УДК: 617-097-085.382/388

Andrivskikh I.A., Tkachev C.I., Omelyanuk M.Yu.

«South Ural State medical university» of Health Ministry of the Russian Federation, chair of Surgery. 454092, 64 Vorovsky str., Chelyabinsk, Russia.

Chelyabinsk city clinical hospital № 1. 454092, 16 Vorovsky str., Chelyabinsk,  Russia.

Plasmapheresis in complex immune correction of vasculitis manifestations in surgical patients

Aim:tostudyinfluenceofaplasmaexchangeonreductionofavascularinflammation.

Key words: plasmapheresis, vascular involvement, immune state, immune correction

Contact person:

Andrievskikh I.A.,

MD, Professor. Head of the Chair of Hospital Surgery Medical University «South Ural State Medical University» Ministry of Health of the Russian Federation. 45409238-57 Tarasovad street. , Chelyabinsk, Russia. Phone: 232-80-11. Mobile: 8-912-774-21-28. E-mail: Этот адрес электронной почты защищен от спам-ботов. У вас должен быть включен JavaScript для просмотра.

Introduction. Prevention of thrombo- hemorrhagic and reparative complications in surgical patients remains an urgent problem nowadays [8, 5, 4]. One of the main issues of their development is the inflammation of the vascular bed simultaneously with the exacerbation of atherosclerotic process and systemic vasculitis [9, 7, 11, 12]. Presently, the most sensitive and specific markers of vascular inflammation as well as meth- ods of correction of these inflammatory conditions are being searched.

Traditionally, corticosteroids and/or cytostatic agents are commonly used to cope with inflammation. However, it results in systemic suppression of protein interactions in patients who develop negative reactions [10, 14, 19, 16]. That prompted the search for new target agents having anti-inflammatory characteristics to be applied in case of vasculitis. Nowadays monoclonal blockers of vascular inflammation, nanotechnologies, inhibitors of abnormal nuclear reactions, redox- polymer therapy are being developed [18, 15, 13, 17].

In this respect, one of the promising approachesis immune correction by means of immunomodulators, plasmapheresis and intravenous immunoglobulin [3, 6, 1, 2]. At the same time the role of plasmapheresis in controlling acute vascular inflammation remains unclear, which prompted the present research.

 The purpose is to study the effect of plasmapheresis to decrease vascular inflammation.

Material  and   methods.   Fifty six patients with vasculitis in the coronary artery, aorta, limb arteries, branches of arcus aortae and visceral arteries underwent discrete plasmapheresis  (Table  1). The studied patients were from 20 to 67 years old. Their average age was 47.03±1.92 years. There were 32 (57.14%) male patients and 24 (42.86%) female patients among them. Incurable vascular damage (diffuse and distal artery damage) was revealed in 35 patients.

As to the etiology and pathogenesis findings atherosclerosis was diagnosed in 36 patients. Twenty patients had nonspecific aortoarteritis, thromboangiit is obliterans and antiphospholipid syndrome. The reason to include plasmapheresis into the complex immune correction was the following clinical and laboratory find- ings:

-     Fast progressof the underlying disease with a negative dynamics in clinical picture in spite of the complex therapy;

-  Increased levels of ESR and C-reactive protein;

-   Low level of neutrophil phagocytosis;

-   Prevalence of T-cytotoxic lymphocytes over T-helpers;

-    High level of compliment C1-in- hibitor and circulating immune complexes (CIC).

Prior to plasmapheresis all these patients were administered synthetic immunomodulators with cytoprotective and antioxidant action (Glutoxim, Polyoxidonium,   Immunophan,  Trental). The course of plasmapheresis included three procedures of discrete plasmapheresis with intervals of 1-2 days between them. Plasmapheresis was performed by standard method according to the guidelines of fractioning of stored blood into cellular components and plasma (guidelines were approved by the Ministry of Health  of the USSR 11.06.1987 #06-14/24).

After plasmapheresis 34 (60.7%) patients underwent a 10 day course of intravenous immunoglobulin therapy. Statistical treatment was carried out by variational statistics using Microsoft Excel 2010, SPSS 17.0 programs. Quantitative variables presented themselves as average values (±) of standard deviations, qualitative ones were the number of observations and portion of general number of patients in percentage terms. The significance of difference was estimated by means of variance analysis of Student test, Mann-Whitney and Wilkinson criteria were also used to compare independent samples. The significance estimate of differences of P values, its critical level being 0.05, was determined. When P <0.05 the groups had significant differences.

Results. Characteristics of some indices of immune state of patients prior to and after plasmapheresis are shown in Table 2. Following plasma- pheresis combined with immune correction such indices as ESR, C-reactive protein, circulating immune complexes became normal. The function of compliment system improved, abnormal activity of T-cytotoxic lymphocytes decreased, neutrophil phagocyte function became normal.

While undergoing plasmapheresis only two patients reported short-time “discomfort” and slight decrease of blood pressure, which were easily controlled by the change of perfusion volume. The rest 54 patients underwent the plasmapheresis procedure uneventfully.

After plasmapheresis 35 patients underwent the following operative procedures: reconstruction of arterial vessels (21), limb sympathetic denervation (9), limb amputation (2) and necrosectomy (3). Twenty one pa tients with diffuse and distal arterial damage did not need operative treat- ment, as they showed good results of conservative therapy including plasmapheresis. After immune correction where plasmapheresis played a major role a stable positive clinical result was obtained in 33 (94.28%)   surgical

patients and 18 (85.71%) patients on conservative therapy. Types of operative intervention are presented in Table 3.

Discussion. Of all the patients included in the study 21 were not operated on and they only underwent conservative therapy including plasmapheresis. Two patients with an acute form of antiphospholipid syndrome (APS) were treated by a short course of “knock-out” doses of hormones and cytostatic agents, which enabled to save life of one patient, though his limb had to be amputated. We con- sider that plasmapheresis played a significant positive role in this patient. The other patient despite all complex therapeutic measures including plas- mapheresis and a lower limb amputa- tion did not survive. In the latter caselate addition of plasmapheresis to the complex therapy had an unfavorable effect. There were no other fatal out- comes in the study group. Improved blood supply to the affected organs was attained. In four other cases thrombohemorrhagic and purulent complications were easily managed by additional surgery and prolonga- tion of complex therapy.

In our opinion characteristics of positive effect of plasmapheresis incorporated in the complex immune correction were due to the following conditions: decreased levels of circulating immune complexes, improved function of com- plement system, decrease of abnor mal activity of T-cytotoxic lymphocytes, normalization of neutrophil phagocyte function. We consider that application of plasmapheresis within the complex anti-inflammatory measures  enabled  to  achieve a major effect due to the synergis- tic interaction with other immunomodulators. Plasmapheresis is particularly effective when disintoxication therapy is required in this category of patients.

Conclusions

1.Plasmapheresis is indicated for surgical patients with vasculitis and ischemic intoxication in the presence of  high  levels  of  circulating immune complexes, complement C1 inhibitor, abnormal levels of T-cytotoxic lym- phocytes and low levels of neutrophil phagocytosis.

2.The indication to carry out plasmapheresis in this category of patients must be determined by the complex of clinical and laboratory findings and instrumental study. The analysis of the patient immune state at the cell-mediated and humoral level is compulsory.

3.The application of plasmapheresis in surgical patients having vascular inflammatory conditions proved quite effective and at times an indispensable method to decrease immune vascular inflammation.

References

1.   Andrievskikh I.A. Effect of immune correction on surgical treatment outcomes in patients with vasculitis and vascular pathology of autoimmune genesis / Andrievskikh I.A., Fokin A.A., Grafov A.A. // Angiologia and Vascular Surgery. – 2008. - # 2. – P.20-26.

2.  AndrievskikhI.A.Personifiedimmunecorrectioninthetreatmentofsystemic vasculitis in surgical patients: a manual for residents / Andrievskikh I.A., Omelya- nuk M.Yu. –Chelyabinsk: Publishers of South Ural state medical university,   2014. – 103, [1] p.: ill.

3.   Butyanyan K.A. Secondary immune deficiency in surgical patients: rational diagnosis and correction: abstract / Butyanyan K.A.; - Moscow, 2007. – P.51.

4.  GostishchevV.K.GeneralSurgery./GostishchevV.K.//Amanualforstudents and lecturers of medical universities. – 5th ed., revised and supplemented. – GEO- TAR-Media, 2015.– P.608.

5.  Kuzmin V.V. Prevention of atherothrombotic and thromboembolic complications postoperatively inatheroscleroticgangrene./KuzminV.V.,TsaregorodtsevN.A., YurchenkoL.N.//Surgery.–2006.-#2.– P.60-62.

6.NasonovE.L.Vasculitisandangiopathy./NasonovE.L.,BaranovA.A.,ShilkinN.P.// Yaroslavl, 1999. – P.616.

7.   Nasonov E.L. Immunological markers of atherosclerosis / Nasonov E.L. // Ther. Arch. -2002. - # 5. – P.80-85.

8.  PlechevV.V.Preventionofpurulentsepticcomplicationsinsurgery/PlechevV.V., Muryseva E.N., Timerbulatov V.M., Lasareva D.N. // - M.: Triada X, 2003. –P. 317.

9.   Pokrovsky A.V. Diagnosis and treatment of nonspecific an aortoarteritis / Pokrovsky A.V., Zotikov A.E., Yudin V.I., Gryaznov O.G. // - M.: Iris, 2003. –P. 144.

10.SaifutdinovR.G.Wegener’sgranulomatosis(aclinicalcase)/SaifutdinovR.G., Ilesanmi M.A. // DKMSh. -2014. # 5. – P. 40-46.

11.Shilkina N.P. Systemic vasculitis and atherosclerosis / Shilkina N.P., Drya- zhenkov I.V. // Ther.arch. – 2007. - #3. – P.84-92.

12.Shlyakhto E.V. Diseases of heart and vessels. Guidelines of European Car- diology Society. Transl. from English / Edit. E.V. Shlyakhto // M.: GEOTAR-Media, 2011. – P. 1480.

13.Barnsley L. Anti-cytokine therapies for primary systemic necrotizing vas- culitis (Protocol) / Barnsley L., Duchdinder R., Riminton S. // The Cochrane Col- laborationandpublishedintheCochraneLibrary2010,Issue1.http://www.thecj- chranelibrary.com.

14.BoschX.TreatmentofAntineutrophilCytoplasmicAntibody-AssociatedVas- culitis/BoschX.,GuilabertA.,EspinosaG.//JAMA.–2007.–v.298.–P.655-669.

15.Eleftheriou D. Biologic therapy in primary systemic vasculitis of  the  young / Eleftheriou D., Melo M., Marks S. // Rheumatology. – 2009. – v.  48. –      P. 978-986.

16.Menahem S.  Induction  and  maintenance  therapy  in  ANCA-associat-  ed systemic vasculitis / Menahem S. et al. // Nephrology. – 2008. - v.  13. –            P. 24-36.

17.Shashni K. The glycolytic enzymes PGKI and PKM2 as novel transcriptional targetsofPPARgammainbreastcancerpathophysiology/ShashniK.etal.//Jour- nal of drug targeting. In Press,(DOI:103109/196118x.2012.736998).

18.Statkute L. Autologous non-myeloablative haematopoietic stem cell trans- plantation for refractory systemic vasculitis / Statkute L., Oyama Y., Barr W.G. // Ann Rheum Dis. – 2008. – v. 67. – P.991-997.

19. Tsuruoka K. MPO-ANCA related vasculitis complicating mucinous cystad- enoma of the pancreas and severe acute pancreatitis after steroid pulse thera- py: a case report / Tsuruoka K. et al. // Nihon Jinzo Gakkai Shi. – 2008. – v. 50. –   P. 948-953.