI: 10.52888/0514-2515-2022-353-2-113-120
  17. Terekhov A.G., Ishutkina Yu.V., Koleva E.G. Modern concepts of trophic ulcers of the lower extremities. Innova. 2022; 1 (26): 31–34 (in Russ.).
  18. Styazhkina S.N., Kirshin A.A., Tihomirova G.I., Sharafutdinov M.R., Antropova Z.A., Subbotin A.V. et al. Features of the course of post- thrombophlebitic disease in patients with connective tissue dysplasia. Bulletin of modern clinical medicine. 2021; 14 (6): 76–81 (in Russ.). DOI: 10.20969/VSKM.2021.14(6).76-81
  19. Finlayson K.J., Wu M.L., Edwards H.E. Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach: a longitudinal study. Int. J. Nurs. Stud. 2015; 52 (6): 1042–1051.
  20. Sun H.J., Wu Z.Y., Nie X.W., Bian J.S. Role of endothelial dysfunction in cardiovascular diseases: The link between inflammation and hydrogen sulfide. Front. Pharmacol. 2020; 10: 1568. DOI: 10.3389/fphar.2019.01568
  21. Shanaev I.N. Modern concepts of the mechanisms of development of varicose and post-thrombotic diseases. Kuban Scientific Medical Bulletin. 2020; 27 (1): 105–125 (in Russ.). DOI: 10.25207/1608-6228-2020-27-1-105-125
  22. Pahomova R.A., Babadzhanyan A.M., Kochetova L.V., Gulikyan G.N. Microflora of trophic ulcers of venous etiology during conservative treatment. Modern Problems of Science and Education. 2019; 2: 161–163 (in Russ.).
  23. Dubrovshchik O.I., Dovnar I.S., Koleshko S.V., Yasyuk L.S., Yasyuk A.A. Trophic ulcers of venous genesis: modern treatment options. Journal of Grodno State Medical University. 2016; 2 (54): 107–111 (in Russ.).
  24. Grivenko S.G., Izosimov V.V., Umerov E.E. Possible ways to improve the complex treatment of trophic ulcers of venous etiology and assess its effectiveness. Medical Bulletin of the South of Russia. 2017; 8 (4): 36–46 (in Russ.). DOI: 10.21886/2219-8075-2017-8-4-36-46
  25. Bosevski M., Krstevski G., Di Mikko P., Fidal’go A., Loring M. Risk of developing post-thrombophlebitic syndrome after deep vein thrombosis of the lower extremities: thrombus localization or residual thrombosis? Angiology and Vascular Surgery. 2021; 27 (2): 62–66 (in Russ.).
  26. Henke P.K., Comerota A.J. An update on etiology, prevention, and therapy of postthrombotic syndrome. J. Vasc. Surg. Mosby Inc. 2011; 53: 500–509.
  27. Kahn S.R., Shrier I., Julian J.A., Ducruet T., Arsenault L., Miron M.J. et al. Determinants and time course of the post-thrombotic syndrome after acute deep venous thrombosis. Ann. Intern. Med. 2008; 149: 698–707.
  28. Lee A., Gu C.S., Vedantham S., Kearon C., Blostein M., Kahn S.R. Performance of two clinical scales to assess quality of life in patients with post-thrombotic syndrome. J.Vasc. Surg.: Venous and Lymphatic Disorders. 2021; 9 (5): 1257–1265.
  29. Fife C.E., Eckert K.A., Carter M.J. Publicly reported wound healing rates: The fantasy and the reality. Adv Wound Care (New Rochelle). 2018; 7: 77–94.
  30. Kahn S.R., Comerota A.J., Cushman M., Evans N.S., Ginsberg J.S., Goldenberg N.A. et al. The postthrom-botic syndrome: evidence-based prevention, diagnosis, and treatment strategies. Circulation. 2014; 130: 1636–1661.
  31. Bihari I., Guex J.J., Jawien A., Szolnoky G. Clinical perspectives and management of edema in chronic venous disease – what about ruscus? Medicines. 2022; 9 (8): 41.
  32. Benfor В., Peden E.K. A systematic review of management of superficial venous reflux in the setting of deep venous obstruction, J. Vasc. Surg.: Venous and Lymphatic Disorders. 2022; 10 (4): 945–954. DOI: 10.1016/j.jvsv.2021.12.087
  33. Porembskaya O.Ya. Microcirculatory disorders in chronic venous diseases and the basics of their systemic pharmacological correction. Phlebology. 2021; 15 (2): 110–116 (in Russ.).
  34. Lobastov K.V. The importance of microcirculatory disorders in the development of symptoms of chronic venous disease and the possibility of their pharmacological correction. Flebologia. 2020; 14 (1): 30–39 (in Russ.).
  35. Labropoulos N. How does chronic venous disease progress from the first symptoms to the advanced stages? A review. Adv. Ther. 2019; 36: 13–19.
  36. Gujja K., Kayiti T., Sanina C., Wiley J.M. Chronic venous insufficiency. Intervent. Cardiol.: Principles and Practice. 2014; 3 (4): 593–605.
  37. Kolluri R., Bashir R., Matros T., Albers A., Fowler B.C., Frederick A. et al. Prevalence and predictors of elevated central venous pressure and obstructive sleep apnea in patients with lower extremity chronic venous disease. J. Vasc. Surg. Venous Lymphat. Disord. 2020; 8 (5): 775–782.
  38. Raffetto J.D., Ligi D., Maniscalco R., Khalil R.A., Mannello F. Why venous leg ulcers have difficulty healing: overview on pathophysiology, clinical consequences, and treatment. J. Clin. Med. 2020; 10 (1): 29–35.
  39. Golovina V.I., Seliverstov E.I., Efremova O.I., Zolotuhin I.A. The role of cytokines in the pathogenesis of varicose veins. Phlebology. 2021; 15 (2): 117–126 (in Russ.).
  40. Gethin G., Vellinga A., Tawfick W., O’Loughlin A., McIntosh C., Mac Gilchrist C., Ivory J.D. The profile of patients with venous leg ulcers: a systematic review and global perspective. J. Tissue Viability. 2021; 30 (1): 78–88.
  41. Castro-Ferreira R., Cardoso R., Leite-Moreira A., Mansilha A. The role of endothelial dysfunction and inflammation in chronic venous disease. Ann. Vasc. Surg. 2018; 46: 380–393. DOI: 10.1016/j.avsg.2017.06.131
  42. Mansilha A., Sousa J. Pathophysiological mechanisms of chronic venous disease and implications for venoactive drug therapy. Int. J. Molecular Sci. 2018; 19 (6): 1669.
  43. Manolache N., Stoleriu G., Brănişteanu D.E., Robu S., Diaconu C., Costache D.O. New pathophysiological aspects in chronic venous disease. Roman. J. Military Med. 2022; 125 (4): 721–725.
  44. Markovic J.N. Fundamental physiologic concepts of venous hemodynamics and systemic venous return. JTAVR. 2020: 05 (2).
  45. Pappas P.J., You R., Rameshwar P., Gorti R., DeFo-uw D.O., Phillips C.K. et al. Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-beta1 gene expression and protein production. J. Vasc. Surg. 1999; 30: 1129–1145.
  46. Gastaldi G., Pannier F., Roztočil K., Lugli M., Mansilha A., Haller H., Van Rijn M.J. Chronic venous disease and diabetic microangiopathy: pathophysiology and commonalities. Int. Angiol. 2021; 40 (6): 457–469.
  47. Martinez-Zapata M.J., Vernooij R.W., Simancas-Racines D., Uriona Tuma S.M., Stein A.T., Moreno Carriles R.M.M. et al. Phlebotonics for venous insufficien-cy. Cochrane Database Syst. Rev. 2020; 3; 11. DOI: 10.1002/14651858.CD003229
  48. Carneiro J.A., Cardoso R.R., Duraes M.S., Guedes M.C.A., Santos F.L., da Costa F.M., Caldeira A.P. Frailty in the elderly: prevalence and associated factors. Rev. Bras. Enferm. 2017; 70 (4): 747–752. DOI: 10.1590/0034-7167-2016-0633
  49. Lal B.K., Saito S., Pappas P.J., Padberg F.T. Jr., Cerveira J.J., Hobson R.W. 2nd, Duran W.N. Altered proliferative responses of dermal fibroblasts to TGF-beta1 may contribute to chronic venous stasis ulcer. J. Vasc. Surg. 2003; 37 (6): 1285–1293. DOI: 10.1016/s0741-5214(02)75295-6
  50. Laurora G., Pizzicannella G., Cesarone M.R., Fisher C., Belcaro G., Nicolaides A.N. Skin flux and histology in venous hypertension. Vasc. Surg. 1993; 27 (2): 110–114.
  51. Ortega M.A., Fraile-Martínez O., García-Montero C., Álvarez-Mon M.A., Chaowen C., Ruiz-Grande F., Bujan J. Understanding chronic venous disease: a critical overview of its pathophysiology and medical management. J. Clin. Med. 2021; 10 (15): 3239.
  52. Cesarone M.R., Belcaro G., Rohdewald P., Pellegrini L., Ledda A., Vinciguerra G. et al. Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with pycnogenol: a prospective, controlled study. Phytomedicine. 2010; 17 (11): 835–839.
  53. Belcaro G., Cesarone M.R., Ledda A., Cacchio M., Ruffini I., Ricci A. et al. O-(beta-hydroxyethyl)-rutosides systemic and local treatment in chronic venous disease and microangiopathy: an independent prospective comparative study. Angiology. 2008; 59 (Suppl 1): 7S–13S.
  54. Partsch H. Compression heals leg ulcers due to abolishment of venous reflux. J. Wound. Care. 2019; 28 (7): 427. DOI: 10.12968/jowc.2019.28.7.427
  55. Prandoni P., Ageno W, Mumoli M, Zanatta N., Imberti D., Visona A. et al. Recanalization rate in patients with proximal vein thrombosis treated with the direct oral anticoagulants. Thromb. Res. 2017; 153: 97–100.
  56. Lattimer C.R., Rudolphi P.B., Recke A., Geroulakos G., Kalodiki E., Kahle B.K. Comparison of four haemodynamic tests that quantify superficial venous insufficiency. Eur. J. Vasc. Endovasc. Surg. 2019; 57 (4): 570–577.
  57. Levy J.H., Iba T., Gardiner E.E. Endothelial Injury in COVID-19 and Acute infections: putting the pieces of the puzzle together. Arterioscler. Thromb. Vasc. Biol. 2021; 41 (5): 1774–1776. DOI: 10.1161/ATVBAHA.121.316101
  58. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagee A. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395 (10234): 1417–1418. DOI: 10.1016/S0140-6736(20)30937-5
  59. Zudin A.M., Shapoval A.S. Sulodexide in the treatment of post-thrombotic disease complicated by the development of trophic defects of the lower extremities in patients who had pneumonia. Atherothrombosis. 2021; 11 (1): 41–50 (in Russ.). DOI: 10.21518/2307-1109-2021-11-1-41-50
  60. Frykberg R.G., Banks J. Challenges in the treatment of chronic wounds. Advances in Wound Care (New Rochelle). 2015; 4 (9): 560–582. DOI: 10.1089/wound.2015.0635
  61. Katorkin S.E., Kushnarchuk M.Yu., Mel’nikov M.A., Zhukov A.A., Kravcov P.F., Repin A.A. Surgical correction of refractory venous trophic ulcers. Bulletin of the Reaviz Medical Institute. Rehabilitation, Doctor and Health. 2021; 1 (49): 38–46 (in Russ.). DOI: 10.20340/vmi-rvz.2021.1.CLIN.3
  62. Gorbachevskij S.V., Rahmonov K.H., Glushko L.A., Dadabaev G.M., Sabitov A.A. A successful case of complex surgical correction of chronic thromboembolic pulmonary hypertension in a patient with extremely high surgical risk. The Bulletin of Bakoulev Center. Cardiovascular Diseases. 2022; 23 (6): 651–657 (in Russ.). DOI: 10.24022/1810-0694-2022-23-6-651-657
  63. Sabitov A.A., Chernogrivov I.E., Sagymbaev B.A., Hakimov M.M., Gorbachevskij S.V. Regression of pulmonary hypertension after thromboendarterectomy in a patient with a long history of chronic thromboembolic pulmonary hypertension and high baseline pulmonary vascular resistance. The Bulletin of Bakoulev Center. Cardiovascular Diseases. 2024; 25 (4): 305–312 (in Russ.). DOI: 10.24022/1810-0694- 2024-25-4-305-312

About Authors

  • Alexander A. Malinin, Dr. Med. Sci., Chief Researcher; ORCID
  • Aida A. Chomaeva, Cardiovascular Surgeon; ORCID
  • Svetlana Sh. Argunova, Cardiovascular Surgeon; ORCID
  • Vitalij R. Dzucev, Cardiovascular Surgeon; ORCID

 If you found mistakes, select text and press Alt+A