Methods for diagnosing and treating hemostatic disorders by modulating P-selectin activity

Abstract

The present invention identifies P-selectin as a modulator of hemostasis. Accordingly, the present invention relates to methods for the identification and use of modulators of P-selectin activity as modulators of hemostasis. The invention also relates to methods and compositions for the diagnosis and treatment of hemostatic disorders, including, but not limited to, hemorrhagic disorders and thrombotic disorders. The present invention describes methods for the diagnostic evaluation and prognosis of various hemostatic conditions, and for the identification of subjects exhibiting a predisposition to such conditions. In addition, the present invention provides methods for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of a hemostatic or vascular disorders, and for monitoring the efficacy of compounds in clinical trials.

1 - 41 . (canceled)  
     
     
         42 . A method for diagnosing a procoagulant state in a subject, comprising determining a P-selectin activity in a biological sample of the subject, wherein an increased P-selectin activity in the sample indicates a procoagulant state in the subject.  
     
     
         43 . The method of  claim 42 , which comprises providing a test sample of blood from a subject and comparing the level of soluble P-selectin in the test sample to the level of soluble P-selectin in a control blood sample from a subject with normal hemostatic activity, wherein an increased level of soluble P-selectin in the test sample as compared to the control sample is an indication of a procoagulant state in the subject.  
     
     
         44 . A method of identifying a subject having a thrombotic disorder, or at risk for developing a thrombotic disorder, comprising determining a P-selectin activity in a biological sample of the subject, wherein an increased P-selectin activity in the sample identifies a subject having a thrombotic disorder, or at risk of developing a thrombotic disorder.  
     
     
         45 . The method of  claim 44  comprising: 
 a) contacting a sample of blood obtained from said subject with a P-selectin binding substance; and    b) detecting the presence of increased levels of soluble P-selectin in said sample, thereby identifying a subject having a thrombotic disorder, or at risk for developing a thrombotic disorder.    
     
     
         46 - 49 . (canceled)  
     
     
         50 . The method of  claim 42 , wherein the agent used to determine the P-selectin activity is a labeled P-selectin antibody.  
     
     
         51 . The method of  claim 45  wherein the thrombotic disorder is arteriosclerosis.  
     
     
         52 . A method for monitoring the effectiveness of a treatment of a subject using a modulator of P-selectin activity comprising: 
 a) obtaining a sample from a subject prior to the administration of the P-selectin modulator;    b) detecting the level of P-selectin activity in the sample;    c) obtaining at least one post-administration samples from the subject;    d) detecting the level of P-selectin in the post-administration sample(s);    e) comparing the level of P-selectin activity in the pre-administration sample with that in the post-administration sample(s); and    f) changing the administration of the modulator in response to the comparison made in step (e).    
     
     
         53 . The method of  claim 52  wherein the modulator is an inhibitor of P-selectin activity.  
     
     
         54 . The method of  claim 52  wherein the modulator is an inducer of P-selectin activity.