Plasmaferesis

1. Membrane plasmapheresis is a pure essence of life PLAMAPHERESIS

2. In this presentation there are represented the following articles : History of “TRACKPORE TECHNOLOGY Corporation” foundation , production technology, manufacturing facilities, products, membrane technology . The main characteristics of “HEMOFENIX” device and “ROSA” plasma filter . Their application sphere and advantages . 3. Membrane plasmapheresis . Indications and contraindications . Application in medical practice and treatment of various diseases . Effects of plasmapheresis and other methods of extracorporal hemocorrection . 4. Examples of applying “HEMOFENIX” devise with “ROSA” plasma filter in clinical practice ( PHOTO ). Membrane plasmapheresis is a pure essence of life

3. MEMBRANE PLASMAPHERESIS DR OLEG TITKOV Scientific and production complex " Alpha " of “TRACKPORE TECHNOLOGY Corporation “. The company was built in 2002. The main products are: membrane "Rosa" plasma filters and “ HEMOFENIX” devices for therapeutic and donor plasmapheresis and hemosorption .

4. Production technology of membrane plasmafilter . Specialized industrial cyclotron “ALFA” In cooperation with scientists from the Joint Institute of Nuclear Research ( JINR) our company designed and built the first industrial cyclotron in Russia and CIS and the world's first specialized irradiation complex for production of track membranes.

5. Production technology of membrane plasmafilter Today scientific and production complex “ Alfa " is a unique complex corresponding to the requirements of ISO 9001 и ISO 13485 standards , has serial production of track membranes ( with pore diameter 400 nanometers ), and medical equipment for plasmapheresis . In clean premises there are held all technological operations on assembling “ROSA” plasma filters and their 100% multistage control . Annual production - 300,000 "Rosa" plasmafilters and 500 “HEMOFENIX" devices. In July 2010 "Trackpore Technology Corporation" received an international quality certificate of CE for the goods produced.

6. Electron microscopic pictures of track membrane Membrane plasmapheresis is based on the use of track membranes Track membrane is a thin polymeric film with through pores. It is produced by physicochemical treatment of a lavsan film irradiated with accelerated charged particles of the inert argon gas. Characteristics of the track membrane: - pore diameter - within the range of 0.4 microns, - thickness - 10 microns.

7. Membrane plasmapheresis Device and plasma filter created by constructers of our company are designed for performing therapeutic and donor membrane plasmapheresis . Therapeutic plasmapheresis is one of the methods of efferent therapy aimed to eliminate various pathologic elements ( autoantibodies, immune complexes, natural metabolites, toxic substances of exo- or endogenous origin ) from the organism. Therapeutic plasmapheresis is used with high efficiency in prevention of occupational and autoimmune diseases, therapy, oncology, obstetrics and gynecology, perinatology, and pediatrics, in cases of mass poisoning, in treatment of drug and alcohol abuse, prevention of premature aging, strengthening of reproductive health.

8. “HEMOFENIX” device with comfortable transporting case

9. “ROSA” plasma filter Plasmafilter is a disposable sterile product which is completed with a disposable line for performing plasmapheresis. The main technical characteristics of “ROSA” plasma filter: Speed of blood flow not less than 40 ml/min Volume of initial blood filling not more than 20 ml Weight 100 g Size – 85х85х35 mm Advantages of plasmafilter “ROSA”: High productivity and safety Solid body and stable filtration process Possibility of erythrocytes’ penetration is eliminated Possibility of damaging blood formed elements is eliminated Donor plasma corresponds to the requirements of European Pharmacopeia and can be used for donation and production of deficit blood preparations including albumin, immunoglobulin, antihemophilic preparations .

10. Device for membrane therapeutic and donor plasmapheresis AMPld-TT, trade mark “HEMOFENIX” Continuous process of membrane plasmapheresis with “HEMOFENIX” device is performed on a single-needle scheme. Volume of initial extracorporal circuit filling – 65 ml . Application of “HEMOFENIX” device allows to perform : Therapeutic plasmapheresis in different spheres of medicine including o bstetrics and g ynecology, narcology, resuscitation, treatment of autoimmune diseases, dermatology, pediatrics, disaster medicine. Donor plasmapheresis in Blood Service Advantages of “HEMOFENIX” device C ompletely automatic plasmapheresis procedure Safety assurance Comfortable use Portability Comfortable transporting case Main characteristics of “HEMOFENIX” device Blood productivity up to 100 ml/min Volume of plasma received - 800 ml/h Dosed anticoagulant supply Period of continuous work up to 10 hours Weight 14,5 kg Size 450х320х120 mm Power consumption 100 W

11. Efferent therapy methods based on filtration : PLASMAPHERESIS – plasma elimination with the help of plasmafilter . PLASMAFILTRATION – filtration of plasma through fiber filters. Indications : familial hypercholesterolemia, cryoglobulinemia, Sjogren's syndrome, rheumatoid vasculitis, polyneuropathy. CASCADE PLASMAFILTRATION – plasma filtration through the system, consisting of 2 different filters.

12. Efferent therapy methods based on sorption: HEMOSORPTION – elimination of exo - and endotoxins by blood perfusion through sorbent. PLASMASORPTION – elimination of exo - and endotoxins by plasma perfusion through sorbent. Sorbents : nonspecific ( activated carbons , ion- exchange and oxidation sorbents ) and specific (receptor - remove protease ; affinity - LDL, Ig ; immunosorbents - Ig , LDL, antibodies to IX factor, antibodies to DNA, Ig , E).

13. TRACK MEMBRANE A thin polymeric film with through pores. It is produced by physicochemical treatment of a lavsan film irradiated with accelerated charged particles of the inert argon gas. Characteristics of the track membrane: - pore diameter - within the range of 0.4 microns, - thickness - 10 microns.

14. SCHEME

15. Laboratory monitoring data during the donor membrane plasmapheresis with “HEMOFENIX” device Parameter Blood before PhM Blood after PhM Plasma Requirements Erythrocytes 3,8±0,2 х 10 12 / l 3,7±0,1 х 10 9 / l 0,0 5±0,0012х 10 9 / l <0,1 х 10 9 / l Leucocytes х 10 9 / l 7,3±0,2 7,25±0,16 0,0 3±0,001 <0,1 Thrombocytes х 10 9 / l 200±18 180±12 4,4 ±1,2 <10,0 Free hemoglobin , g / l <0,1 <0,1 < 0,1 <0,1 Content of VIII factor , МЕ 1,1±0,07 - 1,1±0,06 >0 ,7 Content of the whole protein , g / l 60-80 - 57,2±1,3 >55

16. The main plasmapheresis effects DETOXICATION elimination of toxic substances activation of natural detoxication systems of organism BLOOD RHEOLOGY CORRECTION reduction of blood viscosity increase of blood cells’ deforming reduction of cell conglomerates’ formation, vasodilatation IMMUNOCORRECTION elimination of antigens, antibodies, circulating immune complexes activation of immune system changing of immune response INCREASE OF SENSITIVITY TO ENDOGENOUS AND DRUG SUBSTANCES

17. Efferent treatment methods are widely used for restoration of disturbed homeostasis. Particular importance in functioning of organs and systems has a constant composition of the liquid base of body - tissue fluid and blood. Disturbance of individual organs’ function will inevitably entail changes in blood and disturbance of physiological processes of other organs and systems.

18. DETOXICATION Elimination of exo - and endotoxins ( med.preparations , chemical agents , Escherichia coli endotoxin , inflammatory mediators , ferments , hormones, products of free radical oxidation ), blood cells deplasming Increase of antioxidant defense factors activity due to exit from the blood cells and decrease of free radicals concentration, reduction of regulatory substances number below the critical level Break of existing vicious circles, improvement of functional detoxification system - a manifestation of “ deblocking " procedures effect

19. Rheocorrection Decrease of blood viscosity, increase of erythrocyte deformability, transcapillary exchange, improvement of microcirculation, oxygen delivery to tissues, normalization of tissue metabolism

20. Immunocorrection Activation of nonspecific resistance. Increase of serum bactericidal activity, content of complement, lysozyme, functional activity of phagocytic system with increase of phagocytic index and phagocytic number of neutrophils, normalization of leukocytes’ spontaneous migration

21. SURGERY Application B efore, Inter, and Post surgery for the following indications: Adequate inflammation.   Good healing. Survival of flaps. Decrease cardiovascular risk. Decrease edema.

22. ALERGIES 1 . Diathesis in children : - atopic dermatitis; - neurodermatitis ; - eczema; - Lyell's syndrome . 2. Hay fever : - rhinosinusopathy ; - Hay fever ; - conjunctivitis . 3. Bronchial asthma . 4. Allergic vasculitis: - Cherga -Strauss syndrome ; - Wissler-Fanconi subsepsis . 5. Anaphylactic shock.

23. PSORIASIS Plasmapheresis (PA) in psoriasis is indicated in the first place to patients suffering from universal affection of the skin - erythroderma , as well as exudative form of the disease.Besides , PA should be applied as additional method in case of insufficient efficiency of traditional therapy of psoriasis, as well as in torpid course of the disease . CRITERIA OF EFFICIENCY Reduction of infiltration in the zone of plaque and the subsequent resolution of eruptions Increase of the quantity of T -lymphocytes Stimulation of phagocytizing activity of neutrophils Elimination of CIC from blood

24. PHOTOS AFTER 6 SESSIONS OF PLASMAPHERESIS

25. PLASMAPHERESIS IN THE THERAPY OF ATOPIC DERMATITIS Congenital breaches of reactions of cellular immunity in atopic dermatitis are closely connected with blockade of beta- adrenoreceptors . As a result of this, the processes of releasing of mediators from fat cells and basophiles are intensified, which brings about suppression of the function of Т-lymphocytes. The defect of Т-suppressors provokes elevated production of IgE in response to antigenic stimulatio . Plasmapheresis (PA) breaks this vicious circle through deblocking of beta- adrenoreceptors and mechanical removal of excess of IgE .

26. INDICATIONS IN ATOPIC DERMATITIS Plasmapheresis is indicated as additional method in combined therapy to patients with severe, disseminated atopic dermatitis of long and torpid evolution, including in its erythrodermic form. CRITERIA OF EFFICIENCY Reduction of the level of IgE (after 48 hours there is registered an increase of its concentration , but in repeated PA procedures the level of IgE falls considerably). Reduction of the level of circulating immune complexes. Stabilization of the pathological process, cessation of the itch, abrupt reduction of edema and hyperemia. Regression of acute manifestations of the disease , partial or complete resorption of the infiltration.

27. PHOTOS OF PATIENS AFTER 10 SESSIONS OF PLASMAPHERESIS

28. PLASMAPHERESIS IN THE THERAPY OF ROSACEA The etiology and pathogenesis of rosacea are polydimensional . Due to this circumstance the range of methods of therapy of this disease is wide. However, the available data about the influence of endogenic irritants, such as bradichinin , calikrein , circulating immune complexes, different toxins, allow to a certain extent to consider plasmapheresis ( PA) as pathogenetic method of treatment of rosacea.

29. INDICATIONS IN ROSACEA Plasmapheresis is indicated in torpid forms of the disease, resistant to traditional methods of t reatment. CRITERIA OF EFFICIENCY Regression of eruptions Long-lasting remission

30. PHOTOS OF PATIENS AFTER 10 SESSIONS OF PLASMAPHERESIS WITH ROSACEA

31. PLASMAPHERESIS IN THE THERAPY OF FOCAL SCLERODERMA Special role in the pathogenesis of the disease is played by autoimmune reactions INDICATIONS The success in the application of plasmapheresis (PA) in this form of the disease as well as in case of a systemic process is explaned by removal of antibodies and inhibition of their syntheses CRITERIA OF EFFICIENCY Cessation of progression of the skin affections Improvement of the mobility of the joints

32. PHOTOS AFTER 7 SESSIONS OF PLASMAPHERESIS

33. PLASMAPHERESIS IN THE THERAPY OF ACUTE EPIDERMAL NECROLYSIS (LYELL’S SYNDROME) What plays a leading role in the pathogenesis of this disease is the allergic reaction, which by its gravity yields only to anaphylactic shock. Important role is played by immune mechanisms, in particular, the cytotoxic action on the cells of the epidermis, accompanied by toxic manifestation of idiosyncrasy on the part of epidermal cells to different agents. INDICATIONS The application of the eliminating effect of plasmapheresis (PA) depends on the etiological variant of the Lyell’s syndrome - infectious, medicinal , toxic-allergic or idiopathic. CRITERIA OF EFFICIENCY Epithelization of the focci of affection Controlling of the symptoms of intoxication

34. PHOTOS AFTER 3 SESSIONS OF PLASMAPHERESIS IN NECROLISIS POSTLIPO

35. GOLD STANDARD OF REJUVENATION PROTOCOL 1 Membrane Plasmapheresis (detoxification, and removal of free radicals) for the use of platelet-poor plasma. 2 E xtraction for preparing platelet rich plasma the conventional protocol. 3 M ixed with 80% of 20% of prp ppp to generate growth factors (TGF- β1, EGF, FGF, IGF-I), and applied subdermal where required. P hysiological and aesthetic rejuvenation Scientifically proven high standards of high-powered microscope and immunologic markers stable . REFERENCES Micropartículas circulantes derivadas de Plaquetas. Su asociación con diversasPatologías . Dra. Norma de Bosch Universidad Central de Venezuela Facultad de Medicina Postgrado de Hematología. Banco Municipal de Sangre Caracas . Venezuela 2011

36. AUTOINMUNE DISEASES Systemic lupus erythematosus Rheumatoid arthritis Fibrosing alveolitis Sarcoidosis Glomerulonephritis Chronic hepatitis Thyroiditis Diabetes mellitus

37. «ACCUMULATION» DISEASES Tumoral diseases ( chemoradiotherapy ) Substance abuse ( alcoholism , drug addiction ) Tuberculosis ( hepato-nephrotoxic antibiotics chroniointoxication , amyloidosis ) Exogenous chroniointoxications ( environment , industry , agriculture ) Radiation sickness ( radionuclides ) Gerontology

38. HEMATOLOGY Macroglobulinemia Cryoglobulinemia Myeloma Waldenström's disease Thrombotic thrombocytopenic purpura Congenital anemia

39. TRANSPLANTATION The reaction of graft-versus-host The reaction of graft rejection ABO - incompatibility

40. What is removed from blood after membrane plasma filtration? Substance Pathogenic influence lipoproteins of low and very low density so-called “bad” cholesterol, which is responsible for atherosclerotic plaques formation Triglycerides their excess is usually associated with lipid, i.e. fat metabolism fibrinogen and its breakdown products thrombogenic factors factor Villebranta, C1 and C3 complement components substances accompanying damage of vessels’ inner lining in various vasculitis , diabetes Immune complexes connection of antibodies to the antigen, bacteria “fragments” migrating in the body for a long time and settling on the kidney tissue, vessel walls, contributing to the formation of autoimmune reactions immunoglobulins, including cryoglobulins, and antibodies modified immunoglobulins , including autoantibodies, contributing to development of autoimmune diseases, damage of own tissues, obstruction of capillaries, etc. fibronectin in excess contributes to cell adhesion

41. Prospective directions Today using a complex of hemapheresis , quantum blood treatment, ozone therapy, cascade plasmapheresis methods is considered to be prospective

42. UPDATES The use of autologous platelet-poor plasma (PPP) dates from 80 in the U.S., by and bypass machines as a byproduct of multicomponent apheresis, separated the components of the patient's blood and now employ through membrane filters (NANOTECHNOLOGY) during surgery as a hemostatic or adhesive gel, rich in fibronectin , Von Willebrans factor, vitronectin , thrombospondin and other adhesive proteins

43. Patient with 5 sessions of plasmapheresis

44. PLASMAPHERESIS CENTER