Methods, compositions and kits useful in the detection, assessment, diagnosis, prognosis and/or treatment of neurological injury or disease or brain injury, such as traumatic brain injury (TBI), are provided in which certain newly discovered protein biomarkers are detected in a biological sample of a subject undergoing testing or evaluation. The methods allow for detection of changes in levels, amounts, or concentrations of the protein biomarkers in a subject compared with those of controls. Detection of the protein biomarkers, and/or levels thereof, provides an indication of biological and biochemical events, e.g., at a cellular level, that are occurring in the subject who is undergoing testing or analysis for the neurological injury or brain injury.

Provided herein is a method of detecting or predicting a relapse of multiple sclerosis in an individual afflicted with a form of multiple sclerosis, comprising: (a) providing a blood sample of the individual; (b) testing the blood sample to determine a protein activity or protein level, wherein the protein is Factor VIII, von Willebrand factor, or Protein C; and (c) detecting or predicting a relapse of multiple sclerosis in the individual if the protein activity or protein level is elevated compared to the protein activity or protein level in an individual not afflicted with the form of multiple sclerosis and patients' own baseline values. Also provided herein is a method of treating an individual afflicted with multiple sclerosis, who is experiencing a relapse or predicted to experience a relapse, comprising treating the individual by administering a dose of a steroid or anti-coagulation compound effective to alleviate the symptom of multiple sclerosis.

The present invention relates to a method for prophylactic treatment of spontaneous bleeding in a subject with severe von Willebrand Disease comprising administering a therapeutic amount of recombinant von Willebrand Factor (rVWF) to the subject.

Subjects with heart failure (HF) are at higher risk of developing thrombosis. The inventors thus determined the thrombin generating capacity in patients with acute decompensated heart failure (ADHF). Their prospective study included 34 ADHF patients and 30 control inpatients without HF. Compared to controls, endogenous thrombin potential (ETP) was higher in ADHF patients at admission using platelet-rich plasma and remained increased during the hospitalization period. Soluble markers of endothelial dysfunction including von Willebrand factor, factor VIII and endothelial protein C receptor were higher in ADHF patients at admission. The plasma levels of DNA-histone complexes were elevated significantly in ADHF patients at admission compared to controls. Higher concentrations of annexin-V/tissue factor (TF)-positive eEVs were also found also in ADHF patients at admission compared to controls. The findings demonstrate that methods of determining the thrombin generating capacity in patients with acute decompensated heart failure (ADHF), which combine measurements of endogenous thrombin potential and endothelial dysfunction, are particularly valuable for stratifying the patients and thus for orienting treatments and following-up of the patients.

Described herein are method(s), kit(s), reagent(s) and the like for determining von Willebrand factor (VWF) activity in a sample in the absence of ristocetin.

Provided is a blood coagulation reaction analysis method. The method includes measuring a blood coagulation reaction of a subject specimen and acquiring first data for calculating a blood coagulation time of the subject specimen and second data for estimating a blood coagulation abnormality factor of the subject specimen, wherein the acquiring of the second data includes: obtaining a first derivative V(i) of a coagulation reaction curve R(i); and determining a point p.sub.k where V(i) assumes X.sub.k before reaching a maximum value of V(i), Vmax, and a point q.sub.k where V(i) assumes X.sub.k after reaching Vmax.

In a first aspect, there is provided an isolated polypeptide substrate for a disintegrin-like and metallopeptidase with thrombospondin type-1 motif, 13 (ADAMTS13) that is from 45 to 70 amino acids in length and has an amino acid sequence that is substantially similar to part of the von Willebrand factor A2 domain sequence set forth in SEQ ID NO: 2, with one or more of the following modifications: (i) the amino acid corresponding to position 1599 of SEQ ID NO: 2 is mutated from Q to K; (ii) the amino acid corresponding to position 1610 of SEQ ID NO: 2 is mutated from N to C; and (iii) the amino acids corresponding to Q1624 to R1641 of SEQ ID NO: 2 are deleted. In another aspect, there is provided an ADAMTS13 polypeptide substrate that is from 50 to 75 amino acids in length and has an amino acid sequence that is substantially similar to part of the von Willebrand factor A2 domain sequence set forth in SEQ ID NO: 2, with one or more of the following modifications: (i) the amino acid corresponding to position 1599 of SEQ ID NO: 2 is mutated from Q to K; (ii) the amino acid corresponding to position 1610 of SEQ ID NO: 2 is mutated from N to C; (iii) the amino acid corresponding to position 1629 of SEQ ID NO: 2 is mutated from G to E; and (iv) the amino acids corresponding to G1631 to R1641 of SEQ ID NO: 2 are deleted.

Provided herein is a method of detecting or predicting a relapse of multiple sclerosis in an individual afflicted with a form of multiple sclerosis, comprising: (a) providing a blood sample of the individual; (b) testing the blood sample to determine a protein activity or protein level, wherein the protein is Factor VIII, von Willebrand factor, or Protein C; and (c) detecting or predicting a relapse of multiple sclerosis in the individual if the protein activity or protein level is elevated compared to the protein activity or protein level in an individual not afflicted with the form of multiple sclerosis and patients' own baseline values. Also provided herein is a method of treating an individual afflicted with multiple sclerosis, who is experiencing a relapse or predicted to experience a relapse, comprising treating the individual by administering a dose of a steroid or anti-coagulation compound effective to alleviate the symptom of multiple sclerosis.

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.

Methods and kits for measuring levels of von Willebrand factor function in a sample without using a platelet aggregation agonist, such as ristocetin, comprising recombinant glycoprotein Ib having a combination of G233V, D235Y and M239V mutations and an agent to detect a complex between the recombinant glycoprotein Ib and von Willebrand factor.