Method of determining functional state of hemostasis system

FIELD: medicine.

SUBSTANCE: for determination of functional state of hemostasis system record of blood coagulation process is performed, current amplitude of blood resistance in first time moment is registered and second resistance of blood at multiple time moment from initial time value is measured. Two resistances and time moments are used to determine maximum blood resistance and time constant, by which blood resistance at the beginning and end of coagulation process is calculated. Obtained parameters are used to determine indices of beginning and end of blood coagulation process. Obtained indices are compared with of the same name indices of blood coagulation process in norm and in case of differently directed deviations disturbances of functional state of hemostasis system are diagnosed.

EFFECT: invention makes it possible to increase measurement accuracy and reduce examination time.

1 tbl, 4 dwg

 

The present invention relates to medicine, namely to hemocoagulase, and can be used to identify individuals at risk of developing hemocoagulation complications.

Famous instrumental method of assessing the functional state of hemostasis - thromboelastography (TAG), consisting of a graphic (photo-optical or mechanical) check the viscosity of blood and plasma in the process of coagulation, followed by determination of indicators thromboelastogram that characterize the process [USSR Author's certificate N 1520450, M CL G01N 33/86, publ. 07.11.89, BI N 41].

The disadvantages of this method are: low sensitivity and reproducibility, the inability to detect subtle changes in the blood clotting system and conduct an analytical assessment of the identified violations.

There is a method of determining the functional status of the hemostatic system by registering electrocochleography blood [see the book. Koblov L. F. Methods and instruments for the study of hemostasis. - M.: Medicine, 1975, p.75-79], which consists in the registration of the change of electrical resistance of the blood sample filled in a cell with two electrodes. The cell performs oscillatory motion, allowing the blood alternately closes and opens the electrodes. Record of the research takes the form of a number of peri is legal pulses with a repetition rate of 0.1 Hz (6 pulses per minute), envelope which describes the process of blood clotting. The amplitude of the pulses corresponds to the resistance of the blood, in the moment between the electrodes of the measuring cell. When evaluating electrocochleography take into account the following parameters: T1 is the start time of the collapse: T2 is the end time of the collapse; T - duration of coagulation; Am is the maximum amplitude; AO is the minimum amplitude. By changing these parameters get ideas about various disorders of the blood coagulation system.

The disadvantages of this method are the inertia, the relatively low accuracy and sensitivity of measurements due to leakage intense side of physico-chemical processes related to the movement of the electrodes and studied medium relative to each other.

For the prototype accepted method for determining the functional state of the hemostatic system [see RF patent №2109297, G01N 33/86, 1998], namely, that performs the measurements of the amplitudes of the recording process of blood clotting in the beginning, then after one, two and three minutes from the beginning determine the speed of blood clotting for the second and third minutes, calculate return them to the values and compare all four with the same blood clotting is normal. In the presence of different abnormalities diagnosed on Uchenie functional state of the hemostatic system.

The disadvantages of the prototype are low accuracy and the duration of its execution.

The technical objective of the method is the improvement of metrological performance, namely, measurement accuracy, and reducing research time.

The goal of the project is achieved as follows.

In the method for determining the functional state of the hemostatic system consists in the fact that they are carrying out the measurement of the amplitude of the recording process of blood clotting in the beginning, determine the indices of the beginning and end of the clotting process electrocochleography blood and compare them with the same indicators of blood coagulation in normal and multidirectional deviations diagnose disorders of the functional state of the hemostatic system, unlike the prototype, register the current amplitude of the resistance of the blood in the first time and measuring a second resistance of blood in multiples of time from the initial time values for the two resistors and the moments of time are the ultimate resistance of the blood and the time constant, which is calculated the resistance of blood at the beginning and end of the clotting process and found the settings determine the indices of the beginning and end of the process of blood clotting.

The essence of the proposed method is illustrated in figure 1-3 Offer ways which includes 2 steps.

1. The measurement limit of the resistance of the blood and the time constant.

2. The indicators of the beginning and end of the process of blood clotting on the measured amplitudes of the resistance.

1. The indices of the beginning and end of the process of coagulation of blood is determined by measuring the limiting resistance of the blood, the time constant and resistance of blood at the beginning and end of the clotting process. To do this, hold the amplitude measurement process of blood clotting in the beginning and define the indicators of early Tnand the end of the clotting process Tto. Compare them with the same indicators of blood coagulation in normal and multidirectional deviations diagnose disorders of the functional state of the hemostatic system.

To do this, register at time t1the current amplitude of the resistance R1in a multiple of the time t2(t2=k·t1when an integer factor of multiplicity k≥2) from the original time measuring a second resistance R2(figure 1). Two resistance R1, R2and the moments of time t1, t2find the value of the limiting resistance R0in the blood sample, the time constant T, which define the start and end of the clotting process.

The experimental dependence of the resistivity R(t)=R dinamicheskoj the process (figure 1, curve 1) are approximated by the exponential law (Fig 1, curve 2):

The dependence (1) connects the measured value of the amplitude R of the resistance at time t research, with a limit of R0resistance and time constant T.

Unique property parameters R0and T is independent from the characteristics of the variable resistance R and time t, i.e. they uniquely identify the dynamic characteristics of the experiment according to (1), therefore, they should be taken for informative parameters of the dynamic process.

The definition of informative parameters R0and T is organized by two measured values of amplitude R1, R2resistance at two points in time t1, t2from the system of equations for the first and second measurement:

Divide the rst equation by the second:

and lead him to a form convenient for taking the logarithm:

.

Logarithmorum both parts of the equations and Express T:

Constitute a system of equations for calculation of the parameter R0:

Divide the rst equation by the second:

and bring him to mind:

.

Given that:

.

Exponential this equation and Express the extreme resistance R0:

Substitute the values of the parameters R0and T in the formula (1), which approximate the experimental dynamic resistance curve of blood (figure 1, curve 2).

2. The start time Tnand the end of Ttoclotting of blood is determined from the expression (1) by the formulas:

where T is the time constant;

R0the ultimate resistance of blood;

Rnand Rtothe resistance of the blood, respectively at the beginning and end of the clotting process.

Define the start and end of the process of blood coagulation by the formulas (4) using the experimental dependence (figure 2).

Figure 2 shows curves of the coagulation characteristic of a healthy person (curve 1), for a patient with hemophilia (curve 2)for a patient with thrombophilia (curve 3). From figure 2 it is seen that the initial resistance of blood for a patient with hemophilia increases, and for a patient with thrombophilia is reduced.

Let us prove the efficiency of the analytical method of determining the clotting time of blood relative to the graphical method.

According the rototype time to begin the process of blood clotting T ndetermine graphically from the beginning of the study to first reduce the amplitude of the resistance of the blood, and the end time of the clotting process Ttodetermine from the beginning of the study to the first oscillation with a minimum amplitude (figure 3). However, to accurately register a moment of hesitation with a reduced amplitude graphically quite difficult.

Since the pulses follow with a frequency of 0.1 Hz or latitude 10 seconds, then the resistance of blood at the beginning and at the end of the process of coagulation is determined with an error of 10%.

Therefore, the start time of blood clotting T1and T2in the prototype will be determined by the formula:

In the proposed method, the start and end of the process of blood clotting determined analytically according to the first formula of equation system (4).

Metrological efficiency ηiby the time blood clotting,is determined by the relation Tn(the start time of the collapse, the proposed method) to Ti(the start time of the collapse in the prototype):

Substituting formulas (4) and (5) into the formula (6) we obtain:

,.

Substituting in these equations the experimental values obtained

analytically and graphically, obtain the value of the η 1and η2.

,.

Table 1 shows the values of the errors in the measurement start time and the end of the blood clotting process to discard the value of the measured resistance of blood at 1%, 5% and 10%.

Table 1
The estimation of the measurement uncertainty
R %Tn, %Tto, %
19-119.6-10
545-5548-50
1090-11096-100

Therefore, determination of the limiting resistance of the blood and the time constant allows, in contrast to the prototype, to improve the accuracy of measurement of clotting time of blood 10 times.

In the proposed solution the definition of informative parameters of blood involves analytical measurements that allow you to automate the determination of the functional state of the hemostatic system, unlike the prototype, in which characteristics determine graphically. Efficiency is the ability for efficiency, defined as the ratio between the total times of the analytical control τ 1and graphical analysis τ2. The analytical control in m times less time subjective analysis and differs at least 10 times. This implies that the efficiency for efficiency, ψ is equal to:

ψ=τ12=m,

i.e. efficiency in efficiency in the proposed solution is not less than an order of magnitude higher than known solutions.

Figure 4 presents the analysis of experimental data the proposed method, proving the adequacy of the results of the analytical control of biomedical experiment (for a healthy person - curves 1, for a patient with hemophilia curves 2, for a patient with thrombophilia - curves 3).

Thus, the method of determining the functional state of hemostasis by informative parameters: the maximum resistance of blood and continuous time, in contrast to known solutions, improves the accuracy and efficiency of measurement of clotting time of blood is no less than an order of magnitude and allows you to automate the control of hemostasis. Ultimately increases the reliability of the measurements and expands the range of control hemocoagulase, which reduces the risk of hemocoagulation complications.

The method for determining the functional state of the hemostatic system consists in the fact that they are carrying out the measurement of the amplitude of the recording process of blood clotting in his early is e, determine the indices of the beginning and end of the clotting process electrocochleography blood and compare them with the same indicators of blood coagulation in normal and multidirectional deviations diagnose disorders of the functional state of the hemostatic system, wherein registering the current amplitude of the resistance of the blood in the first time and measuring a second resistance of blood in multiples of time from the initial time values for the two resistors and the moments of time are the ultimate resistance of the blood and the time constant, which calculates the resistance of blood at the beginning and end of the clotting process and found the settings determine the indices of the beginning and end of the process of blood clotting.



 

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1 tbl

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