JP6799245B2 - How to measure changes in the amount of fibrin in blood - Google Patents

Description

The present invention relates to a method of estimating the presence or absence of blood coagulation such as a thrombus from the outside of a blood flow path, and more particularly to a method of continuously measuring a change in the amount of fibrin in order to continuously obtain information on the formation of a thrombus.

Thrombosis due to adhesion of coagulated blood to the walls of blood vessels is known to cause circulatory diseases such as cerebral infarction and economy syndrome. In addition, in medical treatment such as artificial heart-lung machine and blood dialysis, in which blood is coagulated through a blood flow path in a device that guides blood to the outside of the body, it may become a thrombus when the blood is returned to the body. .. Further, if the blood is coagulated, it may stay in the blood flow path of the device and cause a malfunction of the device. Therefore, there is a need for a method that can estimate the presence or absence of blood coagulation such as thrombus from the outside of blood vessels and blood flow paths.

For example, in Patent Document 1, as a method of estimating the presence or absence of coagulation of blood, a laser beam having a wavelength of 600 to 1200 nm is incident on the blood layer, a change in the amount of transmitted light or reflected light is measured, and the blood is flowing. It discloses a method of detecting a thrombus floating in blood from the outside of a blood vessel. In a thrombus, a partial difference in hemoglobin density can be measured as a change in the amount of transmitted light or reflected light, whereby the thrombus can be detected. The blood composition other than thrombus such as hematocrit changes depending on the blood flow, and the amount of light can also be changed by this, but it is a gradual change compared to the change in the amount of light due to the blood clot that moves by the flow of blood, and the blood clot It is said that it can be identified.

Further, in Patent Document 2, as a method of estimating the presence or absence of coagulation of blood, an optical monitoring means and an ultrasonic monitoring means are installed in the blood flow path, and an individual such as a clot due to coagulation of flowing blood is transmitted through light. It discloses a method of detecting by change. The optical monitoring means includes a light source that irradiates a narrow band near-infrared light having a wavelength of about 805 nm and an optical sensor installed on the opposite side of the blood flow path, and the change in the transmitted light from the light source causes the blood to flow. It detects lumps due to solidification. Near-infrared light of such wavelength is absorbed by hemoglobin in erythrocytes very little and is irrelevant to oxygen contained in it, so that it is suitable for detecting a mass due to blood coagulation. Although air bubbles in the blood are also detected by the optical monitoring means, they are also detected by the ultrasonic monitoring means at the same time, so that they can be distinguished from the clots due to blood coagulation.

In the methods disclosed in Patent Documents 1 and 2, thrombi and the like that move based on the time change of the amount of transmitted light or reflected light are detected. On the other hand, there is also known a method that can estimate the presence or absence of blood coagulation regardless of the temporal change in the amount of light.

For example, in Patent Document 3, as a method of estimating the presence or absence of coagulation of blood, a white light source is used, and a reference wavelength on the short wavelength side and a measurement wavelength on the long wavelength side having a wavelength of 600 nm or more and sandwiching 670 nm are used. A method is disclosed in which a blood flow path is continuously imaged by transmitted light or scattered light (reflected light) of two wavelengths to obtain a difference in brightness of an image depending on a measurement wavelength with respect to an image at a reference wavelength. When blood coagulates, the transparency of light of 670 nm or more increases. That is, the brightness of the image due to the transmitted light at the measurement wavelength becomes high, and the brightness of the image due to the scattered light becomes low, and the solidified portion can be detected by obtaining the difference between any of these and the image at the reference wavelength. .. In this way, since the difference in intensity of transmitted light or scattered light of different wavelengths is used, the presence or absence of blood coagulation can be estimated regardless of the temporal change in the amount of light.

Special Table 2002-345787 Special Table 2013-534160 Japanese Unexamined Patent Publication No. 2015-152480

By the way, a thrombus is formed by coagulating fibrin fibrin produced from fibrinogen in blood. That is, by measuring the change in the amount of fibrin, it is possible to estimate the coagulation of blood, the formation of thrombus, and the probability of its occurrence. Here, since fibrin also gives a change in the intensity of transmitted light and scattered light depending on the amount of red blood cells, the change in the amount of fibrin can be measured by measuring the scattered light intensity. However, since it interferes with the scattered component by red blood cells in the scattered light intensity, it is difficult to extract and detect only the scattered component of the amount of fibrin. Further, even if an attempt is made to measure the amount of red blood cells so as to remove the scattered component by red blood cells, it is difficult to continuously measure the change in the amount of fibrin because a step such as taking out blood and centrifuging is required.

The present invention has been made in view of the above circumstances, and an object of the present invention is to continuously change the amount of fibrin in order to continuously obtain information such as thrombus formation and its occurrence probability. The purpose is to provide a method of measurement.

It is known that the intensity ratio of scattered light by erythrocytes decreases significantly from the short wavelength side to the long wavelength side across a wavelength region of 584 to 600 nm. In the intensity ratios of scattered light R _λ1 and R _{λ2 at the} short wavelength side wavelength λ1 and the long wavelength side wavelength λ2 that sandwich this wavelength region, the intensity ratio of the scattered light by erythrocytes is on the long wavelength side on the short wavelength side. Greater than, and very sensitive to change. On the other hand, the intensity ratio of scattered light by fibrin is almost the same. Therefore, if the contribution of red blood cells to the scattered light can be removed on the long wavelength side where the measured intensity ratio is stable, the scattered light by fibrin can be obtained. However, on the long wavelength side, the scattered light intensities of erythrocytes and fibrin are close to each other, and separation is difficult. Therefore, the hematocrit value related to the intensity ratio of scattered light by erythrocytes is assumed from the intensity ratio R _λ2 of scattered light on the long wavelength side, thereby _changing from the intensity ratio R _λ1 of scattered light on the short wavelength side to scattered light by erythrocytes. The idea is to eliminate the contribution of.

That is, the measurement method according to the present invention is a method of continuously measuring the change in the amount of fibrin of the blood flowing in the flow path of the blood circulation device that takes out the blood from the body and returns it to the body, The scattered light that is scattered by giving incident light from the side is measured, and the scattered light with respect to the incident light at each of the short wavelength side wavelength λ1 and the long wavelength side wavelength λ2 that sandwich the wavelength region of 584 to 600 nm. In an optical device that continuously measures the intensity ratios R _λ1 and R _λ2 , the hematocrit value at the intensity ratio R _λ2 removes the contribution of red blood cells to scattered light at the intensity ratio R _λ1 and changes the amount of fibrin. Is characterized by giving.

According to such an invention, the change in the amount of fibrin can be continuously measured. In other words, it is possible to continuously obtain information such as thrombus formation and its occurrence probability from changes in the amount of fibrin required for coagulation.

In the above invention, if the function of the intensity ratio R _{λ1 with} respect to the hematocrit value H at the wavelength λ1 is f, and the function of the intensity ratio R _{λ2 with} respect to the hematocrit value H at the wavelength λ2 is g, then R _λ1 = f (H) and R _λ2 = g (H), the hematocrit value at the intensity ratio R _λ2 is represented by g ^-1 (R _λ2 ), and the change in the amount of fibrin is f (g) with respect to R _λ1 . ^It may be characterized by giving by a change of ^-1 (R _{λ 2} )). According to such an invention, this can be expressed from the intensity ratio of scattered light without using the hematocrit value, and the change in the amount of fibrin can be continuously measured in correspondence with the intensity ratio of scattered light.

In the above invention, the fibrin amount change may be given by f (g ^-1 (R _{λ 2} )) / R _{λ 1} . Further, in the above invention, the fibrin amount change may be given by f (g ^-1 (R _{λ 2} )) − R _{λ 1} . According to such an invention, the change in the amount of fibrin can be obtained relatively easily from the intensity ratio of scattered light, and the change in the amount of fibrin can be continuously measured.

In the invention described above, the functions f and g may be given using reference blood of a known hematocrit value that is substantially free of fibrin in the optical device. According to such an invention, the functions f and g can be obtained relatively easily, and the change in the amount of fibrin can be continuously measured.

In the above invention, the wavelength λ1 and the wavelength λ2 may be characterized in that the wavelengths having the same absorbance of oxygenated hemoglobin and deoxygenated hemoglobin. According to such an invention, the change in the amount of fibrin can be continuously measured without being affected by the oxygen saturation of blood.

In the above invention, the wavelength λ1 may be 420 nm and the wavelength λ2 may be 810 nm. According to such an invention, both the wavelength λ1 and the wavelength λ2 can be set to this absorption wavelength, and the change in the amount of fibrin can be continuously measured without being affected by the oxygen saturation of blood.

In the above invention, the incident light is white light, and the measurement of the scattered light may be characterized by spectroscopic measurement of a wavelength band including the wavelength λ1 and the wavelength λ2. According to such an invention, scattered light having a wavelength of λ1 and a wavelength of λ2 can be obtained relatively easily and reliably, and a change in the amount of fibrin can be continuously measured.

It is a figure of the spectroscopic spectrum about the blood without coagulation. It is a figure of the spectroscopic spectrum about the blood containing a coagulated part. It is a figure about a hematocrit value. It is a block diagram which shows the test apparatus for the blood coagulation test. It is a side sectional view of a gyro pump. It is a side sectional view of the main part of a gyro pump. It is a figure which shows the change of the amount of fibrin in a blood coagulation test.

The principle of the present invention will be described in detail with reference to FIGS. 1 and 2.

FIG. 1 shows the intensity ratio of scattered light to incident light for each wavelength when white light is irradiated to blood without coagulation such as blood clots and a spectral spectrum of the scattered light is obtained. This scattered light is mostly due to red blood cells. The intensity ratio of scattered light from erythrocytes gradually decreases as the wavelength becomes longer, but decreases sharply in the wavelength region of 584 to 600 nm. The wavelength λ1 on the short wavelength side and the wavelength λ2 on the long wavelength side are defined for this wavelength region, respectively. That is, the intensity ratio of the scattered light having the wavelength λ1 changes more sensitively to the change of the red blood cells than the intensity ratio of the scattered light having the wavelength λ2, while the intensity ratio of the scattered light having the wavelength λ2 is stable. If the intensities of the incident light having the wavelength λ1 and the wavelength λ2 are the same, the same can be done by using the intensity as it is instead of the intensity ratio for the scattered light.

Here, by calibrating the relationship between the hematocrit value, which is said to indicate the amount of red blood cells in blood, and the intensity ratio of scattered light at wavelength λ1 and wavelength λ2, respectively, the intensity ratio of scattered light at that wavelength can be determined. Can be used to represent a hematocrit value. For example, the calibration curve function at wavelength λ1 is R _λ1 = f (H).
And. Here, H is a hematocrit value, and R is a dimensionless quantity as the intensity ratio of the measured scattered light to the irradiation light. Similarly, the calibration curve function at the wavelength λ2 on the long wavelength side is R _λ2 = g (H).
Can be done. The hematocrit value indicates the ratio of the volume of blood cells in blood, and since erythrocytes generally occupy 96% of the volume of blood cells, it is used as a value substantially equal to the volume ratio of erythrocytes. When obtaining a calibration curve function, the hematocrit value is measured by collecting a part of blood and centrifuging it.

FIG. 2 shows the intensity ratio of scattered light for each wavelength when white light is irradiated to blood containing a coagulated portion such as a blood clot and a spectral spectrum of the scattered light is obtained. When a coagulated portion is included, fibrinogen in the blood is used as a precursor to generate fibrin fibrin, which takes in red blood cells to coagulate the blood. On the other hand, the non-coagulated blood described above is substantially free of fibrin. That is, by continuously measuring the change in the amount of fibrin, for example, it is possible to continuously obtain information on blood coagulation for estimating the formation of thrombus and the probability of its occurrence.

Further, in blood containing fibrin, scattered light can be obtained not only from erythrocytes but also from fibrin. That is, the scattered light to be measured is a combination of the scattered light by red blood cells and the scattered light by fibrin. Here, the intensity ratio of the scattered light by fibrin gradually decreases as the wavelength becomes longer, but there is no sudden change depending on the wavelength as in erythrocytes. As a result, at the wavelength λ1 on the short wavelength side, the scattered light intensity ratio b by fibrin to the scattered light intensity ratio a by erythrocytes becomes small (for example, to a size of about 20%), and compared to this, on the long wavelength side. At the wavelength λ2, the scattered light intensity ratio d by fibrin to the scattered light intensity ratio c by erythrocytes becomes large (for example, almost the same size).

Here, if the contribution of red blood cells to the scattered light can be removed on the long wavelength side where the intensity ratio of the scattered light to be measured is stable, the intensity ratio of the scattered light by fibrin can be obtained. Therefore, the hematocrit values H _λ1 and H _λ2 are obtained from the intensity ratios of scattered light measured at wavelength λ1 and wavelength λ2 by the above-mentioned calibration curve function of blood without coagulation. At this time, since the true hematocrit value in blood does not depend on the wavelength to be measured, the true hematocrit value corresponding to the scattered light intensity ratio a of erythrocytes at wavelength λ1 and the scattered light intensity ratio c of erythrocytes at wavelength λ2 are set. The corresponding true hematocrit values are equal.

That is, as shown in FIG. 3, the hematocrit values H _λ1 and H _λ2 are obtained by adding the values Hb or Hd corresponding to the scattered light intensity ratio b or d (see FIG. 2) by fibrin to the true hematocrit value H, respectively. It is an apparent hematocrit value and is calculated to be larger than the true hematocrit value H. Further, as described above, the ratio of the scattered light intensity by fibrin to the scattered light intensity ratio (the scattered light intensity ratio by erythrocytes) corresponding to the true hematocrit value is large on the long wavelength side. Therefore, the deviation from the true hematocrit value is larger on the long wavelength side than on the short wavelength side. That is, in the case of blood containing a coagulated portion, H <H _λ1 <H _λ2 . In the case of blood without coagulation, fibrin does not increase with respect to the weighed blood, and H = H _λ1 = H _λ2 .

Here, for example, among the scattered light intensity ratios at wavelength λ1, the ratio of the scattered light intensity ratio by red blood cells to the intensity ratio of scattered light by fibrin is 1: 0.2, and similarly, the ratio at wavelength λ2 is 1: 2. It is assumed to be 1. Further, if the hematocrit value H _λ2 at the wavelength _λ2 where the intensity ratio of the scattered light to be measured is stable is subtracted from the hematocrit value H _{λ1 at} the wavelength λ1 to obtain H _λ1 −H _λ2 = ΔH, the wavelength λ1 on the short wavelength side is obtained. Contribution to scattered light by erythrocytes can be removed. At this time, since the true hematocrit values are equal to each other, they are offset, that is, the contribution of red blood cells to the scattered light can be removed, and the hematocrit value corresponding to the intensity ratio corresponding to about 0.8 times the intensity ratio of the scattered light by fibrin. The difference ΔH (the length on the drawing cannot be displayed as a negative value, so it is displayed with a reverse sign) can be calculated. That is, it can be seen that the larger the absolute value of H _λ1 −H _λ2, the larger the amount of fibrin, and thus the change in the amount of fibrin can be measured.

As described above, the change in the amount of fibrin in blood can be measured by calculating the apparent hematocrit values H _λ1 and H _λ2 , respectively, and obtaining the change in the difference ΔH between these hematocrit values. That is, by continuously measuring the scattered light intensity ratio as described above, the difference ΔH of the hematocrit value can be continuously obtained, the change in the amount of fibrin can be continuously measured, and the formation of thrombus and its generation thereof. Information on blood coagulation from which the probability can be estimated can be continuously obtained. Even if the apparent hematocrit value H _λ1 is divided by the apparent hematocrit value H _λ2 to remove the contribution of red blood cells to scattered light, the quotient is that the larger the difference ΔH in the hematocrit value (that is, the smaller the absolute value). (I see) it gets bigger, so you can also get a change in the amount of fibrin.

Here, since the apparent hematocrit value H _λ2 at the intensity ratio R _λ2 can be expressed as g ^-1 (R _λ2 ) by the inverse function of the above-mentioned calibration curve function, this is substituted into the calibration curve function f of the wavelength λ1. (G ^-1 (R _{λ 2} )) is the intensity ratio of scattered light corresponding to the apparent hematocrit value H _{λ 2} by the calibration curve function of the wavelength λ 1. In other words, it is the intensity ratio of the scattered light on the short wavelength side corresponding to the hematocrit value assumed by the intensity ratio R _λ2 on the long wavelength side. That is, it can be compared with the intensity ratio R _λ1 of scattered light in the same manner as the comparison based on the hematocrit value described above, and by such comparison, the contribution of red blood cells can be removed from the intensity ratio R _λ1 on the short wavelength side, and the amount of fibrin changes as described above. The corresponding scattered light intensity ratio can be obtained. For example, f (g ^-1 (R _λ2 )) −R _λ1 may be used. In this way, by expressing by the intensity ratio of scattered light, it is possible to express the change in the amount of fibrin without using the hematocrit value. Further, similarly to the above, a quotient may be obtained in the manner of f (g ^-1 (R _{λ 2} )) / R _{λ 1} .

In this way, the hematocrit value is assumed by the intensity ratio R _λ2 on the long wavelength side where the measured intensity ratio is stable, and the contribution of scattered light by red blood cells to the scattered light is removed from the intensity ratio R _λ1 of the scattered light on the short wavelength side. Then, the change in the amount of fibrin is obtained.

Next, using the above principle, a test device for continuously measuring a change in the amount of fibrin in blood in a gyro pump of a simulated circulation circuit for circulating blood will be described with reference to FIGS. 4 to 6.

As shown in FIG. 4, the simulated circulation circuit 10 accommodates a gyro pump (centrifugal pump) 1, an artificial lung 2 that exchanges blood gas, a reservoir 3 that stores blood, and a reservoir 3 to store blood. Includes a constant temperature bath 4 (water chamber) for keeping warm. The simulated circulation circuit 10 is connected with a vinyl chloride tube or the like so that blood is sent from the reservoir 3 through the gyro pump 1 to the artificial lung 2 and returned to the reservoir 3. Further, the artificial lung 2 is provided with a bypass path 2', and two clamps 5 can switch between a path passing through the artificial lung 2 and a path passing through the bypass path 2'. As blood, 900 cc of porcine blood supplemented with 100 cc of a 3.2% sodium citrate solution as an anticoagulant was used. Further, the circuit is connected to a syringe pump 6 for adding a calcium chloride solution as a coagulant for coagulating blood, and is also provided with a pressure gauge and a flow meter as appropriate.

Further, the gyro pump 1 includes a light source 21 including a xenon lamp for irradiating white light toward the blood in the gyro pump 1 as a device for measuring the amount of fibrin in the blood inside the gyro pump 1, and a light source 21 including scattered light from the blood. A measuring unit 25 including a small spectroscope for obtaining a spectrum is attached. An irradiation side optical fiber 22 is connected to the light source 21, and white light can be irradiated toward a predetermined position in the gyro pump 1. Further, a light receiving side optical fiber 26 for receiving scattered light from such a predetermined position is connected to the measuring unit 25. The measurement unit 25 is connected to a calculation unit 27 that performs a calculation for measuring a change in the amount of fibrin from the measured intensity of scattered light.

As shown in FIGS. 5 and 6, the gyro pump 1 includes a casing 16 made of a transparent resin and an impeller 12 that rotates inside the casing 16, and has an upper end portion of a shaft body 13 that forms a rotation axis of the impeller 12. A supporting pivot bearing 11 is provided on its top 14. Inside the gyro pump 1, a thrombus is likely to be formed in the gap 15 between the pivot bearing 11 and the shaft body 13. Therefore, the region including the gap 15 is set as the measurement region, and the irradiation side optical fiber 22 is arranged from the upper portion to the lower gap 15 of the top portion 14 so as to irradiate the white light toward the measurement region. The fiber 26 is placed on the side surface of the top 14 with the gap 15 facing. As a result, the blood around the gap 15 can be irradiated with white light, and the scattered light can be incident on the light receiving side optical fiber 26.

Next, a test method for measuring a change in the amount of fibrin in the simulated circulation circuit 10 will be described with reference to FIGS. 4 and 7. Here, "Gyro C1E3 Pump" manufactured by KYOCERA Medical Corporation was used as the gyro pump 1. Such a pump is a double pivot centrifugal blood pump.

Prior to such a test, the relationship between the hematocrit value and the intensity of scattered light for blood without coagulation was calibrated for two wavelengths, wavelength λ1 and wavelength λ2, and the respective calibration curve functions were obtained. Here, the wavelengths λ1 and λ2 are set at 420 nm and 810 nm, respectively, on the short wavelength side and the long wavelength side of the wavelength region of 584 to 600 nm, where the intensity of scattered light by red blood cells greatly decreases from the short wavelength side to the long wavelength side. did. All of these wavelengths are equal absorption wavelengths in which the absorbance of oxygenated hemoglobin and deoxygenated hemoglobin are equal, and are wavelengths that do not affect the intensity of scattered light depending on the oxygen saturation of blood.

The calibration curve function was in the form of calculating the hematocrit value from the scattered light intensity, and was a linear function of H _λ1 = αx + A and H _λ2 = βx + B. Here, H _λ1 and H _λ2 are hematocrit values at wavelength λ1 and wavelength λ2, respectively, and x is the intensity of scattered light to be measured. The coefficients of the calibration curve function were A = 136.99 and α = 6.4988 for H _λ1 and B = 33.634 and β = 4.5245 for H _λ2 . As for the correlation coefficient ^{R 2} was 0.97 and 0.92, respectively. In other words, a high correlation was obtained with the result of calibration by linear approximation, that is, a linear function.

The test blood was circulated in advance so as to pass through the artificial lung 2 to adjust the oxygen saturation to 100%. Further, in order to avoid the formation of a thrombus in the artificial lung 2, the circuit was subsequently switched by the clamp 5 so that the blood passed only through the bypass path 2'and not through the artificial lung 2. 225 cc of blood was retained in the artificial lung 2, and the remaining 775 cc was circulated in the simulated circulation circuit 10. The water temperature of the constant temperature bath 4 is 37 ° C.

As shown in FIG. 4, while circulating blood in the simulated circulation circuit 10, a 2% calcium chloride solution is added from the syringe pump 6 to promote blood coagulation. The gyro pump 1 was operated at a rotation speed of 2000 rpm and a flow rate of 2 L / min, and calcium chloride was added at 7.75 mL / min for 1 minute, and then continuously added at 0.15 mL / min. Further, white light is irradiated from the irradiation side optical fiber 22 to the above-mentioned measurement region, the scattered light is received from the light receiving side optical fiber 26, the spectrum of the scattered light is obtained by the small spectroscope of the measurement unit 25, and the wavelength λ1 The intensity of the scattered light of λ2 and λ2 are measured and continuously recorded at predetermined time intervals. The above-mentioned calibration curve function is stored in the calculation unit 27, and the hematocrit values H _λ1 and H _λ2 are calculated from the calibration curve function according to the measured intensity of scattered light of wavelengths λ1 and _λ2 , respectively. Further, FIG. 7 shows the relationship between ΔHct obtained by ΔHct (%) = (H _λ1 −H _λ2 ) and the time after the start of the test. The spectrum of the scattered light may be measured as a ratio to the spectrum of the scattered light before the gyro pump 1 is filled with blood to remove the influence of the scattered light from the components of the gyro pump 1.

As shown in FIG. 7, ΔHct changes from about 0% to about -5% around 53 minutes after the start of the test. That is, it can be seen that H _λ1 and H _λ2 are almost the same before 53 minutes, and H _λ2 becomes larger than H _λ1 after 53 minutes. That is, around 53 minutes, the amount of fibrin in the blood increases, and as a result, the apparent hematocrit value obtained from the intensity of scattered light becomes larger than the true hematocrit value. In this way, H _λ2 is subtracted from the apparent hematocrit value H _λ1 to remove the contribution of red blood cells to the intensity of scattered light at the wavelength λ1, and the change in ΔHct shown as a ratio to the apparent hematocrit value H _λ1 is Represents a change in the amount of fibrin. That is, it is possible to measure the change in the amount of fibrin in the measurement area.

The calculation formula for obtaining the change in the amount of fibrin due to the difference in hematocrit value is not limited to the above ΔHct. For example, even if H _λ1 −H _λ2 or H _λ1 / H _λ2 is used, the wavelength λ2 is the same. The hematocrit value of can eliminate the contribution of red blood cells to the intensity of scattered light at wavelength λ1.

Further, even if the wavelengths λ1 and λ2 are not set to the isosbestic wavelengths, the change in the amount of fibrin can be detected by correcting the influence of the oxygen saturation of blood on the scattered light. As a correction method, for example, there are the following methods. That is, the wavelength λ1 is set on the shorter wavelength side than the wavelength region of 584 to 600 nm described above, and the wavelength λ2 and the wavelength λ3 are set on the long wavelength side. Assuming that the oxygen saturation is Sa, the calibration curve function h for obtaining the intensity I of the dispersed light is I _λ1 = h _λ1 (H _λ1 , Sa), I _λ2 = h _λ2 (H _λ2 , Sa) I _λ3 = h _λ3 (H) It can be obtained as _λ3 , Sa). Here, in the intensity of scattered light having wavelengths λ2 and λ3, the ratio of the scattered light intensity by red blood cells to the scattered light intensity by fibrin (the ratio of c and d in FIG. 2) is almost the same on the long wavelength side, so that it is true. The deviation of the apparent hematocrit value with respect to the hematocrit value of is almost the same. That is, even in blood containing coagulation, the apparent hematocrit values H _λ2 and H _λ3 calculated from the intensity of scattered light are equivalent to each other (H _λ2 = H _λ3 ). That is, there are three unknowns, H _λ1 , H _λ2, and Sa, and a solvable simultaneous equation can be obtained by measuring the scattered light intensity of the three wavelengths λ1, λ2, and λ3, regardless of the oxygen saturation. Changes in the amount of fibrin can be obtained.

Although the examples according to the present invention and the modifications based on the present invention have been described above, the present invention is not necessarily limited to this, and those skilled in the art deviate from the gist of the present invention or the appended claims. Without doing so, various alternative and modified examples could be found.

1 Gyro pump 21 Light source 22 Irradiation side optical fiber 25 Measuring unit 26 Light receiving side optical fiber 27 Calculation unit

Claims (8)

In a measuring device that continuously measures changes in the amount of fibrin in the blood flowing through the flow path of the blood circulation device that takes blood out of the body and returns it to the body.
The measuring device measures scattered light that is scattered by giving incident light from the side of the flow path, and has a wavelength λ1 on the short wavelength side and a wavelength λ2 on the long wavelength side that sandwich a wavelength region of 584 to 600 nm, respectively. The intensity ratios R _λ1 and R _λ2 of the scattered light to the incident light in the above are continuously measured, and the hematocrit value at the intensity ratio R _λ2 contributes to the scattered light by the erythrocytes at the intensity ratio R _λ1. A measuring device having a means for removing the above-mentioned material and giving a change in the amount of fibrin. Let f be the function of the intensity ratio R _λ1 to the hematocrit value H at the wavelength λ1 and g be the function of the intensity ratio R _λ2 to the hematocrit value H at the wavelength λ2.
R _λ1 = f (H), and
R _λ2 = g (H),
The hematocrit value at the intensity ratio R _{λ 2} is represented by g ^-1 (R _{λ 2} ).
Measurement apparatus according to claim 1, characterized in providing a change in ^f the fibrin amount change relative to ^{_{R λ1 (g -1 (R λ2}} )). The measuring device according to claim 2, wherein the change in the amount of fibrin is given by f (g ^-1 (R _{λ 2} )) / R _{λ 1} . The measuring device according to claim 2, wherein the change in the amount of fibrin is given by f (g ^-1 (R _λ2 )) −R _λ1 . The measuring device according to any one of claims 2 to 4, wherein the functions f and g are given in the measuring device using a reference blood having a known hematocrit value that is substantially free of fibrin. .. The measuring device according to any one of claims 1 to 3, wherein the wavelength λ1 and the wavelength λ2 are wavelengths at which the absorbances of oxygenated hemoglobin and deoxygenated hemoglobin are equal. The measuring device according to claim 4, wherein the wavelength λ1 is 420 nm and the wavelength λ2 is 810 nm. The measuring apparatus according to any one of claims 1 to 7, wherein the incident light is white light, and the scattered light is measured by spectroscopic measurement of a wavelength band including the wavelength λ1 and the wavelength λ2. ..