WO2022102734A1 - Method for determination of blood samples, and determination system and computer program therefor - Google Patents

Abstract

This method comprises: depending on the Hb, MCV and CRP values of blood samples, eliminating blood samples derived from subjects with inflammatory anemia; and, depending on the serum ferritin values of the remaining blood samples (A1), determining whether the blood samples (A1) are blood samples that are derived from subjects with hypoferric anemia or blood samples (A2) that are derived from subjects with thalassemia.

Description

Judgment method of blood sample, judgment device and computer program for that

The present invention is a determination method for determining whether or not a blood sample is derived from a thalassemia subject, a determination device for carrying out the determination method, and a computer for performing the determination method. Regarding computer programs.

Thalassemia is anemic due to hereditary abnormalities in globin that make up hemoglobin (a tetramer consisting of two molecules each of α-globin with 141 amino acids and non-α-globin (β, γ, δ) with 146 amino acids). It is a disease that shows symptoms. Thalassemia includes α-thalassemia, which is a disease caused by a deficiency in the synthesis of the α chain of globin, and β-thalassemia, which is a disease caused by a deficiency in the synthesis of the β chain of globin.

Conventionally, when it is differentiated that the disease of a patient showing anemia symptoms is thalassemia instead of iron deficiency anemia, the following determination steps (i) to (iii) have been performed.
(I) A CBC (complete blood count) test is performed on a blood sample collected from a patient, and among the test values, anemia is observed based on the hemoglobin value and the mean corpuscular volume value (MCV value). Determine if.
(Ii) If anemia is determined in (i) above, a ferritin test is performed on the blood sample of the patient to determine whether the anemia is due to iron deficiency anemia or thalassemia. Although the determination result at this stage indicates a high possibility, it is not as reliable as the next determination step (iii).
(Iii) When it is determined to be thalassemia in the above (ii), the blood sample of the patient is further subjected to hemoglobin fractionation and PCR test (polymerase chain reaction test), whereby it is said to be thalassemia. The judgment is confirmed and used as the discrimination result.

Note that Patent Document 1 describes an invention that attempts to determine whether iron deficiency anemia or thalassemia is present by using fluorescence.

Japanese Unexamined Patent Publication No. 2016-50931

However, when the present inventors examined the determination steps (i) to (iii) in detail, it was found that the following problems to be improved were included.

First, the ferritin test in the determination step of (ii) above is a test that requires an expensive reagent. Moreover, even with a ferritin test, thalassemia cannot be distinguished from inflammatory anemia (particularly chronic inflammatory anemia). Therefore, if the patient had inflammatory anemia, the expensive ferritin test that should not have been done wasted, and the patient with inflammatory anemia was provided with a blood sample for the ferritin test. Was unnecessarily demanded and burdened. In addition, the patient with inflammatory anemia is unnecessarily handed over to the next examination step so as to undergo the next (iii) determination step.

Further, the PCR test in the determination step of (iii) above is a test that requires an expensive reagent. Moreover, if the patient had inflammatory anemia, as in (ii) above, the expensive hemoglobin fraction and PCR test that should not have been done was wasted, and the inflammatory anemia It was a wasteful request for the patient to provide blood samples for these tests, which was a burden.

An object of the present invention is to solve the above-mentioned problems that the present inventors have focused on, and to prevent unnecessary tests from the step of determining whether or not the blood sample is derived from a thalassemia patient.

[1] A determination method for determining whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject.
Based on the hemoglobin value, mean corpuscular volume value, and C-reactive protein value of the blood sample (A), the blood sample (A) is a blood sample derived from a subject with inflammatory anemia, or inflammatory anemia. The first step of determining whether the blood sample (A1) is derived from a subject with anemia other than the above,
Based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). The determination method comprising a second step of determination.
[2] In the first step, when the hemoglobin value and mean corpuscular volume value of the blood sample (A) indicate a blood sample derived from an anemic subject.
When the C-reactive protein value of the blood sample (A) is higher than a predetermined value, it is determined that the blood sample (A) is a blood sample derived from a subject with inflammatory anemia.
When the C-reactive protein value of the blood sample (A) is lower than the predetermined value, it is determined that the blood sample (A) is a blood sample (A1) derived from an anemia subject other than inflammatory anemia. , The determination method according to [1].
[3] The determination method according to [1], wherein the anemia is microcytic hypochromic anemia in the first step.
[4] A third step of determining whether or not the blood sample (A2) is a blood sample derived from a thalassemia subject based on the hemoglobin fraction of the blood sample (A2) and the result of the PCR test. The determination method according to any one of [1] to [3], which is further possessed.
[5] A determination method for determining whether or not the blood sample to be analyzed is derived from a thalassemia subject, which is a hemoglobin value, mean corpuscular volume value, C-reactive protein value, and serum of the blood sample. The determination method for determining whether or not the blood sample is a blood sample derived from a thalassemia subject based on the ferritin value.
[6] A determination device for determining whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject, and the determination device is a determination device.
A first test value receiving unit that receives a blood test value including at least the hemoglobin value, mean corpuscular volume value, and C-reactive protein value of the blood sample (A), and
Based on the blood test value, it is determined whether the blood sample (A) is a blood sample derived from a subject with inflammatory anemia or a blood sample (A1) derived from a subject with anemia other than inflammatory anemia. Then, the first determination unit and the first determination unit, which are output as the first determination result,
A second test value receiving unit that accepts the serum ferritin value of the blood sample (A1) when the first determination unit determines that the blood sample (A) is the blood sample (A1).
Based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). It has a second determination unit that determines and outputs as a second determination result.
The determination device.
[7] When the second determination unit determines that the blood sample (A1) is the blood sample (A2), the third determination unit accepts the hemoglobin fraction and the result of the PCR test of the blood sample (A2). Inspection value receiving part and
Based on the hemoglobin fraction of the blood sample (A2) and the result of the PCR test, it is determined whether or not the blood sample (A2) is a blood sample derived from a thalassemia subject, and output as a third determination result. The determination device according to [6], further comprising a third determination unit.
[8] A computer program for causing a computer to determine whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject.
Computer,
A first test value receiving unit that receives a blood test value including at least the hemoglobin value, mean corpuscular volume value, and C-reactive protein value of the blood sample (A).
Based on the blood test value, it is determined whether the blood sample (A) is a blood sample derived from a subject with inflammatory anemia or a blood sample (A1) derived from a subject with anemia other than inflammatory anemia. Then, the first determination unit, which is output as the first determination result,
When the first determination unit determines that the blood sample (A) is the blood sample (A1), the second test value receiving unit and the second test value receiving unit that accept the serum ferritin value of the blood sample (A1), and
Based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). The computer program for making a determination and outputting it as a second determination result, for functioning as a second determination unit.
[9] Computer
A third test value that accepts the results of the hemoglobin fraction and PCR test of the blood sample (A2) when the second determination unit determines that the blood sample (A1) is the blood sample (A2). Receiving section and
Based on the hemoglobin fraction of the blood sample (A2) and the result of the PCR test, it is determined whether or not the blood sample (A2) is a blood sample derived from a thalassemia subject, and output as a third determination result. The computer program according to [8], further comprising a computer program for functioning as a third determination unit.

In the present invention, in determining whether or not the blood sample to be analyzed is derived from a Sarasemia subject, the C-reactive protein (CRP) value is measured at an early stage of the determination step, and the C-reactive protein (CRP) value is measured based on the CRP value. Therefore, a blood sample derived from a patient with inflammatory anemia is determined, and the serum ferritin level of the blood sample derived from the patient with inflammatory anemia is not measured. The present invention also avoids unnecessary hemoglobin fractionation and PCR testing in determining whether the blood sample to be analyzed is from a thalassemia subject.

On the other hand, in the past, there was no idea of eliminating inflammatory anemia in the early stage of blood test, and let's use the CRP value that can be obtained inexpensively in the early stage of blood test for detection of inflammatory anemia. There was no idea that.

According to the present invention, patients with inflammatory anemia do not have to undergo tests for determining thalassemia, such as measurement of serum ferritin level, measurement for obtaining a hemoglobin fraction, and PCR test. Therefore, the burden on the patient with inflammatory anemia can be reduced, and the wasteful use of expensive reagents and the labor required for the determination of thalassemia can be suppressed.

FIG. 1 is a flowchart illustrating a first aspect of the determination method of the present invention. The flowchart of the figure includes a third step as a preferred embodiment for more accurately determining whether or not the thalassemia is thalassemia. Further, the flowchart is also a flowchart for explaining the determination operation of the determination device of the present invention, and is also a flowchart for explaining the configuration of the computer program of the present invention. FIG. 2 is a flowchart illustrating a second aspect of the determination method of the present invention. FIG. 3 is a block diagram showing an example of the configuration of the blood analyzer of the present invention.

(Determination Method of the Present Invention)
The determination method is a method for determining whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject. As shown in the flowchart of FIG. 1, the determination method (first aspect) includes a first step S1 for excluding a blood sample showing inflammatory anemia from a blood sample showing general anemia, and the first step. For a blood sample of a patient whose inflammatory anemia has been ruled out by, at least a second step S2 for determining whether or not thalassemia is present. This eliminates blood samples of inflammatory anemia at the initial determination stage and prevents subsequent tests for thalassemia in patients with inflammatory anemia.
Further, as shown in the flowchart of FIG. 2, the determination method (second aspect) is a blood sample (A) to be analyzed based on a hemoglobin value, a mean corpuscular volume value, a C-reactive protein value, and a serum ferritin value. Is a method of determining whether or not it is thalassemia. This prevents unnecessary hemoglobin fractionation and PCR rights inspection, which were performed when determining thalassemia.

(subject)
The subject may be a patient who complains of anemia symptoms or a healthy person who has undergone a medical examination or the like. That is, the blood sample (A) to be judged by the judgment method may be a blood sample collected from an anemia subject to some extent from the beginning, and the health condition is unknown. It may be a blood sample collected from the subject. The blood sample (A) used in the determination method may be all or a part of blood collected from the subject. Further, as long as it does not affect the value of the measurement target such as CRP in the determination method, a plurality of blood samples separately collected in different sample tubes (collection blood vessels) may be used in the determination method. The separate collection of the blood sample may be, for example, continuous collection in which the blood collection tubes are exchanged one after another in the same blood sampling needle puncture, or another blood collection needle may be collected after a predetermined time has elapsed within the permissible range. It may be collected in another blood collection tube by puncturing the blood sample.

The determination method of the present invention will be described in detail below. The following description is described based on FIG. 1 showing the first aspect of the determination method of the present invention, but the necessary parts regarding the second aspect of the determination method of the present invention shown in FIG. 2 are as follows. All the descriptions in the above shall be incorporated.

(Step S1a for determining anemia in the first step S1)
In the first step S1, as shown in step S1a in the flowchart of FIG. 1, the hemoglobin value (Hb value) and the hemoglobin value (Hb value) of the blood sample collected from the subject (referred to as “blood sample (A)” for distinction) and Based on the mean corpuscular volume value (MCV value), it is determined whether or not the blood sample (A) is a blood sample derived from a subject with anemia, more specifically, microglobin hypochromic anemia. The microcytic hypochromic anemia includes iron deficiency anemia, inflammatory anemia, and thalassemia as its pathological conditions.

(Relationship between Hb value, MCV value and anemia)
The Hb value (hemoglobin concentration) of a blood sample derived from an anemia patient may differ depending on the gender and age of the patient, but usually, for example, the common standard range of the Japanese Committee for Clinical Laboratory Standards (JCCLS) or the clinical test method. It can be set as appropriate based on the numerical values and the like described in the proposal (revised 35th edition). Specifically, for example, 11.0 g / dl or less, less than 11.6 g / dl, less than 12.0 g / dl, 13.0 g / dl or less, less than 13.7 g / dl, less than 14.0 g / dl. .. In addition, the MCV value of blood samples derived from patients with anemia, especially microcytic hypopigmentation anemia, is usually, for example, the common standard range of the Japanese Committee for Clinical Laboratory Standards (JCCLS) and the clinical test method requirements (revised 35th edition). ) Can be set as appropriate based on the numerical values and the like described in. Specifically, for example, it is 80.0 fl or less and less than 83.6 fl.

(Method of acquiring Hb value and MCV value)
The method for acquiring the Hb value and the MCV value is not particularly limited, and a conventionally known blood test method (blood test device) can be used. For example, in the case of a blood analyzer such as the whole blood cell immunoassay device described in JP-A-11-108923, not only the blood cell count result (number of blood cells and volume frequency distribution of blood cells) but also , Hb value and MCV value can be obtained, and these Hb value and MCV value can also be obtained as a data signal through the interface.

(Regarding the additional test values that can be used in the first step S1)
In the first step S1, in addition to the Hb and MCV values, for example, mean corpuscular hemoglobin concentration (MCHC) may be used to determine anemia, more specifically microcytic hypochromic anemia. .. MCHC is expressed by the following formula (I):

Can be calculated by Regarding the value of MCHC, for example, a blood analyzer such as the whole blood cell immunoassay device described in JP-A-11-108923 can also obtain the value of hematocrit, and thus the value can be obtained from the measuring device. It can be obtained based on the value to be obtained. The MCHC value can also be obtained as a data signal through the interface. The MCHC value of blood samples derived from patients with anemia, especially microcytic hypopigmentation anemia, is usually found in, for example, the common standard range of the Japanese Committee for Clinical Laboratory Standards (JCCLS) and the clinical test method guidelines (revised 35th edition). It can be set as appropriate based on the described numerical values and the like. Specifically, for example, it is less than 30 g / dl, less than 31 g / dl, and less than 31.7 g / dl.

(Step S1b for determining inflammatory anemia in the first step S1)
In the first step S1, as shown in step S1b in the flowchart of FIG. 1, the blood sample (A) is a blood sample derived from a subject with inflammatory anemia based on the CRP value of the blood sample (A). Determine if it exists.

(Relationship between CRP value and inflammatory anemia)
The CRP value derived from a patient with inflammatory anemia is usually set as appropriate based on, for example, the common standard range of the Japanese Committee for Clinical Laboratory Standards (JCCLS) and the numerical value described in the clinical test method proposal (revised 35th edition). Can be. Specifically, for example, it is 0.14 mg / dl or more and 0.2 mg / dl or more.

(How to get CRP value)
The method for obtaining the CRP value is not particularly limited, and a conventionally known blood test method (blood test device) can be used. Similar to the acquisition of the Hb value and MCV value described above, any blood analyzer equipped with a CRP value measuring function such as the whole blood cell immunoassay device described in JP-A-11-108923 can be used as a blood sample. A CRP value can also be obtained, and the CRP value can also be obtained as a data signal through an interface.

The order of determination in step S1a and step S1b described above is not particularly limited, and either of them may come first.

(Step S1c for determining anemia other than inflammatory anemia in the first step S1)
As shown in step S1c in the flowchart of FIG. 1, it is determined in step S1a (a blood sample derived from a subject of anemia (more specifically, microcytic hypopigmental anemia)), and in step S1b. For a blood sample determined to be (not a blood sample derived from a subject with inflammatory anemia), step S1c is a result of the determination in the first step (anemia other than inflammatory anemia (more specifically, small). A determination result of a blood sample (referred to as "blood sample (A1)" for distinction) derived from a subject of (spherical hypopigmented anemia) is given. In the present invention, the blood sample (A1) obtained from this determination result is sent to the second step.

On the other hand, in step S1a (a blood sample derived from a subject of anemia (more specifically, microcytic hypopigmental anemia)), and in step S1b (a blood sample derived from a subject of inflammatory anemia). For the blood sample determined to be), step S1c gives a determination result (a blood sample derived from a subject of inflammatory anemia) as the determination result of the first step. In the present invention, the blood sample obtained from this determination result is not sent to the second step, and as the determination result of the determination method, (a blood sample derived from a subject of inflammatory anemia and derived from a subject of thalassemia). The determination result (not a blood sample) is given, and the determination regarding thalassemia can be completed.

Further, when the determination result (not the blood sample derived from the subject with anemia) is obtained in step S1a, the determination is not performed in step S1c, and the determination result of the determination method is (blood derived from the subject not anemic). The determination result (which is a sample) is given, and the determination regarding thalassemia can be completed.

Further, in a preferred embodiment of the present invention, when a determination result (a blood sample derived from a subject of anemia (more specifically, microcytic hypochromic anemia)) is obtained in step S1a, step S1b is performed. , The CRP value of the blood sample (A) may be sent to step S1c, and step S1c may give the following determination result.
(A) When the CRP value of the blood sample (A) is higher than a predetermined value, it is determined that the blood sample (A) is a blood sample derived from a subject with inflammatory anemia. Here, the predetermined value of the CRP value is 0.2 mg / dl, preferably 0.14 mg / dl.
(B) When the CRP value of the blood sample (A) is lower than the predetermined value, it is determined that the blood sample (A) is a blood sample (A1) derived from an anemia subject other than inflammatory anemia. do.

When the judgment of (a) above is made, the blood sample obtained from the judgment result is given the judgment result (the blood sample is derived from the subject of inflammatory anemia, not the blood sample derived from the subject of thalassemia). You can finish the judgment about thalassemia.

When the determination in (b) above is made, the blood sample obtained from the determination result is a blood sample (A1) derived from a subject (anemia other than inflammatory anemia (more specifically, microcytic hypochromic anemia)). )) May be given, and the blood sample (A1) having the determination result may be sent to the second step.

(Second step S2)
As shown in the flowchart of FIG. 1, in the second step S2, the blood sample (A1) has iron deficiency anemia based on the serum ferritin value of the blood sample (A1) determined in the first step S1. It is determined whether the blood sample is derived from the subject of thalassemia or the blood sample derived from the subject of thalassemia (referred to as "blood sample (A2)" for the sake of distinction).

The blood sample (A1) to be determined in the second step is contained in the same blood sample (for example, in the same sample tube) as the blood sample determined to be the blood sample (A1) in the first step. It may be a blood sample), or it may be separately collected from the same subject as the blood sample determined to be the blood sample (A1) in the first step (as described above, continuously different sample tubes). It may be a blood sample (a blood sample derived from the same subject) collected in a different sample tube after a predetermined time has elapsed within an allowable range.

(Relationship between serum ferritin level, iron deficiency anemia and thalassemia)
The serum ferritin level of healthy adults depends on the measurement method, but as an example, it is about 32 to 126 ng / ml for Japanese men (adults) and 9 to 94 ng / ml for Japanese women (adults). Degree. When anemia is suspected, the reference value (normal range) of serum ferritin is usually 25 to 250 ng / ml.
In contrast, in iron deficiency anemia, serum ferritin levels decrease, and in thalassemia-induced anemia, serum ferritin levels increase. Therefore, based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject of iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). Can be determined.

In the determination in the second step, the reference value and threshold value of the serum ferritin level for determining that the blood sample is derived from the subject of iron deficiency anemia, and the thalassemia, depending on the race and gender of the subject. The reference value and the threshold value of the serum ferritin level for determining that the blood sample is derived from the subject may be appropriately determined. For example, the reference value of the serum ferritin value for determining that the blood sample is derived from a subject with iron deficiency anemia is 12 ng / ml or less, particularly 10 ng / mL or less. Further, for example, the reference value of the serum ferritin value for determining that the blood sample is derived from a thalassemia subject is more than 12 ng / ml.

(How to get serum ferritin level)
The method for obtaining the serum ferritin level is not particularly limited, and a conventionally known test method can be used. Specific examples thereof include a latex loneferrometry method, a chemiluminescence immunoassay method (Kemilmimi method), and a latex agglutination immunoturbidimetric method.

When a determination result (a blood sample derived from a subject with iron deficiency anemia) is obtained in the second step S2, the determination regarding thalassemia can be terminated by using this as the determination result of the determination method. Further, when a determination result of (a blood sample (A2) derived from a thalassemia subject) is obtained in the second step S2, even if the determination regarding thalassemia is completed, this is used as the determination result of the determination method. Alternatively, in the third step S3 described later, it may be more accurately determined whether or not the blood sample (A2) is derived from a thalassemia subject.

(Third step S3)
As shown in the flowchart of FIG. 1, in a preferred embodiment of the determination method, the third step S3 is carried out. In the third step S3, the blood sample (A2) is a blood sample derived from a Sarasemia subject (A2) based on the hemoglobin fraction of the blood sample (A2) determined in the second step S2 and the result of the PCR test. For the sake of distinction, it is determined whether or not it is a "blood sample (A3)"). According to the third step S3, the accuracy and reliability of the determination result that the blood sample is a blood sample derived from a thalassemia subject can be further improved. In addition, since blood samples of inflammatory anemia have been removed, hemoglobin fractionation and PCR tests are not wasted.

(How to get the hemoglobin fraction)
The hemoglobin fraction used in the third step S3 can be obtained by a conventionally known analytical method. For example, high performance liquid chromatography (HPLC method), capillary electrophoresis (CE method) and the like are preferable. Further, from the obtained fraction results, thalassemia can be determined using the increase in HbA ₂ and Hb F as an index.

(PCR test)
The PCR test used in the third step S3 is a test configured to utilize a polymerase chain reaction to determine thalassemia. More specifically, mutations in the α-globin gene or non-α-globin gene of hemoglobin are measured or detected by a method known per se, such as a quantitative (real-time) PCR method or a next-generation sequencing method, and the measurement results and the like. The thalassemia may be determined based on. At that time, the above results may be used to determine what kind of thalassemia (eg, α-thalassemia (-SEA, --THAI, --FIL, etc.)). In the present specification, the "result of PCR test" is derived from a thalassemia subject whose blood sample is derived from a thalassemia subject, using a mutation in an α-globin gene or a non-α-globin gene as an index in a blood sample to be subjected to the PCR test. It means the judgment result of whether or not there is.

(Second aspect of the determination method of the present invention)
FIG. 2 is a flowchart showing a second aspect of the determination method of the present invention. As shown in the flowchart, in the second aspect, the Hb value, MCV value, CRP value, and serum ferritin value of the blood sample are obtained, and based on these values, the blood sample is the blood derived from the subject of thalassemia. Determine if it is a sample.
The blood sample is a blood sample derived from a thalassemia subject, considering how to measure the Hb value, MCV value, CRP value, and serum ferritin value, the meaning of each of these values, and how to consider these values. With respect to whether or not it is determined, the above description of the first aspect can be referred to.

(Determination device of the present invention)
The determination device is an device for carrying out the above-mentioned determination method of the present invention, and is configured to determine whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject. Is. As an example of the outline of the configuration in FIG. 3, the determination device 1 uses the inspection values (including the inspection results) obtained by various inspection means as the determination method (first or second aspect) of the present invention. According to, at least the inspection value receiving unit 10 configured to accept and the determination unit 20 configured to make a determination according to the determination method (first aspect or second aspect) of the present invention based on the inspection value. Have. FIG. 3 shows a configuration that is particularly preferable for the implementation of the first aspect, but the configuration can be appropriately changed so as to be preferable for the implementation of the second aspect. The inspection value receiving unit 10 has at least a first inspection value receiving unit 11 and a second inspection value receiving unit 12, and the determination unit 20 has a first determination unit 21 and a second determination unit 22. (1st inspection value receiving unit 11 and 1st determination unit 21) and (2nd inspection value receiving unit 12 and 2nd determination unit 22) carry out the determination method of the present invention. Each works as a pair. In the example of FIG. 3, as a preferred embodiment, a third inspection value receiving unit 13 and a third determination unit 23 for confirming the determination of thalassemia are further added.

(1st inspection value receiving unit and 1st judgment unit)
The first test value receiving unit 11 is configured to receive a blood test value including at least the Hb value, MCV value, and CRP value of the blood sample (A) collected from the subject. Further, the first determination unit 21 processes the blood test value received by the first test value receiving unit 11, and the blood sample (A) is derived from the subject of inflammatory anemia based on the blood test value. It is determined whether it is a blood sample or a blood sample (A1) derived from an anemia subject other than inflammatory anemia.

The blood test value (at least the Hb value, the MCV value, and the CRP value) received by the first test value receiving unit 11 and the determination made by the first determination unit 21 based on the blood test value are determined in the determination method of the present invention. As described in the description of the first step.

In the example of FIG. 3, the hemoglobin counting device 110 for measuring the complete blood count (CBC value) such as the Hb value and the MCV value and the blood analyzer 120 for measuring the CRP value are the first as separate devices. Although the blood cell counting device 110 and the blood analyzer 120 are connected to the test value receiving unit 11 of the above, the same one analyzer (such as the device described in JP-A-11-108923 described above) is used. It may be, or it may be three separate devices for measuring the Hb value, the MCV value, and the CRP value respectively.

The test value input to the first test value receiving unit 11 may be data transmitted by data communication from a device such as the blood cell counting device 110 and the blood analyzer 120, or the blood cell counting device 110 or blood. The inspection value obtained by the analyzer 120 may be input to the first inspection value receiving unit 11 by manual input, bar code input, or the like. The same applies to the inspection values input to the second inspection value receiving unit 12 and the third inspection value receiving unit 13, which will be described later.

The determination device may be included in the control unit of a measurement device having a measurement mechanism such as the above-mentioned blood cell counter, blood analyzer, whole blood cell immunoassay device, serum ferritin level, hemoglobin fraction, PCR test. It may be configured to accept inspection values that cannot be obtained by the measuring device, such as the result of the above, from another external measuring device.

(Output of the first judgment result)
The first determination unit 21 outputs the determination result to the external device 400 as the first determination result. In the example of FIG. 3, the external device 400 is a display device such as a liquid crystal display, but a device such as a lamp display device or a printer that can convey the determination result to the user can be used.

(Display content of the first judgment result)
The display contents of the first determination result are, for example, "this blood sample is derived from a subject of inflammatory anemia", "inflammatory anemia", "high possibility of inflammatory anemia", and "this blood". The sample is derived from a subject with anemia other than inflammatory anemia, "" anemia other than inflammatory anemia, "and" there is a high possibility of anemia other than inflammatory anemia. " It may be a display or symbol that can be understood by the operator or the doctor who sees the judgment result.

When displaying the determination result (a blood sample derived from a subject with anemia other than inflammatory anemia), the serum ferritin level of the blood sample is used to proceed to the second step in the determination method of the present invention. It may be displayed asking the user to input.

(Second inspection value receiving unit and second judgment unit)
When the first determination unit 21 determines that the blood sample (A) is (a blood sample (A1) derived from an anemia subject other than inflammatory anemia), the second test value acceptance unit 12 is the present. The serum ferritin level of the blood sample (A1) is accepted in order to perform the second step (thalassemia determination) in the determination method of the present invention. Further, the second determination unit 22 determines whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a subject derived from thalassemia, based on the serum ferritin value of the blood sample (A1). It is determined whether it is a blood sample (A2) of.

The serum ferritin value received by the second test value receiving unit 12 and the determination performed by the second determination unit 22 based on the serum ferritin value are as described in the description of the second step in the determination method of the present invention.

In the example of FIG. 3, the measuring device 210 for measuring the serum ferritin level is connected to the second test value receiving unit 12, but the determination device is a measuring device having a mechanism for measuring the serum ferritin level. It may be included in the control unit of the above, and may be configured to receive inspection values such as Hb value, MCV value, and CRP value from an external measuring device.

(Output of the second judgment result)
The second determination unit 22 outputs the determination result to the external device 400 as the second determination result. Similar to the description of the output of the first determination result, the external device 400 is a display device such as a display, but a device such as a lamp display device or a printer that can convey the determination result to the user can be used.

(Display content of the second judgment result)
The display contents of the second determination result are, for example, "this blood sample is derived from a subject with iron deficiency anemia", "iron deficiency anemia", "high possibility of iron deficiency anemia", "This blood sample is derived from a thalassemia subject", "thalassemia", "anemia due to thalassemia", "probably thalassemia", etc. with indications and symbols that the user of the judgment device can understand. It may be there.

When displaying the determination result (a blood sample derived from a thalassemia subject), the user inputs the hemoglobin fraction and the PCR test result in order to proceed to the third step in the determination method of the present invention. And comments recommending that these tests be used to more accurately determine for thalassemia, rather than requiring the user to enter hemoglobin fractions and PCR test results. It may be displayed.

(Third inspection value receiving unit and third judgment unit)
In a preferred embodiment of the determination device, the third determination method of the present invention prepares for the case where the second determination unit determines that the blood sample (A1) is (a blood sample (A2) derived from a thalassemia subject). A third inspection value receiving unit 13 and a third determination unit 23 for carrying out the step (confirmation of thalassemia) may be provided. The inspection values referred to in the present specification include the results of inspections other than numerical values. When the second determination unit determines that the blood sample (A1) is the blood sample (A2), the third test value receiving unit 13 determines the hemoglobin fraction of the blood sample (A2) and the result of the PCR test. accept. Further, the third determination unit 23 determines whether or not the blood sample (A2) is a blood sample derived from a thalassemia subject, based on the hemoglobin fraction of the blood sample (A2) and the result of the PCR test. judge.

The hemoglobin fraction received by the third test value receiving unit 13, the result of the PCR test, and the determination made by the third determination unit 23 based on the result are described in the description of the third step in the determination method of the present invention. That's right.

In the example of FIG. 3, the measuring device 310 for measuring the hemoglobin fraction and the device 320 for performing the PCR test are connected to the third test value receiving unit 13, and the determination device is, for example, It may be included in the control unit of the measuring device 310 for measuring the hemoglobin fraction or the device for performing the PCR test, and the test values such as the Hb value, MCV value, CRP value, and serum ferritin value are measured by an external measuring device. It may be configured to accept from.

(Output of the third judgment result)
The third determination unit 23 outputs the determination result to the external device 400 as the third determination result. Similar to the description of the output of the first and second determination results, the external device 400 is a display device such as a display, but a device such as a lamp display device or a printer that can convey the determination result to the user can be used. be.

(Display content of the third judgment result)
The display contents of the third determination result are, for example, "This blood sample is derived from a subject of thalassemia", "thalassemia", "anemia due to thalassemia", "very likely to be thalassemia", " This blood sample is understood by the user of the determination device, such as "not derived from a thalassemia subject", "not thalassemia", "not anemia due to thalassemia", "very unlikely to be thalassemia". It may be a display or symbol that can be used.

The determination device may be constructed by a logic circuit or the like, but it is appropriate that the determination device is configured by a computer. The computer executes a computer program (described later) of the present invention configured to control the operation of the inspection value receiving unit and to perform a determination operation in the determination unit.

When the determination device is a computer, the inspection value receiving unit 10 has an interface as hardware and software (computer program) that accepts the received inspection value signal as an inspection value data set and delivers it to the determination unit 20. May be configured with. The inspection value receiving unit 10 may store each received inspection value in a storage device (not shown).

(Computer program of the present invention)
The computer program according to the present invention (hereinafter, also referred to as the program) uses the computer as the above-mentioned determination device of the present invention (first inspection value receiving unit 11, first determination unit 21, second inspection value receiving unit 12). , The purpose is to function as a second determination unit 22). The program is also for causing a computer to perform the above-mentioned determination method of the present invention (first step S1 and second step S2). That is, the program is for causing a computer to determine whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject. The program can be appropriately configured to cause a computer to carry out the first or second aspect of the determination method of the present invention.

Further, the program further causes the computer to function as the third inspection value receiving unit 13 and the third determination unit 23 described above (that is, the computer is subjected to the determination method of the present invention described above. A computer program for performing step S3 of 3) may be included.

The program may be provided installed on a computer, as recorded on a computer-readable medium, or provided via a network from another computer or external storage device. May be good.

Example 1
Blood samples from subjects suspected of having anemia and those derived from healthy subjects are obtained by obtaining written informed consent from each subject. Hemoglobin (Hb) value, mean corpuscular volume (MCV) value, and C-reactive protein (CRP) value in each collected blood sample were measured, and each measured value was compared with the common reference range (reference value) of JCCLS. Then, it is determined whether or not the sample is derived from an anemia subject other than inflammatory anemia (first step S1 in FIG. 1). The serum ferritin level in each blood sample derived from the subject of anemia other than the inflammatory anemia determined above was measured, the measured value was compared with the reference value (12 ng / ml), and the sample having a value exceeding the reference value. Is determined to be a blood sample derived from the subject of thalassemia.

Example 2
For each blood sample from a subject suspected of having anemia and a healthy subject collected in Example 1, it is determined whether or not the blood sample is derived from a thalassemia subject by using the PCR (Gap PCR) method and the hemoglobin fractionation method. do.

Example 3
The validity of the determination method of the present invention will be verified based on the determination result regarding the blood sample derived from the subject of thalassemia of Example 1 and the same determination result in Example 2. From the results of the verification, it is demonstrated that the determination method of the present invention is particularly suitable for determining whether or not the prepared blood sample is derived from the subject of thalassemia.

Example 4
The Hb value, MCV value, CRP value, and serum ferritin value in each blood sample obtained in Example 1 were measured, and each measured value was used as a common reference range (reference value) of JCCLS and a reference value (12 ng) of serum ferritin. / Ml), and a sample having a value exceeding the reference value is determined to be a blood sample derived from the subject of salacemia.

Example 5
The validity of the determination method of the present invention will be verified based on the determination result regarding the blood sample derived from the subject of thalassemia of Example 4 and the same determination result in Example 2. From the results of the verification, it is demonstrated that the determination method of the present invention is particularly suitable for determining whether or not the prepared blood sample is derived from the subject of thalassemia.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to exclude a blood sample of a patient with inflammatory anemia from a blood sample of a patient complaining of anemia at an early stage. It has become possible to prevent unnecessary tests such as PCR tests.

This application is based on Japanese Patent Application No. 2020-189678 (Filing date: November 13, 2020), the contents of which are all included in the present specification.

S1 1st step S2 2nd step S3 3rd step

Claims (9)

It is a determination method for determining whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject.
Based on the hemoglobin value, mean corpuscular volume value, and C-reactive protein value of the blood sample (A), the blood sample (A) is a blood sample derived from a subject with inflammatory anemia, or inflammatory anemia. The first step of determining whether the blood sample (A1) is derived from a subject with anemia other than the above,
Based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). The determination method comprising a second step of determination. In the first step, when the hemoglobin value and mean corpuscular volume value of the blood sample (A) indicate a blood sample derived from an anemic subject,
When the C-reactive protein value of the blood sample (A) is higher than a predetermined value, it is determined that the blood sample (A) is a blood sample derived from a subject with inflammatory anemia.
When the C-reactive protein value of the blood sample (A) is lower than the predetermined value, it is determined that the blood sample (A) is a blood sample (A1) derived from an anemia subject other than inflammatory anemia. The determination method according to claim 1. The determination method according to claim 1, wherein in the first step, the anemia is microcytic hypochromic anemia. It further comprises a third step of determining whether the blood sample (A2) is from a thalassemia subject, based on the hemoglobin fraction of the blood sample (A2) and the results of the PCR test. The determination method according to any one of claims 1 to 3. It is a determination method for determining whether or not the blood sample to be analyzed is derived from a thalassemia subject, and is used to determine the hemoglobin value, mean corpuscular volume value, C-reactive protein value, and serum ferritin value of the blood sample. Based on the above-mentioned determination method, which determines whether or not the blood sample is a blood sample derived from a thalassemia subject. A determination device for determining whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject, and the determination device is
A first test value receiving unit that receives a blood test value including at least the hemoglobin value, mean corpuscular volume value, and C-reactive protein value of the blood sample (A), and
Based on the blood test value, it is determined whether the blood sample (A) is a blood sample derived from a subject with inflammatory anemia or a blood sample (A1) derived from a subject with anemia other than inflammatory anemia. Then, the first determination unit and the first determination unit, which are output as the first determination result,
A second test value receiving unit that accepts the serum ferritin value of the blood sample (A1) when the first determination unit determines that the blood sample (A) is the blood sample (A1).
Based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). The determination device having a second determination unit for determining and outputting as a second determination result. A third test value that accepts the results of the hemoglobin fraction and PCR test of the blood sample (A2) when the second determination unit determines that the blood sample (A1) is the blood sample (A2). Receiving department and
Based on the hemoglobin fraction of the blood sample (A2) and the result of the PCR test, it is determined whether or not the blood sample (A2) is a blood sample derived from a thalassemia subject, and output as a third determination result. The determination device according to claim 6, further comprising a third determination unit. A computer program for causing a computer to determine whether or not the blood sample (A) to be analyzed is derived from a thalassemia subject.
Computer,
A first test value receiving unit that receives a blood test value including at least the hemoglobin value, mean corpuscular volume value, and C-reactive protein value of the blood sample (A).
Based on the blood test value, it is determined whether the blood sample (A) is a blood sample derived from a subject with inflammatory anemia or a blood sample (A1) derived from a subject with anemia other than inflammatory anemia. Then, the first determination unit, which is output as the first determination result,
When the first determination unit determines that the blood sample (A) is the blood sample (A1), the second test value receiving unit and the second test value receiving unit that accept the serum ferritin value of the blood sample (A1), and
Based on the serum ferritin level of the blood sample (A1), whether the blood sample (A1) is a blood sample derived from a subject with iron deficiency anemia or a blood sample derived from a subject of thalassemia (A2). The computer program for making a determination and outputting it as a second determination result, for functioning as a second determination unit. Computer,
A third test value that accepts the results of the hemoglobin fraction and PCR test of the blood sample (A2) when the second determination unit determines that the blood sample (A1) is the blood sample (A2). Receiving section and
Based on the hemoglobin fraction of the blood sample (A2) and the result of the PCR test, it is determined whether or not the blood sample (A2) is a blood sample derived from a thalassemia subject, and output as a third determination result. The computer program according to claim 8, further comprising a computer program for functioning as a third determination unit.

Images