Methods for treating bleeding disorders using a platelet subpopulation

Abstract

The present invention relates to a platelet subpopulation with high binding capacity to recombinant activated factor VII (rFVIIa), and its use for the treatment of bleeding disorders and for determining whether a subject is a candidate for treatment with rFVIIa.

1 - 70 . (canceled) 
     
     
         71 . A subpopulation of platelets isolated from a platelet population, wherein the platelets in the subpopulation of platelets have at least a 4-fold higher binding capacity to rFVIIa as compared to the binding capacity to rFVIIa of the other platelets in the platelet population. 
     
     
         72 - 75 . (canceled) 
     
     
         76 . The subpopulation of platelets of  claim 71 , wherein the platelets in the subpopulation of platelets have about a 6-fold higher binding capacity to rFVIIa, as compared to the binding capacity to rFVIIa of the other platelets in the platelet population. 
     
     
         77 - 79 . (canceled) 
     
     
         80 . A pharmaceutical composition comprising the subpopulation of platelets of  claim 71 . 
     
     
         81 - 84 . (canceled) 
     
     
         85 . A method of determining whether a subject is a candidate for treatment with rFVIIa, the method comprising
 a) obtaining a sample of platelets derived from the subject;   b) incubating a platelet population from the sample with rFVIIa; and   c) detecting whether the platelet population contains a subpopulation of platelets having at least a 4-fold higher binding capacity to rFVIIa, as compared to the binding capacity to rFVIIa of the other platelets in the platelet population,   wherein a subject is a candidate for treatment with rFVIIa if   the subject does not have an unacceptable risk of thrombosis and the platelet population contains a subpopulation of platelets having at least a 4-fold higher binding capacity to rFVIIa, as compared to the binding capacity to rFVIIa of the other platelets in the platelet population, or   (ii) the subject has an unacceptable risk of thrombosis and the platelet population does not contain a subpopulation of platelets having at least a 4-fold higher binding capacity to rFVIIa, as compared to the binding capacity to rFVIIa of the other platelets in the platelet population.   
     
     
         86 - 89 . (canceled) 
     
     
         90 . The method of  claim 85 , wherein the platelet population contains a subpopulation of platelets having about a 6-fold higher binding capacity to rFVIIa, as compared to the binding capacity to rFVIIa of the other platelets in the platelet population. 
     
     
         91 - 95 . (canceled) 
     
     
         96 . The method of  claim 85 , wherein the subject has a bleeding disorder. 
     
     
         97 . The method of  claim 96 , wherein the bleeding disorder is hemophilia, blood loss from trauma, FVII deficiency, FV deficiency, FX deficiency, FXI deficiency, FXIII deficiency, fibrinogen deficiency, prothrombin deficiency, dilutional coagulopathy, thrombocytopenia, blood loss from high-risk surgeries, intracerebral hemorrhage, von Willebrand disease or von Willebrand disease with inhibitors to von Willebrand factor. 
     
     
         98 . The method of  claim 85 , wherein the subject is a human. 
     
     
         99 - 181 . (canceled)