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.

A method carried out by a system configured to analyze platelet aggregation includes retaining a ferromagnetic object at an elevation of a chamber in which a sample of blood or plasma is disposed. The ferromagnetic object is retained at the elevation for a period of time. The ferromagnetic object is then released from the elevation. The ferromagnetic object minimal position is measured following the release of the ferromagnetic object. The object minimal position may be correlated with amount of platelet aggregation in the sample.

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.

Disclosed is a method for measuring a blood coagulation activity, comprising: acquiring a parameter related to differentiation of a coagulation waveform in a blood specimen collected from a patient administered with (1) a polypeptide containing a sequence represented by SEQ ID NO: 1, or (2) a polypeptide containing a polypeptide having 95% or more identity with the sequence represented by SEQ ID NO: 1 and having an activity as a blood coagulation factor VIII; and acquiring an activity value of a blood coagulation factor VIII in the blood specimen based on the acquired parameter.

The present invention relates to polypeptides comprising at least one single domain antibody directed against vWF, vWF A1 domain, A1 domain of activated vWF, vWF A3 domain, gpIb and/or collagen, homologues of said polypeptides, and/or functional portions of said polypeptides, for the treatment for conditions which require a modulation of platelet-mediated aggregation and which overcomes the problems of the prior art. A further aspect of the invention is methods of production of said polypeptides, methods to coat devices with such polypeptides used in medical procedures (e.g. PCTA, stenting), methods and kits for screening for agents that modulate platelet-mediated aggregation and kits for the diagnosis of diseases related to platelet-mediated aggregation.

A method of detecting Factor VIII level in a subject, particularly in a subject in need of treatment with at least one Factor Xa inhibitor. The method comprises (a) selecting at least one subject in need of treatment with at least one Factor Xa inhibitor; and (b) detecting Factor VIII level in a sample obtained from the at least one subject with the aim to determine an appropriate dosage of the at least one Factor Xa inhibitor. Preferably, the method comprises a further step of administering at least one Factor Xa inhibitor to the subject.

Disclosed herein are methods for determining the presence of a coagulation inhibitor in a patient. A patient curve associated with the patient sample and having a patient slope (Ps) and a a standard curve associated with a control sample and having a control slope (Cs) are generated, and the Ps and the Cs are compared to obtain a Ps/Cs parallelism ratio. A Ps/Cs parallelism ratio of less than a predetermined ratio is indicative of presence of a coagulation inhibitor in the patient sample.

The present invention relates to an improved method for determining the amount of FVIII inhibitors in a patient sample, comprising the provision of a patient plasma sample, a normal pool plasma samples, and a control plasma sample which is FVIII/VWF deficient, inactivating all clotting factors present in the samples, addition of recombinant FVIII (rFVIII) to the control plasma sample, combination of the patient plasma sample with the control plasma sample with rFVIII to obtain a test mixture, and of the normal plasma pool sample with the control plasma sample with rFVIII to obtain a control mixture, incubation of the test mixture and the control mixture for less than 30 minutes, and analyzing the mixtures for residual rFVIII activity in the absence of VWF.

The invention generally relates to methods of testing the effectiveness of a von Willebrand factor (VWF) in treating von Willebrand disease (VWD) in a subject comprising measuring VWF cleavage fragments in a blood sample from the subject before and after treatment. In particular, the invention relates to methods of measuring VWF cleavage fragments, wherein an increase in VWF cleavage fragments after the treatment indicates that endogenous a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in the subject is cleaving the VWF and wherein a decrease or absence of VWF cleavage fragments after the treatment indicates that endogenous ADAMTS13 in the subject is not cleaving the VWF.

The present invention provides methods of dosing Factor VIII or Factor IX chimeric and hybrid polypeptides. The present invention further provides high-sensitivity methods of quantifying an amount of activated FIX protein in a test sample.