1

I.P.Pavlovs First Saint-Petersburg Medical University

V.Voinov

Plasmapheresis
in preventive
medicine

Saint-Petersburg
2016
 2

BBC 53.53
V 65
UDC 616-085.23/.27+615.382

Reviewer:
M.M. Ilkovich, M.D., Professor, Director of pulmonology clinic of I.P. Pavlovs First
St Petersburg State Medical University.

V.A.Voinov
V 65 Plasmapheresis in preventive medicine.
Saint-Petersburg . 30 p., illus.
ISBN 5-9900263-4-

The book provides pathogenetic substantiation of apheresis therapy

and indications to it in preventing of premature ages. Are discussed a role
of the autoimmune and metabolic disorders leading to premature involution
of the person. There are shown advantages of membrane plasmapheresis.
The book is intended for both, specialists in apheresis therapy,
gerontologists and doctors of various specialties.

ISBN 5-99-00-263-4- BBC 53.53

.A.Voinov 2016
 3

Preface

The article in question discusses issues related to metabolic and autoimmune

mechanisms of human aging, which lead to the accumulation of various auto-
antibodies, damaging major tissues and organs. The organism is unable, on its own, to
filter out such large molecules. For the purpose of prevention of premature aging, those
large molecules could be separated from the organism only with the help of
plasmapheresis.
Key words: plasmapheresis, autoantibodies, premature aging.

There is no doubt that the biologically predetermined person's age is not less than
110 years, and according to some reports should reach 150 years, although in reality
the average life expectancy does not exceed half of that period. Was it ever a golden
age of mankind, when people lived to this age, as evidenced by the biblical sources,
hard to say. On the other hand, there are those evidence that ancient man lived an
average of about 40 years.
Course of illness, injury peace- and wartimes significantly shorten the period of life.
So, according to insurance companies of Europe and the USA (and they deserve the
greatest trust) of 2% of the population perish aged till 1 year, 5% - till 40 years, 15% - till
60 years. Till 80 years don't live 65%, till 90 years - 90% of people and only unit pass a
centenary boundary. If a person for life even avoid any diseases and injuries, anyway,
he will inevitably die "of old age." But why in some cases the "old age" carries 60-year-
olds, and other 90-year-old spared? What is the basis of aging?
Many authors affecting these issues are limited to the directions on the "slagging"
body for life, a kind of self-poisoning him. What are the mechanisms of subsequent
disorders? How does the immune system our main guardian of Health, which largely
depends on the quality of our lives?

Internal environment of the humans and mechanisms

of its regulation

Human, like any biological entity, is in constant contact and interaction with the
environment. Life is a constant process of metabolism both within the body, and with
environment, absorption of oxygen and release of carbon dioxide, water and food intake
and excretion of end products of metabolism. The very existence of the organism
depends on the ability of constancy maintaining within certain limits of its internal
environment.
 4

During thousands of years of evolution there were perfected mechanisms of

autoregulation of internal environment - homeostasis and protection against aggressive
influences both from outside, and from poisonous and toxic substances, and microbial-
viral contamination. But during the process of own metabolism as well, there are formed
relatively toxic intermediate and final products of metabolism, which are subject to slow
inactivation or removal. Therefore, formed a complex and multi-stage system of
protection and correction of the internal environment. It consists of three main
components:
1. Microsomal monooxygenase system of liver detoxification.
2. Immune system
3. Excretory system.

Hundreds of thousands of foreign compounds - xenobiotics - always get to the

body from outside. The main liposoluble toxic substances undergo biotransformation
during the process of digestion in intestine, from which by portal vein they can not
bypass liver, where due to oxidation and enzymatic processes they finally convert into
non-toxic water-soluble compounds, which are further metabolized in all organs and
tissues.
Liver is a barrier not only for exogenous, but also for endogenous toxic compounds,
constantly arising during the process of metabolism - synthesis of some and decay of
other substances: lactate and pyruvate, urea and creatinine, ammonia and fatty acids,
aromatic amino acids, alcohols and aldehydes, phenols and ketones, products of
proteolysis and hydrolysis, activity of automicroflora and viruses, etc.
Immune system, in its turn, consists of three components: the central organs
(thymus and bone marrow), lymphoid structures scattered over the body (spleen, lymph
nodes), and immunocompetent cells.
There are the following parts of the immune system: recognition of foreign
substances - antigens, phagocytosis, a cooperative function of T-lymphocytes and
antibody production, interaction of antibodies with antigen and of complement with
immunoglobulins and target cells. There are physical and chemical processes occuring:
reception, immune adhesion and adsorption.
Interaction of antibodies with antigen is an adsorption process of forming the
immune complex "antigen + antibody + complement". It is retained in the lymphoid
tissue, phagocytized and degraded by lysosomal enzymes. Natural serum factors -
opsonins - promote adherence of microorganisms, dead cells and their fragments
("detritus") to the plasma membrane of phagocytes (monocytes, neutrophils), increase
the velocity of phagocytosis. It should be borne in mind that in case of depletion or
absence of opsonins of complement, even normal phagocyte is not capable of capturing
the bacteria, so defects in humoral immunity entails failure and cell-phagocytic defense
mechanism.
 5

But humoral immunity depends on the cell immunity as well, since T-cells are
required for both, start of antibody forming by B-lymphocytes, and regulation of this
process. In particular, T-helper cells (CD4) stimulate production of antibodies, and T-
suppressor (CD8) inhibit this process, and, depending on the relations between the two
subclasses (CD4/CD8), there are possible hyperimmune reactions and
immunosuppression.
The task of the immune system also includes a struggle not only with food of foreign
origin, but also with those arising within the body, including ever-emerging abnormal
cells, which include tumor ones. Here also works a mechanism of a "friend or foe"
reaction, and own cell with anomalous properties is destroyed along with the foreign
ones by natural killer cells (T-killers) and other macrophages.
All final products of own metabolism and degradation of foreign substances, require
removal from the body. The structure of excretory system consists of four components:
kidneys, gastrointestinal tract, lungs, sweat and sebaceous glands of skin.
Kidneys remove water (1.5-2 liters a day) and dissolved urea, creatinine,
potassium, sodium, chloride, calcium, magnesium, sulfates, phosphates. In addition,
kidneys eliminate water-soluble products of biotransformation xenobiotics, products of
proteolysis of immune complexes, remains of bacteria, viruses, protozoa, fungi digested
by phagocytes, and substances spontaneously transformed into foreign substances.
Gastrointestinal tract eliminates lipids, cholesterol, bile acids, steroids, bilirubin,
water, food debris, nonviable microbial body unabsorbed xenobiotics.
Through lungs there are removed carbon dioxide, water, volatile xenobiotics
(ethanol, ether, etc.).
Sweat and sebaceous glands of skin derive water (400-600 ml), sodium, potassium,
calcium, magnesium, phosphorus, chloride. Also urea, creatinine in case of uremia; in
diabetes - glucose; in hepatic failure - ammonia, bile acids; in poisonings - mercury,
arsenic, iron, iodine, bromine, quinine, benzoic acid, succinic and hippuricacid,
salicylates, salol, antipyrine, methylene blue, etc.

Ecology and homeostasis

That is not to say that earlier it was "well". Even in Garden of Eden environment
was not probably really clean. However, civilization in all its benefits and achievements
has brought in a lot of anthropogenic pollutions growing from year to year. Every year
millions of tons of nickel, arsenic, cadmium, silicon, cobalt and zinc are emitted to the
atmosphere. It is polluted with oxides of carbon and nitrogen, sulfuric anhydride and
sulfuric acid, sulfates, etc.
Tens of thousands of toxic or at least unnecessary substances are constantly
penetrating to the human body through food, water, air. These are products of
"household" chemicals, chemicalization of agriculture (pesticides, insecticides,
 6

defoliants, chemical fertilizers), products of tobacco smoke, transport and industries

fumes, alcohol, drugs, even medicines, including antibiotics and hormones fed to
domestic animals and contained in their meat.
To an even greater extent this is applied to large industrial centers. Usually the
maximum permissible concentrations (MPC) of toxic compounds are established for a
workplace, considering that within the rest of a plant, not to mention sites outside it,
there should not be any of these products at all, but in our practice multiple excess of
MPC is usual not only inside plants themselves, but also outside.
It should be noted that about 30% in the structure of atmospheric pollution of
residential areas make toxic exhaust fumes of motor vehicles, which is not uncommon
even for the suburbs and recreation areas.
Water purification system, though with difficulty, but is capable of maintaining
satisfactory titers of microorganisms, but purification from harmful chemical substances,
including oxides and salts of heavy metals, is far from being perfect. Food does not
always comply with environmental regulations.
There is another aspect of human relationship with the environment, and this
problem arose back in ancient times, when people began to build houses, depriving
themselves of the opportunity to breathe the outer air. The latter, in addition to the
oxygen necessary for life, contains so-called atmospheric electricity in the form of
negatively charged ions resulting from thunderstorm electrical discharges in the
atmosphere and other natural phenomena. The whole evolution of living beings
proceeded in such ionized air, and all internal metabolic processes also formed on the
basis of electrical phenomena - transfer of nerve impulses, muscle contraction, and
metabolism - transfer of molecules across biological membranes.
When breathing, negative air ions charge the walls of airways with negative
potential and, proceeding from them, quickly reach the alveoli. All body fluids are
electrostatic colloids and carry a negative charge. Blood, enriched with air ions, washes
all tissues and cells, providing them with a negative charge and sol condition of their
cytoplasm, which is essential for optimal metabolism. Reduction of electric negative
potential of cell membranes leads to their "electrical discharge" with sol-gel transition of
colloidal state of the cytoplasm, which contributes to their coagulation with severe
violation of metabolism.

Developed during millennia, system of protection and correction of the internal

environment is not able to deal with ever-increasing flow of a wide variety of
substances, both of organic and inorganic origin. A number of compounds can not be
metabolized at all. As a result of spontaneous reactions of xenobiotics or their
intermediate reaction compounds with proteins, cell membranes or nucleic acids there
are formed autoallergens, membranotoxins or carcinogens even.
 7

Age immune disorders

Indeed, with advancing age, the changes in the immune system grow up also,
affecting all of its elements stem cells, T- and B-lymphocytes, macrophages. Since
early childhood, there is a gradual deceleration "thymic hours" that manifests itself in
reduced proliferative activity of T-cells and a decrease in their effector and helper
functions predisposes to infections and malignancies, the frequency of which is known,
increases with age. In old age really increased susceptibility to infections, which are
some of the main direct causes of death. There are especially frequent respiratory
infections, pyelonephritis [Kenarov P., 2004]. With age, the frequency increases also
many other diseases cardiovascular disease and cancer, diabetes and dementia.
Such changes in the body are often referred to as "age", "normal age appropriate."
The immunodeficiency weakens control of emergence of abnormal mitoses cell
fissions and emergence of tumor cells. In a body they appear constantly and rather
often, however, possessing alien anti-gene structure, they get at once to "field of vision"
of immune guards and are right there destroyed. If these guards "looked through" the
moment of their emergence and in due time them didn't destroy, soon their anti-gene
structure admits already "to" that under all-biological laws blocks development of the
corresponding antibodies and predetermines an outcome of this antagonism of an
organism and a tumor. Therefore the most terrible consequence of an age
immunodeficiency at elderly people is increase of probability of tumoral growth [Ses T.P,
2005] that finds confirmation also in special researches of oncologists [Barchuk A.S.,
2005].
Function of the immune system depends on the diversity of antigen receptors of
lymphocytes. With age, the general decline in the ability of the thymus and bone
marrow lymphocytes in the generation of antigenic stimulation combined with their
clonal expansion. This leads to the emergence of monoclonal antibodies, and the
direction of their reactions varies with the external (foreign) to autoantigens [Le Maoult
J. et al., 1997]. Accurate correlation between decrease in depressor function of thymus
gland and development of autoimmune frustration is found with age [Steinberg D.,
1974].
But the greatest danger is the weakening of suppressor T-cell function, which is
accompanied by the appearance of "forbidden" under normal conditions of lymphoid cell
clones reacting to self-antigens of the organism that causes different types of
autoimmune pathologies, which is consistent with a higher prevalence in the elderly and
 8

senile various autoimmune diseases [Ses .P., 2005]. More than 50% of the elderly
many different autoantibodies can be detected, but not at high concentrations of
[Berezhnova I.A., Korshunov G.V., 2006]. Therefore, rheumatoid factor is the
emergence of signs of arthritis, is not as pronounced as in true rheumatoid arthritis,
but a rare person in old age does not suffer from joint pain, considering them only
consequence "salt deposits".
There are characterized by the appearance of antibodies to thyroglobulin, causing
autoimmune thyroiditis with hypothyroidism. On the other hand, thyroid hormones are
necessary to maintain proper immune system activity, and hypothyroidism only
aggravates immunodeficiency in old age. Interestingly, autoantibodies to three major
thyroid antigens thyrolobulin, peroxidase and thyroid-stimulating hormone found in
healthy individuals aged 18-24 years 10.6-14.9% of cases, but in the age of 55-64
years, this frequency increased to 24.2-30.3% [Balabolkin N.I., 1997]. Even healthy
donors showed anticardiolipin antibodies with frequency 27%, of anti-DNA antibodies
17% [Kryukova M.G. et al., 1995].
Even senile dementia is a consequence of the appearance of autoantibodies to the
elements of the central nervous system. In Alzheimer's disease mutations in genes
may contribute to the appearance of autoantibodies presenilin-1 and presenilin-2 protein
detectable by immunochemical methods in relation to the nerve fibers postmortem
studies of the brain of these patients [Murphy G.M. et al., 1996]. Mutations in DNA and
RNA contribute to the appearance of protein molecules that differ from normal, and
further leading to metabolic disorders. In particular, during Alzheimer's disorder there
are arrived cascade successive disorders leading to the deposition of amyloid as
plaques in the vascular walls, infiltration of microglia cell, apoptosis and ultimately
increasing neuronal loss. One reason for this is the mutation of presenilin-1, which
depends on the increase of amyloid- deposits [Mann D.M.A., 1977]. There are find
also the signs of a cerebral amyloid angiopathy which are an important pathogenetic
factor of the brain vascular disorders and even intracerebral hemorrhage in the elderly
persons having Alzheimer's disease.
Both as reasons, and methods of treatment of this severe brain pathology are
unknown, however the above-stated facts testify to the autoimmune nature of this
illness of "accumulation" and with all definiteness raise a question of possibility of use of
apheresis therapy methods. They need, at least, for delay of progressing of this serious
illness with the unpromising forecast and in recent years successful experience of
application of a plasmapheresis with replacement of the deleted plasma with albumin is
 9

already described [Boada M. et al., 2009, 2014; Boada-Rovira M., 2010; Roca I.,
Cuberas-Borros G., 2010]. It is based that 90% of the circulating beta-amyloid are
connected with albumin and after a plasma exchange donor albumin will mobilize
amyloid from a brain, thereby promoting improvement of cognitive functions of these
patients [Anaya F., 2010].
As a result of autoimmune processes appear and symptoms of Parkinson's
disease, but also do not reach the intensity observed in Parkinson's disease itself.
Etiopathogenesis of it is not entirely clear, though there is evidence of the presence of
autoimmune disorders. Revealed are elevated levels of cytokines and complement in
the cerebrospinal fluid increases against T-cell autoantibodies (anti-alpha-synuclein and
anti-GM1-ganglioside) and vasoactive peptides in peripheral blood [Staines D.R., 2007;
Monahan A.J., 2008; Benkler M et al., 2009]. This points to the possibility of using
plasmapheresis in the treatment of this disease [Leopold N.A. et al., 1999; Staines D.R.
et al., 2008]. S.G.Morozov et al. (1997) successfully performed courses of
plasmapheresis in 29 patients with severe manifestations of Parkinson's disease with a
decrease in the index of neuro defeciency from 28 to 8 units of Webster scale and levels
of autoantibodies. Probably that carrying out preventive courses of a plasma exchange
will be able to prevent emergence of symptoms and this disease also as the risk of its
development increases with age.
Autoimmune processes underlie the formation also demyelinating disease with
the advent of widespread sclerosis type of multiple sclerosis and muscular dystrophy
type myasthenia. Characteristic of old age is the appearance of signs of
paraproteinemia with accumulation of monoclonal immunoglobulin M-components
resembling now myeloma.
The reason of many neurologic and mental disorders are also such metabolic
violations as disturbance of a cycle of uric acid, a remetylation, copper metabolism
(Wilson's illness), a homocystinuria, cerebrotendinous xanthomatosis, an
adrenoleukodystrophies and many others [Bonnot O. et al., 2014; Demly C., Sedel F.,
2014; Bandmann O. et al., 2015].

Age metabolic disorders

True amyloidosis resemble amyloid deposition in the intercellular spaces,

including the formation of the so-called senile plaques that 60% of older age
 10

characteristic feature appears. Amyloid deposition in the myocardium is also common in

the elderly [Benson M.D., 1997].

The hypertrophic obstructive cardiomyopathy is the reason about 50% of cases

of heart failure at elderly patients. It develops only owing to diastolic dysfunction at
preservation of systolic function of heart ventricles. Consolidation of the central arteries
with increase of a vascular impedance promotes to a hypertrophy of the left ventricle at
elderly persons, even without development in them of arterial hypertension and other
cardiovascular diseases. This pathology can come to light at persons is more senior
than 50-60 years at an Echo-Doppler-cardiography. Among the reasons leaders are
gene mutations with accumulation the contractil of proteins cardiac -myosin, a
cardiac troponin T, -tropomyosin and heart protein of a myosin C [Zieman S.J., Fortuin
N.J., 1999].
The restrictive cardiomyopathy results from an infiltration and fibrosis of the left
ventricle walls, resulting in its rigidity with earlier increase of diastolic pressure during its
filling. It leads to increase of diastolic pressure in all of heart cameras with stasis of both
a small, and big circle of blood circulation, with a syndrome of small heart stroke
volume. Is the most frequent reason primary amyloidosis. The forecast at such process
the extremely adverse and depends on degree of expressiveness of pathology. So, at a
thickness of a wall of the left ventricle less than 12 mm life expectancy averages 2,4
years, and at its thickness over 15 mm only 0,4 years [Zieman S.J., Fortuin N.J.,
1999].
Thus it must be kept in mind that against violations of a coronary circulation there is
a mass of preparations, in extreme cases stenting and shunting such vessels, but
against a restrictive cardiomyopathy of such reliable methods doesn't exist in general.
And here it is possible to hope only for possibilities of removal of such immunoglobulins
or the amyloid proteins from a myocardium by means of a plasmapheresis.

In recent years, drawn attention to the condition of the liver parenchyma in old
age. A size of the liver, hepatic blood flow and perfusion of the liver is reduced by 30-
40% between the third and tenth decades of life. Accrues and the frequency of detection
of a virus of hepatitis C from 10% at persons till 35 years to 42% (!) at persons is more
senior than 60 years, though there was no communication with such risk factors as
intravenous drugs, tattoos, acupuncture and surgeries [Osella A.R. et al., 1997]. Many
elderly people, even in 20 years after HCV infection identification, had no symptoms of
damage of a liver, however at a biopsy these signs came to light with a sufficient
frequency. But until recently communication between aging and autoimmune damages
of a liver there was ignored.
 11

In this case, age is much worse prognosis in chronic hepatitis and cirrhosis. Thus,
with age the forecast considerably worsens at chronic hepatitis and cirrhosis. If at
persons till 60 years mortality in a year after detection of these diseases makes 5%, and
in 3 years - 24%, at persons is more senior than 60 years - 34% and 54% respectively,
and for persons is more senior than 70 years already 75% die in a year. Half of those
over 70 years of developing hepatocellular carcinoma, usually on a background of
cirrhosis [James O.F.W., 1997].

With age increases the risk of renal lesions associated with disorders of
biochemical and immune homeostasis.
In particular, the growing number of patients suffering from the metabolic
syndrome with disorders of lipid metabolism, hypertension and type 2 diabetes. All this
is accompanied by the development of diabetic nephropathy, which is often as severe,
requiring hemodialysis. Despite the maintenance of blood sugar levels, thus there is
microvascular endothelial damage accumulating substances which are not amenable to
drug therapy.
On the other hand, there are vascular disorders associated with atherosclerosis
due to narrowing of the lumen of blood vessels, including the renal, and also not always
amenable to drug therapy. And stent placement or bypass surgery of the coronary
vessels can not be used for correction of the small renal vessels. Amyloid deposits are
common in the intercellular spaces, including the formation of the so-called senile
plaques. All this there is accompanied by a picture of the renal amyloidosis also.
With age, growing and autoimmune disorders accompanied by systemic lesions of
different organs, including the kidney. Especially for different types of systemic
vasculitis affecting the kidneys vessels. Characteristic of old age is the appearance of
signs of paraproteinemia with accumulation of monoclonal immunoglobulin M-
components resembling now myeloma. It increases the content of cryoglobulins also. All
this is largely disturbed microcirculation, including at the level of the glomeruli. With age
increases the frequency of hepatitis C virus infection in which there is autoimmune
hepatitis, which is often accompanied by renal outcomes.

Metabolic syndrome or insulin resistance syndrome naturally accompanied not

only impaired glucose tolerance and the development of diabetes mellitus type 2, but
also accompanied by dyslipidemia with visceral obesity, hypertension, and
prothrombotic status [Grundy S.M., 1999]. Furthermore, the metabolic syndrome is
 12

practically an early stage of development of type 2 diabetes. It has spread from 2.5 to
3.8% of the population with a doubling of the number of patients every 10-15 years. If at
the end of XX century with diabetes in the world, there were 135 million, by 2025 this
number will increase to 300 million [Davis R.M. et al., 1999].
Diabetic patients can develop severe cardiomyopathy associated more with
disorders of microcirculation in the myocardium than with atheromatous narrowing of
the coronary arteries. It has a non-specific functional and morphological changes
including: cardiomyocyte hypertrophy, interstitial fibrosis, arteriolar thickening,
decreasing capillary microaneurysms their network, disturbances of left ventricular
diastolic disorders first and then systolic its function also.
The risk of coronary lesions of diabetics is 10-20 times higher and death after
myocardial infarction in these patients is 2 times higher than those without diabetes
[Connaughton M., Webber J., 1998]. Occlusive vascular diseases with disorders of both
central and peripheral circulations are almost constant and severe enough satellites of
diabetes. According to the U.S. National Commission for diabetes, these patients is 25
times more likely to go blind, 17 times more likely to suffer from kidney disease, 5 times
more often affected limb gangrene, 2 times more likely heart disease, and life
expectancy is 30% shorter.
Diabetic retinopathy results in permanent loss of vision. Diabetes generally is a
leading cause of blindness among working-age population. In the United States the
number of newly blinded patients with diabetic retinopathy increased by 8,000 people,
and in Germany as a result of diabetic retinopathy blindness rate reaches 2.01 per
100,000 population [Krumpaszky H.G. et al., 1999]. The changes of the retina at
different time from the onset of diabetes founds in 98.8% (!) cases [Sdobnikova S.V.,
Stolyarenko G.E., 1999]. Upcoming polyneuropathy accompanied by disturbances as
motor and sensory nerve fibers, as well as elements of the autonomic system.
The presence of both immune and metabolic changes in this form of diabetes
makes reasonable use of apheresis therapy at all stages of the disease. Attempts to use
drugs against hypercholesterolemia, can lead to a number of adverse complications.
So, clofibrate effectively reduced content of atherogenic lipids, but in patients with
diabetes increased mortality from non-cardiac diseases. Moreover, the treatment with
statins in patients with type 2 diabetes more significantly decreased the content of
antiatherogenic HDL and increased triglycerides than patients without diabetes
[Bruckert E. et al., 2007].
 13

Plasmapheresis is essentially the only way to correct these complications

elimination of secondary metabolic disorders. Only by plasmapheresis can remove
many damaging factors such as the autoantibodies, glycoproteins, lipids, uric acid,
endothelins, antibodies against insulin and others. Plasmapheresis needs in patients
with a comprehensive picture of the disease in order to prevent a number of secondary
complications of diabetes.

One of the manifestations of involutive processes in women is menopause. This

period of adjustment of the hormonal status is accompanied by a number of specific
menopausal symptoms feeling "tide", "heat", sweating, irritability, which is a sufficiently
long period violates health and "quality of life" of women. Upset not only the functions of
the ovaries, but also in other endocrine glands, in particular with the development of
thyroid symptoms of autoimmune thyroiditis. There are broken also metabolic
processes, decreasing the level of enzyme activity, in particular the succinate
dehydrogenase, being marker of mitochondrial and energy processes in the Krebs cycle
[Fursova Z.K., et al., 1999].
In cases where the usual therapeutic measures do not help, plasmapheresis
courses allow in a relatively short time to achieve the disappearance of the above
symptoms, especially at small "seniority" climacteric syndrome when these symptoms
are still unstable and did not develop pronounced psycho-vegetative disorders [Foteeva
T.S. et al., 2013]. The positive effect of plasmapheresis courses lasted for 3-18 months
[Fedorova T.A., et al., 2004]. At 75% of such women signs of hypercoagulation are
observed and courses of a plasmapheresis in such cases promote normalization of a
coagulogram, decrease in extent of aggregation of platelets, disappearance of soluble
complexes of monomers of fibrin. In 67.5% of the women with climacteric syndrome
marked hypercholesterolemia and courses of plasmapheresis also help to normalize
lipid metabolism also [Foteeva T.S., 2006].
Thus, as a result of disorders of detached parts of the immune system in old age
there is a wide range of symptoms, more worn out than the corresponding actual
nosologic forms of diseases, but it is they who determine the shape of an old man
slow response time, stiffness and incoordinate movements, muscle weakness and
forgetfulness etc.
With aging occurs and discharging the electrostatic forces of the organism also,
decreasing membrane potential, decrease of the ionization cytoplasm with coarsening
of biocolloids particles, a decrease of their ability to swell, degradation and induration of
 14

protoplasm, its transition from a sol to a gel state. During ontogeny it is generally
reduced hydrophilic colloids. So the content of water in a brain decreases from 90% at
the newborn to 80% at the elderly person that indirectly speaks and about decrease in
size of electric charge of colloids and deterioration of a tissue electroexchange. To some
extent promotes dehydration in some cases and decrease in feeling of thirst at elderly
persons, in comparison with young that is also fraught more with accumulation of slags
[Rowland N.E. et al., 1997]. Limiting the content of negatively charged ions in the
inhaled air is one of the main factors accelerating the processes of biotransformation
colloidal state of cells and tissues and premature aging.

It needs no special explanation the role of atherosclerosis in the process of

premature aging also. Many researchers even consider atherosclerosis as a natural
process associated with aging [Orekhov A.N., 2001]. It forced also S.M.Grundy [1999] to
declare: "You are so old, how old your arteries". However perfidy of atherosclerotic
vascular lesions is almost complete asymptomatic until the moment of blockage of the
lumen when late to think not only on the prevention of these lesions, but even a
qualitative treatment. Therefore it is necessary to closely monitor how the content of
lipoproteins in the blood, and for known soft signs of vascular disorders.
Besides, it is necessary to consider also a role of an inflammation in pathogenesis
of atherothrombosis with accumulation of a number of cytokins. T.B.Harris et al. (1999)
found out in a large number of the persons who didn't have cardiovascular diseases that
at increase of the IL-6 level over 3,19 pg/ml the risk of development of a myocardial
infarction twice increased, increase in C-reactive protein over 2,78 mg/l it is also
connected with higher risk of death, and at increase in both indicators the risk of death
increased by 2,6 times.

Recently, there is growing interest in such autoimmune vascular disease as

antiphospholipid syndrome that manifests itself in the development of recurrent
thrombosis of the venous and arterial systems of various organs [Sinescu C., 2011]. ].
Antiphospholipid antibodies are heterogenous group of autoantibodies with different
properties, including different specific phospholipid-associated proteins, as well as
reactive phospholipid molecules. These patients have a higher risk of thrombosis and
their recurrence.
There is the most dangerous thrombosis of cerebral vessels with the appearance
of strokes. In 25% of young patients with stroke it can be found anticardiolipin
 15

antibodies [DOlhaberriaque L. et al., 1998; Glueck C.J. et al., 1999]. It is also

conceivable that some of the manifestations of migraine could be explained by vascular
disorders for the same reasons. In particular, there may be repeated episodes of
transient ischemic brain disorders, accompanied by headaches [Atanassova P., 2007].
There can communicate antiphospholipid syndrome with amyloid deposits in the walls
of cerebral vessels with a local weakening of the mechanical properties of their way to
tears, is the cause of hemorrhagic stroke in 10-15% of cases [Greenberg S.M.,
Hyman B.T., 1997].
It is believed that the age of onset of cerebral ischemia associated with
antiphospholipid antibodies, a few tens of years younger than in the population of a
typical cerebral ischemia. Perhaps there are development the venous sinus thrombosis
also. It can not be excluded due to vascular dementia disorders caused by aPL
antibodies. The same applies to cases of late-onset epilepsy, which once again
highlights the need for an immunological study of patients with neurological symptoms,
especially young women [Dorofeev A.E., 2004]. Neurological disorders are described in
the background of an increased level of anticardiolipin antibodies without causing visible
vascular lesions [Chen W.H., Chen C.J., 2009]. There relations is possible also of some
mental disorders with antiphospholipid syndrome [Raza H., et al, 2008].
Antiphospholipid antibodies may be the cause of coronary heart disease and
myocardial infarction, hepatic lesions [Nasonov E.L., et al, 1995; Konyaev B.V., 1997;
Krnie-Barrie S. et al., 1997]. In this case, myocardial infarction due to coronary artery
damage as well as on the background of coagulation disorders of lipid metabolism and
hypercholesterolemia, can occur even in young adults [Karpov Yu.A., 1995].
Anticardiolipin antibodies are detected in more than 70% of patients with coronary artery
disease at a young age.
Impact of antiphospholipid antibodies on 2-glycoprotein I, which is anti-
atherogenic factor may play a complementary role in promoting atherosclerosis in
patients with aPL syndrome [Hasunuda Y. et al., 1997]. Patients with antiphospholipid
syndrome have a greater tendency to atherogenesis [Ames p., et al., 2004 ; Margarita
A., 2007]. Oxidation of plasma proteins and endothelial damage oxidant-dependent
reduce physiological anticoagulant endothelial function [Vaarala O., 1997].
Antiprothrombin antibodies increase the risk of myocardial infarction, and antibodies
against 2-glycoprotein I contribute to increasing platelet aggregation. It is possible that
aPL antibodies occur as a result of systemic arterial inflammatory process and are the
 16

part of an autoimmune response to the appearance of different antigens, modified

atherosclerotic vascular wall [Makatsaria A.D., Bicadze V.O., 2003].
Nevertheless, given the autoimmune nature of the disease, most pathogenetically
justified is plasmapheresis with removal of the course up to 3.8 liters of plasma, which
reduces the frequency of recurrent thrombosis [Barkagan Z.S., 1988].
Nevertheless, in usual clinical practice of very few people connects processes of
an atherogenesis with autoimmune disorders. Even in the presence of clinic of
violations of coronary or brain blood circulation they pay attention only to cholesterol
level. And at increase of its contents only hypocholesterol preparations are appointed,
without paying attention to existence and an autoimmune component of an
atherogenesis. Or are limited only to vasodilating medicines. At the same time,
antipospholipid antibodies damaging a vascular wall, lead to formation of a lipidic
plaque even at the normal level of cholesterol.
Ignoring of a possible autoimmune component of vascular frustration brings to
their more severe current and high mortality at even enough young patients.
Nevertheless, given the autoimmune nature of the disease, most pathogenetically
justified is plasmapheresis with removal of the course up to 3.8 liters of plasma, which
reduces the frequency of recurrent thrombosis [Barkagan Z.S., 1988].
Moreover, it is necessary to appoint in due time and preventive courses of a
plasmapheresis at the slightest suspicion to existence of such autoimmune pathology.

The examination of elderly persons whose average age was observed

hypertension, there are found greater frequency of intellectual disability and
depression with symptoms of cerebral atrophy [Swan G.E. et al., 1998]. Increasing age
occurs also the accumulation of toxic products of lipid peroxidation on the background
of depressed antioxidant defense system [Pristrom M.S., Shtonda M.V., 2001]. Older
people are also observed higher levels of acute phase proteins with signs of oxidative
stress, which confirms the special clinical value of apheresis therapy [Goncharova V.A.,
Dotsenko E.K., 2005]. The same signs of increase in the autoantibodies activity (anti-
DNK-IgM, the anticardiolipin of IgG and IgM, antibodies to a microsomal anti-gene of a
thyroid gland) were found in all elderly patients with inflammatory processes in lungs
[Vinogradov D. L. et al.., 2008].
 17

Ways of presenilation prevention

On the one hand one could regret that the Creator or Nature itself (depending on
the outlook) were not wise enough, without providing more stringent ban on the
formation of autoimmune processes. However, on the other hand, maybe this is and the
highest their wisdom, because otherwise life would go on indefinitely long, and if it is
impossible to completely avoid the accumulation of such "micro-errors" of immune and
metabolic processes, it would create a number of other intractable problems.
So more and more clearer picture of disorders of homeostasis, leading to
progressive organ disorders. At the same time there is an accumulation of many
pathological products, the size of molecules that do not allow them to pass through the
kidney, the liver does not destroy them. On the other hand, the fact that their
accumulation suggests that no drugs were able to help in their removal from the body.
Even such disorders of homeostasis can lead to premature aging. More Seneca
said that "old age an incurable disease", and therefore the attitude to it should be as a
disease. And disease can and should be treated! Mainly you should stop these vicious
circles interdependent violations that can only be done in a timely removal of all
accumulated large molecular pathological products from the body. And to completely
solve this problem could be only apheresis therapy, mainly plasmapheresis.
The main task is not just an extension of life. If such a life will be extended with
symptoms of dementia and helplessness in a wheelchair or on a bed, then such work is
not worth pursuing. It should be borne in mind that the level of health physical function
and psychological status are more important for the elderly than the duration of their
lives [Covinsky K.E. et al., 1999]
The challenge is to increase the immune potency, which means the extension of
the productive middle age while maintaining the level of health and energy, ie, quality
of life, on which depends the creative and physical performance, the opportunity to
experience life in all its colors. The challenge is maintaining the "youth to old age"
[Lopukhin Yu.M., 1996; Uglov F.G., 1997].
The question is when it starts aging and when to start its treatment? Wait for the
development of appropriate age manifesting symptoms or prevent their occurrence? Of
course the last one!
 18

As mentioned above, many diseases, as well as old age creep up unnoticed. For
many months, even years growing micro-disorders various parts homeostasis until
reaching a critical level when the symptoms of a particular disease [Poletaev A.B.,
2008].
Thus, according to the summary data of research pathologists who reviewed the
results of 3000 autopsies of young people aged 15-34 years who had no clinical
evidence of cardiovascular disease and died as a result of accidents [Wissler R.W.,
1996; Fausto N., 1998] revealed the following picture: all teens surveyed were found
fatty streaks in some segments of the arteries. These changes grew with age, with
lesions of the coronary arteries were found in their walls leukocytes and circulating
immune complexes; obesity increased the risk of vascular lesions; changes in the
growth of abdominal aorta increased sharply in smokers; smoking and hypertension
clearly correlated with the development of primary atherosclerotic plaques in young
humans. Given that none of these young people have not seen any manifestations of
cardiovascular disease, it is clear that their primary prevention was necessary to
begin without waiting for the manifesting symptoms.
The same can be said about micro-shears and soft signs of other diseases. Task is
to find these micro-disorders, not turn a blind eye and do not consider them a fluke.
Attempts to cope with some rheumatoid manifestations by means of nonsteroid
anti-inflammatory medicines can lead to development of various damages of mucous
membranes of a digestive tract, especially at elderly persons. The risk of developing of
peptic ulcers and their complications increases. Salycylates lead to violation of
transmembrane permeability, electric activity of ionic transport and metabolism in
general, cyclooxygenase inhibition [Lee M., 1997].
In many cases, involutive processes in old age do not require medical treatment,
and even more so, the drugs can harm because even when used correctly, they can
cause a number of other functional disorders [Kryukova M.G. et al., 1995]. In recent
years, many authoritative experts note that "pills strategy", which is based on Western
medicine, practically exhausted itself. This not only practitioners, but even
pharmacologists recognized that "tablets" really effective in less than 30% of cases
[Poletaev A.B., 2008].
Timely primary prevention of diseases will serve as the primary prevention and
early aging also. And the main point of such prophylaxis is apheresis therapy aimed at
removing what can be seen now, and that is still not even manifested [Lopoukhin Y.M.,
1996; Voinov V.A. , 2001, 2005, 2010].
 19

Various cosmetic surgery is certainly justified, but after the elimination of defects in
shape, posture, wrinkles, remain inside "wrinkles of internal environment" and all the
reasons that caused them. Therefore, these operations must be accompanied by
reorganization of the internal environment, and some complicated plastic surgery should
be performed only after the apheresis- and immunotherapy for the prevention of
inflammatory complications, bringing to naught all the cosmetic effects.
Not only an honor, but old age is necessary to protect from an yearly ages! This
means that there can not be any specific age at which we should start measures to
prevent senile disorders. We must realize that this was the organic changes of organs
and tissues are resistant reverse development, so effort should be made before the
onset of these lesions.
These measures are indicated at almost any age, when there's some soft signs
showing deviations from the normal state excessive fatigue, unusual sensations and
body aches, joint pain, and changes in the form of the sclera of eyes, hair, nails, skin
wrinkled face, hands; memory disorders and tinnitus, changes in gait, elasticity and
movement coordination, potency, and many others. Of course it is important to pay
attention to the appearance of more than one of these symptoms, and their whole
complex, especially if they are held for many days and weeks. Should not be ignored
rises in blood pressure (assuming their natural or age), pain in the heart, even if using
drugs they can be quickly cut short no smoke without fire! So creeps atherosclerosis
one of the main precursors of age.
Founder application apheresis therapy in gerontology can be considered Greek
hero Jason, who tried to restore youth to his father, replacing his blood with new red
wine. Although this attempt and failed, however, that removal of pathological products
together with part of the normal components of the internal environment of the body that
are in the blood plasma, is achieved not only its reorganization, but also given a
powerful impetus to the renewal of her fresh, young ingredients. That is, the effect of
rejuvenation is achieved simultaneously with the removal of accumulated gradually
autoantibodies and other pathological metabolites such as exo- and endogenous origin.
Thus, based on the apheresis preventive therapy should be an annual rate of up to
four sessions of plasmapheresis and immunocorrection in the case of signs of allergy
or appropriate it is expedient to add also photohemo-therapy (UVR or laser blood
irradiation).
 20

Should not be neglected and aeroionotherapy, ie, walks on "fresh air" that should
help restore mechanisms to maintain electrostatic state of all components of the internal
environment to the prevention of pathological biotransformation cytoplasm.
These actions can be considered as primary prevention also malignant tumors,
as removal of "a toxic press" from immune system has to promote also to its restoration,
including systems of antineoplastic control. Report, what even external laser radiation at
patients of advanced age with osteoarthroses was followed by immunocorrective effect
with increase to normal quantities of lymphocytes of CD3 + and CD8+ [Miroshnichenko
I.V. et al., 2001].
Naturally, the apheresis therapy should not preclude the need to lead a healthy
lifestyle exercise, proper diet (the main thing do not overeat), and, of course, not to
poison himself smoking, alcohol, drugs [Ses T.P., 2005]. It was noted that food
restriction increases life span of mammals, reducing the frequency age-depending
pathologies including cardiomyopathy, and slows physiological disorders associated
with aging. Limitation of food leads to an increase in myocardial contractility [Klebanov
S. et al., 1997]. At the same time we must recognize that obesity is the most common
disorder and its frequency increases with age. In particular, H. Li et al. (1997) note that
at more than 30% of Americans body weight, at least, for 20% exceeds "ideal", thus the
frequency of obesity increases with age.
However, even in old age plasmapheresis also indicated, although show a
significant regression of already occurring organ and systemic lesions is not expect.
Nevertheless, even at the expressed clinical manifestations of coronary heart disease,
the obliterating atherosclerosis of vessels of the lower extremities and rheumatoid
polyarthritis courses of a plasma exchange lead to significant improvements. E.A.
Chumaeva et al. (2004) reported that after a course of plasmapheresis and
photohemotherapy at 91.9% of elderly patients improved overall health, in 68.9% of
patients with elevated blood pressure levels it decreased with disappearance of
headaches and tinnitus, vision improved.

Plasmapheresis methods

But if the treatment of a variety of acute and chronic diseases now there is no
doubt the advisability of apheresis therapy, then with respect to the more practically
healthy person may have doubts about the justification for such action. After all, there is
no assurance that the expected health problems do arise. Virtually impossible to prove
 21

that we really have prevented the development of the disease, which still has not been
diagnosed. On the other hand, we must be absolutely sure that such an invasive
procedure as plasmapheresis will not cause any complications.
Such confidence is still there, as experience shows that methodically correct
operation well-trained personnel, using only disposable needles and systems, virtually
no threat to health of the patient. In addition, avoiding the use of donor plasma and
other protein-based drugs to replace deleted plasma gives an additional guarantee to
prevent infection viral diseases and immunization of foreign antigens (donor
lymphocytes, for example). Stop can only sufficiently high cost of apheresis therapy.
However the most widespread devices and methods of a plasma exchange
demand special conditions for the application, up to offices of intensive therapy.
Besides, it is usually necessary to use the central veins with their traumatic
cateterisation. Moreover, usually is removed from one up to two volumes of the
circulating plasma (2-4 liters) that, naturally, demands for the completion donor plasma
and others blood preparations. It is fraught with transfer and the transmission of viral
diseases as there are no guarantees that donor plasma examined on all possible
causative agents of infections.
On the other hand, the portable device "Hemofenix" of the Russian company
Treckpor Technology allows to carry out a one-needle membrane plasma exchange with
use of any peripheral veins with catheters of smaller diameter, up to 1 mm. The small
volume of filling (65-70 ml) allows to carry out a plasma exchange and for patients with
hemodynamics disbalances, had a heart attack and a stroke consequences [Voinov
V.A., 2015].
Thus it is quite enough to remove not all volume of the circulating plasma but only
a third it that allows to replace only with usual isotonic sodium chloride solution.
However for four such sessions which are carried out every other day nevertheless is
removed up to 1,5 of the circulating plasma volumes that is quite enough for
achievement of clinical effect. Thus isn't present the slightest risk of transfer of any viral
infections. It isn't required any special conditions for carrying out such plasma exchange
which can be carried out in the procedural room of any hospital. Thus it isn't required
also continuous finding of such patient in hospital. After the small period of supervision it
can be allowed freely to go home, also as it happens to ordinary blood or plasma
donors.
That is, such simple and safe plasmapheresis methods can quite be carried out in
out-patient conditions. And it just those conditions which most are suitable for carrying
 22

out a plasmapheresis for almost healthy people for the purpose of presenilation
prevention. Also expenses on such procedures are respectively cut down.

Conclusion

Thus, these data suggest an important role of disorders of the internal environment
in the genesis and development of the processes promoting presenilation of the person.
From them immune deteriorations with the advent of various autoantibodies and also
accumulation of various metabolites are main. Generally it is large size molecular
substances which kidneys isn't able to remove, and the liver and other organs of a
detoxication don't destroy. And medicamentous therapy is also powerless. It is possible
to remove them from an organism only together with plasma by means of a
plasmapheresis. The simplest and safe technique is the membrane plasmapheresis on
the portable device of Hemofenix which can be carried out even in out-patient
conditions in any hospital.

Hemophenix device
 23

The one-needle membrane plasmapheresis with Hemofenix device

 24

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Valery A. Voinov Doctor of Medicine, Professor, Head of Therapeutic apheresis Department,

Pulmonology clinic of the First St. Petersburg State I.P. Pavlovs Medical University. He is the
author of more than 370 scientific papers, 25 inventions and patents. Sphere of his scientific
interests includes studying of the problems of endotoxemia and therapeutic apheresis, including
pathogenesis of premature ageing and principles of its prevention. Valery Voinov participated in
creating and development of devices and methods of membrane plasmapheresis and their
deployment in medical institutions of Russia and abroad.