Abstract: The present inventors examined the procoagulant activity of a multispecific antigen-binding molecule that functionally substitutes for FVIII using blood and plasma derived from FIX disorder patients. The result showed that multispecific antigen-binding molecules that functionally substitute for FVIII can be used not only as methods for preventing and/or treating bleeding in hemophilia A, acquired hemophilia A, von Willebrand disease, and hemophilia C, which are caused by FVIII dysfunction, but also as methods for preventing and/or treating bleeding in FIX disorders, because of their procoagulant activity. Furthermore, the effect of a FIX formulation could be enhanced by using it in combination with a multispecific antigen-binding molecule that functionally substitutes for FVIII, and it was shown that the combined use is promising as a combination therapy that shows stable hemostatic effects.

Abstract: An APTT prolongation factor estimation system includes one or more facilities each including an analyzer which measures a blood coagulation reaction of a subject blood specimen, a database which stores data on a blood coagulation reaction and APTT prolongation factor of blood specimens, and a computer which estimates an APTT prolongation factor of the subject blood specimen based on the data on the blood coagulation reaction from the analyzer and the data stored in the database. The facilities each further includes a data transmission unit which transmits, to the computer, the data on the blood coagulation reaction of the subject blood specimen obtained by the analyzer, and a data reception unit which receives a result of the estimation of the APTT prolongation factor, which is obtained by the computer, regarding the subject blood specimen measured by each of the analyzers.

Abstract: Provided is a method by which a titer of a coagulation factor inhibitor can be measured simply and in a short time. The present invention relates to a method for measuring a titer of a coagulation factor inhibitor. The method includes: preparing a mixed specimen containing a subject blood specimen and a normal blood specimen; heating the mixed specimen and acquiring a coagulation reaction curve for the heated mixed specimen; acquiring a coagulation reaction curve for the mixed specimen that has not been heated; calculating a parameter related to the coagulation reaction curve of the mixed specimen that has not been heated as a first parameter; calculating a parameter related to the coagulation reaction curve of the heated mixed specimen as a second parameter; and calculating a titer of a coagulation factor inhibitor in the subject blood specimen on the basis of the ratio or the difference between the first parameter and the second parameter.

Abstract: To provide a method for analyzing coagulation characteristics of a blood specimen. To provide a method for analyzing a blood specimen, including: acquiring a waveform related to a coagulation rate or coagulation acceleration of a sample obtained by mixing a subject blood specimen with a reagent for measuring coagulation time; extracting multiple parameters characterizing the waveform related to a coagulation rate or a coagulation acceleration; and determining an activity level or activity abnormality of a coagulation factor in the subject blood specimen on the basis of the multiple parameters.

Abstract: Disclosed is a method for analyzing a blood specimen, including the steps of: coagulating a blood specimen in the presence of an activating agent for fibrinolytic system to acquire a coagulation waveform; and acquiring information about fibrinolytic capacity of the blood specimen based on the acquired coagulation waveform.

Abstract: The inventors produced substances that neutralize the activity of a bispecific antibody having an activity of functionally substituting for FVIII, and undertook the construction of methods for measuring the reactivity of FVIII that can ensure accuracy even in the presence of this bispecific antibody. As a result, the inventors discovered that in APTT-based one-stage clotting assay, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately, and also that in APTT-based Bethesda assay, FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately.

Abstract: Various methods for evaluating hemostatic effect and various blood coagulation initiation reagents were studied to construct a method for evaluating blood coagulation reaction mediated by a substance having an activity of substituting for coagulation factor VIII (FVIII). As a result, it was discovered that by using a coagulation initiation reagent containing activated coagulation factor XI (FXIa) and phospholipids, the effect of a substance having an activity of substituting for coagulation factor VIII (FVIII) on blood coagulation reaction can be evaluated using the amount of thrombin generated in the blood sample as an indicator.

Abstract: The present inventors examined the procoagulant activity of a multispecific antigen-binding molecule that functionally substitutes for FVIII using blood and plasma derived from FIX disorder patients. The result showed that multispecific antigen-binding molecules that functionally substitute for FVIII can be used not only as methods for preventing and/or treating bleeding in hemophilia A, acquired hemophilia A, von Willebrand disease, and hemophilia C, which are caused by FVIII dysfunction, but also as methods for preventing and/or treating bleeding in FIX disorders, because of their procoagulant activity. Furthermore, the effect of a FIX formulation could be enhanced by using it in combination with a multispecific antigen-binding molecule that functionally substitutes for FVIII, and it was shown that the combined use is promising as a combination therapy that shows stable hemostatic effects.

Abstract: The present invention relates to a method for evaluating coagulability of a blood specimen obtained from a subject to whom a substance having a coagulation factor VIII-substituting activity is administered. The present invention also relates to a reagent for blood coagulation analysis, a reagent kit for blood coagulation analysis, and an apparatus for blood coagulation analysis. Furthermore, the present invention relates to an apparatus and computer program for evaluating coagulability of a blood specimen.

Abstract: Disclosed is a blood sample determination method including: emitting light to a measurement specimen prepared by mixing a clotting time measuring reagent and a blood sample suspected to be derived from a subject having lupus anticoagulant or a coagulation factor inhibitor, to obtain optical information about an amount of light from the measurement specimen; obtaining at least one parameter regarding derivative of clot waveform, based on the obtained optical information; and determining, based on a value of the obtained parameter, whether the blood sample is suspected to be a sample derived from a subject having lupus anticoagulant or is suspected to be a sample derived from a subject having a coagulation factor inhibitor.

Abstract: The present invention relates to a method for evaluating coagulability of a blood specimen obtained from a subject to whom a substance having a coagulation factor VIII-substituting activity is administered. The present invention also relates to a reagent for blood coagulation analysis, a reagent kit for blood coagulation analysis, and an apparatus for blood coagulation analysis. Furthermore, the present invention relates to an apparatus and computer program for evaluating coagulability of a blood specimen.

Abstract: Disclosed is a method for determining the severity of hemophilia, the method including the steps of: coagulating a blood specimen to acquire a coagulation waveform; acquiring an average change rate of a coagulation rate from the coagulation waveform; and determining the severity of hemophilia in the blood specimen based on the average change rate of the coagulation rate.

Abstract: The inventors produced substances that neutralize the activity of a bispecific antibody having an activity of functionally substituting for FVIII, and undertook the construction of methods for measuring the reactivity of FVIII that can ensure accuracy even in the presence of this bispecific antibody. As a result, the inventors discovered that in APTT-based one-stage clotting assay, FVIII activity in the plasma of a hemophilia A patient can be evaluated accurately, and also that in APTT-based Bethesda assay, FVIII inhibitor titer in the plasma of a hemophilia A patient carrying a FVIII inhibitor can be evaluated accurately.

Abstract: Disclosed is a method for analyzing a blood specimen, including the steps of: coagulating a blood specimen in the presence of an activating agent for fibrinolytic system to acquire a coagulation waveform; and acquiring information about fibrinolytic capacity of the blood specimen based on the acquired coagulation waveform.

Abstract: Disclosed is a blood sample determination method including: emitting light to a measurement specimen prepared by mixing a clotting time measuring reagent and a blood sample suspected to be derived from a subject having lupus anticoagulant or a coagulation factor inhibitor, to obtain optical information about an amount of light from the measurement specimen; obtaining at least one parameter regarding derivative of clot waveform, based on the obtained optical information; and determining, based on a value of the obtained parameter, whether the blood sample is suspected to be a sample derived from a subject having lupus anticoagulant or is suspected to be a sample derived from a subject having a coagulation factor inhibitor.

Abstract: Various methods for evaluating hemostatic effect and various blood coagulation initiation reagents were studied to construct a method for evaluating blood coagulation reaction mediated by a substance having an activity of substituting for coagulation factor VIII (FVIII). As a result, it was discovered that by using a coagulation initiation reagent containing activated coagulation factor XI (FXIa) and phospholipids, the effect of a substance having an activity of substituting for coagulation factor VIII (FVIII) on blood coagulation reaction can be evaluated using the amount of thrombin generated in the blood sample as an indicator.

Abstract: For the first time, the present invention provides antibodies that enhance the generation of activated blood coagulation factor VIII. The antibodies enhance the cleavage of blood coagulation factor VIII at the Arg of position 372 and suppress the cleavage at the Arg of position 336 by recognizing and binding to the A2 domain of blood coagulation Factor VIII. Such antibodies are expected to be useful in preventing or treating diseases that develop or progress due to decrease or loss of the blood coagulation factor VIII activity, for example, hemophilia A, acquired hemophilia, and von Willebrand's disease.

Abstract: For the first time, the present invention provides antibodies that enhance the generation of activated blood coagulation factor VIII. The antibodies enhance the cleavage of blood coagulation factor VIII at the Arg of position 372 and suppress the cleavage at the Arg of position 336 by recognizing and binding to the A2 domain of blood coagulation Factor VIII. Such antibodies are expected to be useful in preventing or treating diseases that develop or progress due to decrease or loss of the blood coagulation factor VIII activity, for example, hemophilia A, acquired hemophilia, and von Willebrand's disease.

Abstract: A method of inactivating a blood coagulation factor is described. The method comprises a step of contacting a sample containing at least one of factors V and VIII with a compound having an iminodiacetate group, whereby at least one of factors V and VIII in the sample is changed into an inactivated form.

Abstract: A method of inactivating a blood coagulation factor is described. The method comprises a step of contacting a sample containing at least one of factors V and VIII with a compound having an iminodiacetate group, whereby at least one of factors V and VIII in the sample is changed into an inactivated form.