WO2015040441A1 - Procédé et système de mesure pour déterminer des caractéristiques de coagulation sangunie - Google Patents

Procédé et système de mesure pour déterminer des caractéristiques de coagulation sangunie Download PDF

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Publication number
WO2015040441A1
WO2015040441A1 PCT/HU2014/000084 HU2014000084W WO2015040441A1 WO 2015040441 A1 WO2015040441 A1 WO 2015040441A1 HU 2014000084 W HU2014000084 W HU 2014000084W WO 2015040441 A1 WO2015040441 A1 WO 2015040441A1
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Prior art keywords
measuring
blood
blood coagulation
optical
time
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PCT/HU2014/000084
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English (en)
Inventor
József ANTAL
József NEUBRANDT
Mátyás PETŐ
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Diagon Ltd.
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Publication of WO2015040441A1 publication Critical patent/WO2015040441A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
    • 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
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood
    • G01N33/4905—Determining clotting time of blood
    • 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

Definitions

  • the subject of the invention relates to a procedure and measuring system for determining blood coagulation characteristics, during which real-time liquid phase tests are performed in a capillary whole blood sample using the same principle applied during traditional laboratory liquid phase measurements giving results comparable with the results of traditional laboratory liquid phase measurements and a user-friendly, easy-to-use measuring system consisting of a measuring device and reagent set is set up to perform the tests.
  • the frequency of the doctor-patient meeting may be favourably formed in a personalised way.
  • a possibility for in vitro POC testing of haemostasis disorders accompanying perioperative or emergency conditions is, for example, the characterisation of the viscoelastic changes of blood using sonoclot, thromboelastometry and thromboelastography [summarised by Ganter M.T., Hofer C.K. (2008): Anesth.Analg. 106: 1366-1375.; Enriquez L.J.,Shore-Lesserson L.(2009): Br.J.Anaesth. 103: il4-i22.].
  • the viscoelastic measurements are not performed in the blood flow but instead under static conditions.
  • sample collection, sample preparation When performing traditional laboratory liquid phase blood coagulation tests first of all plasma is created from the one millilitre volume of anticoagulated vein blood sample, therefore the traditional laboratory liquid phase analysis is preceded by a pre-analytic period of varying duration ("sample collection, sample preparation").
  • sample preparation After sample preparation the characteristics of the biochemical process of blood coagulation are measured by monitoring prothrombin-thrombin activation, fibrinogen-fibrin transformation catalysed by the formed thrombin and the fibrin polymerisation induced by various inducing processes, like, for example, determining Prothrombin Time, in which case the prothrombin-thrombin activation is initialised by thromboplastin.
  • the monitoring of the fibrin polymerisation may be realised by detecting optical change (for example light dispersion change, nephelometry or turbidity change, automatic laboratory coagulometers detecting based on the principle of turbidimetry), or by measuring the changes of viscoelastic characteristics (for example, automatic laboratory coagulometers detecting using a mechanical principle) [Gogstad G.O. et al. (1986): Clin.Chem. 32: 1857-1862.; Hoffmann J.J.M.L.,Verhappen M.A.L.(1988): Clin.Chem. 34: 2135-2140.].
  • optical change for example light dispersion change, nephelometry or turbidity change, automatic laboratory coagulometers detecting based on the principle of turbidimetry
  • viscoelastic characteristics for example, automatic laboratory coagulometers detecting using a mechanical principle
  • the parameters characteristic of the sample may be determined with a POC measuring device, then they may be converted using the software of the measuring device and then forwarded to a central data store for diagnostic, comparative and risk-analysis purposes.
  • the advantage of the POC test is that the analysis of the blood sample takes place at the currently selected location, usually using a few tens of microlitres of capillary blood mostly originating from the fingertip [Perry D.J. et al.(2010): Br.J.Haematol. 150: 501-514.].
  • the POC tests used to date do not usually follow the entire process due to the complex composition of the sample (enzymatically active blood plasma and active cellular elements), instead they usually examine thrombin activity. Therefore the comparison of the results obtained in traditional laboratory liquid phase measurements with blood plasma testing and the result obtained in POC tests with whole blood testing usually requires special assessment, as in the case of blood plasma testing the effect of the active cellular elements on thrombin activity and fibrin polymer structure cannot be assessed, furthermore, during the time between sample taking and traditional laboratory processing various changes have to be taken into account in the blood sample components, primarily in the coagulation factors (deactivation- activation).
  • Patent numbers WO 94/16095 and WO 95/30770 concern dry chemistry POC tests set up to determine blood coagulation characteristics.
  • recombinant thromboplastin reagent is applied to a solid absorbent carrier, for example onto plastic polymer strips, onto a reaction zone with a diameter of approximately 0.5 cm by drying-lyophilisation, then the liquid phase component containing the test sample is reacted with this zone.
  • the progress of the enzyme-substrate reaction is measured with sensing electrodes formed on the carrier material, with the change in electrical resistance of the reaction zone while connected to a POC measuring device, the measured value is then displayed on a monitor in a measurable way.
  • test reagents are immobilised in the detection zone of a non-porous carrier card serving for carrying out POC Prothrombin Time (PT), Activated Coagulation Time (ACT), Activated Partial Thromboplastin Time (APPT), platelet aggregation and fibrinogen tests. Following this the detection zone is reacted with a liquid component containing the test sample.
  • PT Prothrombin Time
  • ACT Activated Coagulation Time
  • APPT Activated Partial Thromboplastin Time
  • platelet aggregation platelet aggregation and fibrinogen tests.
  • the other disadvantage here also is that it is not the blood coagulation process that is characterised, instead one of its physical consequences is detected, and for this redox particles ensuring ion migration are dissolved into the liquid component of the reaction, the presence of which may influence the blood coagulation processes that require space and surface area.
  • the third disadvantage is apparent in the limited ability to assess blood flow-free viscosity measurement.
  • test sample is transported using capillarity to the detection zone of a non-porous carrier card prepared with a coagulation reagent.
  • the elegant solution's advantage is its disadvantage: these in vitro reactions cannot be compared with enzyme substrate reactions taking place in in vivo aqueous reaction spaces.
  • the reactions of whole blood samples or blood samples treated with anticoagulant and reagents in a cuvette are monitored so that the haematocrit value is determined by optical measurement of the reaction and the Prothrombin Time INR value is determined with rheological measurement.
  • the advantage of the solution is that the blood coagulation reaction takes place in a cuvette, which provides space and surface area for the process similarly to blood coagulation reactions taking place in in vivo aqueous reaction spaces.
  • the disadvantage of the solution is that it is complex, and also that rheological measurement does not appear in traditional laboratory liquid phase measurement solutions, due to which the comparability of the results is questionable.
  • the surface of the depression created on the test card is covered with a blood coagulation initiator, for example with thromboplastin.
  • the key participant in the test arrangement is a blade wheel moving element with which the blood sample is taken into the reaction chamber, the reaction mixture is mixed and the coagulate created is removed, and the blood coagulation in the plasma sample or whole blood sample is detected by the completion of the electrical circuit performed by the coagulate.
  • the advantage of this solution is the blade wheel moving element. Its advantage is also its disadvantage: the solution is complex.
  • the objective of with our invention was to overcome the disadvantages of the aforementioned solutions and to elaborate a simple, fast, specific and reproducible procedure in which real time, liquid phase tests are performed in a capillary whole blood sample for determining blood coagulation equivalent to the principle used in traditional laboratory liquid phase measurements and with results comparable to the results of the measurements of traditional laboratory liquid phase measurement, and in order to perform the tests a user friendly, easy-to-handle measuring system of a measuring device and reagent set is set up. Furthermore, our objective with our invention was to determine blood coagulation characteristics by monitoring the optical changes over time accompanying the entire blood coagulation process, both its cellular and non-cellular reactions, which is solved by detecting optical turbidity as a function of time.
  • test reaction space is created in an easy-to-handle, small volume reaction vessel, measuring cuvette.
  • PT Prothrombin Time
  • PT-INR Prothrombin International Normalised Ratio
  • ACT Activated Coagulation Time
  • the active perishable component of the reagent set is stored in the measuring cuvette forming a part of the reagent set in a vacuum-dried/lyophilised state until used.
  • the measuring cuvette is fitted into the heat- regulated measuring position of the measuring device of the measuring system and the dried content in the measuring cuvette is dissolved with the liquid stable component of the reagent set. With this step the measuring system is now suitable for receiving the test sample.
  • the active, perishable component(s) of the reagent set is (are), among others, a blood coagulation component(s) sensitive to oxidative processes, temperature fluctuations, pH and ion shifts like, for example thromboplastin and fibrinogen.
  • a very preferable solution that can be well compared with traditional laboratory liquid phase measurements is if the real time reactions are detected as a function of time not indirectly but directly by optically monitoring the change in turbidity accompanying the entire process of the blood coagulation process (thrombin activation enzyme cascade, thrombin activity, fibrinogen-fibrin transformation, fibrin polymerisation, and possibly the enzymatic cross-linking of the fibrin network), the sum total of the cellular and non-cellular reactions, preferably with the help of nephelometry and turbidimetry.
  • the subject of the invention then is a procedure for the real-time determination of the blood coagulation characteristics in blood samples, for the optical detection of reactions taking place in in vivo aqueous reaction spaces in in vitro reaction spaces, preferably in a small- volume reaction vessel, in a measuring cuvette by using a reagent set.
  • the essence of the procedure is that real time, liquid phase tests are performed on blood samples equal to the principle used in traditional laboratory liquid phase measurements and with results comparable to the results of the measurements of traditional laboratory liquid phase measurement in such a way that the active, perishable component(s) and the stable component(s) of the reagent set are handled in a separate way, in separate phases.
  • a coagulation curve is produced (figure 2a), i.e. the optical changes occurring due to the fibrin network, fibrin fibres created during coagulation in the entire volume of the measuring cuvette are monitored as a function of time, from which the blood coagulation characteristics may be determined and then preferably displayed.
  • the rotation of the mixing element creates optical noise in the path of the light, which noise may also be detected in the optically opaque reaction mixture (e.g. determination of APTT, ACT with whole blood), and which noise increases during the creation and thickening of the fibrin fibres.
  • the subject of the invention then relates to a further procedure for the real-time determination of blood coagulation characteristics in blood samples, to the optical detecting of reactions taking place in in vivo aqueous reaction spaces in in vitro reaction spaces, preferably in a reaction vessel with a small volume, with the use of a reagent set.
  • a mechanical mixing element is placed in the measuring cuvette, preferably balls rotated on the base of the measuring cuvette for the entire time of the examined coagulation process, as a result of which fibrin polymerisation is initiated on the bordering interface of the mechanical mixing element and the reaction mixture. Then the mechanical mixing is continued until the breaking off of the polymerised fibrin from the bordering interface of the mechanical mixing element and the reaction mixture is achieved, at which breaking-off time the simultaneous, sudden and abrupt change in the optical transparency and optical noise level is detected, and then the breaking off time is assessed as being the coagulation time.
  • the change in blood coagulation characteristic is determined using the principle of turbidimetry.
  • the blood coagulation characteristic is Prothrombin Time (PT), and/or Prothrombin International Normalised Ratio (PT-INR), and/or Activated Coagulation Time (ACT), and/or D-Dimer.
  • the determination of Prothrombin Time is realised through the optical monitoring of fibrin polymerisation.
  • the blood coagulation characteristic of Prothrombin International Normalised Ratio is derived by calculation using the reagent-specific calibration data, from the determination of the Prothrombin Time (PT).
  • the opto-active biochemical component in the active, perishable component of the reagent set is blood coagulation initiating recombinant thromboplastin.
  • the blood coagulation initiating component is silicate particles.
  • the subject of the invention furthermore, also relates to a measuring system for the realtime determination of blood coagulation characteristics in blood samples, which has a reagent set and a measuring device with a central unit performing the optical detecting of the blood samples.
  • the measuring system is set up so that the measuring device contains a measuring unit supplied with an optical measuring cell suitable for accommodating the measuring cuvette forming a part of the reagent set.
  • the active, perishable component required for the detecting of the blood coagulation characteristics, to which an opto-active biochemical component is also added, is stored in the measuring cuvette in a lyophilised state.
  • the liquid, stable component of the reagent set is placed in the measuring cuvette placed in the optical measuring cell.
  • the optical measuring cell is supplied with a mixing element and heating unit connected to the central unit via a mixing controller and a heating controller.
  • the measuring cuvette connected to the heating controller and placed in the optical measuring cell has a temperature sensor that measures the temperature, furthermore, the reagent set also contains a reagent dispenser and a blood sample dispenser.
  • the mixing element is preferably moved at the optical measuring cell with the help of a rotating magnetic field.
  • a preferable embodiment of the measuring system is when a reagent-identifying radio frequency RPID device is built into the measuring device that is set up to input calibration and control data and perform data registration.
  • FIG. 1 - figures la and lb show the previously presented two-step and single-step coagulation curves
  • - figure 2a depicts the coagulation curve obtained by turbidimetry detecting
  • figure 2b depicts the coagulation curve obtained with the application of the further procedure according to the invention
  • - and figure 3 depicts the block diagram of the measuring system.
  • the curve marked A is the result of a measuring arrangement in which the active, perishable component of the reagent set is stored in the measuring cuvette forming a part of the reagent set in a lyophilised state, and following placing the measuring cuvette at the optical measuring cell, the liquid, stable component of the reagent set was added for the purpose of dissolving and incubation.
  • the curve marked B is the result of a measuring arrangement in which the active, perishable component of the reagent set was stored in the measuring cuvette forming a part of the reagent set in the liquid state preceding lyophilising, and following placing the measuring cuvette at the optical measuring cell, the liquid, stable component of the reagent set was added for the purpose of incubation.
  • the increased optical sensitivity established with the addition of fibrinogen and the lyophilised arrangement is striking (figure lb, curve A).
  • FIG 2a the optical change caused by the fibrin network, fibrin fibres built up during the coagulation is shown as a function of time with the traditional coagulation curve.
  • the measuring device M As soon as the measuring device M is ready for performing measurements (the block temperature is at 37 °C), it reads in the reagent set R calibration and expiry data with the help of the RFID device 8 from the unique RFID label of the reagent set R. If it finds that the expiry date of the reagent set R is appropriate, after inputting the sample/patient identifier it notifies the user, for example, via the display 7 connected to the central unit 1 , to position the measuring cuvette forming a part of the reagent set R into the measuring unit 10. Every measuring cuvette contains the active, perishable component Rl in a lyophilised, dry state.
  • D-Dimer is determined via the optical monitoring of latex agglutination.
  • Blood sample dispenser R4 for accommodating at the most, preferably 20 ⁇ of blood sample
  • the following table 1 serves to support that stated above, in which the results of Prothrombin International Normalised Ratio (PT-INR) tests are compared with the measurement results of Prothrombin International Normalised Ratio (PT-INR) tests performed on the same blood sample series by another POC system,
  • Measuring system A The measuring system according to the invention
  • Laboratory device B laboratory device detecting using the principle of nephelometry

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Abstract

L'invention concerne un procédé en temps réel de détermination de caractéristiques de coagulation sangunie dans des échantillons de sang, pour la détection optique de réactions aqueuses in vivo effectuées dans des espaces de réaction in vitro, de préférence dans un récipient de réaction de petit volume, dans une cuvette de mesure, au moyen d'un kit de réactifs, selon lequel des tests en phase liquide d'échantillons de sang entier basés sur les principes identiques à ceux utilisés dans les mesures en phase liquide de laboratoire classiques sont effectués en temps réel, et avec des résultats comparables aux résultats des mesures en phase liquide de laboratoire classiques. Dans ces tests, le ou les composants périssables actifs et le ou les composants stables du kit de réactifs sont manipulés dans des phases séparées.
PCT/HU2014/000084 2013-09-19 2014-09-19 Procédé et système de mesure pour déterminer des caractéristiques de coagulation sangunie WO2015040441A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017123266A1 (fr) * 2016-01-16 2017-07-20 Hewlett-Packard Development Company, L.P. Mesure de caractéristiques sanguines
JP2019507345A (ja) * 2016-02-18 2019-03-14 ダイアグノスティカ スターゴ 静脈血栓塞栓症に対して特異的なｄダイマーをアッセイするための方法、ならびに肺塞栓症および深部静脈血栓症を診断するためのその使用
CN111551701A (zh) * 2020-04-03 2020-08-18 深圳大学 一种用于检测凝块收缩力的柔性微柱环阵列及其制备方法和应用
CN112394183A (zh) * 2021-01-19 2021-02-23 潍坊库恩曼动力机械有限公司 基于交叉配血的智能血液检测系统

Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1013192A (en) * 1962-11-13 1965-12-15 Warner Lambert Pharmaceutical Diagnostic reagent composition for use in determining blood coagulation factors
US3228841A (en) * 1965-06-10 1966-01-11 Warner Lambert Pharmaceutical Diagnostic reagent composition for determining blood coagulation factors and method of use
US4458015A (en) * 1981-04-02 1984-07-03 Boehringer Mannheim Gmbh Reagent for the optical determination of the blood coagulation
US4784944A (en) * 1984-04-09 1988-11-15 Behringwerke Aktiengesellschaft Prothrombin time determining reagent and methods of using and preparing the same
WO1994016095A1 (fr) 1993-01-13 1994-07-21 Avocet Medical, Inc. Procede, article de test et systeme pour effectuer des titrages
US5443960A (en) * 1991-11-13 1995-08-22 Dahlbaeck; Bjoern Method for the diagnosis of blood coagulation disorders
WO1995030770A1 (fr) 1994-05-06 1995-11-16 Avocet Medical, Inc. Methode de mesure a sec du temps de prothrombine
US5522255A (en) 1993-08-31 1996-06-04 Boehringer Mannheim Corporation Fluid dose, flow and coagulation sensor for medical instrument
US6060323A (en) 1997-06-27 2000-05-09 Hemosense, Inc. Method and device for measuring blood coagulation or lysis by viscosity changes
US20030180824A1 (en) 2002-03-25 2003-09-25 Mpock Emmanuel C. System for performing blood coagulation assays and measuring blood clotting times
WO2004111656A1 (fr) 2003-06-15 2004-12-23 Zafena Ab Teste de coagulation à température ambiante
WO2005054847A1 (fr) 2003-12-02 2005-06-16 Zafena Aktiebolag Determination de la teneur en hematocrite et en une substance a analyser
WO2010122158A1 (fr) 2009-04-23 2010-10-28 Dublin City University Dispositif d'essai à écoulement latéral pour la surveillance de la coagulation et procédé correspondant
WO2011148207A1 (fr) 2010-05-28 2011-12-01 Diagon Kft. Procédé pour la préparation biphasique de liposomes et son utilisation dans la fabrication de réactifs de diagnostic
WO2013072710A1 (fr) * 2011-11-16 2013-05-23 Diagon Kft. Procédure et appareil automatique pour tests diagnostiques de coagulation sanguine in vitro

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1013192A (en) * 1962-11-13 1965-12-15 Warner Lambert Pharmaceutical Diagnostic reagent composition for use in determining blood coagulation factors
US3228841A (en) * 1965-06-10 1966-01-11 Warner Lambert Pharmaceutical Diagnostic reagent composition for determining blood coagulation factors and method of use
US4458015A (en) * 1981-04-02 1984-07-03 Boehringer Mannheim Gmbh Reagent for the optical determination of the blood coagulation
US4784944A (en) * 1984-04-09 1988-11-15 Behringwerke Aktiengesellschaft Prothrombin time determining reagent and methods of using and preparing the same
US5443960B1 (en) * 1991-11-13 1999-01-12 T A C Thrombosis And Coagulati Method for the diagnosis of blood coagulation disorders
US5443960A (en) * 1991-11-13 1995-08-22 Dahlbaeck; Bjoern Method for the diagnosis of blood coagulation disorders
WO1994016095A1 (fr) 1993-01-13 1994-07-21 Avocet Medical, Inc. Procede, article de test et systeme pour effectuer des titrages
US6189370B1 (en) 1993-08-31 2001-02-20 Roche Diagnostics Corporation Fluid dose, flow and coagulation sensor for medical instrument
US5522255A (en) 1993-08-31 1996-06-04 Boehringer Mannheim Corporation Fluid dose, flow and coagulation sensor for medical instrument
US6575017B1 (en) 1993-08-31 2003-06-10 Roche Diagnostics Corporation, Inc. Fluid dose, flow and coagulation sensor for medical instrument
WO1995030770A1 (fr) 1994-05-06 1995-11-16 Avocet Medical, Inc. Methode de mesure a sec du temps de prothrombine
US6060323A (en) 1997-06-27 2000-05-09 Hemosense, Inc. Method and device for measuring blood coagulation or lysis by viscosity changes
US6338821B1 (en) 1997-06-27 2002-01-15 Arvind N. Jina Method and device for measuring blood coagulation or lysis by viscosity changes
US6673622B1 (en) 1997-06-27 2004-01-06 Hemosense, Inc. Coagulation or lysis assays by measuring impedance
US20030180824A1 (en) 2002-03-25 2003-09-25 Mpock Emmanuel C. System for performing blood coagulation assays and measuring blood clotting times
WO2004111656A1 (fr) 2003-06-15 2004-12-23 Zafena Ab Teste de coagulation à température ambiante
WO2005054847A1 (fr) 2003-12-02 2005-06-16 Zafena Aktiebolag Determination de la teneur en hematocrite et en une substance a analyser
WO2010122158A1 (fr) 2009-04-23 2010-10-28 Dublin City University Dispositif d'essai à écoulement latéral pour la surveillance de la coagulation et procédé correspondant
WO2011148207A1 (fr) 2010-05-28 2011-12-01 Diagon Kft. Procédé pour la préparation biphasique de liposomes et son utilisation dans la fabrication de réactifs de diagnostic
WO2013072710A1 (fr) * 2011-11-16 2013-05-23 Diagon Kft. Procédure et appareil automatique pour tests diagnostiques de coagulation sanguine in vitro

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
ANTON VAN DEN BESSELAAR ET AL: "Preparation of lyophilized partial thromboplastin time reagent composed of synthetic phospholipids: usefulness for monitoring heparin therapy", CLINICAL CHEMISTRY, vol. 43, no. 7, 1 July 1997 (1997-07-01), pages 1215, XP055163919, ISSN: 0009-9147 *
ENRIQUEZ L.J.; SHORE-LESSERSON L., BR.J.ANAESTH., vol. 103, 2009, pages I14 - 122
GANTER M.T.; HOFER C.K., ANESTH.ANALG., vol. 106, 2008, pages 1366 - 1375
GOGSTAD G.O. ET AL., CLIN.CHEM., vol. 32, 1986, pages 1857 - 1862
HOFFMANN J.J.M.L.; VERHAPPEN M.A.L., CLIN.CHEM., vol. 34, 1988, pages 2135 - 2140
HUCKLE D., EXPERT REV.MOL.DIAGN., vol. 8, 2008, pages 679 - 688
JACKSON C.M. ET AL., CLIN.CHEM., vol. 51, 2005, pages 483 - 485
PERRY D.J. ET AL., BR.J.HAEMATOL., vol. 150, 2010, pages 501 - 514
WEBSTER S., EUR.CLIN.LAB., vol. 25, 2006, pages 10 - 11
WU H.M. ET AL., PER.MED., vol. 7, 2010, pages 65 - 73

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017123266A1 (fr) * 2016-01-16 2017-07-20 Hewlett-Packard Development Company, L.P. Mesure de caractéristiques sanguines
US11112400B2 (en) 2016-01-16 2021-09-07 Hewlett-Packard Development Company, L.P. Blood characteristic measurement
JP2019507345A (ja) * 2016-02-18 2019-03-14 ダイアグノスティカ スターゴ 静脈血栓塞栓症に対して特異的なｄダイマーをアッセイするための方法、ならびに肺塞栓症および深部静脈血栓症を診断するためのその使用
CN111551701A (zh) * 2020-04-03 2020-08-18 深圳大学 一种用于检测凝块收缩力的柔性微柱环阵列及其制备方法和应用
CN112394183A (zh) * 2021-01-19 2021-02-23 潍坊库恩曼动力机械有限公司 基于交叉配血的智能血液检测系统

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