Apparatuses, Compositions, and Methods for Prolonging Survival of Platelets

Abstract

The present invention provides modified platelets having a reduced platelet clearance and methods for reducing platelet clearance. Also provided are compositions for the preservation of platelets. The invention also provides methods for making a pharmaceutical composition containing the modified platelets and for administering the pharmaceutical composition to a mammal to mediate hemostasis.

What is claimed is: 
     
         1 . An apparatus for processing a sample of platelets, the apparatus comprising a first sterile container having one or more ports including a first container port and containing a preparation of blood cells comprising platelets, a second sterile container having one or more ports including a second container port and containing a blood cell modifying agent which comprises cytidine 5′-monophospho-N-acetylneuraminic acid, the first container being adapted to the second container through a first sterile conduit reversibly attachable to the first container port and the second container port, the first sterile conduit further comprising a valve, wherein the blood cell modifying agent present in the second sterile container is introduced into the first sterile container and the platelets in the preparation of blood cells therein are rendered cold storage competent after the platelets are contacted with the blood cell modifying agent. 
     
     
         2 . The apparatus of  claim 1 , further comprising a third sterile container having one or more ports including a third container port adapted to the first container through a second sterile conduit reversibly attachable to the first container port and the third container port, the second sterile conduit further comprising a valve. 
     
     
         3 . The apparatus of  claim 1 , wherein the first sterile conduit is adapted to an in-line filter having a median pore diameter small enough to substantially prevent the flow of bacteria through the in-line filter. 
     
     
         4 . The apparatus of  claim 1 , wherein the first container, second container, the third container, the first container and the second container, the first container and the third container, the second container and the third container, or the first container, the second container, and the third container are blood bags. 
     
     
         5 . The apparatus of  claim 1 , wherein the blood cells further comprise a population of platelets obtained from individual random donor blood, pooled random donor blood, or single donor blood. 
     
     
         6 . The apparatus of  claim 1 , wherein the second container port has a frangible barrier. 
     
     
         7 . The apparatus of  claim 1 , wherein the first conduit or the second conduit reversibly attaches to the first container port, the second container port, or the third container port through a sterile dock. 
     
     
         8 . An apparatus for processing a sample of platelets, the apparatus comprising a first sterile container having one or more ports and containing a blood cell modifying agent which comprises cytidine 5′-monophospho-N-acetylneuraminic acid, and an array comprising a first conduit and a plurality of sterile docks, wherein each of the sterile docks is reversible adaptable to blood storage containers, the blood storage containers having a sample of blood cells comprising platelets and further comprising at least one port for connecting to the sterile docks of the array, wherein the platelets are introduced into the first sterile container through the conduit and are rendered cold storage competent by contacting the platelets with the blood cell modifying agent present in the sterile first container. 
     
     
         9 . The apparatus of  claim 8 , wherein the blood cells further comprise a population of platelets obtained from individual random donor blood, pooled random donor blood, or single donor blood. 
     
     
         10 . The apparatus of  claim 8 , further comprising a second container having one or more ports and containing a blood cell modifying agent that modifies the platelet cell surface, the first container adapted to the second container through a second sterile conduit reversibly attachable to the first container port and the second container port. 
     
     
         11 . The apparatus of  claim 10 , wherein the second sterile conduit is adapted to an in-line filter having a median pore diameter small enough to substantially prevent the flow of bacteria through the in-line filter. 
     
     
         12 . The apparatus of  claim 11 , wherein the second container port has a frangible barrier. 
     
     
         13 . An apparatus for processing a sample of platelets, the apparatus comprising a first sterile container having one or more ports, the first container further comprising a subcontainer disposed therein, the subcontainer having a port and a frangible barrier and containing a blood cell modifying agent which comprises cytidine 5′-monophospho-N-acetylneuraminic acid, and an array comprising a conduit and a plurality of sterile docks, wherein each of the sterile docks is reversible adaptable to blood storage containers, the blood storage containers having a sample of blood cells comprising platelets and further comprising at least one port for connecting to the sterile docks of the array, wherein the platelets are introduced into the first sterile container through the conduit and are rendered cold storage competent after the platelets are contacted with the blood cell modifying agent present in the first sterile container. 
     
     
         14 . The apparatus of  claim 13 , wherein the blood cells further comprise a population of platelets obtained from individual random donor blood, pooled random donor blood, or single donor blood. 
     
     
         15 . A method for treating a platelet using an apparatus, wherein the apparatus is selected from the group consisting of:
 a. an apparatus comprising a first sterile container having one or more ports including a first container port and containing a preparation of blood cells comprising platelets, a second sterile container having one or more ports including a second container port and containing a blood cell modifying agent, the first container being adapted to the second container through a first sterile conduit reversibly attachable to the first container port and the second container port, the first sterile conduit further comprising a valve;   b. an apparatus comprising a first sterile container having one or more ports and containing a blood cell modifying agent, and an array comprising a first conduit and a plurality of sterile docks, wherein each of the sterile docks is reversible adaptable to blood storage containers, the blood storage containers having a sample of blood cells comprising platelets and further comprising at least one port for connecting to the sterile docks of the array; and   c. an apparatus comprising a first sterile container having one or more ports, the first container further comprising a subcontainer disposed therein, the subcontainer having a port and a frangible barrier and containing a blood cell modifying agent, and an array comprising a conduit and a plurality of sterile docks, wherein each of the sterile docks is reversible adaptable to blood storage containers, the blood storage containers having a sample of blood cells comprising platelets and further comprising at least one port for connecting to the sterile docks of the array; wherein the steps of the method comprise contacting the platelets with the one or more blood cell modifying agents, wherein the one or more blood cell modifying agents comprise cytidine 5′-monophospho-N-acetylneuraminic acid or both UDP-galactose and cytidine 5′-monophospho-N-acetylneuraminic acid, to thereby obtain treated platelets.   
     
     
         16 . The method of  claim 15 , wherein the conduit further comprises a valve, and wherein the platelets, after being processed using the apparatus such that the platelets are contacted with the one or more blood cell modifying agents, are rendered cold-storage competent. 
     
     
         17 . The method of  claim 15 , wherein the blood cells are contacted with the one or more blood cell modifying agents before infusion of the treated blood cells into a patient. 
     
     
         18 . The method of  claim 15 , wherein the blood cells are contacted with the one or more blood cell modifying agents before cold storage of the blood cells. 
     
     
         19 . The method of  claim 15 , wherein the blood cells are contacted with the one or more blood cell modifying agents at the time of blood collection from a blood donor. 
     
     
         20 . The method of  claim 15 , further including separating the blood cells into subpopulations of platelets, plasma, red blood cells, and white blood cells. 
     
     
         21 . The method of  claim 15 , wherein the blood cells are contacted with the one or more blood cell modifying agents after the blood cells have been separated by apheresis. 
     
     
         22 . The method of  claim 15 , wherein an amount of each of the one or more blood cell modifying agents is between about 1 micromolar and about 10 millimolar. 
     
     
         23 . The method of  claim 15 , further comprising storing the treated platelets for a period of time ranging between about 24 hours and about 20 days. 
     
     
         24 . The method of  claim 15 , further comprising storing the treated platelets at a temperature ranging between about 0° C. and about 4° C. 
     
     
         25 . A treated blood cell obtained through a method for treating a platelet using an apparatus, wherein the apparatus is selected from the group consisting of:
 a. an apparatus comprising a first sterile container having one or more ports including a first container port and containing a preparation of blood cells comprising platelets, a second sterile container having one or more ports including a second container port and containing a blood cell modifying agent, the first container being adapted to the second container through a first sterile conduit reversibly attachable to the first container port and the second container port, the first sterile conduit further comprising a valve;   b. an apparatus comprising a first sterile container having one or more ports and containing a blood cell modifying agent, and an array comprising a first conduit and a plurality of sterile docks, wherein each of the sterile docks is reversible adaptable to blood storage containers, the blood storage containers having a sample of blood cells comprising platelets and further comprising at least one port for connecting to the sterile docks of the array; and   c. an apparatus comprising a first sterile container having one or more ports, the first container further comprising a subcontainer disposed therein, the subcontainer having a port and a frangible barrier and containing a blood cell modifying agent, and an array comprising a conduit and a plurality of sterile docks, wherein each of the sterile docks is reversible adaptable to blood storage containers, the blood storage containers having a sample of blood cells comprising platelets and further comprising at least one port for connecting to the sterile docks of the array;   
       wherein the steps of the method comprise processing the platelets using the apparatus such that the platelets are exposed to the two or more blood cell modifying agents that include cytidine 5′-monophospho-N-acetylneuraminic acid or both UDP-galactose and cytidine 5′-monophospho-N-acetylneuraminic acid. 
     
     
         26 . The treated blood cell of  claim 25 , wherein the blood cells, following cold storage, are suitable for transfusion into a patient.