The modern technologies of extracorporal hemocorrection
Until recently the basic technologies of extracorporal hemocorrection were plasmaspheres and hemosorbtion. These two methods are now used widely in many medical establishments. At the same time, it must be reported that both plasmapheresis and hemosorption – are non selective methods of extracorporal hemocorrection. That is to say, during the application of both plasmapheres and hemosorption, certain substances that that play a role in the development of the pathological process are removed from the blood stream. However, along with these pathogeneticaly significant substances, some additional substances which are simply necessary in the process of plasmapheresis and hemosorption are unjustifiably removed. For this reason isolated use of a plasmapheresis and a hemosorption from positions of a modern extracorporal hemocorrection – in most cases, is not justified. There are now developed, tested, and approved technologies that are more capable of purposefully deleting from the bloodstream factors of pathogenicity – the so called selective and semiselective extracorporal hemocorrection technologies that have been used for quite some time.
We shall not list all of the modern extracorporal hemocorrection technologies, for the list is too long. Besides, there is now a great deal of literature available in this area, for example, there has recently been a fine monograph by a group of authors from Saint Petersurg, there is a magazine devoted to questions of efferent therapy. Therefore on the following pages we shall dwell only on some of the modern technologies of extracorporal hemocorrection which are used in our center for the treatment of diversified diseases.
This technology (technology Cryomodification of autoplasma - Cryoplasmasorption) is based on the ability of some proteinaceous components of plasma which are contained in normal, polymerization at presence the addition of certain cofactors and under certain temperature conditions. The surfaces of the polymeric molecules which are formed contain many active centers which have a selective affinity to circulating immune complexes (CIC), auto aggressive antibodies (aAB), atherogenic lipoproteins and a number of other pathogeneticaly significant factors. Between 30% and 50% of these methabolites are removed from the plasma during processing. These products include lipoproteins, products which degrade fibrinogen-fibrin, collagen, Villibrant factor, the C3-component of compliment, bacteria, viruses, fungi, the CIC, Ig M, A, G, more than 80% of the cryoglobulin, about 90% of the fibronectin, and the preservation of 85% of the albumin. After the removal of the cryoprecepitat, the newly formed plasma is returned to the patient in subsequent sessions of exrtacprporal hemocorrection.
This established technology enables the processing of significant volumes of plasma for a course of treatment without using a donor plasma or albuminous. This is quite significant because of a wide range of diseases which may be transmitted thru donor blood or its components.
The application of this extracorporal hemocorrection technology (Cryoplasmasorption) is effective for the treatment of many diseases.
Upon treatment of a metabolic syndrome, complications of antherosclerosis (ischemic illness of the heart, cerebrovascular illness and atherosclerotic defeat of vessels of the lower level finitenesses) – a process of plasma cryomodification which requires 1.5 to 2 weeks to reduce the atherogenic lipoproteins to a normal level. For this purpose we use the special procedure of hemocorrection with the subsequent realization of usual plasmapheresis with its cryomodification.
In figures 1 and 2 the plasma of the patient with expressed dis-, hiperlipideemia, hipertriglyceridemia, is presented initially and during the mid course of treatment.
Fig. 1. The initial plasma of the patient with expressed dis-, hiperlipidemia and hipertriglyceridemia
Fig. 2. Plasma of the patient after the 3rd session of extracorporal hemocorrection (4 days after beginning the course of treatment).
We realize that there are similar procedures of correction of the lipid structure of blood, and we are first and foremost guided by changes of laboratory parameters. In the table below, changes of the basic patogeneticaly significant parameters of the patient, with expressed metabolic syndrome (MS).
The changes in lipids during extracorporal hemocorrection
Patient N., 47 years old (20.03.04 – 03.04.04)
|After the procedure|
|LPHD||0,9 - 1,8|
|Total protein||65 - 85 g/l||74||72||68||-8|
After completion of the course of treatments, patients frequently question how long the achieved results will last. The answer to this question, plus the list of results of controlled research of the same patient 3 and 6 months after completion of the treatment is shown below.
changes in lipids
after completion of the extracorporal hemocorrection course of treament
changes in lipids
after completion of the extracorporal hemocorrection course of treament
patient N., 47 years old
|LPHD||0,9 - 1,8||1,21||1,24|
|Total protein||65 - 85 g/l||70||72|
Comparison with the method of medicamentous therapy
It is certainly possible, in most cases, to achieve similar results using the common methods of medicamentous therapy. The difference is that to achieve the same level of reduction of atherogenic lipoproteins as achieved in our course of treatment would take at least 4 to 6 months of standard medicamentous therapy. One should remember that in this case practically all holesterin lowering preparations have a negative effect on the liver or kidneys. And also of great importance for men is that the majority of such preparations adversely affect their sexual potency.
The ability of the technology of autoplasma cryomodification to selectively remove autoaggressive antibodies from an organism, has produced good results upon the application of this method in the treatment of autoimmune diseases.
There are numerous diseases that develop within such a mechanism. Some of these diseases are wide spread enough to be well known. These include rheumatism, rheumatoid arthritis, glomerulonephrit, autoimmune tireoidit, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus. Others such as scleroderma, antiphospholipid syndrome, Gudpascher's syndrome, Vegener's granulematosis are seen less often.
Such diseases have a chronic character. At many of them unique effective medical products are such as anti-inflammatory hormonal (prednisolone and its analogues) and cystostatic (cyclophosphamid etc.) preparations. Unfortunately, many of these preparations are applied in large doses and - over a long period of time – will commonly result in complications such as adiposity, bleeding or thrombosis, stomach ulcers, heavy bacterial and fungoid infections, and infringements upon the function of the bone and endocrine systems.
Contrary to medicinal therapy, the programs of extracorporal hemocorrection, that we have developed and used in the treatment of this group of disease, has effectively influenced all areas of the pathogenetic chain, and has shown no negative effects on any organisms of the patient.
We have used similar programs of extracorporal hemocorrection in the treatment of more than 5,000 patients suffering from autoimmune diseases. The results obtained have shown that the efficiency of the extracorporal hemocorrection technologies considerably exceeds the efficiency of standard medicamentous therapy and is not accompanied by the characteristic complications and side effects of traditional medicamentous therapies.
After the treatment of such illnesses as rheumatoid arthritis, Schonlein-Henoch disease, autoimmune thyroiditis, glomerulonephritis, multiple sclerosis, systemic lupus erythematosus, dermatosclerosis, neurodermatitis, eczema, autoimmune hepatitis, diabetes mellitus and many others, it was possible to observe a remission of the disease in more than 90% of the patients after the first course of treatment. It is important to note that the duration of of this course of treatment is generally 10 – 14 days, and the duration of remision achieved as a result of this treatment was 10 – 12 months, and extended to 3 - 5 years and more in some patients. With the common therapies of these illnesses the course of treatment, as a rule, is not less than 3 weeks, but the remission rarely exceeds half a year.
The effectiveness and the possibilities of the modern technologies of extracorporal hemocorrection can be illustrated upon the example of the treatment of patients with multiple sclerosis.
Unfortunately, the complex medicamentous treatments of multiple sclerosis has remained – up to now – unsatisfactory, and does not substantially decrease the degree of individualism of patients, nor does it prolong the time in which they are able to work.
We have observed more than 150 patients afflicted with multiple sclerosis for periods up to 10 years. All patients have repeatedly passed the complex treatment, which included massive doses of glucocorticoid hormones. In all of these patients with multiple sclerosis, we observed beginning neurologic disturbances from very light to extremely heavy.
Upon termination of the cryoplasmasorbtion procedures, the level of neurologic symptoms had decreased by 70%. The observed clinical results were confirmed by many laboratory and functional methods of research, including reduction of the myelin antibodies, disappearance or reduction of the demielinisation centers in the brain, and the increase of the speed of passage of nervous pulses. The subsequent supervision of these patients, over 5 years, has shown that the period of remission was extended in some cases, and the subsequent aggravations proceeded much more slowly and with smaller neurologic defects.
Similar results were obtained with the use of extracorporal hemocorrection methods in the treatment of System lupus erythematosis (SLE).
Only 20 – 30 years ago a confirmed diagnosis of «system lupus erythematosis», in essence, doomed the patient to rapidly developing disablement and, after several tears, death. The successes of medicine in recent decades has made it possible to somewhat postpone so unfavorable finale.
Modern extracorporal hemocorrection technologies developed in recent years, as a matter of fact, have allowed us to revolutionize the treatment of this disease. Now we can firmly say that the diagnosis of system lupus erythematosis is not a death verdict for the patient. The use of programs of extracorporal hemocorrection in the treatment has enabled us to considerably improve the forecast.
Unfortunately, patients with this disease are often referred to us with advanced stages of the disease, and more often after several unsuccessful attempts of traditional medicamentous therapy. Nevertheless, even in this case it is possible to suspend the pathological process and return the patient to a level of stable remission, and with repeated preventative courses of extracorporal hemocorrection provided every 8 – 12 months, the patient can be supported at this level to a natural old age.
In the treatment of other illnesses in pathogenesis, including the processes of immune inflammation, for example Psoriasis, the results are less impressive but still dramatically exceed the results of standard drug therapy. In the treatment of psoriasis we have succeeded in obtaining positive clinical results after the first course of extracorporal hemocorrection in 75 – 80% of the cases. Apparently, hidden under the mask of this diagnosis are sufficiently different mechanisms of the pathological processes which are similar in their clinical manifestations. It is true that the last experience showed that in 25% of the cases where we have not succeeded in having remissions after the first course of extracorporal hemocorrection, subsequent courses of treatment considerably improved the condition of the patient.
The problem of direct transport of medicines directly into the area at the center of the pathologic process has long bothered the minds of scientists. The urgency of this question is completely understandable – why "hunt" the organisms with significant doses of generally quite harmful medicines, introducing them in such doses as being dissolved in tens of liters of water into the organism hoping the concentration of the preparation in the pathologic center would have a therapeutic effect? A more reasonable approach would be the introduction of hundreds and thousands of smaller doses of the preparation directly into the center.
One of the solutions to this problem is the application of methods of extracorporal antibacterial therapy, which have been developed over a number of years by many scientists - including us.
First, this relates to the incubative technology of the application of antibiotics and the method of introduction of super high doses of antibiotics against the background of plasmafereza.
This method of introduction of antibiotics in the composition of its own cells of blood (incubation of the cellular mass of blood with antibiotic – ICM) was first proposed in 1984 by professor J.P. Senford. For the first time it with success is applied at people for treatment of purulent diseases lungs in 1992 by professor S.V. Lokhovitskiy. Subsequent scientific works performed by us, made it possible to substantially modify the parameters of the utilized procedures, to determine the criteria for the application of the method and to expand the circle of diseases for which it is highly effective.
Besides use with antibiotics, the method of Incubation of cellular mass is used for the introduction of other medicines (glucocorticoid, nonsteroidal anti-inflammatory preparations, benzodiazepine, anticholinesterase preparations).
Using the process of the Incubation of cellular mass makes it possible to radically change the distribution of the preparations in the organism and the process of their metabolism and removal. Specifically, the application of the process made it possible to reduce by 6 – 8 times the course doses of antibiotics, and create a high bactericidal concentration only within the centers of the infectious inflammation. In this case, the introduction of preparations into other tissue and related toxic action on the organism is kept to a minimum.
In 1995 we developed and introduced into clinical practice the metod of introducing super high, one time doses of antibiotics against the background of plasmapheresis (S.V. Mamaev) in the treatment of heavy pyoinflammatory processes (sepsis, infectious endocarditis). This method made it possible to substantially improve the blood supply to the inflamed tissues and make them more accessible to the action of the antibiotics. This also made it possible to simultaneously introduce into the organism multiples (from 3 – 5) of the daily doses of antibiotics and their subsequent removal from the blood flow with the aid of plasmapheresis. Using this procedure, allows, within a short time the introduction of a super high concentration of antibiotics, capable of destroying many «protected» microorganisms. In these instances, we have not observe the negative reactions of such high concentrations of antibiotics on the organisms of the patient.
The performed investigations and the long standing practical use of methods of extracorporal antibacterial therapy demonstrated that their application:
- Makes it possible to safely and repeatedly increase the effectiveness of the use of antibiotics
- Makes it possible to reduce the course doses several times (which sees a reduction in price and a decrease in the negative reaction on the organism).
Another variety of incubative technologies is the incubation of a leukocytal mass with immunomodulators, with the subsequent recovery of these activated leukocytes in the blood flow of the patient.
In contrast to the usual methods of immunotherapy – when the immunomodulating preparations begin in the form of tablets and are either introduced intramuscularly or intravenously (i.e. they are diluted in several tens of liters of water within the organism), the use of Extracorporal immunopharmacotherapy makes it possible to selectively isolate from the blood leukocytes directly from the cell immune system. After recovery into the blood system these activated leukocytes are capable themselves, of synthesizing the factors of the activation of the immune system and, consequently activating other cells of the immune system.
The extracorporal processing of leukocytes by immunomodulators has the following advantages:
- During processing by this preparation, cells are located out of the control of factors which are formed in the organisms of the patient and which impede cell activation in vivo
- The preparation is not introduced directly into the patient (on one hand it eliminates side reactions and complications and on the other hand it allows the application in a concentration which considerably exceeds therapeutic levels)
This method has been successfully used by us in treatment of hundreds of patients, both with heavy purulent – septic processes, and in out patient with a variety of immunodeficiency conditions. In out patient patients these technologies were applied as a treatment of chronic infection-inflammatory processes of a bacterial and viral nature. Thus, our practice has shown that the efficiency of these methods is incomparably higher than the efficiency of traditional methods of medicamentous correction of the acquired infringements of the functions of the immune systems.
Compared to a method of autoplasma cryomodification – in this case actions of plasma treatments are not low and are opposite to high temperature.
The Technology of autoplasma thermomodification (thermoplasmasorbtion technology) was developed rather recently by a the collective effort of Siberian scientists (V.M. Krejnes, S.V. Vlasov, and A.I. Kravchenco) and was based on the property of some albuminous components of plasma to change the physical and chemical properties by warming them up to certain temperatures.
For example, warming plasma up to temperatures of 56о C results in fibrinogen molecules changing their spatial structure and precipitate. The use of other hemocorrection technologies allows the removal of precipitate. As such, practically deprived fibrinogen plasma is returned to the patient. This technology has been applied as treatment to patients with coagulopathy. For example, in an unstable stenocardia and in the short period of a heart attack of a myocardium. Use of this method suppresses further blood clot formation and stops the expansion of the initial zone of defeat.
Other example of use of this technology of an extracorporeal hemocorrection is correction thrombohemorrhagic syndrome at pregnant women with antiphospholipid syndrome.
One variant of the application of this method is the ability of certain temperature ranges to suppress Fc-fragments of IgE. That has allowed the successful application of this technology in the treatment of patients with bronchial asthma.
To finish the discussion of modern technologies of extracorporal hemococorrection, the following thesis is desirable:
It is our point of view that these technologies are not the universal panacea for all illnesses. Simply, it is a technology of different levers or tools, different methods of influence on the pathogenetic mechanisms that under lie different diseases. And these methods offer a number of unique opportunities which are not present in other methods of common medicamentous therapy and which organically supplement the other approaches to treatment.
In use, there are strict indications and contra indications. In general these indications can be reduced to 4 substantive provisions.
- The absence of effect or insufficient effect from applied medicamentous therapy.
- The absence of effective pharmacological means for the treatment of diseases or the contraindications for their use.
- The development of resistance upon the application of long term medicamentous therapy.
- Medical and social contraindications for surgery.
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