JP2746386B2 - Blood coagulation test using whole blood - Google Patents
Blood coagulation test using whole bloodInfo
- Publication number
- JP2746386B2 JP2746386B2 JP63223836A JP22383688A JP2746386B2 JP 2746386 B2 JP2746386 B2 JP 2746386B2 JP 63223836 A JP63223836 A JP 63223836A JP 22383688 A JP22383688 A JP 22383688A JP 2746386 B2 JP2746386 B2 JP 2746386B2
- Authority
- JP
- Japan
- Prior art keywords
- blood
- coagulation
- test
- time
- anticoagulant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)
- External Artificial Organs (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
【発明の詳細な説明】 〔発明の技術分野〕 本発明は新規な全血を用いた血液凝固能検査法に関す
るものである。Description: TECHNICAL FIELD The present invention relates to a novel blood coagulation test using whole blood.
一般に血液凝固能が亢進して速く凝固する場合ではた
とえば手術後血栓をおこすおそれがあり又これが抑制さ
れ、なかなか凝固しない場合は手術部位からの出血が長
引くおそれがありいずれも危険である。特に人工心肺等
の機械を用いて手術を行なう場合或は人工透析を行なう
場合等血液を体外の機械に流すいわゆる体外循環の場合
血液は凝固し易いので抗凝固剤たるヘパリンを血液に入
れてその凝固を防いでいる。従って手術する前、透析す
る前でヘパリンが投与されていない血液や手術中又は人
工透析中ヘパリンを入れて循環させている血液の凝固能
をはかってその測定値又はその変動をチェックして例え
ばもしヘパリン投与による凝固能抑制が期待以上の場
合、思わぬ出血のおそれがあるためヘパリンを硫酸プロ
タミンで中和するなど所要の処置をとって、血液凝固能
の抑制又は亢進からもたらされるおそれのある危険を回
避するようにしている。In general, when blood coagulation ability is enhanced and blood clots rapidly, there is a risk that thrombus may be caused after surgery, for example, and the blood clot may be suppressed. In particular, in the case of performing so-called extracorporeal circulation, in which blood is passed through an extracorporeal machine, such as when performing surgery using a machine such as a heart-lung machine or when performing artificial dialysis, heparin, which is an anticoagulant, is added to blood. Prevents coagulation. Therefore, before the operation, before the dialysis, blood without heparin administered or during the operation or during the hemodialysis, the blood circulating with heparin is measured for the coagulation ability and the measured value or its fluctuation is checked, for example. If the suppression of coagulation by administration of heparin is more than expected, there is a risk of unexpected bleeding. Try to avoid.
このように血液の凝固能が適性な値であるか否かを特
に手術時、人工透析時に検査することが必要でありこれ
を検査する方法として種々のものがあるが、いくつかの
問題点があった。As described above, it is necessary to check whether the blood clotting ability is an appropriate value, particularly at the time of surgery and at the time of artificial dialysis, and there are various methods for testing this, but there are some problems. there were.
たとえば全血を用いる検査法としては、リー・ホワイ
ト（Lee−White）法、賦活凝固時間法、全血活性化部分
トロンボプラスチン時間があるが夫々次のような問題点
がある。For example, as a test method using whole blood, there are a Lee-White method, an activated coagulation time method, and a whole blood activated partial thromboplastin time, but each has the following problems.
（１） Lee−White法、賦活凝固時間法は抗凝固剤を用
いないので、採血後直ちに検査を実施しなければなら
ないため、検査時期に融通性が無く、検査時期を拘束さ
れる。採血に時間がかかった場合検査値に誤差を生ず
る等の問題点があった。(1) Since the Lee-White method and the activated coagulation time method do not use an anticoagulant, the test must be performed immediately after blood collection, so the test time is not flexible and the test time is restricted. If blood collection takes time, there is a problem that an error occurs in the test value.
（２） 全血活性化部分トロンボプラスチン時間は操作
が２段階となっており繁雑である。測定操作において
時間の正確さが検査値に影響するため、熟練した技術が
ない場合には誤差を生ずる等の問題があった。(2) The whole blood activation partial thromboplastin time is complicated because the operation is performed in two steps. Since the accuracy of the time affects the inspection value in the measurement operation, there is a problem that an error occurs if there is no skilled technique.
本発明はかかる問題点を解決して血液凝固能を迅速、
簡便に検査する方法を提供することを目的とするもので
あり、本発明者らの研究、実験によれば、抗凝固剤を加
えた全血に、遊離カルシウム供与体及び血液凝固因子I
X、Ｘ、XIの少なくとも一種からなる凝固開始剤を添加
し、凝固を形成するまでの時間を測定することによって
かかる目的が達成し得ることが見出されたのである。The present invention solves such a problem to speed up blood coagulation,
The purpose of the present invention is to provide a simple test method.According to the research and experiments of the present inventors, free calcium donor and blood coagulation factor I are added to whole blood containing an anticoagulant.
It has been found that such a purpose can be achieved by adding a coagulation initiator composed of at least one of X, X, and XI and measuring the time until coagulation is formed.
本発明を以下詳細に説明する。 The present invention will be described in detail below.
まず全血に抗凝固剤を加える。通常用いられる公知の
抗凝固剤がここでも用いられる。たとえば、3.8％クエ
ン酸ナトリウム、3.12％クエン酸ナトリウム等の濃度の
クエン酸ナトリウム又はカリウムの水溶液、適当な濃度
のシユウ酸ナトリウム又はカリウム塩、エチレンジアミ
ンテトラ酢酸（EDTA）の塩類又はその溶液等を挙げるこ
とができる。たとえば、全血＋抗凝固剤の合計量の約10
容量％の量の抗凝固剤が用いられる。これは採血時に用
いられる。First, an anticoagulant is added to whole blood. The commonly used known anticoagulants are also used here. For example, an aqueous solution of sodium or potassium citrate having a concentration of 3.8% sodium citrate, 3.12% sodium citrate, or the like; a sodium or potassium oxalate salt having an appropriate concentration; a salt of ethylenediaminetetraacetic acid (EDTA) or a solution thereof; be able to. For example, about 10 times the total amount of whole blood + anticoagulant
An anticoagulant in an amount of% by volume is used. This is used during blood collection.
このように抗凝固剤が添加された全血に遊離カルシウ
ム供与体及び血液凝固因子IX、Ｘ、XIの少なくとも一種
からなる凝固開始剤を加える。A free calcium donor and a coagulation initiator composed of at least one of blood coagulation factors IX, X and XI are added to the whole blood to which the anticoagulant has been added.
ここに凝固開始剤の１種として用いられる遊離カルシ
ウム供与体としては、塩化カルシウム、臭化カルシウ
ム、沃化カルシウム等のハロゲン化カルシウム、燐酸カ
ルシウム、硫酸カルシウム、硝酸カルシウム、重炭酸カ
ルシウム等の無機酸カルシウム塩、蟻酸、酢酸、プロピ
オン酸、酪酸等の脂肪酸のカルシウム塩、アルギン酸、
グルコン酸、乳酸、グリセリン酸、グリセロリン酸等の
有機酸のカルシウム塩等の水溶液を挙げることができ
る。Here, free calcium donors used as one kind of coagulation initiator include calcium halides such as calcium chloride, calcium bromide and calcium iodide, and inorganic acids such as calcium phosphate, calcium sulfate, calcium nitrate and calcium bicarbonate. Calcium salts, calcium salts of fatty acids such as formic acid, acetic acid, propionic acid, butyric acid, alginic acid,
Aqueous solutions of calcium salts of organic acids such as gluconic acid, lactic acid, glyceric acid and glycerophosphoric acid can be mentioned.
また、ここに凝固開始剤のもう１つの種類として用い
られる血液凝固因子IX、Ｘ、XIの少なくとも一種として
は、活性化血液凝固第IX因子（IX a）、活性化血液凝固
第Ｘ因子（X a）、活性化血液凝固第XI因子（XI a）等
を挙げることができる。At least one of the blood coagulation factors IX, X, and XI used as another type of coagulation initiator is activated blood coagulation factor IX (IXa), activated blood coagulation factor X (X a), activated blood coagulation factor XI (XIa) and the like.
４ このような遊離カルシウム供与体及び血液凝固因子
IX、Ｘ、XIの少なくとも一種からなる凝固開始剤は、こ
れらの活性化因子を併用することにより凝固塊の形成を
明瞭に測定することができる。4. Such free calcium donor and blood coagulation factor
The coagulation initiator composed of at least one of IX, X, and XI can clearly measure the formation of a clot by using these activators in combination.
これらの中では、塩化カルシウムの水溶液と活性化血
液凝固第Ｘ因子とを組み合わせて用いることが好まし
い。Among these, it is preferable to use an aqueous solution of calcium chloride in combination with activated blood coagulation factor X.
血液凝固開始剤の添加は採血直後でもよく、又氷冷に
保存しておけば後で添加して任意の時期に検査を開始す
ることも可能である。The blood coagulation initiator may be added immediately after blood collection or, if stored on ice, may be added later to start the test at any time.
検査は抗凝固剤を加えた全血に凝固開始剤を加えて測
定を開始し、注入されたガラス試験管を37℃の水浴中に
30秒間静止した後10秒毎に取出してこれを傾斜させ凝血
塊が認められるまでの時間を計測する。ヘパリン不投与
の正常者の場合100秒前後で凝固し0.5U/mlのヘパリン血
中濃度の場合も９分前後で凝固し通常長くとも15分以内
で検査は終了する。The test is started by adding a coagulation initiator to whole blood with anticoagulant added, and the injected glass test tube is placed in a 37 ° C water bath.
After resting for 30 seconds, take out every 10 seconds, tilt it and measure the time until a clot is recognized. Heparin-non-administered normal subjects coagulate in around 100 seconds, and heparin blood concentration of 0.5 U / ml coagulates in around 9 minutes, and the test is usually completed within 15 minutes at most.
実施例１ 凝固開始剤（0.0625M塩化カルシウム、0.2U/ml X a）
0.2ml 血液（3.8％クエン酸ナトリウム１容＋血液９容）1ml をガラス試験管に注入し測定を開始させ、30秒間37℃の
水浴中に静止した後10秒毎に試験管を傾斜させ凝血塊が
認められるまでの時間を計測する。Example 1 Coagulation initiator (0.0625M calcium chloride, 0.2U / ml Xa)
1 ml of 0.2 ml of blood (1 volume of 3.8% sodium citrate + 9 volumes of blood) was injected into a glass test tube to start the measurement, and after standing still in a water bath at 37 ° C. for 30 seconds, the test tube was tilted every 10 seconds to coagulate blood. Measure the time until lumps are observed.
ヘパリン不投与の正常者32名について検査を実施した
ときの測定値分布を表に示す。これをグラフに示せば第
１図のとおりである。ほぼ70〜180秒の範囲であり、そ
の中90％は80〜130秒の範囲にある。The distribution of measured values when the test was performed on 32 normal subjects who did not administer heparin is shown in the table. This is shown in the graph of FIG. It is in the range of approximately 70-180 seconds, of which 90% is in the range of 80-130 seconds.
〔効 果〕 このように本発明によるときは、採血時に抗凝固剤を
用いるため、採血後検体を保存し後で任意の時期に凝固
開始剤を添加して検査を開始することも可能であり、検
査時間を任意に選択することができる。又採血に時間を
要する時も抗凝固剤の添加により血液凝固の開始が防止
されているため検査血に影響を与えることはなく誤差が
生じにくい。 [Effect] As described above, in the case of the present invention, since an anticoagulant is used at the time of blood collection, it is possible to store the sample after blood collection and add a coagulation initiator at any time later to start the test. The inspection time can be arbitrarily selected. Also, even when a long time is required for blood collection, the addition of an anticoagulant prevents the start of blood coagulation, so that it does not affect the test blood and does not easily cause errors.
又一般的に抗凝固剤を用いるときは血漿分離等の試験
操作を行なう等煩雑な操作を必要とし簡便に血液凝固能
の測定ができなかったが、本発明では血漿分離等の繁雑
な操作を省き全血に凝固開始剤を添加することによって
簡便に血液凝固能を測定することができるようになっ
た。更に従来の方法では10分以上の時間を必要としたが
本発明のときは通常数分間で終了でき迅速に検査するこ
とができる。Generally, when an anticoagulant is used, a complicated operation such as a test operation such as plasma separation is required, and the blood coagulation ability cannot be easily measured.However, in the present invention, a complicated operation such as plasma separation is performed. By adding the coagulation initiator to the omitted whole blood, the blood coagulation ability can be easily measured. Further, in the conventional method, a time of 10 minutes or more was required, but in the case of the present invention, the inspection can be normally completed in a few minutes and the inspection can be performed quickly.
尚本発明は全血を用いた血液凝固能検査法に関する
が、例えばヘパリン等の抗凝固剤を投与された患者の血
液についても検査が可能となる。Although the present invention relates to a blood coagulation ability test method using whole blood, for example, a blood test of a patient to which an anticoagulant such as heparin has been administered can be performed.
図面第１図は本発明の方法の一実施例の測定結果を示す
グラフである。FIG. 1 is a graph showing the measurement results of one embodiment of the method of the present invention.
Claims (1)
与体及び血液凝固因子IX、Ｘ、XIの少なくとも一種から
なる凝固開始剤を添加し、凝固を形成するまでの時間を
測定することを特徴とする、全血を用いた血液凝固能検
査法。An anticoagulant-added whole blood is added with a free calcium donor and a coagulation initiator composed of at least one of blood coagulation factors IX, X and XI, and the time required to form coagulation is measured. A blood coagulation test using whole blood.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63223836A JP2746386B2 (en) | 1988-09-07 | 1988-09-07 | Blood coagulation test using whole blood |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63223836A JP2746386B2 (en) | 1988-09-07 | 1988-09-07 | Blood coagulation test using whole blood |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0271154A JPH0271154A (en) | 1990-03-09 |
| JP2746386B2 true JP2746386B2 (en) | 1998-05-06 |
Family
ID=16804482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63223836A Expired - Fee Related JP2746386B2 (en) | 1988-09-07 | 1988-09-07 | Blood coagulation test using whole blood |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2746386B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014050926A1 (en) * | 2012-09-28 | 2014-04-03 | 中外製薬株式会社 | Method for evaluating blood coagulation reaction |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4958139B2 (en) * | 2006-02-14 | 2012-06-20 | 日置電機株式会社 | Displacement magnifying mechanism with displacement final output end and processing apparatus provided with the displacement magnifying mechanism |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA84588B (en) * | 1983-01-26 | 1985-09-25 | Univ New Jersey Med | Hematological prediction of sepsis and other disease states |
| JPS60115519A (en) * | 1983-11-28 | 1985-06-22 | Sekisui Chem Co Ltd | Promotor for blood clotting |
-
1988
- 1988-09-07 JP JP63223836A patent/JP2746386B2/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014050926A1 (en) * | 2012-09-28 | 2014-04-03 | 中外製薬株式会社 | Method for evaluating blood coagulation reaction |
| KR20150068406A (en) * | 2012-09-28 | 2015-06-19 | 추가이 세이야쿠 가부시키가이샤 | Method for evaluating blood coagulation reaction |
| CN104937423A (en) * | 2012-09-28 | 2015-09-23 | 中外制药株式会社 | Method for evaluating blood coagulation reaction |
| EP2902787A4 (en) * | 2012-09-28 | 2016-03-23 | Chugai Pharmaceutical Co Ltd | Method for evaluating blood coagulation reaction |
| JPWO2014050926A1 (en) * | 2012-09-28 | 2016-08-22 | 中外製薬株式会社 | Evaluation method of blood coagulation reaction |
| CN104937423B (en) * | 2012-09-28 | 2017-05-24 | 中外制药株式会社 | Method for evaluating blood coagulation reaction |
| RU2683933C2 (en) * | 2012-09-28 | 2019-04-03 | Чугаи Сейяку Кабусики Кайся | Method for evaluating reaction of blood coagulation |
| KR102134305B1 (en) | 2012-09-28 | 2020-07-15 | 추가이 세이야쿠 가부시키가이샤 | Method for evaluating blood coagulation reaction |
| US11078518B2 (en) | 2012-09-28 | 2021-08-03 | Chugai Seiyaku Kabushiki Kaisha | Method for evaluating blood coagulation reaction |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0271154A (en) | 1990-03-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |