Freeze-dried platelet derivative compositions for treating antiplatelet induced coagulopathy

Abstract

Provided herein are methods and compositions for treating a coagulopathy in a subject. Such methods can include administering to the subject in need thereof, for example because they have been administered an anticoagulant agent, an effective amount of a composition including platelets, or in illustrative embodiments platelet derivatives, and in further illustrative embodiments freeze-dried platelet derivatives (FDPDs). Various properties of exemplary embodiments of such methods and platelet derivatives used therein, as well as numerous additional aspects and embodiments are provided herein.

1 . (canceled) 
     
     
         2 . A method for treating a coagulopathy in a subject having an increased potential for bleeding as a result of being administered or having been administered an antiplatelet, wherein the method comprises:
 administering to the subject having the increased potential for bleeding, an effective amount of a composition comprising freeze-dried platelet derivatives (FDPDs) such that the bleeding potential of the subject is reduced,   wherein the composition comprising FDPDs comprises a population of FDPDs having a reduced propensity to aggregate such that no more than 10% of the FDPDs in the population aggregate under aggregation conditions comprising an agonist but no platelets, thereby treating the coagulopathy.   
     
     
         3 . The method of  claim 2 , wherein the method further comprises before the administering, determining that the subject was administered an antiplatelet agent. 
     
     
         4 - 10 . (canceled) 
     
     
         11 . The method of  claim 2 , wherein the antiplatelet agent is selected from aspirin, cangrelor, ticagrelor, clopidogrel, prasugrel, eptifibatide, tirofiban, abciximab, terutroban, picotamide, elinogrel, ticlopidine, ibuprofen, vorapaxar, atopaxar, cilostazol, prostaglandin E1, epoprostenol, dipyridamole, treprostinil sodium, and sarpogrelate. 
     
     
         12 . The method of  claim 2 , wherein the antiplatelet agent is selected from cangrelor, ticagrelor, abciximab, terutroban, picotamide, elinogrel, ibuprofen, vorapaxar, atopaxar, cilostazol, prostaglandin El, epoprostenol, dipyridamole, treprostinil sodium, and sarpogrelate. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 2 , wherein the FDPDs have a potency of at least 1.5 thrombin generation potency units (TGPU) per 10 6  platelet derivatives. 
     
     
         15 . The method of  claim 2 , wherein at least 50% of the FDPDs are CD 41-positive FDPDs, wherein less than 5% of the CD 41-positive FDPDs are microparticles having a diameter of less than 0.5 μm, and wherein the FDPDs have a potency of at least 1.5 thrombin generation potency units (TGPU) per 10 6  platelet derivatives. 
     
     
         16 . The method of  claim 15 , wherein the antiplatelet agent targets a CD41/CD61 complex. 
     
     
         17 . The method of  claim 16 , wherein at least 75% of the FDPDs are CD41-positive FDPDs. 
     
     
         18 . The method of  claim 16 , wherein the antiplatelet agent is selected from one or more of abciximab, eptifibatide, and tirofiban. 
     
     
         19 . The method of  claim 2 , wherein the composition comprising FDPDs comprises a population of FDPDs having a reduced propensity to aggregate such that no more than 10% of the platelet derivatives in the population aggregate under aggregation conditions comprising an agonist but no platelets; and
 having one or more characteristics of a super-activated platelet selected from   A) the presence of thrombospondin (TSP) on their surface at a level that is greater than on the surface of resting platelets;   B) the presence of von Willebrand factor (vWF) on their surface at a level that is greater than on the surface of resting platelets; and   C) an inability to increase expression of a platelet activation marker in the presence of an agonist as compared to the expression of the platelet activation marker in the absence of an agonist.   
     
     
         20 - 21 . (canceled) 
     
     
         22 . The method of  claim 2 , wherein the composition comprising FDPDs comprises a population of FDPDs comprising a population of platelet derivatives comprising CD 41-positive platelet derivatives, wherein less than 5% of the CD 41-positive platelet derivatives are microparticles having a diameter of less than 0.5 μm, and
 comprising platelet derivatives having: 
 a reduced propensity to aggregate such that no more than 10% of the platelet derivatives in the population aggregate under aggregation conditions comprising an agonist but no platelets; 
 an inability to increase expression of a platelet activation marker in the presence of an agonist as compared to the expression of the platelet activation marker in the absence of the agonist; 
 the presence of thrombospondin (TSP) on their surface at a level that is greater than on the surface of resting platelets; 
 the presence of von Willebrand factor (vWF) on their surface at a level that is greater than on the surface of resting platelets; and 
 a potency of at least 1.5 thrombin generation potency units (TGPU) per 10 6  platelet derivatives. 
 
     
     
         23 . The method of  claim 2 , wherein the FDPDs comprise the receptor targeted by the antiplatelet reversal agent that was administered or is being administered to the subject. 
     
     
         24 . The method of  claim 2 , wherein the effective amount of the composition comprising FDPDs is between 1.0×10 7  to 1.0×10 11 /kg of the subject. 
     
     
         25 . The method of  claim 2 , wherein the effective amount of the composition comprising FDPDs is between 1.6×10 7  to 5.1×10 9 /kg of the subject. 
     
     
         26 . The method of  claim 2 , wherein the effective amount of the composition comprising FDPDs is an amount that has a potency between 250 and 5000 TGPU per kg of the subject. 
     
     
         27 . The method of  claim 2 , wherein the treating the coagulopathy decreases the bleeding potential of the subject such that normal hemostasis is restored in the subject. 
     
     
         28 - 64 . (canceled) 
     
     
         65 . The method of  claim 2 , wherein the composition comprises trehalose. 
     
     
         66 - 67 . (canceled) 
     
     
         68 . The method of  claim 65 , wherein the composition further comprises polysucrose. 
     
     
         69 . (canceled) 
     
     
         70 . The method of  claim 2 , wherein the antiplatelet agent is present in the subject at the time the composition comprising the FDPDs is administered at a level that increases the bleeding potential of the subject. 
     
     
         71 . (canceled) 
     
     
         72 . The method of  claim 2 , wherein the FDPDs are surrounded by a compromised plasma membrane.