MEMBRANE PLASMAPHERESISDR 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.

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.

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.

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.

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.

“HEMOFENIX” devicewith comfortable transporting case

“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.

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 obstetrics and gynecology, narcology, resuscitation, treatment of autoimmune diseases, dermatology, pediatrics, disaster medicine.

• Donor plasmapheresis in Blood Service

Advantages of “HEMOFENIX” device• Completely 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

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.

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).

SCHEME

Laboratory monitoring data during the donor membrane plasmapheresis with “HEMOFENIX” device

ParameterBlood before PhM

Blood after PhM

PlasmaRequirement

s

Erythrocytes3,8±0,2 х 1012/l

3,7±0,1 х 109/l

0,005±0,0012х 109/l

<0,1 х 109/l

Leucocytes х 109/l 7,3±0,2 7,25±0,16 0,003±0,001 <0,1

Thrombocytes х 109/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, МЕ1,1±0,07 - 1,1±0,06 >0,7

Content of the whole protein, g/l 60-80 - 57,2±1,3 >55

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

• 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.

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

Rheocorrection

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

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

SURGERY

• Application Before, Inter, and Post surgery for the following indications:

Adequate inflammation.  Good healing.

Survival of flaps.Decrease cardiovascular risk.

Decrease edema.

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.

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

PHOTOS AFTER 6 SESSIONS OF PLASMAPHERESIS

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.

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.

PHOTOS OF PATIENS AFTER 10 SESSIONS OF PLASMAPHERESIS

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.

INDICATIONS IN ROSACEA

• Plasmapheresis is indicated in torpid forms of

the disease, resistant to traditional methods of

treatment.

CRITERIA OF EFFICIENCY

Regression of eruptions Long-lasting remission

PHOTOS OF PATIENS AFTER 10 SESSIONS OF PLASMAPHERESIS

WITH ROSACEA

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

PHOTOS AFTER 7 SESSIONS OF PLASMAPHERESIS

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, thecytotoxic action on the cells of the epidermis, accompanied by toxic manifestation of idiosyncrasy on the part of epidermal cells todifferent agents.

INDICATIONSThe 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 affectionControlling of the symptoms of intoxication

PHOTOS AFTER 3 SESSIONS OF PLASMAPHERESIS IN NECROLISIS

POSTLIPO

GOLD STANDARD OF REJUVENATION

PROTOCOL 1 Membrane Plasmapheresis (detoxification, and removal of free radicals) for the use of platelet-poor plasma. 2 Extraction for preparing platelet rich plasma the conventional protocol. 3 Mixed with 80% of 20% of prp ppp to generate growth factors (TGF-β1, EGF, FGF, IGF-I), and applied subdermal where required. Physiological 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

AUTOINMUNE DISEASES

• Systemic lupus erythematosus

• Rheumatoid arthritis

• Fibrosing alveolitis

• Sarcoidosis

• Glomerulonephritis

• Chronic hepatitis

• Thyroiditis

• Diabetes mellitus

«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

HEMATOLOGY

• Macroglobulinemia• Cryoglobulinemia• Myeloma• Waldenström's disease• Thrombotic thrombocytopenic

purpura• Congenital anemia

TRANSPLANTATION

• The reaction of graft-versus-host• The reaction of graft rejection• ABO - incompatibility

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

Prospective directions

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

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

Patient with 5 sessions of plasmapheresis

PLASMAPHERESIS CENTER