RU2693939C1 - Device and method for express assessment of functional state of haemostasis system - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, more specifically to devices and methods for express assessment of functional state of hemostasis system. Disclosed is a device for rapid assessment of the state of the hemostasis system, consisting of a measuring chamber, electrodes connected to a frequency generator and a recording unit, a measuring chamber and electrodes are placed on the base of the cartridge connected to the registration unit through the connector using a group of contact electrodes, wherein measuring chamber is located inside piezoelectric sensor, made in form of hollow cylinder, outside of which there is an external electrode, divided by symmetrical slots into two equal parts, one part of which is a generator and the second part is a ultrasonic oscillation receiver, on the inner surface of the measurement chamber there is an internal electrode, which central contact is built into the cartridge body, also the recording unit comprises a power supply system, a digital signal generator, a signal correction circuit, a microcontroller, an analog signal conversion amplification board, a display, a keyboard, a Wi-Fi module, a USB output to the computer, non-volatile clocks. Also disclosed is a rapid assessment method of functional state of hemostasis system using said device.

EFFECT: group of inventions provides higher effectiveness of the method of assessing the state of the haemostasis system due to the possibility of real-time monitoring of hemocoagulation in the analysed microvolumes of blood, higher convenience and accessibility of the study for the patient and the doctor.

2 cl, 8 dwg, 1 tbl, 3 ex

Description

The invention relates to the field of medicine, specifically to devices and methods for rapid assessment of the functional state of the hemostasis system.

The functional state of the hemostatic system is of greatest importance for maintaining normal blood flow, preventing and stopping hemorrhage, thrombosis, ischemia and organ infarction, protecting against the dissemination of bacteria and toxins from lesions. This is the most important general biological significance of the hemostasis system and the role of its disorders in the pathogenesis of diseases [3].

All of the above determines the high importance of hemostasiological laboratory tests in medical practice. The particular importance of monitoring the state of the blood coagulation system is associated with the active use in clinical practice of modern highly effective anticoagulants of direct and indirect action, antiplatelet agents and thrombolytics. In these cases, the greatest therapeutic effect is achieved as a result of targeted correction of hemostasis disorders [1, 3].

To prevent thrombotic complications, as in cardiac diseases and in other nosologies, great importance is given antiplatelet therapy, components of which are COX-1 platelet blockers P ₂ Y ₁₂ receptor antagonists, GPIIb / IIIa-receptor, phosphodiesterase inhibitors and t. used in the form of monotherapy, as well as in the form of dual antiplatelet therapy. Many of the ongoing studies reveal not only resistance to the antiagregant therapy obtained, but also a perverse response, manifested by an increase in the functional activity of the blood corpuscles after taking an antiplatelet agent. The above dictates the need to monitor the effectiveness of the use of antiplatelet agents to prevent the development of thrombotic complications during long-term, and often lifelong, therapy.

The most early and accurate diagnosis of disorders in the hemostasis system is a factor that determines the timely treatment of the patient and the start of preventive measures to prevent complications [3, 6].

The complexity of studying the state of the hemostasis system is explained by the fact that this system has high biological variability and instability of its factors, the difficulty of isolating the parameter being determined from a cascade of interrelated reactions, the impossibility, in many cases, direct measurements of concentrations, and the ability of methodological and instrumental unification [3].

To date, there is a wide range of methods to assess the functional state of the blood coagulation system. However, in order for the information obtained to have a high diagnostic value, the correct choice of a set of tests, often requiring special, clarifying studies, is necessary. The detailed study of all links of hemostasis is cumbersome and time-consuming, requires large quantities of the blood of the patient, is not efficient enough and is primarily of research, and not of an applied nature. [2, 3, 4].

The desire for a more economical, purposeful and operational research of the hemostatic system is quite understandable and justified. In this regard, the methods of graphical registration of blood coagulation and fibrinolysis can have advantages.

There is a method of assessing the functional state of the hemostatic system [RU No. 2282855 C2, publ 10.10.2005]. The method includes measuring the conductivity of blood by passing a current through it, recording an electrocoagulogram and determining chronometric and amplitude characteristics of it, wherein the blood sample is placed in a thermostatted cell, the plate electrodes connected to the frequency generator and the recording unit are immersed in it, and the conductivity of the blood is measured when an alternating current with a frequency of 200 Hz is passed through it, then the indicators are determined from the obtained image of the functional curve of the electrocoagulogram: t ₁ - the time elapsed from the arrival of a portion of blood in the cuvette before the amplitude of the functional curve changes downwards by 20 relative units of conductivity, t ₂ is the time to reduce the amplitude of the functional curve by 100 units, T is the formation time of the fibrin-platelet clot structure and K = ( t ₂ -t ₁ ) / 100 - the intensity of thrombin formation, compare their values with the norm, and when the values of the indicators are lower relative to the norm, they determine the state of hypercoagulation; coagulation.

The disadvantage of this method is that when conducting a study of the functional state of the hemostasis system using this method, large volumes of blood are used, and registration of a process lasting up to 100 minutes does not allow monitoring the hemocoagulation process in real time.

There is a method of rapid assessment of the state of the hemostasis system [patent RU No. 2413954, 10.03.2011], which consists in measuring the blood conductivity when an alternating current with a frequency of 200 Hz is passed through it, recording an electrocoagulogram and determining the chronometric and amplitude characteristics of it: A is the amplitude of decrease functional curve, mV; T - time to reduce the amplitude of the functional curve to the minimum value in minutes, while the blood sample is placed in the capillary, the walls of which are located electrodes connected to a frequency generator and a recording unit, measure the electrical conductivity of blood and measure the activation intensity of the coagulation process according to the resulting functional curve blood A / T, with values of A / T equal to 3-5, assess the state of hemostasis as normal, with values of A / T less than 3 determine hypocoagulation, and with values of A / T more than 5 hypercoagulation.

The device for assessing the state of the hemostasis system consists of a thermostatted cell and plate electrodes connected to a frequency generator and a recording unit.

These method and device are closest to the claimed and selected as prototypes.

The disadvantage of the prototype is that when conducting a study of the functional state of the hemostasis system in this way, the accuracy of the method is influenced by the protein composition of the blood (fibrinogen, albumin, globulins, etc.); the adsorption of which on the electrodes significantly affects the nature of the curve of the electrocoagulogram and, accordingly, the measurement accuracy.

A new technical result is an increase in the efficiency of the method, due to the possibility of real-time monitoring of the hemocoagulation process in real-time in the studied microvolumes of blood, increasing the convenience and accessibility of the study for the patient and the physician.

To achieve a new technical result in a device for rapid assessment of the state of the hemostasis system consisting of a measuring chamber, electrodes connected to a frequency generator and a recording unit, the measuring chamber and electrodes are placed on the base of a cartridge connected to the recording unit through a connector using a group of contact electrodes, moreover, the measuring chamber is located inside a piezoelectric sensor made in the form of a hollow cylinder, outside of which an external electrode is located, is divided Symmetric cuts into two equal parts, one part of which is the generator, and the second is the receiver of ultrasonic vibrations, the internal electrode is located on the inner surface of the measuring chamber, the central contact of which is built into the base (housing?) of the cartridge, the recording unit contains the power supply system, digital generator signals, signal correction circuit, microcontroller, analog signal conversion gain board, display, keyboard, Wi Fi module, USB - computer output, non-volatile clock, and The power supply unit output is connected to the microcontroller input, the microcontroller output is connected to the display input, the microcontroller output is connected to the digital signal generator input, as well as the digital signal generator output is connected to the microcontroller input, the digital signal generator output is connected to the input of the signal correction circuit, the output the signal correction circuit is connected to the input of the cartridge, the output of the cartridge is connected to the input of the amplification board, the conversion and decoding of analog signals, the output of the amplification board , converting and decoding analog signals are connected to the microcontroller input, keyboard outputs are connected to microcontroller inputs, nonvolatile real-time clock outputs, Wi-Fi module, USB output to computer and display are connected to microcontroller inputs as well as microcontroller outputs to nonvolatile clock inputs real time, Wi-Fi module, USB output to the computer and the display.

и интегральный показатель: площадь сектора S, ограниченную с одной стороны отрезком кривой между точками А1 и А4 с другой осью абсциссы, далее с помощью программного обеспечения сравнивают их значения с референтными аналогичными значениями, определенными у здоровых добровольцев для различных возрастных групп и при увеличении интегральных показателей не менее, чем на 20% - определяют состояние гиперкоагуляции, а при снижении амплитудных и интегральных показателей не менее чем на 20% - определяют состоянии гипокоагуляции.In the method of rapid assessment of the functional state of the hemostasis system, including the placement of a blood sample in the measuring chamber, the impact of a physical factor on it and the recording of chronometric and amplitude characteristics of the blood, the whole blood sample placed in the measuring chamber of the device described above (p.1) is affected ultrasonic oscillations with a frequency of 150-160 kHz, after which, an echocoagulogram is recorded and, at intervals of time T1 = 0x, 3 min, T2 = 2 minutes, T3 = 4 minutes, T4 = 5 minutes, determine the magnitude of the amplitude exponents 0A1,0A2,0A3 Leu, A04, respectively, the angle of slope of the curve between points A ₁ and A ₂ -

and integral indicator: sector S area, bounded on one side by a curve between points A1 and A4 on the other abscissa axis, then using their software, their values are compared with reference values determined in healthy volunteers for different age groups and with increasing integral indicators not less than 20% - determine the state of hypercoagulation, and with a decrease in amplitude and integral indicators not less than 20% - determine the state of hypocoagulation.

New in the device is that the measuring chamber and the electrodes are placed on the base of the cartridge connected to the recording unit through the connector using a group of contact electrodes, moreover, the measuring chamber is located inside a piezoelectric sensor made in the form of a hollow cylinder, outside of which is an external electrode separated symmetric cuts into two equal parts, one part of which is the generator, and the second - the receiver of ultrasonic vibrations, on the inner surface of the cylinder Internal electrode, central and lateral contacts can be built into the base of the cartridge and fixed on its base; the registration unit contains the power supply system, digital signal generator, signal correction circuit, microcontroller, analog signal conversion gain board, display, keyboard, Wi Fi module, USB output on a computer, a nonvolatile clock, with the output of the power supply unit connected to the input of the microcontroller, the output of the microcontroller connected to the input of the display, the output of the microcontroller connected to the input of the digital The signal generator, as well as the digital signal generator output is connected to the microcontroller input, the digital signal generator output is connected to the input of the signal correction circuit, the output of the signal correction circuit is connected to the cartridge input, the cartridge output is connected to the input of the amplification board, converting and decoding analog signals, the output of the amplification, conversion and decoding of analog signals is connected to the input of the microcontroller, the outputs of the keyboard are connected to the inputs of the microcontroller, the outputs of the power supply unit imyh real-time clock module Wi-Fi, USB output to a computer and a display connected to the inputs of the microcontroller as well as the outputs of the microcontroller connected to the inputs of non-volatile real-time clock module Wi-Fi, USB output to your computer and display.

рассчитывают интегральный показатель: площадь сектора S, ограниченную с одной стороны отрезком кривой между точками А1 и А4 с другой осью абсциссы, далее с помощью программного обеспечения сравнивают его значения с аналогичным референтными значениями, определенными у здоровых добровольцев для различных возрастных групп и при увеличении интегрального показателя не менее чем на 20% - определяют состояние гиперкоагуляции, а при снижении интегрального показателя не менее чем на 20% - определяют состоянии гипокоагуляции.New in the method is that the whole blood sample placed in the measuring chamber of the device according to claim 1 is affected by ultrasonic vibrations with a frequency of 150-160 KHz, after which the echo-coagulogram is recorded at time intervals T1 = 0.3 min, T2 = 2 minutes, T3 = 4 minutes, T4 = 5 minutes, determine the amplitude indicators 0A1.0A2.0A3, A0, respectively, the slope of the curve between the points A ₁ and A ₂ -

calculate the integral indicator: the area of the sector S, bounded on one side by the curve between the points A1 and A4 with the other abscissa axis, then using the software compare its values with similar reference values determined in healthy volunteers for different age groups and with an increase in the integral indicator not less than 20% - determine the state of hypercoagulation, and with a decrease in the integral index not less than 20% - determine the state of hypocoagulation.

The essential features of the technical solutions have shown in the inventive combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist.

An identical set of features characterizing the method and device for rapid assessment of the hemostasis system was not found in the patent and scientific and medical literature.

Experimental and clinical studies have confirmed that the proposed method for rapid diagnosis and device for its implementation can be used in practical health care to correct hemocoagulation disorders and improve the quality of treatment and life of patients.

The proposed device for the rapid diagnosis of hemostasis is illustrated by the drawings presented in Figures 1-3.

The Figure 1 shows a device cartridge for rapid assessment of the hemostatic system, where a piezoceramic ultrasonic sensor of a cylindrical shape (PKD) is 1, a measuring chamber is 2, the outer electrode 4 is divided into two equal halves by the ultrasonic oscillator 4.1 and the ultrasonic oscillator 4.2. The internal electrode of the PCD 5 is located on the base 3 of the cartridge housing; contact group for switching 6; center pin 7; side contact 8.

The Figure 2 shows a general view of the device for the rapid diagnosis of the hemostatic system assembly, where the display for displaying the results is -9; USB output for charging / connecting with PC 10; groove for placing the cartridge 11; the registration unit for rapid assessment of the state of the hemostatic system 12; keyboard 13.

The Figure 3 shows the block diagram of the device for the rapid assessment of the state of the hemostatic system,

The measuring chamber 2 is placed inside a piezoceramic ultrasonic sensor 1 made in the form of a hollow cylinder on the outer surface of which an external electrode 4 is located, divided by symmetrical slots into two equal parts, one part of which is a generator of ultrasonic vibrations 4.1, and the second The inner surface of the cylinder is an internal electrode 5, connected to the central contact 7, embedded in the base 3 of the cartridge. The microcontroller of the recording unit 12 contains software for processing the results of research and connects all the device parts together: a power supply system that supplies voltage to all elements of the device: a digital signal generator (Figure 3) that generates a signal of a given frequency (F = 150-160 kHz) supplied to the piezoceramic ultrasonic sensor 1 (Figure 1); signal correction circuit; Analog signal amplification conversion board — receiving signal from a piezoceramic ultrasonic sensor and transmitting information already in digital form to a microcontroller display — to display the results; keyboard - connected directly to the microcontroller, and allowing you to turn on / off the device, start / stop the study; Wi-Fi module for PC connectivity and research details; USB output for charging / connecting to a PC; non-volatile clock for accurate fixation of the time and date of each study (Figure 3).

The method is as follows.

и рассчитывают интегральный показатель: площадь сектора S, ограниченную с одной стороны отрезком кривой между точками А1 и А4 с другой осью абсциссы, далее с помощью программного обеспечения сравнивают их значения с аналогичными референтными значениями, определенными у здоровых добровольцев для различных возрастных групп и при увеличении интегрального показателя не менее, чем на 20% -определяют состояние гиперкоагуляции, а при снижении не менее, чем на 20% - определяют состоянии гипокоагуляции.A sample of whole capillary blood in a volume of about 30 μl is placed in the measuring chamber 2 of the PKD 1, the cartridge, the cartridge is inserted into the connector 11 of the recording unit, the ultrasonic vibrations with a frequency of 150-160 KHz are applied, and then the echo-coagulation is recorded and at time intervals T1 = 0.3 min, T2 = 2 minutes, T3 = 4 minutes, T4 = 5 minutes, determine the amplitude indices 0A1.0A2.0A3, A04, respectively, the slope of the curve between the points A ₁ and A ₂ -

and calculate the integral indicator: the area of the sector S, bounded on one side by the curve between the points A1 and A4 with the other abscissa axis, then using the software compare their values with similar reference values determined in healthy volunteers for different age groups and with an increase in the integral indicator not less than 20% determine the state of hypercoagulation, and with a decrease of not less than 20% - determine the state of hypocoagulation.

The proposed device for rapid assessment of the hemostatic system works as follows.

The control circuit of the process of charging and discharging the built-in battery works continuously, regardless of whether the main components of the device are turned on. When an external charger is connected to the device, this circuit ensures that the battery is charged to the maximum level, after which it stops this process, even if the charger is still connected so that the battery does not fail. With the consumption of energy from the battery, this scheme ensures that the battery does not discharge below a certain value, which will also lead to its failure. When the minimum permissible value of the battery charge level is reached, its control circuit disables its consumption.

If the battery charge level is greater than the minimum allowable value, the secondary stabilized voltage generation circuit that feeds all the other nodes of the device always works. In the off state of the device, this voltage is applied only to the microcontroller 15, which is in “sleep” mode, consuming very little power. This mode of low power consumption of the microcontroller 15 in conjunction with a low-power supply circuit 14 ensures a long stay of the device in the off state without discharging the built-in battery.

Also, the real-time clock circuit 20 is constantly working, providing the correct count of astronomical digital clocks, including date, month, year (with leap year correction) and day of the week. To ensure the continuity of the counting of time, this site provides for a miniature battery. This allows the digital clock to work without always losing, even when the built-in battery is disconnected. This allows the user not to constantly enter the date and time, and only sometimes to correct them if the time difference becomes significant. Thus, the microcontroller 15 during operation always receives accurate data on the date and time, which are used to record in memory of the periods of research.

When you press the power button on the control keyboard, the microcontroller switches to the main mode of operation, and connects the power to the display 9. If necessary, the display backlight can be additionally turned on at night. Using the keyboard 13, the user can select modes of operation. View previous results stored in non-volatile memory, or start a new study.

After the user selects in the instrument menu the mode of conducting a new study, the microcontroller 15 sets the mode of operation of the digital signal generator 16 so that it generates a signal of the desired shape (sinusoidal) and frequency. Further, this signal is converted by amplitude by signal correction circuit 17 and fed to the connector to which cartridge 3 is connected. The response signal from cartridge 3 is received by a separate part of circuit 18, which sequentially performs its amplification and conversion from alternating to constant voltage. The resulting constant voltage, proportional to the viscosity of the blood inside the cartridge 3, is fed to the analog input of the microcontroller 15, which digitizes it. The values of the measured signal accumulated over a certain time interval are stored in the nonvolatile memory of the controller. At the same time, the microcontroller 15 analyzes the signal amplitude changes over time, and using the algorithm embedded in it, it calculates the required blood clotting indicators, displaying them on the display 9. After the time allotted for the study, the device disables the signal generation and analysis circuits, and the study data in his memory. To save battery power, the device is automatically turned off if the user does not take any actions with it for a long time.

If the device is connected to the computer via a wired USB 10 connector, then in addition to charging from the computer, it is possible to monitor the conduct of the study in real time. When a special program is launched on a computer, for example, in its window, a graph of the blood clotting process over time will be drawn and the corresponding calculated parameters of this process will be displayed.

The device provides for a wireless connection to a computer or laptop via Wi-Fi interface 19. However, due to the fact that this module in the device consumes quite a lot of energy, in order to avoid a fast battery discharge, the process of receiving data from the device is different. It does not allow to watch data from the device in real time. Wi-Fi is used by the device so that the user can connect wirelessly to the PC and quickly transfer the data of several recent studies there. After that, they can be viewed and analyzed in the program on the computer, and the power supply of the wireless interface module in the device is turned off.

After recording the echo-coagulogram, indicators are determined according to the claims, which are processed using software that compares the obtained values with reference indicators of healthy individuals and, when the integral index increases by at least 20%, determine the state of hypercoagulation, and with a decrease of no less than 20% - determine the state of hypocoagulation.

Calculation of the area under the curve produced, for example, using the trapezoid method. Each graph from the X-Gemo3 program can be saved in Excel format (Figure 4), where it is saved as two columns of coordinates X and Y. Where X is time, and Y is amplitude.

Knowing the formula for finding the area of a trapezium,

where A = Y _n , B = Y _{n + 1} , and height h equals 0.1, respectively, S ₁ = 0.5 * (B3 + B2) * 0.1

We put in the column “C” (Figure 5) in this formula and summing up the resulting values (∑ S _n ), we obtain the value of the area under the echoagulagram curve.

The final formula for calculating the area under the curve.

Examples on the implementation of the method

Example 1. Conditionally healthy volunteer D. 28 years old, venous blood was taken at the same time into a vacutainer for carrying out clotting tests, venous blood was taken with an insulin syringe for conducting piezotromboelastography and capillary blood was taken for echoagulogram (Figure 6).

The following results were obtained.

Coagulogram indicators: APTT - 32; PV - 12; Fibrinogen - 3.2; D-dimer - 380.

Indicators NPTEG: ICC - 15.7; CTA -36; T3 - 7.4; ICD - 35; IPS - 17.3; T5 - 37.

Conclusion: The indicators correspond to the norm of conditionally healthy person.

Additionally, studies using the proposed method and device deviations of the functional state of hemostasis from the norm were not revealed.

- 30°; S1 - 54.Echo-coagulogram indicators: A2 - 228; A3 - 352; A4 - 376;

- 30 °; S1 - 54.

Echo-coagulogram data correspond to data obtained from 15 conditionally healthy volunteers (Table 1) using piezotromboelastography.

Example 2. Patient T. is 26 years old (Thrombophilia, MTHFR-homozygote, Leiden mutation (FV)), pregravidary stage, venous blood was taken at the same time into the vacuiner for carrying out clotting tests, the venous blood was taken with an insulin syringe for carrying out piezotrombo elastography. blood for research using the proposed method by recording echo-coagulogram.

The following data was obtained:

1. Coagulogram indicators: APTT - 24; PV - 9; Fibrinogen - 4.6; D-dimer - 480

2. Indicators NPTEG: ICC - 17; CTA -66; T3 - 5.2; ICD - 78; IPS - 27.3; T5 - 39.7

Conclusion: Indicators correspond to the state of hypercoagulation.

Additionally conducted a study according to the proposed method

- 40°; S2-68, S1 (норма) - 54. По результату исследования значение величин интегрального показателя на 25,93% выше нормы.The results of echo-coagulogram are obtained: A2 - 350; A3 - 390; A4 - 396;

- 40 °; S2-68, S1 (norm) - 54. According to the result of the study, the value of the integral index is 25.93% higher than the norm.

Conclusion: Indicators correspond to the state of hypercoagulation

According to the research, it was decided to assign heparin subcutaneously.

1 hour after subcutaneous administration of 5000 IU of heparin, all tests were repeated.

Figure 7 depicts echo-coagulograms before and after administration of heparin; Figure 7 shows the NTTEG before and after administration of heparin.

Coagulogram indicators: APTT - 44; PV - 12; Fibrinogen-3.18; D-dimer -382.

Indicators NPTEG: ICC - 10.5; CTA -15; T3 - 15.6; ICD - 15.7; IPS - 10.9; T5 - 66.9.

- 23°; S2 - 41; S1-68 (базальный уровень).Parameters of echo-coagulogram: A2 - 190; A3 - 290; A4 - 295;

- 23 °; S2 - 41; S1-68 (basal level).

Conclusion: According to the research results, a decrease in the value of the integral index (S2) by 40% was revealed. Pronounced effect of hypocoagulation.

Example 3. Patient S., 29 years old, (Pregravidary anticoagulant therapy of LMWH (Clexan 0.4 [4000 ME])), venous blood was taken at the same time to vacutainer for carrying out clotting tests, venous blood was taken with an insulin syringe for carrying out piezotromboelastography and capillary blood for research using the proposed method by registering echocoagulogram.

The following data was obtained:

1. Coagulogram indicators: APTT - 46; PV - 14; Fibrinogen - 2.8; D-dimer - 240

2. Indicators NPTEG: ICC - 6; CTA -14; T3-18; ICD - 14; IPS - 9.6; T5 - 7.0

Conclusion: Indicators correspond to the state of hypocoagulation.

Additionally conducted a study according to the proposed method (Figure 8).

- 19°; S2-41, S1 (норма) - 54. По результату исследования значение величин интегрального показателя S2 на 24% ниже нормы S1.The results of echo-coagulogram are obtained: A2 - 140; A3 - 220; A4 - 220;

- 19 °; S2-41, S1 (norm) - 54. According to the result of the study, the value of the values of the integral indicator S2 is 24% lower than the norm of S1.

Conclusion: Indicators correspond to the state of hypocoagulation

The proposed method of rapid assessment of the state of the hemostasis system and a device for its implementation are developed on the basis of an analysis of the results of a series of experimental and clinical studies, the materials of which include patients taking drugs and groups of conditionally healthy volunteers. To assess the state of the hemostasis system, a physical factor was chosen to affect the whole blood sample with ultrasonic vibrations, as well as an exposure mode of 150-160 kHz, which allows to obtain accurate results and prevent blood elements from sticking to the walls of the measuring chamber. A device has also been developed that allows research using the effects of ultrasonic vibrations on a blood sample and obtaining reliable diagnostic indicators.

The advantage of the proposed method with the use of the original device is the possibility of using microvolumes of capillary blood (about 30 μl) placed in the measuring chamber of the PKD and conducting a rapid assessment of the state of the proteolytic stage of fibrinogenesis (initiation, amplification, propagation) in real-time detection of disorders of the hemostatic system, the possibility of immediate Correction of antiplatelet and anticoagulant therapy (dose / discreteness). Given the scale of the use of antiplatelet agents and anticoagulants for the correction of coagulation disorders in various diseases, it is not difficult to imagine the enormous need of practical public health to use convenient, compact devices that are accessible and easy to use.

A source of information

1. Description of the invention to patent No. 2413954. The method of assessing the functional state of the hemostasis system. I.I. Tyutrin, A.I. Stetsenko, V.V. Udut, S.A. Mushrooms, T.A. Semiglazova, M.A. Soloviev, E.V. Borodulin. Published: 03/10/2011 Byul. №7.

2. Description of the invention to patent No. 2282855. The method of assessing the functional state of the hemostasis system. I.I. Tyutrin, V.O. Sorokozherdiev, Yu.A. Ovsyannikov, M.N. Spismann, V.E. Shipakov, M.B. Tsyrenzhapov. Published: 08/27/2006. Bul №24.

3. Description of the invention to patent No. 2216745. The method of differentiated assessment of hemostasis in premature infants. E.V. Mikhalev, S.P. Ermolenko, G.P. Filippov. Published 11/20/2003.

4. Description of the invention to patent No. 2063037. The method of assessing the functional state of the hemostasis system. I.I. Tyutrin, A.N. Parshin, O. Yu. Bees. Published 06/27/1996.

5. Description of the invention to patent No. 2109297. The method of determining the functional state of the hemostatic system. G.V. Korshunov, A.G. Korshunov, D.M. Puchignan Published 04/20/1998.

6. Zabolotskikh I.B. and others. Diagnosis and correction of disorders of the hemostatic system. / Practical medicine, 2008, 333 p. [found on the Internet: http://www.hemostas.ru].

7. Mathematical analysis: integrals: study guide / А.А. Tuganbaev. - Flint, 2017. - 76 p.

8. Volkov V.B. Clear Excel 2008 tutorial. - St. Petersburg: Peter, 2010. - 256 p.

application

Figure 1. Cartridge device for rapid assessment of the state of the hemostatic system

1. Phyzoceramic ultrasonic sensor (in section);

2. Measuring chamber;

3. Cartridge housing;

4. External electrode;

4.1. Ultrasonic oscillator;

4.2. Receiver of ultrasonic vibrations;

5. Internal electrode;

6. Contact group for switching;

7. Central contact;

8. Side contact.

Figure 2. Device for rapid assessment of the state of the hemostatic system (general view)

1. Phyzoceramic ultrasonic sensor (specify cut)

9. Display to display the results;

10. USB output for charging / connecting with PC;

11. Connector for placing the cartridge;

12. The registration unit for the rapid assessment of the state of the hemostatic system;

13. Keyboard.

Figure 3. The block diagram of the device for the rapid assessment of the state of the hemostatic system

Figure 4. Table for calculating the integral indicator

Figure 5. Table for calculating the integral indicator

Figure 6. Echo-coagulogram normal coagulation

Figure 7. Ehocoagulogram before subcutaneous administration of 5,000 IU of heparin and 60 minutes after administration (for example, hypercoagulation).

Figure 8. Echo-coagulogram hypocoagulation

Table 1. Indicators of 15 conditionally healthy volunteers

Claims (2)

1. Device for rapid assessment of the state of the hemostatic system, consisting of a measuring chamber, electrodes connected to a frequency generator and a recording unit, characterized in that the measuring chamber and electrodes are placed on the base of the cartridge connected to the recording unit through a connector using a group of contact electrodes , moreover, the measuring chamber is located inside a piezoelectric sensor, made in the form of a hollow cylinder, outside of which there is an external electrode, separated by symmetrical slots and into two equal parts, one part of which is a generator, and the second is a receiver of ultrasonic vibrations, an internal electrode is located on the inner surface of the measuring chamber, the central contact of which is built into the cartridge housing, also the recording unit contains a power supply system, a digital signal generator, a signal correction circuit , microcontroller, analog signal conversion gain board, display, keyboard, Wi Fi module, USB - computer output, non-volatile clock, with the output of the power supply unit connecting not connected to the microcontroller input, the microcontroller output connected to the display input, the microcontroller output connected to the digital signal generator input, as well as the digital signal generator output connected to the microcontroller input, digital signal generator output connected to the signal correction circuit input, output of the signal correction circuit connected to the input of the cartridge, the output of the cartridge is connected to the input of the amplification board, converting and decoding analog signals, the output of the amplification board, converting and decoding I have analog signals connected to the microcontroller input, keyboard outputs are connected to microcontroller inputs, nonvolatile real-time clock outputs, Wi-Fi module, USB output to a computer and display are connected to microcontroller inputs, as well as microcontroller outputs connected to nonvolatile real-clock inputs time, Wi-Fi module, USB output to the computer and the display. 2. The method of rapid assessment of the functional state of the hemostatic system, including placing a blood sample in a measuring chamber, affecting it with a physical factor and recording the chronometric and amplitude characteristics of blood, characterized in that the whole blood sample placed in the measuring chamber of the device according to claim 1 , they are affected by ultrasonic vibrations with a frequency of 150-160 kHz, after which an echocoagulogram is recorded and, at intervals of time T1 = 0.3 min, T2 = 2 minutes, T3 = 4 minutes, T4 = 5 minutes, determine the magnitude of the amplitude display teley 0A1, 0A2, 0A3, A04, respectively, the angle of slope of the curve between points A ₁ and A ₂ -

α, calculate the integral indicator: the area of the sector S, bounded on one side by the curve between the points A1 and A4 with the other abscissa axis, then using the software compare their values with the reference similar values determined in healthy volunteers for different age groups and with increasing integral indicator not less than 20% determine the state of hypercoagulation, and when it is reduced not less than 20% determine the state of hypocoagulation.

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