Abstract:
Systems and methods for collecting blood substantially free of residual air and undesired matter also assure that accurate crossmatching and typing of cellular blood components can be done prior to transfusion.

Description:
FIELD OF THE INVENTION  
         [0001]    The invention generally relates to blood collection and processing systems and methods. In a more particular sense, the invention relates to systems and methods for removing white blood cells from red blood cells prior to transfusion or long term storage.  
         BACKGROUND OF THE INVENTION  
         [0002]    Systems composed of multiple, interconnected plastic bags have met widespread use and acceptance in the collection, processing and storage of blood components.  
           [0003]    Before storing red blood cells for later transfusion, it is believed to be desirable to minimize the presence of impurities or other materials that may cause undesired side effects in the recipient. For example, because of possible febrile reactions, it is generally considered desirable to store red blood cells with a reduced number of—leukocytes. Filtration is conventionally used to accomplish leuko-reduction.  
           [0004]    Systems and methods for reducing the number of leukocytes by filtration in multiple blood bag configurations are described. e.g., in Stewart U.S. Pat. No. 4,997,577, Stewart et al. U.S. Pat. No. 5,128,048, Johnson et al U.S. Pat. No. 5,180,504, and Bellotti et. al. U.S. Pat. No. 5,527,472. In these filtration systems and methods, a transfer assembly dedicated solely to the filtration of leukocytes from red blood cells is used. The transfer assembly also has a second fluid path that bypasses the filtration for the purpose of transferring liquid or venting air around the separation device.  
           [0005]    In addition, before transfusing stored cellular blood components like red blood cells, it is important to assure that the blood type of the recipient matches the blood type of the donor. For this reason, conventional blood collection procedures collect several small aliquots or samples of the donated blood component for use in crossmatching and typing the donor&#39;s blood prior to transfusion.  
           [0006]    [0006]FIG. 1A shows a representative conventional system that filters leukocytes from red blood cells, vents air from the filtered cells, and creates segmented aliquots of the filtered cells for crossmatching and typing purposes. In use, red blood cells are conveyed from a transfer bag  1  through a leukocyte reduction filter  2  into a storage bag  3 . An in-line clamp C controls this flow. Once filtration is completed, the storage bag  3  is squeezed to expel air through a bypass line  4  around the filter  2  into the transfer bag  1 . An in-line check valve CV permits one-way fluid flow toward the transfer bag  1 , but blocks fluid flow in the opposite direction toward the storage bag  3 . A conventional heat sealing device (for example, the Hematrons dielectric sealer sold by Baxter Healthcare Corporation, not shown) forms a hermetic, snap-apart seal X 1  in the tubing just downstream of the filter  2 . The system components upstream of the seal X 1  are disconnected and discarded. As FIG. 1B shows, the remaining tubing  5  (still attached to the storage bag  3 ) carries alpha or numeric identification markings  6  (which may also be machine-readable), which are printed in a spaced-apart pattern along its length. As FIG. 1A shows, a label  7  on the storage bag  3  carries the same identification markings  6 . Using a conventional blood tube stripper (also not shown), the technician displaces residual air from the remaining tubing  5  into the storage bag  3 . Upon removal of the tube stripper, the air displaced into the storage bag  3  expels filtered cells into the remaining tubing  5  to occupy the numbered segments  6 . As FIG. 1D shows, the sealer is then used to form sealed, snap-apart seals X 2  between the identification markings  6 , creating segmented pockets  8  where the samples of the filtered cells are retained. The donor-specific label  7  is removed from the transfer bag  1  and attached to the storage bag  3 , to thereby preserve a link between the transfer bag  1 , the storage bag  3 , the numbered blood segments  8 , and the donor.  
           [0007]    Alternatively, as shown in FIGS. 1A and 1C, the conventional storage bag  3  can also include an attached tubing segment, or “pigtail” P, which carries the same identification markings  6  printed in a spaced-apart pattern along its length. Once filtration and air venting is completed, the technician uses the blood tube stripper to displace residual air from the pigtail P into the storage bag  3 , which in turn displaces filtered cells into the pigtail P. The sealer can then be used to form sealed, snap-apart pockets, as before described, one for each numbered segment, where the samples of the filtered cells are retained.  
           [0008]    Prior techniques require the technician to perform mutiple, separate functional steps. First, the technician must vent air from the storage bag. Then, the technician must pick up and operate a tube stripper, to expel blood from the storage bag into tubing to create segmented samples for crossmatching and blood typing.  
         SUMMARY OF THE INVENTION  
         [0009]    The invention provides more straightforward and convenient systems and methods to remove undesired matter from blood cells, which permit air venting and sample expulsion to take place in one functional step. The invention obviates the need for tube strippers, thereby simplifying the overall blood manipulation process. Still, the invention assures that accurate crossmatching and typing of the blood occurs.  
           [0010]    One aspect of the invention provides a blood processing assembly comprising a blood receiving container having first and second ports. A first flow path is included, which has an inlet region for coupling the first flow path in fluid communication with a blood source container and an outlet region coupled to the first port. The first flow path includes a separation device positioned between the inlet and outlet regions that separates undesired matter from blood en route the blood receiving container. A second flow path is also included, which has an entry region coupled to the second port, and not the first port, and an exit region coupled to the inlet region of the first flow path at a junction. The second flow path includes a one-way valve between the entry region and the exit region. The one-way valve permits fluid flow through the second flow path, bypassing the separation device, only from the blood receiving container toward the blood source container and not vice versa.  
           [0011]    Another aspect of the invention provides a method of using the assembly. The method directs blood through the first flow path and separation device to remove undesired matter. The blood is collected in the blood receiving container after passage through the separation device. The method squeezes the blood receiving container to expel residual air from the blood receiving container through the second flow path. The one-way valve permits air flow only in a direction away from the blood receiving container, and not vice versa. The method squeezes the blood receiving container to convey a sample of blood from the collection container into the second flow path. Again, the one-way valve permits blood flow only in the direction away from the blood receiving container, and not vice versa. The method seals the second flow path to retain the sample of blood in the second flow path.  
           [0012]    By virtue of the above described structure and method of use, a sample of blood from the blood receiving container can be transferred into the second flow path simply by squeezing the blood receiving container, and coincident with air venting. There is no need for separate air venting and blood sample collecting steps, and there is no need for a tube stripper.  
           [0013]    In a preferred embodiment, the separation device removes leukocytes from blood.  
           [0014]    Other features and advantages of the invention will become apparent upon review of the following description, drawings, and appended claims. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0015]    [0015]FIG. 1A is a schematic view of a conventional blood collection system to remove leukocytes from red blood cells;  
         [0016]    [0016]FIGS. 1B and 1C are enlarged views of tubes associated with the system shown in FIG. 1A, which, in use, retain a sample of the processed blood, showing the identification markings used to link the blood samples to the stored blood product following leuko-reduction;  
         [0017]    [0017]Fig. 1D is an enlarged view of a portion of the prior art system shown in FIG. 1A, showing the tube shown in FIG. 1B after having been segmented by heat sealing into blood sample-retaining pockets;  
         [0018]    [0018]FIG. 2 is a schematic view of a blood collection system having a blood collection assembly and a blood filtration assembly, which embodies features of the invention;  
         [0019]    [0019]FIG. 3 is a schematic view of the blood collection assembly shown in FIG. 2, after whole blood collected in the assembly has been centrifugally processed into red blood cells containing leukocytes, retained in a primary bag, and platelet-rich plasma, retained in a transfer bag;  
         [0020]    [0020]FIG. 4 is a schematic view showing the connection of the blood filtration assembly to the primary bag of the blood collection assembly for the purpose of removing leukocytes from the red blood cells while being conveyed to a storage bag;  
         [0021]    [0021]FIG. 5 is a schematic view of the connected blood filtration assembly and the blood collection assembly after the red blood cells have been filtered, showing the venting of residual air from the storage bag into the primary bag through a tube segment that bypasses the filter;  
         [0022]    [0022]FIG. 6A is a schematic view of the connected blood filtration assembly and the blood collection assembly after residual air has been vented from the storage bag, showing the advancement of filtered red blood cells into the same tube segment used to vent air from the storage bag without the use of a tube stripper;  
         [0023]    [0023]FIG. 6B is an enlarged schematic view of the tube segment shown in FIG. 6A, into which filtered red blood cells have been advanced while venting air from the storage bag, showing the identification markings printed on the tube segment;  
         [0024]    [0024]FIG. 7A is a schematic view of the storage bag and attached tube segment, after having been separated from the rest of the system for storage of the red blood cells;  
         [0025]    [0025]FIG. 7B is an enlarged schematic view of the tube segment attached to the storage bag shown in FIG. 7A, showing the tube segment after having been segmented by heat sealing into blood sample-retaining pockets; and  
         [0026]    [0026]FIG. 8 shows a schematic view of another blood collection system having an integrally attached a blood filtration assembly, which embodies features of the invention. 
     
    
       [0027]    The invention may be embodied in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the appended claims, rather than in the specific description preceding them. All embodiments that fall within the meaning and range of equivalency of the claims are therefore intended to be embraced by the claims.  
       DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0028]    A blood collection system  10 , which embodies features of the invention, is shown in FIG. 2. The system  10  comprises a blood collection and processing assembly  12  and a filtration assembly  14 .  
         [0029]    The blood collection and processing assembly  12  comprises a multiple blood bag system having a primary bag or container  16  and one or more integrally attached transfer bags or containers  18  and  26 . In use, the primary bag  16  (which is typically also called a donor bag) receives whole blood from a donor through integrally attached donor tubing  20  by means of a phlebotomy needle  22 . A suitable anticoagulant A (e.g., CPD or ACD) is contained in the primary bag  16 .  
         [0030]    The transfer bag  18  is attached to the primary bag  16  by integrally attached transfer tubing  30 . The transfer bag  18  is intended to receive the platelet-rich plasma blood component for processing. The transfer bag  26  contains a suitable storage solution S for red blood cells. The storage solution S will ultimately be conveyed from the transfer bag  26  to the primary bag  16  during the course of blood processing. A representative storage solution S is disclosed in Grode et al U.S. Pat. No. 4,267,269. A conventional in-line frangible cannula  24  and in-line clamps  25  control fluid flow through the tubing  30 .  18  among the bags  16 ,  18 , and  26 .  
         [0031]    All of the bags  16 ,  18 , and  26  and tubing  30  associated with the processing assembly  12  can be made from conventional approved medical grade plastic materials, such as polyvinyl chloride plasticized with di-2-ethylhexylphthalate (DEHP). The blood collection assembly  12 , once sterilized, constitutes a sterile, “closed” system, as judged by the applicable standards in the United States.  
         [0032]    Preferably (as FIG. 2 shows), before whole blood is collected, a removable donor-specific label  25  is attached to the primary blood bag  16 . The label  25  carries a unique identification number assigned to the particular donor at the time of donation.  
         [0033]    Whole blood is collected from the donor in the primary bag  16 . The whole blood is separated by centrifugation in the primary bag  16  into red blood cells and platelet-rich plasma. In the process of centrifugally separating these components, a layer rich in leukocytes forms between the red blood cells and the platelet-rich plasma.  
         [0034]    The platelet-rich plasma is transferred by conventional techniques into the transfer bag  18 , leaving the red blood cells (designated RBC) and leukocytes (designated LC) in the primary bag  16 . The red cell storage solution S is then transferred from the bag  26  to the primary bag  16  through the transfer tubing  30 . As FIG. 3 shows, the donor tubing  20  and the bags  18  and  26  are detached using snap apart seals “x” formed by a conventional dielectric sealing device, as previously described.  
         [0035]    The platelet-rich plasma can undergo subsequent centrifugal separation within the first transfer bag  18  into platelet concentrate and platelet-poor plasma. An additional preattached transfer bag (not shown) can be included to receive the platelet-poor plasma.  
         [0036]    As FIG. 2 shows, the filtration assembly  14  comprises an initially separate subassembly not joined to the blood processing assembly  12 . The entire filtration assembly  14  can be provided in a “dry” condition, free of any fluids, storage mediums, and the like (except for any entrapped air).  
         [0037]    The filtration assembly  14  includes a storage bag  34  and an associated main tube path  36 . The tube path  36  further includes an inline device  40  for separating undesired matter from blood cells.  
         [0038]    The filtration assembly  14  also includes an integrally attached tube segment  32 . The far end of the tube segment  32  joins the main tube path  36  upstream of the separation device  40 , via a conventional Y-coupler  28 .  
         [0039]    The storage bag  34 , main tube path  36 , and the tube segment  32  can all made of low cost medical grade plastic materials, such as polyvinyl chloride plasticized with DEHP.  
         [0040]    In the illustrated embodiment, the filtration assembly  14  serves to remove undesired matter from blood cells by filtration. For this reason, the assembly  14  and the device  40  will be referred to as a “filtration” assembly and device. It should be appreciated, however, that separation can occur by various centrifugal and non-centrifugal techniques, and not merely “filtration” in the technical sense. Separation can occur by absorption, columns, chemical, electrical, and electromagnetic means. The term “filtration assembly” or “filtration device” is broadly used in this specification encompass all of these separation techniques as well.  
         [0041]    It should be appreciated that the filtration assembly  14  can be used to remove all types of undesired materials from different types of blood cells, depending upon its particular construction. In the illustrated embodiment, the filtration assembly  14  is intended to remove leukocytes from the red blood cells prior to storage. Still, it should be appreciated the features of the assembly  14  and its method of use can be used for separating matter from other blood products, such as plasma or platelets or whole blood itself.  
         [0042]    In this arrangement, the filtration device  40  includes a housing  42  containing a conventional filtration medium  44  suited for the removal of leukocytes from red blood cells. The filtration medium  44  can include cotton, wool, cellulose acetate or another synthetic fiber like polyester.  
         [0043]    A clamp  38 , e.g., a conventional roller clamp, regulates flow through the main tube path  36  into the storage bag  34  via the filtration device  40 .  
         [0044]    A one-way check valve  48  controls fluid flow through the tube segment  32 . The valve  48  does not allow passage of fluid (liquid or air) in the direction of the storage bag  34 . However, the valve  48  does allow passage of fluid (liquid and air) in the opposite direction, away from the storage bag  34 .  
         [0045]    If desired, another conventional clamp  46  can be provided to further regulate flow through the tube segment  32  upstream of the valve  48 .  
         [0046]    A connection assembly  50  is associated with the initially separate blood collection and filtration assemblies  12  and  14 . The connection assembly  50  permits selective attachment of the filtration assembly  14  to the blood collection assembly  12 , as FIG. 4 shows. The technician closes both clamps  38  and  46  before attachment of the assemblies  12  and  14 .  
         [0047]    In the illustrated and preferred embodiment, both assemblies  12  and  14 , once sterilized, comprise sterile, “closed” systems, as judged by the applicable United States standards. In this arrangement, the connection assembly  50  serves to attach the donor bag  16  to the filtration assembly  14  in a manner that preserves the sterile integrity of the closed systems  12  and  14 .  
         [0048]    The connection assembly  50  can be variously constructed. It can comprise the conventional sterile connecting system disclosed in Spencer U.S. Pat. No. 4,412,835 (not shown), which is incorporated herein by reference. In this arrangement (which is shown in FIG. 4), the system forms a molten seal between the transfer tube  30  of the primary bag  16  (after having been separated from the transfer bags  18  and  26 , as FIG. 3 shows) with the end  52  of the tube path  36  of the filtration assembly  14 . Once cooled, a sterile weld  64  is formed. In an alternate arrangement (not shown), the connection assembly  48  can comprises two mating sterile connection devices of the type shown in Granzow et al U.S. Pat. Nos. 4,157,723 and 4,265,280, which are incorporated herein by reference. In either case, the attachment is made without otherwise opening the assemblies  12  and  14  to communication with the atmosphere. As a result, the filtered cells can be stored for the maximum allowable dating period.  
         [0049]    The end  52  of the tube path  36  can also carry a conventional blood spike  54 . Instead of forming a sterile weld  64 , the technician can insert the blood spike  54  in conventional fashion into a port  56  of the primary bag  16 , thereby joining the two assemblies  12  and  14  together. This attachment technique, however, opens the assemblies  12  and  14  to communication to the atmosphere. As a result, the filtered cells must be transfused within 24 hours.  
         [0050]    Once attachment of the assemblies  12  and  14  is made, the donor bag  16  is gently squeezed to mix the unfiltered red blood cells. The donor bag  16  is lifted above the storage bag  34  (as FIG. 4 shows), and the flow clamp  38  is opened. The red blood cells (designated RBC) are conveyed by gravity flow from the donor bag  16  through the tube path  36  and filtration device  40  and into the transfer bag  34 . The closed clamp  46  or the check valve  48  (in the absence of or the opening of the clamp  46 ) prevents flow through the tube segment  32 .  
         [0051]    In the process, the leukocytes are removed by the filtration device  40  from the blood cells. Once the red blood cells are transferred, the donor-specific label  25  is removed from the primary bag  16  and applied to the storage bag  34 , to preserve the link to the donor.  
         [0052]    As FIG. 5 shows, once the filtration is completed, the clamp  46  is opened. The storage bag  34  is squeezed gently. The squeezing expels residual air (designated RA in FIG. 5) from the storage bag  34  through the tube segment  32  and into the primary bag  16 . The tube segment  32  thereby provides an air venting path around the filtration device  40 . The check valve  48  prevents back flow of air and other fluid toward the storage bag  34 .  
         [0053]    As FIGS. 6A and 6B show, as residual air RA is removed from the storage bag  34 , the same squeezing action will displace filtered red blood cells (designated FRBC) from the storage bag  34  into the tube segment  32 . The filtered red blood cells FRBC from the bag  34  fill the tube segment  32 . The check valve  48  prevents back flow of filtered red blood cells FRBC toward the storage bag, retaining the samples in the tube segment  32 .  
         [0054]    As FIG. 6B shows, the tube segment  32  carries alpha or numeric identification markings  58  printed in a spaced-apart series along its length. The markings  58  can also be formatted to be machine readable. A label  60  on the storage bag  34  also carries the same identification marking  58 , which can also be formatted to be machine readable.  
         [0055]    As FIG. 7A shows, when the desired volume of filtered cells occupies the marked tube segment  32 , the technician employs the dielectric tube sealer previously described to form snap-apart seals “x” in the tube path  36  downstream of the filter  40 , as well as in the marked tube segment  32  above the uppermost segment marking  58 , which is preferably located near and downstream of the check valve  48 . This frees the filter  40 , associated dependent upstream tube path  36  and tube segment  32 , and the attached primary bag  16 , which is now empty, except for the residual air RA. These detached components are discarded as a unit.  
         [0056]    As FIG. 7B shows, the technician uses the dielectric sealer to form sealed, snap-apart pockets  62  along the length of the tube segment  32 , which is still attached to the storage bag  34 . The pockets  62  retain discrete samples of the filtered cells. The tube segment  32  thereby serves, not only as an air venting path around the filtration device  40 , but also as a segmented blood sample tube attached to the storage bag  34 . Unlike prior segmented sample tubes, the tube segment  32  can be filled with blood samples by squeezing the storage bag  34 , and without need of a conventional tube stripping device.  
         [0057]    The resulting fully processed assembly  80  (shown in FIG. 7A) comprises the air-vented storage bag  34 , to which the tube segment  32  with sealed pockets  62  retaining the samples of the donor&#39;s filtered blood is secured. The storage bag  34  also carries the donor-specific label  25  and linking sample label  60 .  
         [0058]    The red blood cells, now substantially reduced of leukocytes, are stored in the air-vented storage bag  34 . The attached sample pockets  62  of the filtered blood can be separated from the tube segment  32  when desired, and can be analyzed at a convenient time prior to transfusion for crossmatching and typing purposes.  
         [0059]    The invention assures direct traceability between a leukocyte-reduced blood product for transfusion and the donor from whom the blood is obtained.  
         [0060]    In the illustrated embodiment (see FIG. 2), the system  10  includes directions  66  for using the system  10  in the manner above described.  
         [0061]    The foregoing embodiment shows the features of the invention in the context of a filtration assembly  14 , which is, during use, coupled to a processing assembly  12  to filter leukocytes from red blood cells. The invention, of course, can be used in the processing of other kinds of blood components and in association with other blood collection system configurations.  
         [0062]    For example, as FIG. 8 shows, an integral blood processing system  68  can include a whole blood collection bag  70  (containing an anticoagulant A) to which a filtration assembly  72  embodying the features of the invention is integrally attached. The assembly  72  includes a transfer bag  74  to which the main tube path  36 , the in line filter device  40 , and tube segment  32  are coupled in the same manner shown in FIG. 2. The tube segment  32  also includes the one-way valve  48 , as also previously described. Additional transfer bags  18  and  26  are integrally attached to the transfer bag  74 , in the same manner the bags  18  and  26  are integrally attached to the primary bag  16  in FIG. 2. Like the primary bag  16  shown in FIG. 2, the whole blood collection bag  70  in FIG. 8 includes a donor tube  20 .  
         [0063]    In use, a unit of whole blood is collected in the bag  70 , where it is mixed with anticoagulant A. After the donor tube  20  is disconnected, whole blood is transferred from the bag  70  through the tube path  36  and filter device  40 , into the transfer bag  74 . In this arrangement, the filter device  40  removes leukocytes from whole blood. In the same manner described in connection with the assembly  14 , the transfer bag  74  is squeezed to vent residual air through the tube segment  32  into the collection bag  70 . Squeezing of the transfer bag  74  conveys a sample of the filtered whole blood into the tube segment  32 . The tube segment  32  and tube path  36  are sealed, and the collection bag  70  is disconnected. Sample segments are formed along the tube  36  still attached to the transfer bag  74 , in the manner already described. This leaves the transfer bag  74 , sample tube segment  32 , and transfer bags  18  and  26  remaining as an integrated assembly.  
         [0064]    The filtered whole blood is thereafter centrifugally separated in the transfer bag  74  into red blood cells and platelet-rich plasma. The platelet-rich plasma is expressed into the transfer bag  18  for storage or further processing. The solution S is added to the red blood cells remaining in the transfer bag  74 , which becomes the storage container for the red blood cells. The blood samples of the filtered whole blood can be separated from the tube segment  32  when desired, and can be analyzed at a convenient time prior to transfusion for crossmatching and typing purposes.  
         [0065]    Various features of the invention are set forth in the following claims.