Issue №3-22, 2023

Cytokine Activity Indicators Dynamics after Non-Drug Rehabilitation including Intravenous Laser Blood Irradiation in Patients with a Lower Limb Post-Thrombophlebitic Syndrome: a Randomized Study

¹ Tatiana V. Konchugova,¹ Tatiana V. Apkhanova, ¹ Detelina B. Kulchitskaya, ¹Anatoliy D. Fesyun, ¹ Maxim Yu. Yakovlev, ¹ Elena M. Styazhkina, ^1,2 Olga M. Musaeva, ^1,2 Valentina A. Morunova, ¹ Olga V. Yurova, ¹Elena A. Rozhkova,¹ Elena S. Berezkina

¹National Medical Research Center for Rehabilitation and Balneology, Moscow, Russia

ABSTRACT

INTRODUCTION. Previous studies have established the association of venous thrombosis risk factors with inflammation, and the important role of inflammatory mediators as prognostic markers of recanalization of veins after deep vein thrombosis and the progression of postthrombophlebitic syndrome (PTPS). Pro-inflammatory cytokines, as key inflammatory mediators, are part of several cascades of pathophysiology in venous thrombosis, as well as predictors of the occurrence and prolongation of acute thrombosis and its resolution. To date, new oral anticoagulants are used, but their use in medical practice does not lead to a decrease in the number of patients with PTPS. AIM. To study the dynamics of proinflammatory cytokine levels under the influence of a complex non-drug method including intravenous laser irradiation of blood (ILBI) in patients with PTPS.
MATERIALS AND METHODS. We conducted a randomized study that included 60 patients aged 58.3 ± 12.56 years with lower extremity PTPS (CVI C4–C5 according to CEAP clinical classification) divided into 2 groups. The subjects of the 1st group (main, n = 30) received: ILBI, pulsed magnetotherapy and dry-air carbon dioxide baths. After a complex of physiotherapy procedures, patients underwent therapeutic gymnastics in the gym according to the Brunner U. method. Subjects of the main group received the above rehabilitation complex against the background of phlebotonics (combination of diosmin and hesperidin) and the use of knitwear of 2–3 compression classes. Patients of the 2nd group (control group, n = 30) received standard elastic compression (2–3 compression class), similar drug therapy with phlebotonics and therapeutic gymnastics in the gym according to the method of Brunner U.
RESULTS. After the course of rehabilitation, the patients of the main group showed positive dynamics of the main clinical symptoms of the disease, a decrease in malleolar volume, correction of microcirculatory disorders and activity of proinflammatory cytokines, accompanied by an improvement in transcapillary metabolism and tissue hypoxia. In patients of the control group, only a decrease in the number of leukocytes and fibrinogen in peripheral blood was recorded, while no changes in the expression of proinflammatory cytokines were observed. In this group of subjects, there was a positive trend in the regression of edema in terms of malleolar volume.
CONCLUSION. As a result of the application of the proposed rehabilitation complex, which includes, along with the traditionally used physical factors (pulsed magnetotherapy, dry-air carbon dioxide baths and therapeutic gymnastics) ILBI procedures, not only decongestant, hypocoagulating effects, positive dynamics of the main clinical symptoms of the disease were noted, but also correction of microcirculatory disorders and the level of pro-inflammatory cytokines was achieved, accompanied by an improvement in transcapillary metabolism and trophic tissues.

KEYWORDS: post-thrombophlebitic syndrome, intravenous laser blood irradiation, pro-inflammatory cytokines, endothelial dysfunction

Acknowledgments: The study had no sponsorship.

Conflict of interest:: The authors declare no apparent or potential conflicts of interest related to the publication of this article.

For citation:

Konchugova T.V., Apkhanova T.V., Kulchitskaya D.B., Fesyun A.D., Yakovlev M.Yu., Styazhkina E.M., Musaeva O.M., Morunova V.A., Yurova O.V., Rozhkova E.A., Berezkina E.S. Cytokine Activity Indicators Dynamics after Non-Drug Rehabilitation including Intravenous Laser Blood Irradiation in Patients with a Lower Limb Post-Thrombophlebitic Syndrome: a Randomized Study. Bulletin of Rehabilitation Medicine. 2023; 22(3): 40-48. https://doi.org/10.38025/2078-1962-2023-22-3-40-48 (In
Russ.).

References:

1. Fuentes H.E., Paz L.H., Al-Ogaili A. et al. Validation of a Patient-Completed Caprini Risk Score for Venous Thromboembolism Risk Assessment. TH OPEN. 2017; 1(2): e106–e112. https://doi.org/10.1055/s-0037-1607339

2. Kumar N.G., Clark A., Roztocil E. et al. Fibrinolytic activity of endothelial cells from different venous beds. Journal of Surgical Research. 2015; 194(1): 297–303. https://doi.org/10.1016/j.jss.2014.09.028

3. MacDougall D.A., Feliu A.L., Boccuzzi S.J., Lin J. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. American Journal of Health-System Pharmacy. 2006; 63(20–6): 5–15. https://doi.org/10.2146/ajhp060388

4. Kucher N., Luder C.M., Dörnhöfer T. et al. Novel management strategy for patients with suspected pulmonary embolism. European Heart Journal. 2003; 24(4): 366–76. https://doi.org/10.1016/s0195-668x(02)00476-1

5. Shbaklo H., Holcroft C.A., Kahn S.R. Levels of inflammatory markers and the development of the post-thrombotic syndrome. Thrombosis and Haemostasis. 2009; 101(3): 505–12.

6. Audu C.O., Gordon A.E., Obi A.T. et al. Inflammatory biomarkers in deep venous thrombosis organization, resolution, and post-thrombotic syndrome. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2020; 8(2): 299–305. https://doi.org/10.1016/j.jvsv.2019.09.008

7. Betensky M., Amankwah E.K., Brandal S. et al. Plasma fibrinolysis, inflammatory markers, and postthrombotic syndrome: preliminary findings from the Kids-DOTT Biobank. Blood Advances. 2021; 5(1): 233–239. https://doi.org/10.1182/bloodadvances.2020002974

8. Bittar L.F., Silva L.Q.D., Orsi F.L.A. et al. Increased inflammation and endothelial markers in patients with late severe post-thrombotic syndrome. PLoS One. 2020; 15(1): e0227150. https://doi.org/10.1371/journal.pone.0227150

9. Raffetto J.D., Ligi D., Maniscalco R. et al. Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment. Journal of Clinical Medicine. 2020; 10(1): 29 p. https://doi.org/10.3390/jcm10010029

10. Kahn S.R., Shrier I., Shapiro S. et al. Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial. CMAJ. 2011; 183(1): 37–44. https://doi.org/10.1503/cmaj.100248

11. [Kulchitskaya D.B., Fesyun A.D., Apkhanova T.V. et al. Non-drug methods of treatment of post-thrombophlebitic syndrome. Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury. 2022; 99(5): 22–27. https://doi.org/10.17116/kurort20229905122 (In Russ.).]

12. [Shevchenko Yu.L., Stoyko Yu.M. Fundamentals of clinical phlebology. Moscow. CJSC «Shiko». 2013: 34–138, 308-334 (In Russ.).]

13. [Andriyashkin V.V., Bogachev V.Yu., Sapelkin S.V., Stoyko Yu.M. Post-thrombotic disease in clinical practice. Realities and prospects. Moscow. Remder. 2017: 51 p. (In Russ.).]

14. Kahn S.R., Galanaud J.P., Vedantham S., Ginsberg J.S. Guidance for the prevention and treatment of the post-thrombotic syndrome. Journal of Thrombosis and Thrombolysis. 2016; 41(1): 144–53. https://doi.org/10.1007/s11239-015-1312-5

15. [Russian clinical guidelines for the diagnosis and treatment of chronic venous diseases. Phlebology. 2018; 7(2-2): 46–47 (In Russ.).]

16. Al-Khafaji R.A., Schierbeck L. Deep Venous Thrombosis in a Patient with a Moderate Pretest Probability and a Negative D-Dimer Test: A Review of the Diagnostic Algorithms. Journal of Blood Medicine. 2020; (11): 173–184. https://doi.org/10.2147/JBM.S244773

17. Mosevoll K.A., Johansen S., Wendelbo Ø. et al. Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis. Frontiers in Medicine. 2018; (5): 147 p. https://doi.org/10.3389/fmed.2018.00147

18. Wakefield T.W., Myers D.D., Henke P.K. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol. 2008; 28(3): 387–391. https://doi: 10.1161/ATVBAHA.108.162289

19. Reitsma P.H., Rosendaal F.R. Activation of innate immunity in patients with venous thrombosis: the Leiden Thrombophilia Study. Journal of Thrombosis and Haemostasis. 2004; 2(4): 619–622. https://doi.org/10.1111/j.1538-7836.2004.00689.x

20. Folsom A.R., Lutsey P.L., Astor B.C., Cushman M. C-reactive protein and venous thromboembolism. A prospective investigation in the ARIC cohort. Thrombosis and Haemostasis. 2009; (102): 615–619. https://doi.org/10.1160/TH09-04-0274

21. Gao Q., Zhang P., Wang W. et al. The correlation analysis of tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk: a meta-analysis. Phlebology. 2016; (31): 625–631. https://doi.org/10.1177/0268355515607405

22. Mahemuti A., Abudureheman K., Aihemaiti X. et al. Association of interleukin-6 and C-reactive protein genetic polymorphisms levels with venous thromboembolism. Chinese Medical Journal. 2012; (125): 3997–4002. https://doi.org/10.3760/cma.j.issn.0366-6999.2012.22.016

23. Matos M.F., Lourenco D.M., Orikaza C.M. et al. The role of IL-6, IL-8 and MCP-1 and their promoter polymorphisms IL-6-–174GC, IL-8–251AT and MCP-1–2518AG in the risk of venous thromboembolism: a case-control study. Thrombosis Research. 2011; (128): 216–220. https://doi.org/10.1016/j.thromres.2011.04.016

24. Poredos P., Jezovnik M.K. The role of inflammation in venous thromboembolism and the link between arterial and venous thrombosis. International Angiology. 2007; (26): 306–311.

25. Branchford B.R., Carpenter S.L. The Role of Inflammation in Venous Thromboembolism. Frontiers in Pediatrics. 2018; (6): 142 p. https://doi.org/10.3389/fped.2018.00142

26. Hamblin M.R. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophysics. 2017; 4(3): 337–361. https://doi.org/10.3934/biophy.2017.3.337

27. Saghazadeh A., Hafizi S., Rezaei N. Inflammation in venous thromboembolism: Cause or consequence? International Immunopharmacology. 2015; 28(1): 655–665. https://doi.org/10.1016/j.intimp.2015.07.044

28. Khakpour S., Wilhelmsen K., Hellman J. Vascular endothelial cell Toll-like receptor pathways in sepsis. Innate Immunity. 2015; 21(8): 827–46. https://doi.org/10.1177/1753425915606525

29. Nourshargh S., Alon R. Leukocyte migration into inflamed tissues. Immunity. 2014; 41(5): 694–707. https://doi.org/10.1016/j.immuni.2014.10.008

30. Nissinen L., Kähäri V.M. Matrix metalloproteinases in inflammation. Biochimica et Biophysica Acta. 2014; 1840(8): 2571–2580. https://doi.org/10.1016/j.bbagen.2014.03.007

31. Dinarello C.A., van der Meer J.W. Treating inflammation by blocking interleukin-1 in humans. Seminars in Immunology. 2013; 25(6): 469–484. https://doi.org/10.1016/j.smim.2013.10.008

32. Narayanan K.B., Park H.H. Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways. Apoptosis. 2015; 20(2): 196–209. https://doi.org/10.1007/s10495-014-1073-1

33. Schaper F., Rose-John S. Interleukin-6: Biology, signaling and strategies of blockade. Cytokine & Growth Factor Reviews. 2015; 26(5): 475–487. https://doi.org/10.1016/j.cytogfr.2015.07.004

34. Proctor M.C., Sullivan V., Zajkowski P. et al. A role for interleukin-10 in the assessment of venous thromboembolism risk in injured patients. Journal of Trauma and Acute Care Surgery. 2006; 60(1): 147–151. https://doi.org/10.1097/01.ta.0000197180.79965.bc

35. Ferroni P., Riondino S., Portarena I. et al. Association between increased tumor necrosis factor alpha levels and acquired activated protein C resistance in patients with metastatic colorectal cancer. International Journal of Colorectal Disease. 2012; 27(12): 1561–1567. https://doi.org/10.1007/s00384-012-1493-8

36. Jezovnik M.K., Poredos P. Factors influencing the recanalisation rate of deep venous thrombosis. International Angiology. 2012; 31(2): 169–175.

37. [Bolotov D.D., Novikov A.A., Novikova N.A. et al. The role of systemic inflammatory response in the initiation and progression of joint lesions. Bulletin of Rehabilitation Medicine. 2019; 5(93): 65–73 (In Russ.).]

38. [Konchugova T.V., Fesyun A.D., Nikitin M.V. et al. Sustaining and Development of Physiotherapy as an Important Condition for Health Resort Treatment Effectiveness Increasing: a Review. Bulletin of Rehabilitation Medicine. 2023; 22(1): 16–21. https://doi.org/10.38025/2078-1962-2023-22-1-16-21 (In Russ.).]

39. Moskvin S.V. Low-Level Laser Therapy and Light Energy. Photobiomodulation, Photomedicine, and Laser Surgery. 2019; 37(5): 267–268. https://doi.org/10.1089/photob.2019.4622 uentes H.E., Paz L.H., Al-Ogaili A. et al. Validation of a Patient-Completed Caprini Risk Score for Venous Thromboembolism Risk Assessment. TH OPEN. 2017; 1(2): e106–e112. https://doi.org/10.1055/s-0037-1607339

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