CN111584083A

CN111584083A - Integrated coagulation index integration algorithm for detecting thrombus elastogram

Info

Publication number: CN111584083A
Application number: CN202010446548.4A
Authority: CN
Inventors: 李钢; 李彤
Original assignee: Changshu Changjiang Biology Technology Co ltd
Current assignee: Changshu Changjiang Biology Technology Co ltd
Priority date: 2020-05-25
Filing date: 2020-05-25
Publication date: 2020-08-25
Also published as: WO2021238110A1

Abstract

The invention discloses a calculation method for detecting platelet function by using thromboelastogram, which integrates a coagulation curve amplitude value MA and a coagulation time CT obtained by detecting the thromboelastogram, wherein the obtained integral value is used for expressing the integral coagulation intensity of a detected sample and is expressed by a parameter DI, and the algorithm of the integral coagulation intensity DI is

. The graphic meaning of the integral coagulation intensity on the thrombelastogram is the area enclosed by the unilateral curve and the X axis in the time t, and the coagulation intensity is more intuitively and objectively represented. The index is not directly related to the R value, the K value, the Angle value and the MA value, so that systematic errors caused by measurement errors of the R value, the K value, the Angle value and the MA value to the comprehensive coagulation index are avoided.

Description

Integrated coagulation index integration algorithm for detecting thrombus elastogram

Technical Field

The invention belongs to the technical field of medical detection, and particularly relates to a blood coagulation index calculation method.

Background

Thromboelastography (TEG) is an index reflecting dynamic changes of blood coagulation (including the rate of fibrin formation, the firmness of dissolution and coagulation, the elastic strength), and therefore, the factors influencing thromboelastography are mainly: the aggregation state of erythrocytes, the rigidity of erythrocytes, the speed of blood coagulation, the level of the activity of the fibrinolytic system, etc. The main indicators of thromboelastography are:

1. the reaction time (R) is the time from the addition of the reagent to the initiation of coagulation, or called coagulation latency time, and represents the time required for the coagulation factor to be activated by the reagent and for the production of fibrin.

2. The clotting time (K) reflects the interaction of fibrin and platelets at the onset of clot formation, i.e., the rate of blood clotting.

3. The angle between the tangent to the maximum curve arc of the maximum slope (Ang) trace and the horizontal, Ang and K are both values reflecting the rate of clot aggregation.

4. The Maximum Amplitude (MA) represents the maximum strength of the fibrin/platelet clot; the MA value is influenced mainly by two factors, fibrinogen and platelets, of which the procoagulant function of platelets plays a major role, and abnormal quality or quantity of platelets affects the MA value.

Blood test results if in a hypercoagulable state: the coagulation speed is high (R is small, K is small, and Ang is large), and the blood clot strength is high (MA is large), so that thrombus of the patient is easily generated; blood coagulation is mainly caused by platelets. Clinically, in order to prevent thrombosis, inhibitors having an inhibitory effect on the blood coagulation function of platelets such as aspirin and borrelidin need to be used for patients, and the inhibition effect of drugs on the blood coagulation function of the patients is clinically judged by comparing elastograms before and after administration.

Complex Coagulation Index (CI): a numerical index comprehensively reflecting the coagulation intensity of a sample is a result parameter which is related to reaction time (R), coagulation time (K) and coagulation intensity (MA) and is subjected to weighted calculation, and the weights of the three indexes are calculated and adjusted through a large number of experiments, so that the CI value of a normal sample is ensured to be between-3 and 3. The concrete formula is as follows:

CI= -R/3-K/2+MA/8-5.208

however, it can be observed from clinical examination that the set of algorithms has the following disadvantages in practical application:

1, the consistency of the R value, the K value and the MA is poor due to errors in measurement of the equipment, so that the data consistency and the accuracy of the CI value are influenced:

r value measurement: when the thromboelastogram testing instrument measures a sample, the actual numerical value of the R value is expressed by the time from the beginning of the experiment when the elastic curve points by 2mm (or the time from the curve to the back of the fitting). Because the X value of the curve is calculated by measuring the Y value of the curve, the actual error of the Y value during measurement is amplified, and the error is larger because the error is limited by the detection frequency and the data uploading frequency in the actual detection.

Through computer simulation, when the Y-axis detection is wrong by 0.05mm (the coefficient of variation CV is 1.3% near 2 mm), the coefficient of variation CV of the R value data is 4.76%. The accuracy is obviously reduced. The difference between the two coefficient of variation CV increases as the error of the Y-axis detection decreases.

And (3) K value measurement: when the thrombus elastogram testing instrument measures a sample, the actual value of the K value is expressed as the difference between the experimental starting time (or the fitted retrogression time of the curve) and the R value when the elastogram curve points to 20 mm. Because the X value of the curve is calculated by measuring the Y value of the curve, the actual error of the Y value during measurement is amplified, and the error is larger because the error is limited by the detection frequency and the data uploading frequency in the actual detection. And the error of the K value is larger due to the error of the R value.

Through computer simulation, when the Y-axis detection is wrong by 0.05mm (the coefficient of variation CV is 0.13% near 20 mm), the coefficient of variation CV of the R value data is 14.14%. The accuracy is obviously reduced. The difference between the two coefficient of variation CV increases as the error of the Y-axis detection decreases.

MA value measurement: when the thrombus elastogram testing instrument measures a sample, the actual numerical value of the MA value is represented as Y-axis data at the point where the elastic chart curve points with the maximum amplitude. But does not reflect the duration of time the sample is in the maximal coagulation state. And when due to data errors, the influence of upward errors on MA is more significant than the influence of downward errors, so that MA is always higher than the true coagulation strength.

2, for some particular samples, there are cases where the R value, K value, MA value are in the abnormal range, and CI is in the normal range.

3, the secondary opening caused by the influence of environmental vibration or sample defects in actual detection can cause CI value distortion.

And 4, the testing time is too long. The CI test requires the maximum solidification strength of the curve to be obtained, so the test must be terminated until the sample enters the fiber fusion process to obtain an accurate MA value. And this often takes more than 40 minutes.

Therefore, the conventional comprehensive Coagulation Index (CI) algorithm has defects, cannot reflect the actual state of the coagulation intensity of the sample, and has a deviation in clinical observation for determining the drug effect of the patient.

Disclosure of Invention

The invention aims to solve the technical problem of providing an algorithm for synthesizing the coagulation index, so that the medication of doctors and the observation of patients are closer to the actual condition.

In order to solve the technical problems, the invention is realized by the following technical scheme: a calculation method for detecting platelet function by using thromboelastogram includes integrating the coagulation curve amplitude value MA and coagulation time CT obtained by detecting thromboelastogram, using obtained integral value to express integral coagulation intensity of detected sample, and using parameter DI to express integral coagulation intensity

。

Further, the integrated calculated clotting time is the time from the beginning of the instrument's detection of the sample to the end of the detection.

Further, the starting point of the coagulation time is when the sample to be measured is added with a reagent.

Further, the starting point of the coagulation time is when the sample begins to coagulate after the reagent is added to the sample to be measured and the coagulation latency time elapses.

Further, the end point of the coagulation time is a fixed time period from the start of the reagent addition of the sample to be measured.

Further, the fixed duration is the longest detection time.

Further, the fixed duration is the shortest time required for effectively judging the detection result.

An algorithm for comprehensively analyzing the coagulation intensity by using the integrated coagulation intensity is characterized in that a new comprehensive coagulation intensity index CCI is used for representing the size of the coagulation intensity, and the algorithm is composed of two parameters of CCI = S (t) ⁄ A-B and A, B so that the normal value, namely the average value of CCI of a normal population is in the range of-3 to 3.

The method has the advantages that the graphic meaning of the integral coagulation intensity on the thrombelastogram is the area enclosed by the unilateral curve and the X axis in the time t, and the coagulation intensity is more intuitively and objectively represented. The index is not directly related to the R value, the K value, the Angle value and the MA value, so that systematic errors caused by measurement errors of the R value, the K value, the Angle value and the MA value to the comprehensive coagulation index are avoided.

Drawings

FIG. 1 is a theoretical curve of a thrombelastogram;

FIG. 2 is a graphical illustration of the integral calculation of the present invention;

FIG. 3 is a graph illustrating an example;

FIG. 4 is a graph of example two.

Detailed Description

The invention is described in detail below with reference to the following figures and embodiments:

the elasticity diagram curves are two vertically symmetrical curves, the MA value is the distance between the upper point and the lower point at the maximum position of the opening of the curve, for explaining the algorithm, the upper curve is taken as a research object, the X axis is moved to the position of the symmetry axis of the curve, and the curve can be recorded as the position of the symmetry axis of the curve at the moment

。

The algorithm according to the original coagulation comprehensive index is as follows: CI = -R/3-K/2+ MA/8-5.208.

The curve is integrated over a certain period of time and is recorded as

：

The algorithm for integrating the coagulation intensity DI is

。

The graphic meaning of the integral coagulation intensity on the thrombelastogram is the area enclosed by the unilateral curve and the X axis in the time t, and the coagulation intensity is more intuitively and objectively represented. The index is not directly related to the R value, the K value, the Angle value and the MA value, so that systematic errors caused by measurement errors of the R value, the K value, the Angle value and the MA value to the comprehensive coagulation index are avoided.

In order to more intuitively reflect whether the blood coagulation strength is too strong or too weak, a new comprehensive blood coagulation index is added, and the comprehensive blood coagulation index of a normal sample is framed to be between-3 and 3 as in the conventional CI.

The algorithm for the new integrated coagulopathy CCI is CCI = S (t)/A-B. A. B two parameters were chosen so that their normal values, i.e., the mean of CCI for the normal population, ranged between-3 and 3.

It has the following advantages:

1, data consistency and accuracy.

The measurement errors of the R value, the K value and the MA value are accumulated due to the actual measurement errors of the blood coagulation testing instrument. The measurement error of the traditional coagulation comprehensive index is large. The new coagulation index DI is smaller in the accumulated error because the error is offset by measuring the amount in the Y axis direction. The following are according to computer simulations:

the test is carried out by using the whole blood quality control product level 1, the R value is 1.2, the K value is 0.6, the MA value is 64, the traditional coagulation comprehensive index CI value is 2.74 under the condition that the instrument detection error is 0.05mm, and the coefficient of variation is 1.517%.

The integrated coagulation intensity DI was 7859.4 with a coefficient of variation of 0.125%.

The new composite coagulation strength CCI was compiled 2.365 with a coefficient of variation of 0.024%.

The new algorithm is significantly better than the conventional algorithm in terms of data consistency and accuracy in consideration of calculation errors.

2, the description of the special-shaped curve is more accurate.

Example 1:

for some particular clinical samples, CI values may also be shown to be normal if R, K and MA values reflect opposite coagulation characteristics. As shown in FIG. 3, the clinical samples had an R value of 0.6, a K value of 1.6 and an MA value of 29, and the samples had MA values which were too small and significantly deficient in blood coagulation ability and CI values of-2.4, which were within the normal range.

The value was calculated to be-4.42 with CCI, which is a lower coagulation value. More accords with the real state that the blood coagulation intensity is lower.

Example 2:

for certain abnormal curves, the CCI coagulation combination index can be better described.

As shown in FIG. 4, the test curves (sample 1, sample 2) for both samples have the same R value, K value and MA value, so that the CI values obtained for both samples are the same. But clearly the two are not of the same character, sample 2 has a secondary opening characteristic, so the composite coagulation index is not valid for this sample description.

When described in terms of CCI, the CCI value behaves differently because the integrated area of sample 2 is smaller than sample 1. The new algorithm avoids such situations where the description fails.

And 3, the detection time is shortened.

Because the method does not need to measure the maximum blood coagulation intensity, the sample does not need to enter a fiber fusion state when the sample is detected, and only needs to exceed an effective diagnosis point or fix all detection time at a reasonable length, the detection time can be realized to be less than 30 minutes and far less than that of the traditional CI.

The integrated calculated clotting time is the time from the beginning of the instrument's detection of the sample to the end of the detection. The starting point of the coagulation time may be when the sample to be measured is added with a reagent, as shown in point A in FIG. 2, or when the sample starts to coagulate after the coagulation latency time elapses after the sample to be measured is added with a reagent, as shown in point B in FIG. 2. The end point of the coagulation time may be a fixed time period from the start of the addition of the reagent to the sample to be measured. The fixed duration may be the longest detection time, such as point D in fig. 2, i.e., the integration time from a or B to D. The fixed time length can also be the shortest time required for effectively judging the detection result, such as point C in fig. 2, that is, the integration time is from a or B to C, so that the detection speed and efficiency can be improved.

It is to be emphasized that: the above embodiments are only preferred embodiments of the present invention, and are not intended to limit the present invention in any way, and all simple modifications, equivalent changes and modifications made to the above embodiments according to the technical spirit of the present invention are within the scope of the technical solution of the present invention.

Claims

1. A computational method for detecting platelet function using thromboelastography, characterized by: integrating the amplitude value MA of the coagulation curve obtained by detecting the thromboelastogram with the coagulation time CT, wherein the obtained integral value is used for expressing the integral coagulation intensity of the detected sample and is expressed by a parameter DI, and the algorithm of the integral coagulation intensity DI is

。

2. The method of claim 1, wherein the computational method for detecting platelet function using thromboelastography comprises: the integrated calculated clotting time is the time from the beginning of the instrument's detection of the sample to the end of the detection.

3. The method of claim 2, wherein the computational method for detecting platelet function using thromboelastography comprises: the starting point of the coagulation time is when the sample to be measured is added with the reagent.

4. The method of claim 2, wherein the computational method for detecting platelet function using thromboelastography comprises: the starting point of the coagulation time is when the sample begins to coagulate after the reagent is added to the sample to be measured and the coagulation latency time elapses.

5. The method of claim 2, wherein the computational method for detecting platelet function using thromboelastography comprises: the end point of the coagulation time is a fixed period of time from the start of the addition of the reagent to the sample to be measured.

6. The method of claim 5, wherein the computational method for detecting platelet function using thromboelastography comprises: the fixed duration is the longest detection time.

7. The method of claim 5, wherein the computational method for detecting platelet function using thromboelastography comprises: the fixed time length is the shortest time required for effectively judging the detection result.

8. An algorithm for comprehensively analyzing coagulation intensity using the integrated coagulation intensity of claim 1, wherein: the new comprehensive blood coagulation intensity index CCI is adopted to represent the blood coagulation intensity, and the algorithm is

A, B to have their normal values, i.e. the average of CCI in the normal population, range between-3 and 3.