Abstract: The invention relates to measuring of the adhesion of platelets ex vivo. In this method, monodisperse polymer particles are added to blood, and the number of platelets in the blood are measured before and after shaking of the sample. The level of adhesion of the platelets is determined by comparing the number of platelets prior to shaking with the number of platelets after shaking. Methods of establishing an adhesion index and diagnosis of a patient are also provided.

Abstract: The present invention provides apparatus and methods for performing assays for determining the time required for a sample of blood to coagulate. The apparatus comprises reaction chambers coated with one or more clotting agent. A drop of blood or equivalent is placed at the sample application port, diluted, and contacted with the clotting agents in the reaction chambers. The diluted blood sample can be moved back and forth through the reaction chambers until blood clots. The blood clotting process forms fibrin stands that prevent the flow of the blood sample in the reaction chambers. The clotting time is the total time from the sample entering the reaction chambers to the time at which the waveform in the reaction chambers change, or the motion or flow of the sample ceases, and can be measured by turbidity.

Abstract: The invention relates generally to a new functional protein S assay and kit that is based on the ability of endogenous protein S to prolong clotting time. In the assay procedure, a test plasma sample is diluted with protein S deficient plasma, followed by the addition of purified or recombinant tissue factor (pTF or rTF), purified natural or synthetic phospholipid (pPL or sPL) and activated protein C (APC) or protein C activator (PCA). The clotting time is then measured and compared to a standard curve or a normal control.

Abstract: The finding that Dickkopf1 (Dkk1) is a dual function protein demonstrates a mechanism for the coordination of cell migration and antagonism of Wnt/?-catenin signaling during developmental and pathological processes. The profile of Dkk proteins expressed by human breast cancers correlates with indicators of outcome: Dkk1 associates with markers of poor prognosis whereas expression of single function Dkk2 or Dkk3 (which inhibit Wnt/?-catenin signaling and promote migration, respectively) correlates with phenotypes reflective of good prognosis. Therefore, the pro-migratory activities of Dkk1 and 3 identified here offer new insights into breast cancer progression and a potential avenue for therapeutic intervention.

Abstract: The present invention provides a device, test cards, methods and kits which are useful for determining the particle fraction and rate of viscosity of a fluid sample, the presence of an analyte in a fluid sample, or the aggregation of particles in a fluid sample to detect an analyte or as an immunologic assay.

Abstract: A system and method for determining a coagulation time, e.g., thrombin time, PT, aPTT, and ACT, of a blood sample deposited in a test cartridge is disclosed. The test cartridge includes a blood receptacle that is open to the atmosphere into which a blood sample is to be deposited, a vacuum port that is open to atmosphere, and a spiral capillary within the test cartridge having a capillary length and cross-section area, a first capillary end of the spiral capillary open to the blood receptacle and a second capillary end of the spiral capillary open to the vacuum port, whereby the spiral capillary is closed to atmosphere. When a blood sample is deposited in the blood receptacle, a vacuum is drawn through the vacuum port and the blood is drawn through the spiral capillary until coagulation occurs. A pressure change is detected, and the coagulation time is measured.

Abstract: The present invention provides a reagent for measuring clotting time comprising a nonionic surfactant, a nickel ion and a tissue factor. A method for stabilizing a tissue factor, and use of a nonionic surfactant and a nickel salt for stabilizing a tissue factor are also disclosed.

Abstract: A system and method for determining a coagulation time, e.g., TT, PT, aPTT, and ACT, of a test sample deposited in a test cartridge is disclosed. A cartridge housing having upper and lower major sides and a minor sidewall encloses a test chamber having a test chamber pivot element and is provided with a cartridge port for introducing a test sample into the test chamber. Ferromagnetic agitator vane leaflets extend from an agitator pivot element supported by the test chamber pivot element intermediate the upper and lower major sides for rotational motion. The agitator vane leaflets can be swept, in response to an external magnetic field, through the test sample in the absence of coagulation. A timer is started when the agitator movement is commenced whereupon the agitator moves freely. Resistance to agitator movement due to coagulation is detected, and the coagulation time is measured.

Abstract: The invention relates to a method for determining the generation of thrombin or factor Xa, said generation of activated coagulation factors in various sample materials, such as whole blood or plasma with different thrombocyte quantities, being triggered by phospholipid micelles with different tissue factor contents (0 to 1000 pM). According to the invention, the generation of thrombin is determined in a coagulation machine, which can simultaneously determine classic conventional coagulation parameters. The device for carrying out the method for the parallel determination of thrombin generation and classic conventional coagulation parameters has a rotating cuvette plate, into which a cuvette ring and cuvette elements are inserted. According to the invention, at least one section of the cuvette ring contains a test station for at least two fluorescent test sets and at least four conventional test sets for coagulation, chromogenic substrates and turbidimetric analysis.

Abstract: Provided is a method of distinguishing among Stanford type A acute aortic dissection, Stanford type B acute aortic dissection, and acute myocardial infarction, which are mutually similar in terms of clinical symptoms, and a kit for the distinguishment. Specifically, provided is a method of distinguishing among Stanford type A acute aortic dissection, Stanford type B acute aortic dissection, and acute myocardial infarction, which comprises detecting both D-dimer and H-FABP in blood separated from a person suspected of having acute aortic dissection and suspected of having acute myocardial infarction, and establishing the diagnosis on the basis of the concentrations detected, and a kit for the distinguishment.

Abstract: A system and method for determining a coagulation time, e.g., TT, PT, aPTT, and ACT, of a blood test sample deposited in a test cartridge is disclosed. A cartridge housing having upper and lower major sides and a minor sidewall encloses a test chamber having a test chamber pivot element and is provided with a cartridge port for introducing a test sample into the test chamber,. Ferromagnetic agitator vane leaflets extend from an agitator pivot element supported by the test chamber pivot element intermediate the upper and lower major sides for rotational motion. The agitator vane leaflets can be swept, in response to an external magnetic field, through the test sample in the absence of coagulation. A timer is started when the agitator movement is commenced whereupon the agitator moves freely. Resistance to agitator movement due to coagulation is detected, and the coagulation time is measured.

Abstract: A method for measuring properties of a fluid including placing a quantity of fluid in a container; inducing flow in the fluid wherein the flow is substantially streamlined in at least a measuring region of the container by constricting flow, and wherein the fluid is recirculated through the measuring region. A mixing region can be created separate from the measuring region sufficient to substantially mix the fluid. Free stream particulates in the fluid can be measured in the streamlined region. The invention is of particular interest in the assessment of blood platelet function. The method provides specific localized regions of thorough mixing that enable reproducible platelet aggregation, and also provides specific localized regions of streamlined flow that enable certain modalities of assessing aggregation. Both of these regions of flow are induced such that damage to platelet aggregates and other blood components as well as undesirable agglomeration on device surfaces is minimized.

Abstract: Unit doses of factor Xa inhibitor compounds and methods of using these compounds for inhibiting blood coagulation in a human patient are taught herein. The unit dose of the factor Xa inhibitor compounds disclosed herein required to inhibit coagulation in a primate is lower than the unit dose required to obtain similar levels of coagulation inhibition in other animal models, such as rodents. Also taught are in vitro assays useful in predicting in vivo antithrombotic activity in humans.

Abstract: The amount of platelet surface proteins in a sample may be measured by collecting a sample containing platelets into a collection tube containing a platelet stabilizing composition, labeling the platelet surface protein and detecting by cytometry.

Abstract: The present invention refers to a novel device for measuring coagulation time and platelet activity wherein the patient can measure his or her coagulation time and platelet activity without the aid of medical professionals due to the fact that this device is fully autonomous. A blood sample (14) is deposited in the dish (3) and reacted with a reactant (16). The display (9) then shows the coagulation time and platelet activity of the patient.

Abstract: The present invention relates to methods and compositions for identifying and treating subjects in need of antithrombotic therapies but who are not responsive to aspirin.

Abstract: Disclosed are improved methods for creating a uniform vascular wound in a zebrafish larva or zebrafish. The methods illustratively include subjecting a zebrafish larva to laser irradiation in an amount and for a period of time effective to cause a uniform vascular wound in the zebrafish larva; or exposing a zebrafish to water containing sodium hydroxide in an amount and for a period of time effective to cause a uniform vascular wound detectable in the gills of the zebrafish.

Abstract: An apparatus and method for measuring blood platelet contractility, hereinafter called a “retractometer” is disclosed. Also disclosed is a system apparatus and method for automatically measuring platelet contractility in a plurality of samples, having an array of retractometer units and an electronic solenoid valve controller to fully automate screening in clinical and research situations and save costs in labor.

Abstract: A disposable apparatus for use in blood testing and being adapted for simultaneous dilution of a blood sample into two different dilution ratios, said apparatus including a block-shaped housing having integrated therein a first and a second receptacle, one of which as a first blood sample receiver being adapted to receive a blood sample; a first and a second container, each containing a defined volume of a diluent; a valve including a valve body having three valve body channels extending therethrough and being positionable in three distinct positions, one of which putting the receptacles in simultaneous communication with a respective one of the containers through pairs of the channels; and displacers for displacing diluent and diluted sample through said channels between said containers and said receptacles.

Abstract: A simplified collecting operation of a biological sample is provided, which enables reduction of the examination cost.

Abstract: A blood sample sensing apparatus includes a moving device which moves a sample container containing a blood sample to a sensing position, a turning mechanism which is connected to the moving device and tilts the sample container such that a bottom of the sample container is directed upward when the sample container is located in the sensing position, and an optical sensor which is located in the sensing position and determines whether the blood sample in the sample container is coagulated.

Abstract: The invention provides a method of monitoring platelet function in a mammal by passing blood removed from the body of the mammal through a passageway to contact an obstruction or irregularity in the passageway to generate a platelet mass in the passageway, and monitoring the flow or composition of the blood in the passageway to detect the platelet mass. The flow and composition change in response to the formation of a platelet mass in the passageway. Devices, articles, and kits for performing the methods are also disclosed.

Abstract: Methods of identifying, monitoring and matching patients with appropriate treatments who are at risk for developing a systemic inflammatory condition prior to development of signs and symptoms using a systemic mediator-associated physiologic test profile are provided.

Abstract: Provided are compositions and methods for accurate determination of the concentration of anticoagulant in a sample such as a blood or plasma sample. The compositions can contain a Factor X compound and Factor V compound, and additional components as well. Methods for performing the assay include one-step methods in which a sample is added to a coagulation assay composition, and time is monitored from the point of adding the sample and coagulation assay composition to an endpoint, such as clot formation.

Abstract: A clot retainer for generally separating liquid from solid components in a specimen enclosed in a container having a closure. The clot retainer includes fingers that are adapted to displace solid components of the specimen. The clot retainer can be inserted through the closure of the container without removing the container. A method of separating liquid from solid components in a specimen is also disclosed.

Abstract: Improved methods and apparatus that make more accurate and reduces risk of filling reaction chambers of cartridge cells with blood samples to conduct blood coagulation tests of the type employing the plunger technique are disclosed. A cartridge holder is provided that secures a test cartridge in a fixed upright position and deflects the plunger flag of each cartridge cell to enable manual insertion of a blood dispenser deeply into the reaction chamber to fill the reaction chamber and avoid contamination of surfaces of the cartridge outside the reaction chamber. Preferably, the cartridge holder provides illumination of the reaction chamber during filling, so that the user can judge when the reaction chamber is properly filled with blood dispensed from the blood dispenser. The cartridge holder may incorporate image magnification to facilitate viewing of the reaction chamber as it is filled.

Abstract: A microsystem for determining clotting time of blood and a low-cost, single-use device for use therein are provided wherein the device has no moving parts or expensive optical sensors or magnets. The device includes a microfluidic channel and a microsensor at least partially in fluid communication with the channel. By analyzing changes in the sensor as a drop of blood flows down the microfluidic channel, the time at which the blood clots can be determined.

Abstract: Methods and apparatus are disclosed for determining a new anticoagulant therapy factor (nATF) for monitoring oral anticoagulant therapy to help prevent excessive bleeding or deleterious blood clots that might otherwise occur before, during or after surgery. In one embodiment, the new anticoagulant therapy factor is based upon a determination of a new fibrinogen transformation rate (nFTR) which, in turn, is dependent on a maximum acceleration point (MAP) for fibrinogen (FBG) conversion. The new anticoagulant therapy factor quantity is also based upon the time to maximum acceleration from the time of reagent injection (TX) into a plasma sample, but does not require the difficulty of obtaining prior art International Normalized Ratio (INR) and International Sensitivity Index (ISI) parameters. Other embodiments provide methods and apparatus for determining an anticoagulant therapy factor without requiring use of a mean normal prothrombin time determination or ISI.

Abstract: An analyzing method of a blood coagulation reaction by detecting an optical change of a blood sample with an elapse of time, the method includes: setting at least one checkpoint or check region between a starting point of the blood coagulation reaction and the endpoint thereof; and monitoring a reaction state of the blood coagulation reaction at the checkpoint or in the check region to detect an abnormality of the blood coagulation reaction.

Abstract: A method and device for blood hemostasis analysis is disclosed. A blood sample is displaced to reach a resonant state. The resonant frequency of the blood sample is determined before, during and after a hemostasis process. The changes in the resonant frequency of the blood sample are indicative of the hemostasis characteristics of the blood sample.

Abstract: A method for measuring properties of a fluid including placing a quantity of fluid in a container; inducing flow in the fluid wherein the flow is substantially streamlined in at least a measuring region of the container, and wherein the fluid is recirculated through the measuring region; creating a mixing region separate from the measuring region sufficient to substantially mix the fluid; and measuring a property of the fluid in the streamlined region. The invention is of particular interest in the assessment of blood platelet function. The method provides specific localized regions of thorough mixing that enable reproducible platelet aggregation, and also provides specific localized regions of streamlined flow that enable certain modalities of assessing aggregation. Both of these regions of flow are induced such that damage to platelet aggregates and other blood components is minimized.

Abstract: The present invention provides methods for diagnosing and/or monitoring thrombophilic disease in a patient that can result from the antiphospholipid antibody syndrome (aPL syndrome). The methods of the invention are premised on the inhibition of binding of an anticoagulant protein, annexin, preferably annexin-V, to phospholipids by antiphospholipid (aPL) antibodies in a patient blood sample.

Abstract: A method and kit for testing a multi-channel blood-testing cartridge. In particular, blood-testing cartridges are tested with plasma samples with clotting times measured to indicate whether a batch of cartridges is suitable for testing the blood of a patient.

Abstract: The instant invention describes a method for establishing the hemostatic competence of blood, wherein the steps of the method include obtaining a blood sample from a subject, contacting the blood sample with an effective amount of tissue factor under conditions conducive to coagulating blood; and detecting the amount of thrombin in the blood sample at a pre-determined time point. The invention also describes a method for testing the capacity of an individual subject to produce thrombin, wherein the steps of the method include obtaining a blood sample from the subject; contacting the blood sample with an effective amount of tissue factor under conditions conducive to coagulating blood; and detecting the amount of thrombin produced in the blood sample at a pre-determined time point.

Abstract: A system for performing a blood coagulation assay, having: a reaction chamber; at least one moveable member configured to mix contents of the reaction chamber; a sensor configured to detect the presence of a blood clot formed in the reaction chamber; and a timer that measures an interval of time between when a blood sample is received into the reaction chamber and when the sensor detects the blood clot formed in the reaction chamber.

Abstract: A method and a device are provided for examining the properties of the global, in particular the primary, hemostasis functions in whole blood or platelet-rich plasma. A volumetric blood flow is preferably adjusted, depending on the measured pressure of the volumetric flow, so that the shear rate or the shear force, whose action in the reaction opening causes blood components, in particular thrombocytes, to deposit, follows a predetermined characteristic curve and in particular is held constant.

Abstract: The invention relates to a method of monitoring the effect of a direct of indirect Factor Xa inhibitors comprising the steps of collecting a plasma sample from a patient, adding a solution of Russell's viper venom to the plasma sample and measuring the clotting time or the residual FXa activity chromogenically.

Abstract: Methods for predicting the presence of haemostatic dysfunction in a patient from a time-dependent measurement profile include performing a time-dependent measurement on an unknown sample and measuring a respective property over time so as to derive a time-dependent measurement profile. The slope of the time-dependent measurement profile is computed prior to clot formation. A biphasic waveform is detected in the time-dependent measurement profile based on the computed slope. The presence of haemostatic dysfunction in the patient is predicted based on the detected biphasic waveform.

Abstract: The invention concerns contact activators for the endogenous coagulation pathway and their use in exploring coagulation anomalies. The activators of the invention are derivatives of gallic acid, preferably polyethylene glycol gallates.

Abstract: Methods for enhancing the lysis of coagulated blood comprise administering to coagulated blood a combination of clot clysis agent and a lysis enhancing amount of apolipoprotein E2 (Apo E2) or a therapeutic derivative thereof. Methods for reducing the risk of blood coagulation comprise administering to blood a combination of a clot lysis agent and a lysis enhancing amount of Apo E2 or a therapeutic derivative thereof. Additional methods for enhancing the lysis of coagulated blood comprise administering to an individual a specific level of clot lysis agent wherein the specific level is based upon the apolipoprotein phenotype of the individual. Further methods for reducing the risks of blood coagulation comprise administering to blood a specific level of a clot lysis agent wherein the specific level is based upon the apolipoprotein phenotype of the individual.

Abstract: Platelet contractile force (PCF) is used as a surrogate marker of thrombin generation. PCF generation occurs concomitant with the burst of prothrombin fragment F 1+2 release. The time between assay start and PCF onset is identified as the thrombin generation time (TGT), and is used in assessing risk of bleeding, in diagnosing various disorders, and in monitoring the effects of pharmaceutical and other treatments. TGT is prolonged in clotting factor deficiencies and in the presence of direct and indirect thrombin inhibitors. TGT shortens to normal with clotting factor replacement and shortens with administration of rVIIa. TGT is short in thrombophilic states such as coronary artery disease, diabetes and thromboangiitis obliterans and prolongs toward normal with oral and intravenous anticoagulants.

Abstract: A sample retention apparatus for use in a device for measuring hemostasis. The device for measuring hemostasis may include a sample articulation apparatus including a guide shaft coupled for articulating motion to a drive motor, a sample carrier secured to and axially moveable along the guide shaft between a sample ready position, a sample testing position and a sample ejection position. The sample carrier therefore articulates in unison with the articulating motion of the guide shaft. A measuring apparatus may include a sensing column. The sample retention apparatus may include a sample cup defining a volume within which a sample may be disposed. The sample cup may be adapted to be operably positioned within an aperture formed within the sample carrier. The sample testing apparatus may also include a sample pin that is engageable with the sensing column. The sample pin may include a tip portion for extending into the sample cup.

Abstract: A hemostasis analyzer, such as the Thrombelastograph® (TEG®) hemostasis analyzer is utilized to measure continuously in real time, the hemostasis process from the initial fibrin formation, through platelet-fibrin interaction and lysis to generate blood hemostasis parameters. The measured blood hemostasis parameters permit evaluation of platelet inhibition therapy.

Abstract: Methods are disclosed for determining, in a sample derived from a human, the functional activity of a component of the human blood coagulation system, which activity can be correlated to conversion of a substrate specific for activated Protein C (APC), by measuring in an assay medium containing the sample and a substrate for APC, the conversion of the substrate by APC and correlating the conversion to the functional activity of the component. When the component is anticoagulant Factor V, at least one of exogenous APC, Protein S or an inhibitor of Protein S activity is added to the medium. When the component is Protein C, APC, or Protein S, exogenous anticoagulant Factor V or an inhibitor of anticoagulant activity of Factor V is added to the medium. Methods are also disclosed for diagnosing a blood coagulation/anticoagulation disorder or for determining a predisposition thereto in a human by determining anticoagulant Factor V activity in an assay medium containing a sample derived from the human.

Abstract: A method and apparatus for determining the stability of dispersions and emulsions accelerates the onset of significant particle agglomeration in a sample by stressing the sample by reducing the height of the interparticle potential energy barrier between the particles. This is achieved by adding one or more of three stress factors: changing the pH of the sample to reduce the surface charge on the particles; adding an adsorbing electrolyte so that ions of the appropriate charge are adsorbed onto the surfaces of the particles to reduce the net charge on the particles; and applying a monovalent, divalent, or trivalent salt to partially screen electrostatic repulsions between the charged particles. In a preferred embodiment, the increase in agglomeration is detected with single particle detection, such as SPOS, to generate a PSD from which a figure of merit is derived. Another embodiment detects turbidity or light scattering to generate a value X indicative of the extent of agglomeration.

Abstract: A thromboplastin reagent includes tissue factor, Factor VIIa, and a net negatively charged phospholipid. The thromboplastin reagent is a synthetic thromboplastin reagent, and is in dried form.

Abstract: In combination, an instrument for determining a characteristic of a biological fluid or a control, and a cuvette for holding a sample of the biological fluid or control, the characteristic of which is to be determined. The instrument comprises a radiation-reflective surface, a first source for irradiating the surface, and a first detector for detecting radiation reflected from the surface. The cuvette has two opposed walls substantially transparent to the source radiation and reflected radiation. The first source and first detector are disposed adjacent a first one of the two opposed walls. The radiation reflective surface is disposed adjacent a second of the two opposed walls. A second source is provided for irradiating the surface. The first detector detects radiation from the second source reflected from the surface.

Abstract: Methods, devices and kits for facilitating medical diagnostic assays and reducing the time required for taking of such assays. The methods comprise initiating a reaction, obtaining at least three measurements, at three different time points, of a value or level of an observable associated with the reaction, and estimating an end point value for the observable from the measurements.

Abstract: The invention relates to methods and products for characterizing and using polysaccharides. Low molecular weight heparin products and methods of use are described. Methods for characterizing purity and activity of polysaccharide preparations including glycosaminoglycans such as heparin are also described.

Abstract: The invention includes an in vitro bleeding time device having an opening through a sheet of material across an outlet. At least a portion the sheet of material contains a coating which includes collagen type I, fibrinogen, fibronectin, and von Willebrand factor. The invention includes a blood coagulation analysis system which has a device with an internal chamber for receiving a blood sample through an inlet. A sheet of material spans a flowpath through a single device outlet. A controller regulates pressure and or flow rate within the device. The invention includes a method for analyzing blood coagulation. Blood provided into a device chamber flows out through an opening through a sheet of material which spans the device outlet. A controller is utilized to control pressure and/or flow rate within the device by controlling the flow rate into the device during formation of a clot blockage of the opening.