CA2068221A1 - Direct fibrinogen assay - Google Patents
Direct fibrinogen assayInfo
- Publication number
- CA2068221A1 CA2068221A1 CA002068221A CA2068221A CA2068221A1 CA 2068221 A1 CA2068221 A1 CA 2068221A1 CA 002068221 A CA002068221 A CA 002068221A CA 2068221 A CA2068221 A CA 2068221A CA 2068221 A1 CA2068221 A1 CA 2068221A1
- Authority
- CA
- Canada
- Prior art keywords
- plasma
- fibrinogen
- sample
- concentration
- delta value
- 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.)
- Abandoned
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/84—Systems specially adapted for particular applications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/745—Assays involving non-enzymic blood coagulation factors
- G01N2333/75—Fibrin; Fibrinogen
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plasma & Fusion (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Steroid Compounds (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
An endpoint assay for measuring fibrinogen utilizing strong thrombin and weak plasma. In a preferred embodiment the assay is based on the direct conversion of a normalized signal from a sensor to fibrinogen concentration.
Description
W091/08~60 ~ PCT/US9OtO698~
~`?7."`, ,, -- 1 ~ :
~ ' , ` .', .. ':
. .
: .
DIRECT FI~RINOGEN ASSAY
..`'', ' .BACKGROUND OF THE INVENTION
The invention relates to a methold for determining the ,concentration o~ fibrinogen in blood ,plasma using thrombin as a reagent.
Prior methods of using thrombin to measure fibrinogen concentration, include the Clauss met~hod which is based on measuring the time it takes for a pla,sma-thrombin reaction ,.
to occur (clotting time) and the ACL3 ~ibrinogen assay. : .
10~ The Clauss method is described in Manual of Hemostasis and Thrombosis, ed. 3, by Arthur R. Thompson and haurence A.
Harker, Appendix A, p. 179 (1983) and~in Gerrinnunqs : hv~iologische ~chnell Methode ur B~stimmun~ des ~,.
EL~irgge~ by A- Clauss, Acta Haematol, 17:237 (1957).
:, 15 The ACL3 method is describe~ in Method for the Determina~
: `tio~ of Functional ~Çlottable) Fibr:inoqen bv ~he_New Family ,.: :
e5_~5l.95~9~ 5~ by E. Rossi, P. Mondonico, A. Lomabar~
di,~L. Preda, Thrombosis ~esaarch 52;~453-469~(1988). ~ , ~These methods rely on th~ measurement of a relevant::
~0 paraméter such as clotting time or changes in;optical transmission and on multiple dilutions of a calibrator plasma to compensiate conditions o~ the instrument and . ! ':
,. :
' ''' ': `" ' ' : .
:
WO~1/0~60 PCT/US90/06988 reagent at a given time. Using calibrator plasmas (i.e.
plasma having known fibrinogen concentrations) "standard lines" or "calibration curves" must be constructed repeatedly whenever conditions warr~nt. In the determiina-tion of ~ibrinogen concentration of an unknown sample, therelevant quantity, such as clotting time, is measured and the concentration is then "read" from the standard curve.
This process can involve considerable calculation, and is often tedious and time consuming.
Another deficiency o~ these prior methods is that the relevant quantity b~ing measured is often instrument depen-dent, as well as reaction dependent. For example, if the instrument used to measure the relevant parameter employs an electro-optical system in which scattered or transmiitted light is detected, the value obtained from the measurement will depend on the signal level measured by the optical sensor, which in turn depends on the amount of light incident on the reaction vessel as well as the electronic gains used in association with the optical sensor. The values of these quantities do not remain constant in time, nor do they remain constant from channel to channel or instrument to instrumient.
SUMMARY OF THE INVENTION
There~ore, it is an object of the invention to pr~vide a method for measuring the concentration of ~ibrinogen in a blood sample that is more efficient and efficacious manner than prior methods.
It is another object o~ the invention to eliminate the effects of instrument variation and channel variation in ~easuring thè changes in optical transmission, which are the ba~is for determining fibrinogen concentration.
It i~ also an object of the invention to employ measured quantities in a manner that eliminates the need to repeatedly establish a standard curve.
'~ ~ ' ,:' ,.
,': ' ' ' W~91/08q~0 - PCT/US90/06988 The present invention provides a method for measuring the concentration of fibrinogen in a hlood plasma sample.
According to the method of the invention, a sample of plasma containing fibrinogen is provided in a container.
Thrombin is added to the sample and mixed with the sample to form a reaction mixture. An initial optical transmit-tance is measured for the reaction mixture. The thrombin and fibrinogen are allowed to react with each other in the reaction mixture. A final optical transmittance is 10 measured for the reaction mixture. The measurements are `
manipulated in the manner described below and concentration of fibrinogen is determined from a previously established standard curve.
It is an aspect of the invention that the standard curve is constructed in such a manner that it remains unchanged by variations in instrument, reagent or sample.
Therefore, once established, it is not necessary to repeatedly reconstruct it.
DESC~IP~ION OF_THE PREFERREi~ ~MBOD~MENTS
The present method is preferably us~d in conjunction with an optical monitoring system such as that disclosed in concurrently fil~d and copending U.S. Patent Application Serial No. 07/443,952 to Swope et al., entitled "Multichan-nel Optical Monitoring System", assigned to the assigne~ of the present application, the disclosure of which is incorporated herein by reference, or in conjunction with commercially available hemostasis instruments such a~ the assignee's model Coag-A-Mate XC or modeI Coag-A-~ate XM. ~ ~ -Approximate reagent/plasma concentrations that are suitable for the method of the invention are known from the Clauss fibrinogen method noted above. The thrombin con-centration is preferably about 100 NI~ units (a strong thro~bin concentration) and the plas~a sample is prPferably diluted in a 1:10 ratio (a weak plasma concentration) with ' ':
.':,' "
- '.'," "
'~
WOgl/0~60 P~T/US90/0~988 Z ~ 4 Owren 's Veronal Buffer (sodium barbital). Other suitabl~
diluents ~or the plasma are described in Clauss.
In the present invention the formation of fibrinogen is photo-optically monitored ~or total change between the optical transmittance before the onset of the reaction and the optical transmittance at the conclusion of the reac-tion. According to the method, reagant is added to plasma and, after a time which allows for co~plete sample-reagent mixing, an initial transmittance signal (Ti) is recorded.
When the clot i5 fully formed, the final transmittance signal ~Tf~ is processed as described below.
The relevant parameter, delta or D, is computed the initial and final transmittance measurements by normalizing the difference in the readings to the initial value plus any offset using the following equation-Ti ~ Tf D = ~ - x R
Ti ~ So where D is the normalized digital value of delta;
Ti is the digital value of the transmitted light prior to the onset of the clot;
Tf is the digital value of the transmitted light subsequent to the formation of the clot;
S0 is the digikal offset that may have been imposed as part o~ the instrument design; and K is an arbitrary constant chosen for convenience.
It should be noted that in prior methods, D was defined as the difference (Ti-Tf) only. The denominator in the above expression represents the normalization of D to the initial value of ths transmittance.
The next step in det~rmining the concentration of fibrinogen of an unknown sample is to refer the above determined value of D to the concentration by the use of a .. ;,, .' ~. .
- , : .
''. -:
'" ~' - . ~:~ . .... .. : . . . .. ., ,., , . ; ,., . .. ,, .. , ,.,:,: . ,: . . ... .
WO91/~60 ~ 3~, ~ PCT/U~90/069~
standard curve. This is done by ~irst computing the ~ -cluantity D
R = lo~
Dc - ~-. .
where Dc is the previously determined delta for a calibrator plasma of known fibri~ogen concentra-tion.
Measurements of Dc are per~ormed relatively infrec~uently as changes in test conditions warrant. The next step is to use a previously determined correlation equation which -~
describes ~he relationship between R and fibrinog~n ~ ~ -concantration to determine the fibrinogen concentration of the sample. It has been discovered that the correlation equation relating R and fibrinogen concentration does not change significantly with different c1esignated reagents and calibrator plasmas. There~ore, it can be permanently stored as part of the computational ~;oftware and does not require periodic recomputation.
The correlation equation is prei~erably derived as follows: Various standard plas~as of known fibrinogen concentration are prepared and a delt:a value Ds is deter-mined for each standard plasma. Next, a value Rs iscalculated for each standard plasma based on the following ~` equation:
Ds s = log(~
Dc -. ,. .: .
where s is the R value ~or a standard plas~a;
Ds is the m~asured delta value ~or the standard ,-plasma; and ~
D~ is the previously determined delta ~or the ~ ~ -~cal1brator plasma. ~ ~ ~
., ,-. ..
.~.
.' ~
.' '".'" ' . ~
WO91/0~60 PCT/US90/06988 "'1g~
The correlation equation is then derived by plotting Rs versus log(Cs/Cc) for the various standard plasmas where Cs is the fibrinogen concentration of a standard plasma and Cc is the fibrinogen concentration of the calibrator plasma~
It will be understood that the above description of the present invention is susceptible to various modifica-tions, changes and adaptations, and the same are intended to be comprehended within the meaning and range of e-quivalents of the appended claims.
' -~
,: .;
' ':
. .:
:
~`?7."`, ,, -- 1 ~ :
~ ' , ` .', .. ':
. .
: .
DIRECT FI~RINOGEN ASSAY
..`'', ' .BACKGROUND OF THE INVENTION
The invention relates to a methold for determining the ,concentration o~ fibrinogen in blood ,plasma using thrombin as a reagent.
Prior methods of using thrombin to measure fibrinogen concentration, include the Clauss met~hod which is based on measuring the time it takes for a pla,sma-thrombin reaction ,.
to occur (clotting time) and the ACL3 ~ibrinogen assay. : .
10~ The Clauss method is described in Manual of Hemostasis and Thrombosis, ed. 3, by Arthur R. Thompson and haurence A.
Harker, Appendix A, p. 179 (1983) and~in Gerrinnunqs : hv~iologische ~chnell Methode ur B~stimmun~ des ~,.
EL~irgge~ by A- Clauss, Acta Haematol, 17:237 (1957).
:, 15 The ACL3 method is describe~ in Method for the Determina~
: `tio~ of Functional ~Çlottable) Fibr:inoqen bv ~he_New Family ,.: :
e5_~5l.95~9~ 5~ by E. Rossi, P. Mondonico, A. Lomabar~
di,~L. Preda, Thrombosis ~esaarch 52;~453-469~(1988). ~ , ~These methods rely on th~ measurement of a relevant::
~0 paraméter such as clotting time or changes in;optical transmission and on multiple dilutions of a calibrator plasma to compensiate conditions o~ the instrument and . ! ':
,. :
' ''' ': `" ' ' : .
:
WO~1/0~60 PCT/US90/06988 reagent at a given time. Using calibrator plasmas (i.e.
plasma having known fibrinogen concentrations) "standard lines" or "calibration curves" must be constructed repeatedly whenever conditions warr~nt. In the determiina-tion of ~ibrinogen concentration of an unknown sample, therelevant quantity, such as clotting time, is measured and the concentration is then "read" from the standard curve.
This process can involve considerable calculation, and is often tedious and time consuming.
Another deficiency o~ these prior methods is that the relevant quantity b~ing measured is often instrument depen-dent, as well as reaction dependent. For example, if the instrument used to measure the relevant parameter employs an electro-optical system in which scattered or transmiitted light is detected, the value obtained from the measurement will depend on the signal level measured by the optical sensor, which in turn depends on the amount of light incident on the reaction vessel as well as the electronic gains used in association with the optical sensor. The values of these quantities do not remain constant in time, nor do they remain constant from channel to channel or instrument to instrumient.
SUMMARY OF THE INVENTION
There~ore, it is an object of the invention to pr~vide a method for measuring the concentration of ~ibrinogen in a blood sample that is more efficient and efficacious manner than prior methods.
It is another object o~ the invention to eliminate the effects of instrument variation and channel variation in ~easuring thè changes in optical transmission, which are the ba~is for determining fibrinogen concentration.
It i~ also an object of the invention to employ measured quantities in a manner that eliminates the need to repeatedly establish a standard curve.
'~ ~ ' ,:' ,.
,': ' ' ' W~91/08q~0 - PCT/US90/06988 The present invention provides a method for measuring the concentration of fibrinogen in a hlood plasma sample.
According to the method of the invention, a sample of plasma containing fibrinogen is provided in a container.
Thrombin is added to the sample and mixed with the sample to form a reaction mixture. An initial optical transmit-tance is measured for the reaction mixture. The thrombin and fibrinogen are allowed to react with each other in the reaction mixture. A final optical transmittance is 10 measured for the reaction mixture. The measurements are `
manipulated in the manner described below and concentration of fibrinogen is determined from a previously established standard curve.
It is an aspect of the invention that the standard curve is constructed in such a manner that it remains unchanged by variations in instrument, reagent or sample.
Therefore, once established, it is not necessary to repeatedly reconstruct it.
DESC~IP~ION OF_THE PREFERREi~ ~MBOD~MENTS
The present method is preferably us~d in conjunction with an optical monitoring system such as that disclosed in concurrently fil~d and copending U.S. Patent Application Serial No. 07/443,952 to Swope et al., entitled "Multichan-nel Optical Monitoring System", assigned to the assigne~ of the present application, the disclosure of which is incorporated herein by reference, or in conjunction with commercially available hemostasis instruments such a~ the assignee's model Coag-A-Mate XC or modeI Coag-A-~ate XM. ~ ~ -Approximate reagent/plasma concentrations that are suitable for the method of the invention are known from the Clauss fibrinogen method noted above. The thrombin con-centration is preferably about 100 NI~ units (a strong thro~bin concentration) and the plas~a sample is prPferably diluted in a 1:10 ratio (a weak plasma concentration) with ' ':
.':,' "
- '.'," "
'~
WOgl/0~60 P~T/US90/0~988 Z ~ 4 Owren 's Veronal Buffer (sodium barbital). Other suitabl~
diluents ~or the plasma are described in Clauss.
In the present invention the formation of fibrinogen is photo-optically monitored ~or total change between the optical transmittance before the onset of the reaction and the optical transmittance at the conclusion of the reac-tion. According to the method, reagant is added to plasma and, after a time which allows for co~plete sample-reagent mixing, an initial transmittance signal (Ti) is recorded.
When the clot i5 fully formed, the final transmittance signal ~Tf~ is processed as described below.
The relevant parameter, delta or D, is computed the initial and final transmittance measurements by normalizing the difference in the readings to the initial value plus any offset using the following equation-Ti ~ Tf D = ~ - x R
Ti ~ So where D is the normalized digital value of delta;
Ti is the digital value of the transmitted light prior to the onset of the clot;
Tf is the digital value of the transmitted light subsequent to the formation of the clot;
S0 is the digikal offset that may have been imposed as part o~ the instrument design; and K is an arbitrary constant chosen for convenience.
It should be noted that in prior methods, D was defined as the difference (Ti-Tf) only. The denominator in the above expression represents the normalization of D to the initial value of ths transmittance.
The next step in det~rmining the concentration of fibrinogen of an unknown sample is to refer the above determined value of D to the concentration by the use of a .. ;,, .' ~. .
- , : .
''. -:
'" ~' - . ~:~ . .... .. : . . . .. ., ,., , . ; ,., . .. ,, .. , ,.,:,: . ,: . . ... .
WO91/~60 ~ 3~, ~ PCT/U~90/069~
standard curve. This is done by ~irst computing the ~ -cluantity D
R = lo~
Dc - ~-. .
where Dc is the previously determined delta for a calibrator plasma of known fibri~ogen concentra-tion.
Measurements of Dc are per~ormed relatively infrec~uently as changes in test conditions warrant. The next step is to use a previously determined correlation equation which -~
describes ~he relationship between R and fibrinog~n ~ ~ -concantration to determine the fibrinogen concentration of the sample. It has been discovered that the correlation equation relating R and fibrinogen concentration does not change significantly with different c1esignated reagents and calibrator plasmas. There~ore, it can be permanently stored as part of the computational ~;oftware and does not require periodic recomputation.
The correlation equation is prei~erably derived as follows: Various standard plas~as of known fibrinogen concentration are prepared and a delt:a value Ds is deter-mined for each standard plasma. Next, a value Rs iscalculated for each standard plasma based on the following ~` equation:
Ds s = log(~
Dc -. ,. .: .
where s is the R value ~or a standard plas~a;
Ds is the m~asured delta value ~or the standard ,-plasma; and ~
D~ is the previously determined delta ~or the ~ ~ -~cal1brator plasma. ~ ~ ~
., ,-. ..
.~.
.' ~
.' '".'" ' . ~
WO91/0~60 PCT/US90/06988 "'1g~
The correlation equation is then derived by plotting Rs versus log(Cs/Cc) for the various standard plasmas where Cs is the fibrinogen concentration of a standard plasma and Cc is the fibrinogen concentration of the calibrator plasma~
It will be understood that the above description of the present invention is susceptible to various modifica-tions, changes and adaptations, and the same are intended to be comprehended within the meaning and range of e-quivalents of the appended claims.
' -~
,: .;
' ':
. .:
:
Claims (5)
1. A method for optically measuring a concentration of fibrinogen in a blood plasma sample, said method compris-ing:
providing a sample of plasma containing fibrinogen in a container;
adding thrombin to the sample;
mixing the thrombin with the sample to form a reaction mixture;
measuring an initial optical transmittance for the reaction mixture;
allowing the thrombin and fibrinogen to react with each other in the reaction mixture;
measuring a final optical transmittance for the reaction mixture;
comparing the final transmittance measurement to the initial transmittance measurement to compute a delta value;
and determining the concentration of fibrinogen based on the delta value.
providing a sample of plasma containing fibrinogen in a container;
adding thrombin to the sample;
mixing the thrombin with the sample to form a reaction mixture;
measuring an initial optical transmittance for the reaction mixture;
allowing the thrombin and fibrinogen to react with each other in the reaction mixture;
measuring a final optical transmittance for the reaction mixture;
comparing the final transmittance measurement to the initial transmittance measurement to compute a delta value;
and determining the concentration of fibrinogen based on the delta value.
2. The method of claim 1, wherein the thrombin is at a concentration of about 100 NIH unit and the plasma sample is diluted in about a 1:10 ratio with sodium barbital.
3. The method of claim 1, wherein the delta value is computed according to the equation:
where D is a normalized value of delta;
Ti is the initial optical transmittance of the sample;
Tf is the final optical transmittance of the sample;
So is an offset which is dependent on the device used to perform said method; and K is a predetermined constant.
where D is a normalized value of delta;
Ti is the initial optical transmittance of the sample;
Tf is the final optical transmittance of the sample;
So is an offset which is dependent on the device used to perform said method; and K is a predetermined constant.
4. The method of claim 1, wherein said step of determining fibrinogen concentration further comprises:
deriving a correlation equation which allows fibrinogen concentration of a sample to be determined from a value R, where R is computed from the equation where D is the delta value of the sample plasma; and Dc is a delta value of a calibrator plasma; and determining the fibrinogen concentration of the plasma sample based on the derived correlation equation.
deriving a correlation equation which allows fibrinogen concentration of a sample to be determined from a value R, where R is computed from the equation where D is the delta value of the sample plasma; and Dc is a delta value of a calibrator plasma; and determining the fibrinogen concentration of the plasma sample based on the derived correlation equation.
5. The method of claim 4, wherein the correlation equation is derived by:
measuring a delta value for a plurality of standard plasmas of different known concentrations;
measuring a delta value for a calibrator plasma of known concentration;
and plotting Rs versus the log(Cs/Cc) for the plurality of standard plasmas where where Rs is the R value for a standard plasma;
Ds is a measured delta value for the standard plasma;
Dc is a measured delta value for a calibrator plasma;
Cs is the concentration of fibrinogen in the standard plasma; and Cc is the concentration of fibrinogen in the calibrator plasma.
measuring a delta value for a plurality of standard plasmas of different known concentrations;
measuring a delta value for a calibrator plasma of known concentration;
and plotting Rs versus the log(Cs/Cc) for the plurality of standard plasmas where where Rs is the R value for a standard plasma;
Ds is a measured delta value for the standard plasma;
Dc is a measured delta value for a calibrator plasma;
Cs is the concentration of fibrinogen in the standard plasma; and Cc is the concentration of fibrinogen in the calibrator plasma.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44394889A | 1989-12-01 | 1989-12-01 | |
| US443,948 | 1989-12-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2068221A1 true CA2068221A1 (en) | 1991-06-02 |
Family
ID=23762843
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002068221A Abandoned CA2068221A1 (en) | 1989-12-01 | 1990-11-30 | Direct fibrinogen assay |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0502103A4 (en) |
| JP (1) | JPH05503008A (en) |
| KR (1) | KR920704117A (en) |
| AU (1) | AU641459B2 (en) |
| CA (1) | CA2068221A1 (en) |
| FI (1) | FI922312A0 (en) |
| IE (1) | IE904244A1 (en) |
| WO (1) | WO1991008460A1 (en) |
| ZA (1) | ZA909564B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5708591A (en) | 1995-02-14 | 1998-01-13 | Akzo Nobel N.V. | Method and apparatus for predicting the presence of congenital and acquired imbalances and therapeutic conditions |
| US6321164B1 (en) | 1995-06-07 | 2001-11-20 | Akzo Nobel N.V. | Method and apparatus for predicting the presence of an abnormal level of one or more proteins in the clotting cascade |
| US6898532B1 (en) | 1995-06-07 | 2005-05-24 | Biomerieux, Inc. | Method and apparatus for predicting the presence of haemostatic dysfunction in a patient sample |
| US6429017B1 (en) | 1999-02-04 | 2002-08-06 | Biomerieux | Method for predicting the presence of haemostatic dysfunction in a patient sample |
| US6502040B2 (en) | 1997-12-31 | 2002-12-31 | Biomerieux, Inc. | Method for presenting thrombosis and hemostasis assay data |
| JP4486260B2 (en) | 1999-02-04 | 2010-06-23 | バイオメリュー・インコーポレイテッド | Method and apparatus for predicting the presence of hemostatic dysfunction in patient samples |
| US7179612B2 (en) | 2000-06-09 | 2007-02-20 | Biomerieux, Inc. | Method for detecting a lipoprotein-acute phase protein complex and predicting an increased risk of system failure or mortality |
| CN110257475B (en) * | 2019-06-28 | 2023-05-02 | 深圳市国赛生物技术有限公司 | Fibrinogen detection reagent, preparation method thereof and detection reagent product |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3432268A (en) * | 1964-08-28 | 1969-03-11 | Peter Unger | Method and apparatus for testing cell suspensions |
| US3658480A (en) * | 1970-04-13 | 1972-04-25 | Bio Data Corp | Coagulation timing apparatus, and method |
| US3833864A (en) * | 1972-11-30 | 1974-09-03 | R Kiess | Digital direct reading colorimeter |
| US3861877A (en) * | 1974-01-21 | 1975-01-21 | Clinical Technology Inc | Optical analysis of fluids |
| US3905769A (en) * | 1974-02-28 | 1975-09-16 | Bagley Wallace E | Method and apparatus for measuring prothrombin time and the like |
| US3989382A (en) * | 1975-01-22 | 1976-11-02 | Bio-Data Corporation | Platelet aggregation monitoring device |
| EP0059277A1 (en) * | 1981-03-02 | 1982-09-08 | J. & P. Coats, Limited | Rapid quantative measurement of fibrinogen in blood plasma |
| AT382971B (en) * | 1981-06-16 | 1987-05-11 | Hoffmann La Roche | METHOD AND DEVICE FOR MEASURING THE BLOOD CLUTTING TIME |
| GB8426004D0 (en) * | 1984-10-15 | 1984-11-21 | Ortho Diagnostic Systems Inc | Coagulation monitoring |
| IT1209604B (en) * | 1984-11-27 | 1989-08-30 | Instrumentation Lab Spa | METHOD AND EQUIPMENT FOR MEASUREMENT OF COAGULATION PARAMETERS. |
-
1990
- 1990-11-23 IE IE424490A patent/IE904244A1/en unknown
- 1990-11-28 ZA ZA909564A patent/ZA909564B/en unknown
- 1990-11-30 JP JP3501113A patent/JPH05503008A/en active Pending
- 1990-11-30 KR KR1019920701275A patent/KR920704117A/en active IP Right Grant
- 1990-11-30 EP EP19910900512 patent/EP0502103A4/en not_active Withdrawn
- 1990-11-30 WO PCT/US1990/006988 patent/WO1991008460A1/en not_active Application Discontinuation
- 1990-11-30 CA CA002068221A patent/CA2068221A1/en not_active Abandoned
- 1990-11-30 AU AU68983/91A patent/AU641459B2/en not_active Ceased
-
1992
- 1992-05-21 FI FI922312A patent/FI922312A0/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU6898391A (en) | 1991-06-26 |
| AU641459B2 (en) | 1993-09-23 |
| EP0502103A4 (en) | 1993-05-05 |
| ZA909564B (en) | 1992-11-25 |
| KR920704117A (en) | 1992-12-19 |
| IE904244A1 (en) | 1991-06-05 |
| EP0502103A1 (en) | 1992-09-09 |
| FI922312A (en) | 1992-05-21 |
| WO1991008460A1 (en) | 1991-06-13 |
| FI922312A0 (en) | 1992-05-21 |
| JPH05503008A (en) | 1993-05-27 |
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