The Scripps Research Institute

Wolfram Ruf

Thomas S Edgington

Zaverio M Ruggeri

Yuichi Kamikubo

Ramona J Petrovan

In various embodiments, disclosed herein are methods of assessing therapeutic efficacy of an anticoagulant. Preferably, the method comprising providing a blood sample; perfusing the blood sample over a surface coated with collagen or immobilized rTF; measuring platelet aggregation and fibrin deposition on the surface coated with collagen or immobilized rTF; and assessing therapeutic efficacy of the anticoagulant based on the volume of platelet aggregates and/or deposited fibrin.

Compositions and methods for evaluating anticoagulant therapeutic efficacy

In various embodiments, disclosed herein are assays for measuring thrombin generated (TG) in a blood sample, comprising: incubating the blood sample with TF, FIXa, and CaCl2; and measuring TG in the blood sample. Also disclosed herein are assays for determining a bleeding risk in a subject, comprising obtaining a blood sample from the subject; adding to the blood sample TF and/or FIXa; determining the amount of coagulation factor VIII (FVIII:C) in the blood sample; and determining (a) a mild bleeding risk in the subject if the amount of FVIII:C in the sample is &#x3e;5 IU/dL, (b) a moderate bleeding risk in the subject if the amount of FVIII:C in the sample is 1-5 IU/dL, and (c) a severe bleeding risk in the subject if the amount of FVIII:C in the subject is &#x3c;1 IU/dL.

Compositions and methods for thrombin generation assay

A modified factor VIIa is provided. The modified factor has increased amidolytic activity in the absence of T.F. and a higher affinity for T.F. when compared to the native factor VIIa but does not have substantially altered proteolytic activity when bound to T.F. Nucleic acid molecules that encode the factor, expression vectors that contain the nucleic acid molecules, cells that contain the nucleic acid molecules, and cells transformed with the expression vector are also provided. In a preferred embodiment, the modified factor is a human factor VIIa.

Modified factor VIIa

The present invention describes a mutant human tissue factor protein which binds functional Factor VII/VIIa but is substantially free of functional procoagulant cofactor activity, and compositions containing the mutant protein. Also disclosed are methods for using the mutant human tissue factor proteins, and recombinant DNA vectors for expressing the protein.

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San Diego, CA, United States of America

Wolfram Ruf