Abstract: Factor VIII polypeptides having FVIII:C activity that contain modifications in the A3 and/or C1 and/or C2 domains of the sequence of the light chain of Factor VIII, characterized by the binding affinity to low density lipoprotein receptor protein, and methods for producing the same.

Abstract: There exists a need in the art for high throughput screening assays that can identify compounds that specifically modulate the activity of fast-acting ion channels, such as TRPM5. Current methods, especially electrophysiological, suffer from a lack of sensitivity, rapid signal loss, low throughput, and are labor intensive. The claimed methods and compositions provide electrophysiology methods that allow prolonged sample testing and fluorescent assays with an optical readout that gives rapid readout of the results, has a high signal to noise background ratio, are easy to use, can be modified for automation and miniaturization, and provide verification that a compound specifically modulates TRPM5.

Abstract: The invention features methods and compositions for assessing risk, particularly immediate risk, of thrombotic events in patients with suspected or known vascular disease, and more particularly to assessing risk of thrombotic events in patients with coronary artery disease, particularly acute myocardial infarction, stroke, unstable angina, stable angina, or restenosis. Risk of thrombosis can be assessed by analysis of platelet reactivity and/or velocity of thrombin or fibrin formation, and determining whether the patient has a score associated above a risk threshold value. In other embodiments, risk of thrombosis in a patient is evaluated in the context of a profile generated from values obtained from one or more assays that evaluate various factors associated with thrombosis and/or atherosclerosis.

Abstract: This invention provides an apparatus for assaying clotting activity. The apparatus includes an inlet for a blood fluid and two or more patches of material in the vessel. The material is capable of initiating a clotting pathway in a blood fluid. This invention also provides an apparatus for measuring clot propagation, which includes a region with material capable of initiating a clotting pathway, and a region where the clot propagation is monitored. Also provided are methods for assaying clotting activity, assaying the integrity of a blood clotting pathway, assaying the effect of a substance on the integrity of a blood clotting pathway, monitoring clot propagation, and preventing clot propagation from one vessel to another.

Abstract: A reagent kit capable of distinguishing between a blood sample containing lupus anticoagulant and blood samples from individuals having other anticoagulant diseases is disclosed. The reagent kit comprises two coagulation time reagents containing phosphatidylserine in a different phosphatidylserine content ratio to the total content of phospholipids from each other, threreby giving different coagulation times with use of corresponding coagulation time reagent.

Abstract: The present invention is directed to a kit and a method for a fast and direct determination of the coagulation potential of a sample of blood or plasma utilising a thrombin substrate. The kit comprises at least one activator of the plasmatic coagulation system and a thrombin substrate with a KM preferably less than or equal to 200 ?M in a relatively low concentration with respect to the sample whereby the substrate is wholly consumed within 5 to 600 seconds. Observations are made leading to a determination of the maximum rate of substrate consumption.

Abstract: Described are determination procedures for fibrinogen and/or fibrinogen-derivatives by matrix-independent turbidimetry. In the FIFTA called procedure the fibrinogen activity is preferably determined in an undiluted sample by addition of thrombin and/or albumin, as well as polybrene if appropriate, in PBS and determination of the increase in absorbance at 405 nm. In the FIATA called procedure the fibrinogen-concentration and/or the concentration of fibrinogen-derivatives is preferably determined by addition of vancomycin and determination of the increase in turbidity at 405 nm. It is standardized by usage of plasma standards of known fibrinogen-activity and/or fibrinogen-concentration.

Abstract: The present invention generally relates to the determination of an analyte concentration (quantitative determination) or whether an analyte threshold level has been passed (qualitative determination) in a biological sample through employment of a disposable analytical microprocessor device. The device can include a batch-specific, self-executable algorithm for the calculation of the analyte concentration.

Abstract: A reagent kit for measuring coagulation time is described herein. This reagent comprises calcium chelator which interferes with the reaction between calcium and substance other than a coagulation factor in a blood sample, and which substantially does not interfere with coagulation reaction. A method for measuring coagulation time is also described herein. The method comprises a contacting step and a measuring step. The contacting step is to contact a blood sample, calcium and compound selected from the group consisting of partial thromboplastin, tissue thromboplastin, and complex of tissue factor and phospholipid, in the presence of calcium chelator. This calcium chelator can interfere with the reaction between calcium and substance other than a coagulation factor in the blood sample and substantially does not interfere with coagulation reaction. The measuring step is to measure coagulation time of the blood sample.

Abstract: There are disclosed a stable factor VIII/vWF-complexes, particularly comprising high-molecular vWF multimers, being free from low-molecular vWF molecules and from proteolytic vWF degradation products, as well as methods of producing these complexes.

Abstract: A method for determining the concentration of factor VIIa-antithrombin complexes is disclosed which has application to estimating the level of intravascular exposure of tissue factor, assessing patient risk for hypercoagulation or other coagulopathies, and monitoring patients for factor VIIa-antithrombin complexes over time which can reveal changes in risk for hypercoagulation or other coagulopathies and/or effectiveness of anticoagulant therapy. Antibodies suitable for use in an in vitro assay for determining the concentration of factor VIIa-antithrombin complexes and methods for making the same are also disclosed.

Abstract: A method of determining a coagulation status of a blood sample is provided. The method comprising determining an expression and/or activity ratio of Tissue Factor (TF) to Tissue Factor Pathway Inhibitor (TFPI) in cellular microparticles of the blood sample, wherein the ratio is indicative of the coagulation status of the blood sample.

Abstract: The present invention is directed to a simple method for absolute quantification of plasma vitellogenin from two or more different fish species such as Rainbow trout and Atlantic salmon, or Atlantic cod and haddock. In the case of Rainbow trout and Atlantic salmon, plasma samples obtained from control and ?-estradiol induced fish were digested with trypsin. A characteristic ‘signature peptide’ was selected and analyzed by high performance liquid chromatography coupled to an electrospray quadrupole-time-of-flight tandem mass spectrometer, using a deuterated homologue peptide as an internal standard. The hybrid tandem mass spectrometer was operated in a ‘pseudo’ selected reaction monitoring mode by which three diagnostic product ions were monitored for identification and quantification purposes. The reproducibility (coefficient of variation ˜5%) and sensitivity (limit of quantification of 0.009 mg/mL) achieved by this simple assay allow it to be considered as an alternative to immunological assays.

Abstract: A pretreatment agent for a sample to be subjected to Limulus assay comprising an alkali metal sulfate and/or an alkaline earth metal sulfate wherein the sulfate(s) has a final concentration of 20 mM or more when the sulfate(s) is allowed to contact with the sample, or an alkali metal halide and/or an alkaline earth metal halide wherein the halide(s) has a final concentration of from 0.4 M to 1.2 M or less when the halide(s) is allowed to contact with the sample, or a kit for Limulus assay reagent comprising thereof as a composing article.

Abstract: A platelet aggregation measuring method comprising: preparing a measurement sample which contains a sample and a reagent which includes a platelet activator; mixing the measurement sample at a first speed; mixing the measurement sample at a second speed which is greater than the first speed after mixing the sample at the first speed; obtaining optical information from the measurement sample while mixing the measurement sample at the second speed; and analyzing aggregation of platelets in the sample based on the optical information is disclosed. A platelet aggregation measuring apparatus is also disclosed.

Abstract: A method for determining a condition of disseminated intravascular coagulation (DIC), by analyzing the amount and/or enzyme activity of a von Willebrand factor (vWF)-cleaving protease (ADAMTS13) (preferably also the amount of vWF) in a patient suffering from DIC, and a kit for determining a condition of DIC, comprising an antibody or a fragment thereof which specifically binds to ADAMTS13, are disclosed. According to the present invention, a differential diagnosis of patients with thrombotic thrombocytopenic purpura (TTP) can be carried out from among patients with DIC, which could not be distinguished on the basis of only clinical findings or known markers.

Abstract: The invention relates to a diagnostic assay for selectively measuring levels of the 35kD form of thrombin-activatable fibrinolysis inhibitor (TAFIa or TAFIai), or a derivative or variant thereof, but not the TAFI proenzyme (TAFI) or the N-terminal activation peptide of TAFI.

Abstract: A method to determine an analyte concentration of an anticoagulated plasma by performing at least two different measurements on a mixture of a blood sample corresponding to said anticoagulant plasma and of liquid reagent is described. The method comprises a) mixing a volume of said blood sample with a five-fold, or more, volume of said liquid reagent, b) performing said at least two measurements on said mixture, at least one of which correlates with the hematocrit of said blood sample and at least one of which correlates with said analyte concentration, and c) computing the results from the measurements when the volumes in a) are precise and accurate or when the hematocrit of said blood sample in b) is known to determine said analyte concentration of said anticoagulated plasma. In addition, a measurement and determination device for performing measurements on blood, anticoagulated blood and/or anticoagulated plasma samples, and an equipment kit are described.

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: A method is provided for measuring inhibition of platelet aggregation by a thrombin receptor antagonist. First, a blood sample is obtained from a patient treated with a thrombin receptor antagonist. The blood sample is mixed in combination with particles including an immobilized GPIIb/IIIa receptor ligand and a thrombin receptor activator. The combination is then incubated under conditions suitable for agglutinating the particles, and platelet-mediated agglutination is assessed in the mixture. The absence of agglutination indicates that the patient has reduced ability to form platelet thrombi in response to the thrombin receptor antagonist treatment. Also provided is a kit for measuring inhibition of platelet aggregation by a thrombin receptor antagonist that includes a GPIIb/IIIa receptor ligand immobilized on a particle, a thrombin receptor activator, an anticoagulant, and a buffer to maintain the anticoagulated blood in a condition suitable for platelet aggregation.

Abstract: The present disclosure concerns methods of analyzing both clot formation and fibrinolysis in a sample, preferably simultaneously. In certain embodiments, the methods may comprise adding a small amount of at least one activator of coagulation and at least one activator of fibrinolysis to a sample and analyzing the sample for kinetic parameters related to clot formation and fibrinolysis. In another embodiment, the methods may comprise analyzing a sample from a subject for clot formation and fibrinolysis and detecting or diagnosing a disease or condition and/or applying information obtained from analyzing clot formation and fibrinolysis to determine a treatment for a medical condition of the subject.

Abstract: It was found that TAT which has not been known biological activity has a role as a new blood vessel smooth muscle proliferation factor, and then a screening method vascular of an inhibitor or promoter of a smooth muscle cell growth with TAT is established.

Abstract: Mutants of the DNA sequence coding for the protease (FSAP) which activates blood clotting factor VII and single-chain plasminogen activators, the mutants comprising a G/C base exchange at nucleotide position 1177 and/or a G/A base exchange at nucleotide position 1601, are described. The corresponding protease has a Glu/Gln exchange at amino acid position 393 and/or a Gly/Glu exchange at amino acid position 534. Diagnostic methods which are used for detecting FSAP in body fluids or tissue cells and also for identifying patients with genetic heterozygous or homozygous FSAP expression are also described. In addition, antibodies against FSAP and its mutants are disclosed and diagnostic methods which can be used to detect antibodies against FSAP and its mutants are specified.

Abstract: The invention is in the field of analytical technique and relates to an improved procedure for determining the concentration or activity of an analyte, an analyte-dependent detection reaction being set in motion and the reaction kinetics determined being evaluated. The procedure makes possible an individual determination of the lag phase of the reaction kinetics for each measurement.

Abstract: A thromboplastin reagent comprises: (i) activated sTF, (ii) a metal-chelating lipid, (iii) a metal ion, and (iv) a phospholipid. Activated sTF preferably includes the extracellular domain of TF and an oligohistidine moiety having at least 2 histidine residues, more preferably 2-10 histidine residues. Preferably, the histidine residues are consecutive. Attaching a metal binding domain, such as an oligohistidine tag, to the C-terminus of sTF allows the protein to bind to phospholipid vesicles that contain metal-chelating lipid. Metal complexes of this activated sTF and metal-chelating lipids have all of the desirable expression, handling, and solubility characteristics of sTF, and exhibit procoagulant activities in plasma clotting tests that are comparable to relipidated rTF. In addition, it was discovered that, under some circumstances, Ni-lipids are themselves procoagulant, even in the absence of activated sTF.

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 relates to novel human coagulation Factor VII/VIIa proteins having coagulant potential/activity as well as pharmaceutical compositions comprising the proteins, uses thereof, and methods of treatment therewith. In particular, the present invention relates to novel, semi synthetic analogues of human coagulation Factor VII and VIIa (FVII and FVIIa) as well as to a method of their production.

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: A protease for activating the blood clotting factor VII is described, which (a) is inhibited by the presence of aprotinin, (b) is increased in its activity by calcium ions and/or heparin or heparin-related substances, and (c) in SDS-PAGE, on subsequent staining in the non-reduced state, comprises one or more bands in the molecular weight range from 50 to 75 kDa; and in SDS-PAGE, on subsequent staining in the reduced state, comprises a band at 40 to 55 kDa, one or more bands in the molecular weight range from 10 to 35 kDa, and a band, which corresponds to a proenzyme, in the molecular weight range between 60 and 65 kDa.

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: 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: The present invention relates to methods for the identification of compounds that increase or decrease the inhibitory effect of TFPI on tissue factor activity and/or Factor Xa activity and/or thrombin formation. The invention also relates to methods for the identification of compounds that increase or decrease the co-factor activity of Protein S in TFPI-mediated inhibition of tissue factor and/or Factor Xa activity. This invention also relates to a pharmaceutical composition comprising the compounds identifiable by such methods. The invention also relates to methods for the regulation of tissue factor activity by influencing the interaction between Protein S and Tissue Factor Pathway Inhibitor.

Abstract: The invention relates to a method for determining the total clotting activity of a blood or plasma sample, characterized in that a highly specific, not irreversible thrombin inhibitor is added to a blood or plasma sample in a defined amount, the clotting of the blood or plasma sample is induced and, after a defined period of time, the consumed amount of the added thrombin inhibitor is determined in a per se known manner, as well as to a kit for obtaining information about the state of coagulation of a blood sample.

Abstract: The invention features methods and compositions for assessing risk, particularly immediate risk, of thrombotic events in patients with suspected or known vascular disease, and more particularly to assessing risk of thrombotic events in patients with coronary artery disease, particularly acute myocardial infarction, stroke, unstable angina, stable angina, or restenosis. Risk of thrombosis can be assessed by analysis of platelet reactivity and/or velocity of thrombin or fibrin formation, and determining whether the patient has a score associated above a risk threshold value. In other embodiments, risk of thrombosis in a patient is evaluated in the context of a profile generated from values obtained from one or more assays that evaluate various factors associated with thrombosis and/or atherosclerosis.

Abstract: Test strips designed to prevent or reduce false results when measuring the condition of a sample are provided. The test strips can be used for analysis of samples by methods including electrical and optical measurements. The reagent test strips and methods are particularly suited for use in the detection of blood coagulation.

Abstract: A reagent for measuring clotting time is described. The reagent comprises a complex of a phospholipid and a recombinant tissue factor obtained by using an insect or a cultured insect cell as a host; and a soluble component derived from the insect or the cultured insect cell. A method for manufacturing the reagent is also described.

Abstract: Novel recombinant anticoagulation proteins, methods of their use and methods of their production are described. In particular, recombinant fusions of annexin V (ANV) and Kunitz protease inhibitors (KPI) that possess potent anticoagulant activity are provided. The fusions, abbreviated ANV:KPI, utilize ANV having high affinity for phosphatidyl-L-serine with various KPI's to target serine proteases in membrane-associated coagulation complexes in the blood coagulation cascade. ANV:KPIs are potentially useful antithrombotic drugs permitting localized passivation of thrombogenic vessel walls and associated thrombi.

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: 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: A method for determining the presence and/or amount of an analyte in a sample of whole blood comprises the step of treating the sample with a nonlytic hypertonic salt composition to reduce the hematocrit by reducing the size of the red blood cells. In optical detection systems, the smaller red blood cells create greater scatter, which allows a more accurate correction to be applied in a dual-wavelength detection system. In electrochemical detection systems, as well as in optical detection systems, the smaller red blood cells provide less obstruction to the diffusion of analyte and reagents in the sample, to facilitate the reactions thereof.

Abstract: Methods, compositions and kits are disclosed for identifying patients with an increased risk of experiencing an adverse cardiovascular event where the patient is undergoing aspirin antiplatelet therapy. A platelet-containing sample from the patient is evaluated for platelet hyperactivity and platelet hyperactivity in the sample is related to the patient's risk of an adverse cardiovascular event. In some embodiments the evaluation for platelet hyperactivity is carried out by assessing the function of platelets in the sample using a high shear platelet function test.

Abstract: A method is provided for the localized intravascular administration of a fibrinolytic metalloproteinase to a human subject in amounts that are both safe and effective to lyse an occluding fibrin-containing blood clot, while also avoiding the neutralizing effects of ?2-macroglobulin in the circulating blood. A method is also provided for the treatment of a blood clot in, around or attached to an indwelling vascular access device. A method for restoring patency and function of an indwelling vascular access device is also provided.

Abstract: A method is provided for the localized intravascular administration of a fibrinolytic metalloproteinase to a human subject in amounts that are both safe and effective to lyse an occluding fibrin-containing blood clot, while also avoiding the neutralizing effects of ?2-macroglobulin in the circulating blood. A method is also provided for the treatment of a blood clot in, around or attached to an indwelling vascular access device. A method for restoring patency and function of an indwelling vascular access device is also provided.

Abstract: An additive for controlling the growth of spores of a fungi growth which is adapted to be added to an aqueous system comprising a salt of formic acid. The salt of formic acid is a metal salt or an organic salt. Additive comprises a salt of formic acid and a different second salt of formic acid.

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: Recombinant fragments of Factor C are disclosed. These proteins and peptides show great potency in recognizing, binding to, neutralizing and removing endotoxin. These molecules can thus be used for anti-microbial, anti-endotoxin, and anti-sepsis therapy. SSCrFCES is a 38 kDa protein representing the LPS-binding domain of Factor C. The ability of SSCrFCES to bind lipid A was analyzed using an ELISA-based assay as well as surface plasmon resonance. Surface plasmon resonance similarly carried out for SSCrFC-sushi-1,2,3-GFP, SSCrFC-sushi-1GFP, and SSCrFC-sushi-3GFP confirmed their superior affinity for endotoxin. The 50% endotoxin-neutralizing concentration of SSCrFCES against 200 EU of endotoxin is 0.069 ?M, suggesting that SSCrFCES is an effective inhibitor of LAL coagulation cascade. Although partially attenuated by human serum, as low as 1 ?M of SSCrFCES inhibits the LPS-induced secretion of hTNF-? and hIL-8 by THP-1 and human pheripheral blood mononuclear cells with a potency more superior than polymyxin B.

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: The invention lies in the area of platelet function diagnostics and relates to an in vitro method for the determination of platelet function under flow conditions. The method is particularly suitable for the determination of the effect of clopidogrel after oral intake and of other P2Y(12) antagonists with antithrombotic activity as well as the determination of P2Y(1) receptor antagonists with antithrombotic activity.

Abstract: The invention lies in the area of platelet function diagnostics and relates to a method for the determination of platelet function under flow conditions as well as a device for the implementation of this method. The method is particularly suitable for the determination of the effect of clopidogrel and of other P2Y(12) antagonists with antithrombotic activity as well as the determination of P2Y(1) antagonists with antithrombotic activity.

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.