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CN108761105A - Clotting time determination method, electronic equipment and storage medium - Google Patents

Clotting time determination method, electronic equipment and storage medium Download PDF

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CN108761105A
CN108761105A CN201810554622.7A CN201810554622A CN108761105A CN 108761105 A CN108761105 A CN 108761105A CN 201810554622 A CN201810554622 A CN 201810554622A CN 108761105 A CN108761105 A CN 108761105A
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time
coagulation
slope
blood coagulation
point search
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CN108761105B (en
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张彤
赵峻祎
汤嘉慧
方磊
周楚青
陈宇薇
王继华
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Guangzhou Wondfo Biotech Co Ltd
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Guangzhou Wondfo Biotech Co Ltd
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    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/86Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors

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Abstract

The present invention discloses a kind of clotting time determination method, electronic equipment and storage medium, method:Obtain the multiple blood clotting characteristic sampled datas sampled at any time in blood coagulation test;Blood coagulation time started and blood coagulation end time are determined based on the blood clotting characteristic sampled data;The clotting time is determined according to blood coagulation time started and blood coagulation end time.The present invention determines the clotting time by data analysis, effectively increases the judging efficiency in clotting time.

Description

Blood coagulation time determination method, electronic device, and storage medium
Technical Field
The present invention relates to the field of blood coagulation testing technology, and in particular, to a blood coagulation time determination method, an electronic device, and a storage medium.
Background
The process by which blood changes from a liquid state to a jelly-like clot is referred to as the blood clotting process. In this process, the blood coagulation factors are activated in a certain order to convert fibrinogen in the blood into insoluble fibrin. The fibrin is cross-linked into a web to form a jelly-like clot. The time for blood to coagulate is called the clotting time, and the length of clotting time is affected by coagulation factors. Currently available clotting Time measurements include Prothrombin Time (PT), Activated Partial Thrombin Time (APTT), Activated Clotting Time (ACT), and Thrombin Time (Thrombin Time, TT). The measurement of the blood coagulation time is important for monitoring blood diseases such as thrombus, monitoring anticoagulant, screening blood coagulation factors and the like.
The existing equipment and method for testing blood coagulation based on a micro-fluidic chip mainly apply a voltage difference to a blood sample in the micro-fluidic chip, measure an electric signal with a certain duration, and analyze a measurement result curve to obtain the accumulative characteristic of a measurement function related to the coagulation time.
However, the prior art has the following disadvantages:
first, the requirements for input data are high. The blood coagulation time is judged based on the area among several points or the intensity of an electric signal, however, the judgment of the several points of the blood coagulation time is not obvious in practical situation due to the influence of noise and the like;
secondly, the real-time robustness is poor. Based on the first defect, when the noise of original data is large, the existing algorithm cannot make correct judgment;
thirdly, the operation speed is slow. Part of post-processing processes are based on the area as a judgment basis, so that the calculation amount is large, the algorithm speed is low, and the requirement of a real-time system is difficult to meet.
Disclosure of Invention
In view of the above, it is necessary to provide a coagulation time determination method, an electronic device, and a storage medium, which solve the problem of low accuracy in determining a coagulation time in the related art.
The present invention provides a blood coagulation time determination method, including:
obtaining a plurality of blood coagulation characteristic sampling data sampled over time in a coagulation test;
determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data;
the clotting time is determined from the clotting start time and the clotting end time.
Further, the determining the coagulation start time and the coagulation end time based on the blood coagulation characteristic sampling data specifically includes: calculating a corresponding slope for each of the blood coagulation characteristic sampled data based on a search step size;
determining a coagulation start time and a coagulation end time based on the slope.
Further, the search step includes a starting point search step and an end point search step;
the calculating of the corresponding slope for each of the blood coagulation characteristic sampling data based on the search step length specifically includes:
calculating a corresponding starting point search slope for each of the blood coagulation characteristic sample data based on the starting point search step length, and calculating a corresponding end point search slope for each of the blood coagulation characteristic sample data based on the end point search step length;
determining a coagulation start time and a coagulation end time based on the slope, specifically comprising:
determining a coagulation start time based on the start point search slope, and determining a coagulation end time based on the end point search slope.
Still further, the end point search step size is determined as follows:
performing multiple polynomial curve fitting on the blood coagulation characteristic sampling data by using a plurality of fitting terms to obtain a plurality of fitting curves with the fitting terms as parameters;
according to the blood coagulation test type, selecting a fitting curve which meets a preset selection rule from the fitting curves as a reference fitting curve, and taking the number of fitting terms of the reference fitting curve as the number of reference fitting terms;
and calculating the end point search step length according to the reference fitting term number.
Still further, the selection rule includes:
if the blood coagulation test type is an activated partial thromboplastin time test or an activated blood coagulation time test, selecting a fitting curve with the largest fitting error as a reference fitting curve;
selecting a fitting curve with the smallest fitting error as a reference fitting curve if the coagulation test type is a thrombin time test, or a prothrombin time test.
Still further, the determining the coagulation start time based on the start point search slope specifically includes:
the sampling time corresponding to the blood coagulation characteristic sampling data with the largest slope is selected as the coagulation start time.
Still further, the determining the coagulation end time based on the endpoint search slope specifically includes:
determining a continuous same slope period or a negative slope period based on the end point search slope after a preset peak interference period following the coagulation start time;
selecting a start time of the consecutive same slope time period, or a start time of the negative slope time period as the coagulation end time.
Still further, the determining a time period with a continuous same slope based on the endpoint search slope specifically includes:
if a plurality of continuous blood coagulation characteristic sampling data with consistent end point search slopes and positive slopes exist, and the number of the blood coagulation characteristic sampling data reaches a preset first number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with consistent end point search slopes as a continuous same slope time period, or;
if a plurality of continuous blood coagulation characteristic sampling data with the end point search slope of zero exist, and the number of the continuous blood coagulation characteristic sampling data reaches a preset second number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with the end point search slope of zero as a continuous same slope time period;
wherein, the end point search slopes are consistent, specifically: the difference of the end point search slopes is within a preset difference threshold range.
Still further, the selecting the start time of the continuous same slope time period or the start time of the negative slope time period as the coagulation end time specifically includes:
calculating a first difference value between the starting time of the negative slope time period and the blood coagulation starting time, and if the first difference value is within a preset first time range, selecting the starting time of the negative slope time period as the blood coagulation finishing time, otherwise;
calculating a second difference value between the starting time of the continuous same slope time period and the coagulation starting time, if the second difference value is out of a preset second time range and the starting time of the continuous same slope time period is less than the starting time of the negative slope time period, selecting the starting time of the negative slope time period as the coagulation finishing time, if the second difference value is out of the preset second time range and the starting time of the continuous same slope time period is greater than the starting time of the negative slope time period, selecting the starting time of the continuous same slope time period as the coagulation finishing time, otherwise;
selecting a start time of a period of consecutive same slope as the coagulation end time if the second difference is within a preset second time range.
The present invention provides an electronic device, including:
at least one processor; and the number of the first and second groups,
a memory communicatively coupled to the at least one processor; wherein,
the memory stores instructions executable by the at least one processor to enable the at least one processor to:
obtaining a plurality of blood coagulation characteristic sampling data sampled over time in a coagulation test;
determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data;
the clotting time is determined from the clotting start time and the clotting end time.
Further, the determining the coagulation start time and the coagulation end time based on the blood coagulation characteristic sampling data specifically includes: calculating a corresponding slope for each of the blood coagulation characteristic sampled data based on a search step size;
determining a coagulation start time and a coagulation end time based on the slope.
Further, the search step includes a starting point search step and an end point search step;
the calculating of the corresponding slope for each of the blood coagulation characteristic sampling data based on the search step length specifically includes:
calculating a corresponding starting point search slope for each of the blood coagulation characteristic sample data based on the starting point search step length, and calculating a corresponding end point search slope for each of the blood coagulation characteristic sample data based on the end point search step length;
determining a coagulation start time and a coagulation end time based on the slope, specifically comprising:
determining a coagulation start time based on the start point search slope, and determining a coagulation end time based on the end point search slope.
Still further, the end point search step size is determined as follows:
performing multiple polynomial curve fitting on the blood coagulation characteristic sampling data by using a plurality of fitting terms to obtain a plurality of fitting curves with the fitting terms as parameters;
according to the blood coagulation test type, selecting a fitting curve which meets a preset selection rule from the fitting curves as a reference fitting curve, and taking the number of fitting terms of the reference fitting curve as the number of reference fitting terms;
and calculating the end point search step length according to the reference fitting term number.
Still further, the selection rule includes:
if the blood coagulation test type is an activated partial thromboplastin time test or an activated blood coagulation time test, selecting a fitting curve with the largest fitting error as a reference fitting curve;
selecting a fitting curve with the smallest fitting error as a reference fitting curve if the coagulation test type is a thrombin time test, or a prothrombin time test.
Still further, the determining the coagulation start time based on the start point search slope specifically includes:
the sampling time corresponding to the blood coagulation characteristic sampling data with the largest slope is selected as the coagulation start time.
Still further, the determining the coagulation end time based on the endpoint search slope specifically includes:
determining a continuous same slope period or a negative slope period based on the end point search slope after a preset peak interference period following the coagulation start time;
selecting a start time of the consecutive same slope time period, or a start time of the negative slope time period as the coagulation end time.
Still further, the determining a time period with a continuous same slope based on the endpoint search slope specifically includes:
if a plurality of continuous blood coagulation characteristic sampling data with consistent end point search slopes and positive slopes exist, and the number of the blood coagulation characteristic sampling data reaches a preset first number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with consistent end point search slopes as a continuous same slope time period, or;
if a plurality of continuous blood coagulation characteristic sampling data with the end point search slope of zero exist, and the number of the continuous blood coagulation characteristic sampling data reaches a preset second number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with the end point search slope of zero as a continuous same slope time period;
wherein, the end point search slopes are consistent, specifically: the difference of the end point search slopes is within a preset difference threshold range.
Still further, the selecting the start time of the continuous same slope time period or the start time of the negative slope time period as the coagulation end time specifically includes:
calculating a first difference value between the starting time of the negative slope time period and the blood coagulation starting time, and if the first difference value is within a preset first time range, selecting the starting time of the negative slope time period as the blood coagulation finishing time, otherwise;
calculating a second difference value between the starting time of the continuous same slope time period and the coagulation starting time, if the second difference value is out of a preset second time range and the starting time of the continuous same slope time period is less than the starting time of the negative slope time period, selecting the starting time of the negative slope time period as the coagulation finishing time, if the second difference value is out of the preset second time range and the starting time of the continuous same slope time period is greater than the starting time of the negative slope time period, selecting the starting time of the continuous same slope time period as the coagulation finishing time, otherwise;
selecting a start time of a period of consecutive same slope as the coagulation end time if the second difference is within a preset second time range.
The present invention provides a storage medium storing computer instructions for performing all the steps of the coagulation time determination method as described above when the computer executes the computer instructions.
The invention determines the blood coagulation time through data analysis, and effectively improves the judgment efficiency of the blood coagulation time.
Drawings
FIG. 1 is a flowchart showing a blood coagulation time determination method according to the present invention;
FIG. 2a is a graphical representation of sample data from a prothrombin time test;
FIG. 2b is a graphical representation of sample data for the activated clotting time test;
FIG. 2c is a graphical representation of sample data for an activated partial thromboplastin time test;
FIG. 2d is a graphical representation of the sample data for the thrombin time assay;
FIG. 3 is a schematic of a coagulation curve;
FIG. 4a is a schematic diagram of a coagulation start time search;
FIG. 4b is a schematic diagram showing the determination of the coagulation completion time according to the continuous same slope time period;
FIG. 4c is a schematic diagram of determining the end of coagulation time based on a continuous zero slope time period;
FIG. 4d is a schematic diagram showing the determination of the coagulation end time according to the negative slope time period;
FIG. 5 is a flowchart illustrating a coagulation time determination method according to a preferred embodiment of the present invention;
FIG. 6 is a flowchart illustrating the operation of the preferred embodiment of the present invention for determining coagulation time based on continuous slope time and negative slope time;
FIG. 7 is a diagram of a hardware structure of an electronic device according to the present invention;
FIG. 8 is a system diagram of the preferred embodiment of the present invention.
Detailed Description
The invention is described in further detail below with reference to the figures and specific examples.
Fig. 1 is a flowchart illustrating a blood coagulation time determination method according to the present invention, including:
step S101, obtaining a plurality of blood coagulation characteristic sampling data sampled along with time in a blood coagulation test;
step S102, determining a blood coagulation starting time and a blood coagulation finishing time based on the blood coagulation characteristic sampling data;
in step S103, the coagulation time is determined based on the coagulation start time and the coagulation end time.
Specifically, the blood coagulation property sampling data may be a graph showing the curves of the sampling data in the tests of the prothrombin time, the activated coagulation time, the activated partial thromboplastin time, the thrombin time, and the like, as shown in fig. 2a to 2 d. The blood coagulation characteristic sampling data can be acquired by a coagulation meter, the coagulation meter can apply an electric signal to the blood sample, and sampling is carried out at each sampling time to obtain the blood coagulation characteristic sampling data. The resulting blood coagulation property sample data may be stored in a file, for example in a binary file.
Step S101 may obtain a file storing blood coagulation characteristic sampling data, and read the file to obtain a plurality of blood coagulation characteristic sampling data sampled over time. The file of blood coagulation property sampling data may be obtained from a real-time blood sample characterization and recording instrument. Specifically, the real-time blood sample collection device uniformly spreads the collected blood sample into the analysis channel according to the capillary motion characteristics of the blood, and the real-time blood sample characteristic analysis and recording instrument records the blood coagulation signal by measuring the electrical characteristics of the analysis channel in the real-time blood sample collection device. The electrical properties were measured by two electrodes spaced between 3mm and 5mm apart. The two electrodes are loaded with a blood coagulation test reagent. . Applying a potential difference between the two electrodes, recording the resistance between the two electrodes, and when the blood fills the analysis channel, the resistance begins to change. The measurement resolution is at 0.000001 Ω, the measurement frequency is at 3 to 9 times per second, and these measurement data are recorded in the storage medium. After measuring the electrical characteristics over a certain period of time, an electrical characteristic-time data stream can be obtained.
Step S102 may determine the coagulation start time based on, for example, a first change point of a curve of the blood coagulation characteristic sampling data, a peak of the curve, or a judgment based on an empirically set threshold value, or the like.
In one embodiment, the determining the coagulation start time and the coagulation end time based on the blood coagulation characteristic sampling data specifically includes: calculating a corresponding slope for each of the blood coagulation characteristic sampled data based on a search step size;
determining a coagulation start time and a coagulation end time based on the slope. Specifically, the acquired blood coagulation characteristic sampling data may be subjected to slope calculation, and the coagulation start time and the coagulation end time may be determined based on the slope corresponding to each blood coagulation characteristic sampling data.
The slope may be calculated as follows:
sampling data for each of said blood coagulation characteristics:
taking the current blood coagulation characteristic sampling data as first blood coagulation characteristic sampling data, taking sampling time corresponding to the first blood coagulation characteristic sampling data as current sampling time, wherein the blood coagulation characteristic sampling data is electrical characteristic data obtained by testing;
taking the sampling time obtained by adding the search step length to the current sampling time as the sampling time to be calculated, and taking the blood coagulation characteristic sampling data corresponding to the sampling time to be calculated as second blood coagulation characteristic sampling data;
calculating the corresponding search slope of the first blood coagulation characteristic sampling data as follows: (first blood coagulation characteristic sample data-second blood coagulation characteristic sample data)/search step.
Figure 3 illustrates a typical coagulation curve. The coagulation curve has five main stages:
in the first stage, before blood is dropped into the reagent card, the two electrodes have no liquid communication, so that the reagent card has larger resistance.
In the second stage, blood is dropped into the reagent card, and the plasma fills the reagent groove, so that the resistance between the two electrodes is reduced sharply.
In the third stage, the red blood cells in the blood are uniformly filled in the reagent card, so that the resistance between the two electrodes is increased.
In the fourth stage, the red blood cells in the rear part of the reagent tank slowly move to the front end of the reagent tank due to capillary action, so that the resistance between the two electrodes is reduced.
And in the fifth stage, because of the coagulation waterfall reaction, the blood coagulation hinders the forward movement of the red blood cells, and the resistance change between the two electrodes is small after the point.
As can be seen from fig. 3, the slope of the coagulation curve changes significantly at different stages, for example, when plasma fills the reagent tank, the slope corresponding to the blood coagulation characteristic sampling data changes specifically, and the coagulation start time can be determined by the change. When the red blood cells slowly move forward to reach a certain time and are coagulated, the slope corresponding to the blood coagulation characteristic sampling data also changes specifically, and the coagulation finishing time can be judged according to the change.
Then, the difference between the coagulation completion time and the coagulation start time may be used as the coagulation time in step S103.
In one embodiment, the search step comprises a start point search step and an end point search step;
the calculating of the corresponding slope for each of the blood coagulation characteristic sampling data based on the search step length specifically includes:
calculating a corresponding starting point search slope for each of the blood coagulation characteristic sample data based on the starting point search step length, and calculating a corresponding end point search slope for each of the blood coagulation characteristic sample data based on the end point search step length;
determining a coagulation start time and a coagulation end time based on the slope, specifically comprising:
determining a coagulation start time based on the start point search slope, and determining a coagulation end time based on the end point search slope.
Blood coagulation property sampling data requires preprocessing of the data. The preprocessing includes calculation of the step size. The step size calculation can be done in a number of ways including, but not limited to, estimation by curve fitting the abstract results. The step value can also be obtained by a preset value or by a comprehensive weighting of the preset value and the curve fitting result. In this embodiment, different search steps are used for the start point and the end point, so that different slopes can be used to determine the coagulation start time and the coagulation end time, respectively. The starting point search step may adopt a preset value, preferably two points, that is, the starting point search slope of each blood coagulation characteristic sampling data is preferably (first blood coagulation characteristic sampling data — blood coagulation characteristic sampling data after two points)/2.
In one embodiment, the starting point searching step is a preset value.
In one embodiment, the end point search step size is determined as follows:
performing multiple polynomial curve fitting on the blood coagulation characteristic sampling data by using a plurality of fitting terms to obtain a plurality of fitting curves with the fitting terms as parameters;
according to the blood coagulation test type, selecting a fitting curve which meets a preset selection rule from the fitting curves as a reference fitting curve, and taking the number of fitting terms of the reference fitting curve as the number of reference fitting terms;
and calculating the end point search step length according to the reference fitting term number.
The existing polynomial curve fitting mode can be adopted to perform curve fitting on the blood coagulation characteristic sampling data so as to obtain a fitting curve. And (4) trying different fitting terms during fitting, determining the number of fitting terms according to a selection rule, and calculating to obtain the end point search step length. There are various methods for calculating the step size by the number of fitting terms, and in this embodiment, the number of fitting terms and the step size are considered to be in a direct proportion relationship, that is, the end point search step size is equal to the number of reference fitting terms/preset value.
In one embodiment, the selection rule includes:
if the blood coagulation test type is an activated partial thromboplastin time test or an activated blood coagulation time test, selecting a fitting curve with the largest fitting error as a reference fitting curve;
selecting a fitting curve with the smallest fitting error as a reference fitting curve if the coagulation test type is a thrombin time test, or a prothrombin time test.
In the embodiment, different fitting terms are adopted for different coagulation tests as the basis for step size calculation, for example, for a curve with a large data size such as APTT/ACT, the fitting term number of the fitting curve with the largest fitting error is used for calculating to obtain the end point search step size, because the fitting term number with the largest fitting error can reflect the trend of the curve to a greater extent and eliminate the noise influence; and calculating the end point search step length by using the fitting term number of the fitting curve with the minimum fitting error for the curve with smaller data quantity, such as TT/PT, because the fitting term number with the minimum fitting error can keep more details of the curve with smaller data quantity.
After the pretreatment, a secondary analysis of the data was started, including a search for the coagulation start time and coagulation end time.
In one embodiment, the determining the coagulation start time based on the start point search slope specifically includes:
the sampling time corresponding to the blood coagulation characteristic sampling data with the largest slope is selected as the coagulation start time.
The main basis of the coagulation start time search is the first curve change of the coagulation curve expressed in the low-dimensional space, for example, the slope change is the most commonly used basis for measuring the low-dimensional space, but the method for searching the coagulation start time includes but is not limited to the judgment by the slope, including any other curve change points based on the low-dimensional space characteristics. The coagulation start time search of the present embodiment is to calculate the start point search slope based on the start point search step size to determine the coagulation start time. The starting point search step may adopt a preset value, preferably two points, that is, the starting point search slope of each blood coagulation characteristic sampling data is preferably (first blood coagulation characteristic sampling data — blood coagulation characteristic sampling data after two points)/2. As can be seen from FIG. 4a, the slope of the reagent tank continuously increases when the second stage plasma fills the reagent tank, and then the slope increases to the highest point and then reverses, and the sampling time corresponding to the highest point is the coagulation start time. Therefore, in the present embodiment, the sampling time corresponding to the blood coagulation characteristic sampling data having the largest slope is searched for as the coagulation start time.
In one embodiment, the determining the coagulation end time based on the end point search slope specifically includes:
determining a continuous same slope period or a negative slope period based on the end point search slope after a preset peak interference period following the coagulation start time;
and taking the starting time of the continuous same slope time period or the starting time of the negative slope time period as the coagulation finishing time.
The embodiment performs a coagulation end time search, in which the coagulation data needs to be subjected to feature extraction from a high-dimensional space to a low-dimensional space once, that is, the coagulation end time is found by analyzing the slope of a low-dimensional space feature curve. The method specifically comprises the following steps:
the coagulation end time search start point is first moved backward. As shown in fig. 3, after the second stage coagulation is started, a peak is formed due to the curves of the third and fourth stages. The appearance of peaks interferes with the search for the end time of coagulation in the fifth stage. Therefore, it is necessary to start searching for the coagulation end time after the peak interference period to avoid the peak interference. The peak interference time period can be derived using preset values for different coagulation tests or a combined weighting of preset values and curve data volume. Next, the slope of the low-dimensional spatial characteristic curve of the blood coagulation characteristic sampling data points is calculated after the start point of the coagulation end time search based on the previously calculated step length, i.e., the end point search slope of each blood coagulation characteristic sampling data is (first blood coagulation characteristic sampling data — blood coagulation characteristic sampling data after the step length point)/step length.
The invention provides a blood coagulation spot estimation method based on the slope of a low-dimensional space characteristic curve, which comprises the following steps: 1) constant data slope: when the data change is continuous, but the data slope is constant. This indicates that the data curve is actually in a steady state, and that the data segment and data point may be the end-of-coagulation time; 2) zero data slope: the lowest data rate of change is the slowest minimum point of change in the low-dimensional features, typically indicating that no change has occurred in the data over this time window. The most common measure of this change is the slope of the low dimensional feature, so this time the slope is zero and the point at which the slope remains zero for a time window is the likely end-of-coagulation time; 3) constant data rate of change based on a smooth window of 1, 2: for a data segment with relatively large noise, although the data change appears jaggy in a low-dimensional space, the data change is a characteristic of data stability and no change. Is also a possible end-time for coagulation; 4) negative data slope: a negative slope of the data change in the low dimensional feature space, which indicates a break in the data change, which in practice is also a possible end-of-coagulation time; 5) most significant data change points: in some actual coagulation data, the most significant point of change in the data, such as a slope extremum, may indicate the end of coagulation. In the part, the priority of the blood coagulation end point estimation method can be set according to an empirical value, different algorithm jumping strategies can also be set, and subsequent algorithm processing is skipped when the first blood coagulation end time with higher feasibility is found, so that the requirement of rapidness and real-time is met.
Therefore, the search for the coagulation end time of the present embodiment includes the search for the continuous slope point and the search for the negative slope point. Wherein the finding of consecutive slope points comprises finding of consecutive positive slope points and finding of consecutive zero slope points. The continuous slope point can be considered as the coagulation end time because the erythrocyte movement stops after the coagulation reaction occurs, resulting in a plateau in the resistance change. The negative slope point can be regarded as the coagulation end time because fibrin cross-links to form a network structure after coagulation occurs, resulting in an increase in electrical resistance, which is reflected in a negative slope.
In one embodiment, the determining a time period with a continuous same slope based on the endpoint search slope specifically includes:
if a plurality of continuous blood coagulation characteristic sampling data with consistent end point search slopes and positive slopes exist, and the number of the blood coagulation characteristic sampling data reaches a preset first number threshold, taking a time period corresponding to the blood coagulation characteristic sampling data with consistent end point search slopes as a continuous same slope time period, or;
if a plurality of continuous blood coagulation characteristic sampling data with the end point search slope of zero exist, and the number of the continuous blood coagulation characteristic sampling data reaches a preset second number threshold, taking a time period corresponding to the blood coagulation characteristic sampling data with the end point search slope of zero as a continuous same slope time period;
wherein, the end point search slopes are consistent, specifically: the difference of the end point search slopes is within a preset difference threshold range.
Specifically, if there are points that have consecutive identical end points searching for a slope and are positive, and the number reaches a first number threshold, for example: 50, recording parameters, stopping searching for points with continuous same slope, if the points with continuous same end point searching slope appear but the number is less than a first number threshold, returning to check whether the end point searching slope of the previous point has a small amount of fluctuation, if so, ignoring the fluctuation and counting, and stopping searching when the threshold is reached; if not, the flush count continues with the forward search.
And the second quantity threshold is used for searching a plurality of blood coagulation characteristic sampling data with zero endpoint search slope, and since the blood coagulation characteristic sampling data with zero endpoint search slope can reflect the end of blood coagulation, the second quantity threshold may be smaller than the first quantity threshold, preferably, the first quantity threshold is 50 and the second quantity threshold is 15.
For the case of a continuous slope, as shown in fig. 4b and 4c, the end-of-coagulation time can be derived jointly with reference to the recorded parameters, the corresponding threshold value and the step size. For example, the parameter coagulation end time (recorded parameter-threshold + step size) is the time to which the parameter corresponds, i.e. the start time of a period of consecutive identical slopes.
For the negative slope case, the end-of-coagulation time is the time at which the recorded parameter corresponds, i.e., the time at which the negative slope point occurs.
In one embodiment, the selecting the start time of the consecutive same slope time period or the start time of the negative slope time period as the coagulation end time specifically includes:
calculating a first difference value between the starting time of the negative slope time period and the blood coagulation starting time, and if the first difference value is within a preset first time range, selecting the starting time of the negative slope time period as the blood coagulation finishing time, otherwise;
calculating a second difference value between the starting time of the continuous same slope time period and the coagulation starting time, if the second difference value is out of a preset second time range and the starting time of the continuous same slope time period is less than the starting time of the negative slope time period, selecting the starting time of the negative slope time period as the coagulation finishing time, if the second difference value is out of the preset second time range and the starting time of the continuous same slope time period is greater than the starting time of the negative slope time period, selecting the starting time of the continuous same slope time period as the coagulation finishing time, otherwise;
selecting a start time of a period of consecutive same slope as the coagulation end time if the second difference is within a preset second time range.
This example separately judges the negative slope and the same slope to select an appropriate coagulation finish time. Since the end-point search slope is negative for blood coagulation property sample data more reflecting the end of coagulation, the parameter appearing when the negative slope point appears is recorded as shown in fig. 4 d.
Fig. 5 is a flowchart illustrating a coagulation time determination method according to a preferred embodiment of the present invention, including:
step S501, reading a txt file comprising blood coagulation characteristic sampling data, and setting parameters;
step S502, checking whether the file is a new file, if so, executing step S503, otherwise, numbering the file, resetting the time, and executing step S503;
step S503, fitting a curve by a polynomial fitting function, trying polynomial fitting of different terms, searching the fitting term with the maximum fitting error, and then calculating the end point search step length by using the term;
step S504, the slope of the blood coagulation characteristic sampling data after two points of each blood coagulation characteristic sampling data is calculated and used as a starting point to search for the slope, and the point with the maximum starting point searching slope is used as a blood coagulation starting point.
Step S505, setting parameters and emptying variables to prepare for the next step;
step S506, searching the coagulation finishing time for 150 after the initial index is adjusted, and avoiding peak interference;
step S507, starting to search the initial index position at the blood coagulation finishing time, and calculating the slope of each blood coagulation characteristic sampling data to the blood coagulation characteristic sampling data after the distance from the end point search step length as an end point search slope;
step S508, if the blood coagulation characteristic sampling data with the same continuous endpoint search slope and the number of the blood coagulation characteristic sampling data reaches 50, recording the sampling time of the blood coagulation characteristic sampling data with the same final endpoint search slope as the continuous slope time, and stopping the continuous same slope point search.
Step S509, if the blood coagulation characteristic sampling data with the same continuous endpoint search slope exists and the number is between 5 and 50, returning to check whether the endpoint search slope of the previous blood coagulation characteristic sampling data has a small amount of fluctuation, if so, ignoring the fluctuation and counting, if the threshold is reached, recording the sampling time of the blood coagulation characteristic sampling data with the same endpoint search slope as the end time of the continuous slope, stopping the search, and if not, emptying the count and continuing the forward search;
step S510, if blood coagulation characteristic sampling data with a continuous endpoint search slope of zero appears and the number reaches 15, recording the sampling time of the blood coagulation characteristic sampling data with the last endpoint search slope of zero as the end time of the continuous slope, and stopping searching;
step S511, if the blood coagulation characteristic sampling data with the end point search slope being negative appears, recording the sampling time of the blood coagulation characteristic sampling data with the first end point search slope being negative as the negative slope time;
step S512, obtaining the blood coagulation time of each channel based on the initial time and the negative slope time of the continuous slope;
and step S513, determining the blood coagulation time value and carrying out error check on the data. For example, if the optimal clotting time estimate determined by the above-described data analysis screening is within an empirically allowable range, then this clotting time will be displayed to the user. However, if the optimal coagulation time estimate determined by the above-described data analysis screening is within an abnormal empirically allowable range, the system displays the estimation failure to the user.
FIG. 6 is a flow chart of the operation of the preferred embodiment of the present invention for obtaining the coagulation time based on the continuous slope time and the negative slope time, which comprises:
step S601, calculating negative slope time-blood coagulation start time, if the time is within (100, 300), taking the negative slope time as blood coagulation end time, executing step S604, otherwise executing step S602, wherein 100 and 300 are the number of data points, the data is suitable for acquiring three points in one second, and the time is converted into 33 seconds and 100 seconds;
step S602, calculating a continuous slope starting time-coagulation starting time, if the continuous slope starting time-coagulation starting time is within (100, 300), taking the continuous slope time as a coagulation finishing time, and executing step S604, otherwise executing step S603;
step S603, calculating a continuous slope time-negative slope time, if the continuous slope time-negative slope time is less than or equal to 0, performing step S604 with the negative slope time as a coagulation end time, otherwise performing step S604 with the continuous slope time as the coagulation end time;
in step S604, the coagulation time is displayed as the coagulation end time-coagulation start time.
Fig. 7 is a schematic diagram of a hardware structure of an electronic device 1 according to the present invention, which includes:
at least one processor 701; and the number of the first and second groups,
a memory 702 communicatively coupled to the at least one processor 701; wherein,
the memory 702 stores instructions executable by the one processor to cause the at least one processor to:
obtaining a plurality of blood coagulation characteristic sampling data sampled over time in a coagulation test;
determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data;
the clotting time is determined from the clotting start time and the clotting end time.
In fig. 7, one processor 702 is taken as an example.
The electronic device may further include: an input device 703 and an output device 704.
The processor 701, the memory 702, the input device 703 and the display device 704 may be connected by a bus or other means, and are illustrated as being connected by a bus.
The processor 701 may be a general purpose processor (CPU), a dedicated digital signal processing chip (DSP), or an FPGA.
The memory 702 is a non-volatile computer-readable storage medium, and can be used for storing non-volatile software programs, non-volatile computer-executable programs, and modules, such as program instructions/modules corresponding to the blood coagulation time determination method in the embodiments of the present application, for example, the method flows shown in fig. 1, 5, and 6. The processor 701 executes various functional applications and data processing, that is, implements the coagulation time determination method in the above-described embodiment, by executing the nonvolatile software program, instructions, and modules stored in the memory 702.
The memory 702 may include a storage program area and a storage data area, wherein the storage program area may store an operating system, an application program required for at least one function; the storage data area may store data created according to the use of the coagulation time determination method, such as intermediate results of systematic operation and final coagulation data. Further, the memory 702 may include high speed random access memory, and may also include non-volatile memory, such as at least one magnetic disk storage device, flash memory device, or other non-volatile solid state storage device. In some embodiments, the memory 702 optionally includes memory located remotely from the processor 701, and these remote memories may be connected over a network to a device that performs the clotting time determination method. Examples of such networks include, but are not limited to, the internet, intranets, local area networks, mobile communication networks, and combinations thereof.
The input device 703 may receive input of user clicks and generate signal inputs related to user settings and function control of the coagulation time determination method. Display device 704 may include a display screen or the like.
The clotting time determination method of any of the method embodiments described above is performed when the one or more modules are stored in the memory 702 and executed by the one or more processors 701.
In one embodiment, the determining the coagulation start time and the coagulation end time based on the blood coagulation characteristic sampling data specifically includes: calculating a corresponding slope for each of the blood coagulation characteristic sampled data based on a search step size;
determining a coagulation start time and a coagulation end time based on the slope.
In one embodiment, the search step comprises a start point search step and an end point search step;
the calculating of the corresponding slope for each of the blood coagulation characteristic sampling data based on the search step length specifically includes:
calculating a corresponding starting point search slope for each of the blood coagulation characteristic sample data based on the starting point search step length, and calculating a corresponding end point search slope for each of the blood coagulation characteristic sample data based on the end point search step length;
determining a coagulation start time and a coagulation end time based on the slope, specifically comprising:
determining a coagulation start time based on the start point search slope, and determining a coagulation end time based on the end point search slope.
In one embodiment, the starting point searching step is a preset value.
In one embodiment, the end point search step size is determined as follows:
performing multiple polynomial curve fitting on the blood coagulation characteristic sampling data by using a plurality of fitting terms to obtain a plurality of fitting curves with the fitting terms as parameters;
according to the blood coagulation test type, selecting a fitting curve which meets a preset selection rule from the fitting curves as a reference fitting curve, and taking the number of fitting terms of the reference fitting curve as the number of reference fitting terms;
and calculating the end point search step length according to the reference fitting term number.
In one embodiment, the selection rule includes:
if the blood coagulation test type is an activated partial thromboplastin time test or an activated blood coagulation time test, selecting a fitting curve with the largest fitting error as a reference fitting curve;
selecting a fitting curve with the smallest fitting error as a reference fitting curve if the coagulation test type is a thrombin time test, or a prothrombin time test.
In one embodiment, the determining the coagulation start time based on the start point search slope specifically includes:
the sampling time corresponding to the blood coagulation characteristic sampling data with the largest slope is selected as the coagulation start time.
In one embodiment, the determining the coagulation end time based on the end point search slope specifically includes:
determining a continuous same slope period or a negative slope period based on the end point search slope after a preset peak interference period following the coagulation start time;
selecting a start time of the consecutive same slope time period, or a start time of the negative slope time period as the coagulation end time.
In one embodiment, the determining a time period with a continuous same slope based on the endpoint search slope specifically includes:
if a plurality of continuous blood coagulation characteristic sampling data with consistent end point search slopes and positive slopes exist, and the number of the blood coagulation characteristic sampling data reaches a preset first number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with consistent end point search slopes as a continuous same slope time period, or;
if a plurality of continuous blood coagulation characteristic sampling data with the end point search slope of zero exist, and the number of the continuous blood coagulation characteristic sampling data reaches a preset second number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with the end point search slope of zero as a continuous same slope time period;
wherein, the end point search slopes are consistent, specifically: the difference of the end point search slopes is within a preset difference threshold range.
In one embodiment, the selecting the start time of the consecutive same slope time period or the start time of the negative slope time period as the coagulation end time specifically includes:
calculating a first difference value between the starting time of the negative slope time period and the blood coagulation starting time, and if the first difference value is within a preset first time range, selecting the starting time of the negative slope time period as the blood coagulation finishing time, otherwise;
calculating a second difference value between the starting time of the continuous same slope time period and the coagulation starting time, if the second difference value is out of a preset second time range and the starting time of the continuous same slope time period is less than the starting time of the negative slope time period, selecting the starting time of the negative slope time period as the coagulation finishing time, if the second difference value is out of the preset second time range and the starting time of the continuous same slope time period is greater than the starting time of the negative slope time period, selecting the starting time of the continuous same slope time period as the coagulation finishing time, otherwise;
selecting a start time of a period of consecutive same slope as the coagulation end time if the second difference is within a preset second time range.
Fig. 8 shows a schematic architecture of a system for collecting and processing coagulation data from a real-time blood collection device, as a preferred embodiment of the present invention.
The system comprises an electronic device 1 as shown in fig. 7, and a real-time blood data characterisation recorder 2 which can record coagulation process data. Such an analyzer recorder may also be an off-line data recording instrument, the system being powered by a mobile or fixed power supply 6.
The system shown in fig. 8 may implement a real-time parallel historical data analysis module 3 that is used to improve the performance of real-time coagulation estimation of a particular sample. The parallel historical data analysis module can be historical data of the same patient or historical data of a large sample of the same patient group.
The system shown in fig. 8 can implement a wireless internet of things communication module 4 to perform local area network communication with other similar devices, so as to implement coagulation estimation analysis of large-scale big data. The data transmitted by the wireless Internet of things communication module can be input into the real-time parallel historical data analysis module for comprehensive analysis. The wireless internet of things communication module can also be upwards accessed to a metacomputing or cloud storage platform of a wide area network, and background analysis is carried out by the cloud resources.
The system shown in fig. 8 may be implemented in connection with the printing device 5 to print the real-time intermediate data and any coagulation data. It is also contemplated that the display may be used to display real-time intermediate data and any coagulation data.
The present invention provides a storage medium storing computer instructions for performing all the steps of the coagulation time determination method as described above when the computer executes the computer instructions.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (19)

1. A coagulation time determination method comprising:
obtaining a plurality of blood coagulation characteristic sampling data sampled over time in a coagulation test;
determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data;
the clotting time is determined from the clotting start time and the clotting end time.
2. The coagulation time determination method according to claim 1, wherein the determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data specifically includes: calculating a corresponding slope for each of the blood coagulation characteristic sampled data based on a search step size;
determining a coagulation start time and a coagulation end time based on the slope.
3. The coagulation time determination method according to claim 2, wherein the search step includes a start point search step and an end point search step;
the calculating of the corresponding slope for each of the blood coagulation characteristic sampling data based on the search step length specifically includes:
calculating a corresponding starting point search slope for each of the blood coagulation characteristic sample data based on the starting point search step length, and calculating a corresponding end point search slope for each of the blood coagulation characteristic sample data based on the end point search step length;
determining a coagulation start time and a coagulation end time based on the slope, specifically comprising:
determining a coagulation start time based on the start point search slope, and determining a coagulation end time based on the end point search slope.
4. The coagulation time determination method according to claim 3, wherein the end point search step is determined as follows:
performing multiple polynomial curve fitting on the blood coagulation characteristic sampling data by using a plurality of fitting terms to obtain a plurality of fitting curves with the fitting terms as parameters;
according to the blood coagulation test type, selecting a fitting curve which meets a preset selection rule from the fitting curves as a reference fitting curve, and taking the number of fitting terms of the reference fitting curve as the number of reference fitting terms;
and calculating the end point search step length according to the reference fitting term number.
5. The coagulation time determination method according to claim 4, wherein the selection rule includes:
if the blood coagulation test type is an activated partial thromboplastin time test or an activated blood coagulation time test, selecting a fitting curve with the largest fitting error as a reference fitting curve;
selecting a fitting curve with the smallest fitting error as a reference fitting curve if the coagulation test type is a thrombin time test, or a prothrombin time test.
6. The coagulation time determination method according to claim 3, wherein the determining a coagulation start time based on the start point search slope specifically includes:
the sampling time corresponding to the blood coagulation characteristic sampling data with the largest slope is selected as the coagulation start time.
7. The coagulation time determination method according to claim 3, wherein the determining a coagulation end time based on the end point search slope specifically includes:
determining a continuous same slope period or a negative slope period based on the end point search slope after a preset peak interference period following the coagulation start time;
selecting a start time of the consecutive same slope time period, or a start time of the negative slope time period as the coagulation end time.
8. The coagulation time determination method according to claim 7, wherein the determining of the continuous same slope period based on the endpoint search slope specifically includes:
if a plurality of continuous blood coagulation characteristic sampling data with consistent end point search slopes and positive slopes exist, and the number of the blood coagulation characteristic sampling data reaches a preset first number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with consistent end point search slopes as a continuous same slope time period, or;
if a plurality of continuous blood coagulation characteristic sampling data with the end point search slope of zero exist, and the number of the continuous blood coagulation characteristic sampling data reaches a preset second number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with the end point search slope of zero as a continuous same slope time period;
wherein, the end point search slopes are consistent, specifically: the difference of the end point search slopes is within a preset difference threshold range.
9. The coagulation time determination method according to claim 7, wherein the selecting the start time of the consecutive same slope period or the start time of the negative slope period as the coagulation end time specifically includes:
calculating a first difference value between the starting time of the negative slope time period and the blood coagulation starting time, and if the first difference value is within a preset first time range, selecting the starting time of the negative slope time period as the blood coagulation finishing time, otherwise;
calculating a second difference value between the starting time of the continuous same slope time period and the coagulation starting time, if the second difference value is out of a preset second time range and the starting time of the continuous same slope time period is less than the starting time of the negative slope time period, selecting the starting time of the negative slope time period as the coagulation finishing time, if the second difference value is out of the preset second time range and the starting time of the continuous same slope time period is greater than the starting time of the negative slope time period, selecting the starting time of the continuous same slope time period as the coagulation finishing time, otherwise;
selecting a start time of a period of consecutive same slope as the coagulation end time if the second difference is within a preset second time range.
10. An electronic device, comprising:
at least one processor; and the number of the first and second groups,
a memory communicatively coupled to the at least one processor; wherein,
the memory stores instructions executable by the at least one processor to enable the at least one processor to:
obtaining a plurality of blood coagulation characteristic sampling data sampled over time in a coagulation test;
determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data;
the clotting time is determined from the clotting start time and the clotting end time.
11. The electronic device according to claim 10, wherein the determining a coagulation start time and a coagulation end time based on the blood coagulation characteristic sampling data specifically comprises: calculating a corresponding slope for each of the blood coagulation characteristic sampled data based on a search step size;
determining a coagulation start time and a coagulation end time based on the slope.
12. The electronic device of claim 10, wherein the search step size comprises a start point search step size and an end point search step size;
the calculating of the corresponding slope for each of the blood coagulation characteristic sampling data based on the search step length specifically includes:
calculating a corresponding starting point search slope for each of the blood coagulation characteristic sample data based on the starting point search step length, and calculating a corresponding end point search slope for each of the blood coagulation characteristic sample data based on the end point search step length;
determining a coagulation start time and a coagulation end time based on the slope, specifically comprising:
determining a coagulation start time based on the start point search slope, and determining a coagulation end time based on the end point search slope.
13. The electronic device of claim 12, wherein the endpoint search step size is determined by:
performing multiple polynomial curve fitting on the blood coagulation characteristic sampling data by using a plurality of fitting terms to obtain a plurality of fitting curves with the fitting terms as parameters;
according to the blood coagulation test type, selecting a fitting curve which meets a preset selection rule from the fitting curves as a reference fitting curve, and taking the number of fitting terms of the reference fitting curve as the number of reference fitting terms;
and calculating the end point search step length according to the reference fitting term number.
14. The electronic device of claim 13, wherein the selection rule comprises:
if the blood coagulation test type is an activated partial thromboplastin time test or an activated blood coagulation time test, selecting a fitting curve with the largest fitting error as a reference fitting curve;
selecting a fitting curve with the smallest fitting error as a reference fitting curve if the coagulation test type is a thrombin time test, or a prothrombin time test.
15. The electronic device according to claim 12, wherein determining a coagulation start time based on the start point search slope comprises:
the sampling time corresponding to the blood coagulation characteristic sampling data with the largest slope is selected as the coagulation start time.
16. The electronic device according to claim 12, wherein the determining a coagulation end time based on the endpoint search slope comprises:
determining a continuous same slope period or a negative slope period based on the end point search slope after a preset peak interference period following the coagulation start time;
selecting a start time of the consecutive same slope time period, or a start time of the negative slope time period as the coagulation end time.
17. The electronic device according to claim 16, wherein the determining of the continuous same slope time period based on the endpoint search slope specifically comprises:
if a plurality of continuous blood coagulation characteristic sampling data with consistent end point search slopes and positive slopes exist, and the number of the blood coagulation characteristic sampling data reaches a preset first number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with consistent end point search slopes as a continuous same slope time period, or;
if a plurality of continuous blood coagulation characteristic sampling data with the end point search slope of zero exist, and the number of the continuous blood coagulation characteristic sampling data reaches a preset second number threshold, taking a sampling time period corresponding to the blood coagulation characteristic sampling data with the end point search slope of zero as a continuous same slope time period;
wherein, the end point search slopes are consistent, specifically: the difference of the end point search slopes is within a preset difference threshold range.
18. The electronic device according to claim 16, wherein the selecting the start time of the consecutive same slope time period or the start time of the negative slope time period as the coagulation end time specifically comprises:
calculating a first difference value between the starting time of the negative slope time period and the blood coagulation starting time, and if the first difference value is within a preset first time range, selecting the starting time of the negative slope time period as the blood coagulation finishing time, otherwise;
calculating a second difference value between the starting time of the continuous same slope time period and the coagulation starting time, if the second difference value is out of a preset second time range and the starting time of the continuous same slope time period is less than the starting time of the negative slope time period, selecting the starting time of the negative slope time period as the coagulation finishing time, if the second difference value is out of the preset second time range and the starting time of the continuous same slope time period is greater than the starting time of the negative slope time period, selecting the starting time of the continuous same slope time period as the coagulation finishing time, otherwise;
selecting a start time of a period of consecutive same slope as the coagulation end time if the second difference is within a preset second time range.
19. A storage medium storing computer instructions for performing all the steps of the coagulation time determination method according to any one of claims 1 to 9 when the computer instructions are executed by a computer.
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CN110967306A (en) * 2019-11-14 2020-04-07 迈克医疗电子有限公司 Method and apparatus for determining reaction stability start time, analyzer, and storage medium
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