Abstract:
Devices and methods that prevent clotting of blood during blood-processing procedures such as hemofiltration, hemodialysis, hemodiafiltration, and peritoneal dialysis are described. The device comprises a cap and a housing that is shaped to receive a blood filter. The housing has an inlet for blood and may have an outlet for waste and ultrafiltrate. The cap is attached to the housing. The cap has an outlet for blood and a port adjacent the outlet for receiving dilution fluid. Methods of use during blood-processing procedures to provide immediate hemodilution to blood exiting a filter are also described.

Description:
FIELD OF THE INVENTION  
         [0001]    The present invention relates generally to devices and methods useful in preventing coagulation in filtered blood during hemofiltration. More specifically, the devices and methods provide a cap having a port, the cap adapted for attachment to a blood filter housing to provide hemodilution of blood as it enters and/or exits the filter.  
         BACKGROUND OF THE INVENTION  
         [0002]    Undesired coagulation of blood often complicates blood-processing procedures such as hemofiltration, hemodialysis, and hemodiafiltration, particularly where a filter is used. Blood generally coagulates by transforming soluble fibrinogen into insoluble fibrin by activation of numerous circulating proteins that interact in a cascading series of limited proteolytic reactions. At each step of reaction, a clotting factor undergoes limited proteolysis and becomes an active protease that in turn activates the next clotting factor until finally a solid fibrin clot is formed. Fibrinogen (factor I) is activated by thrombin (factor IIa), which is converted from prothrombin by activated factor X. There are two separate coagulation pathways that activate factor X—the intrinsic system and the extrinsic system. Activation of the extrinsic system requires tissue thromboplastin (factor III), which is released from damaged tissue into the circulating blood to activate clotting. The intrinsic system, on the other hand, has all the factors necessary for coagulation contained in the circulating blood. The intrinsic system is, for example, partially responsible for clotting of blood in a test tube. Aggregation of platelets caused by stagnation of blood also facilitates blood coagulation.  
           [0003]    During hemofiltration, for example, blood is removed from the patient, filtered through a filtering column to remove waste products, and returned to the patient&#39;s circulation. However, during removal of waste products, fluid is also removed, causing concentration of blood leaving the outflow tubing. As a result of hemoconcentration, hematocrit rises, and the intrinsic coagulation pathway and platelets are activated causing clotting of blood around the outlet of the filtering column, thereby compromising the hemofiltrating process.  
           [0004]    What is needed are devices and methods that can be used with a filtering column during blood-processing procedures, such as hemofiltration, hemodialysis, hemodiafiltration, and peritoneal dialysis, to prevent clotting. Existing devices are inadequate for this purpose.  
         SUMMARY OF THE INVENTION  
         [0005]    The present invention provides devices and methods that prevent clotting of blood during blood-processing procedures, such as hemofiltration, hemodialysis, and hemodiafiltration. More particularly, blood is diluted by replacement fluid, such as saline, Ringer&#39;s lactate, or other physiological solutions, as it enters and/or exits the filter. In a first embodiment, the device, also known as a filter, is comprised of a bundle of hollow fiber membrane made of resins such as polysulfone that is fixed in a cylindrical housing with a potting material. The interior of the fibers is the blood flow path. The exterior of the fibers is the dialysate and/or waste space. The potting material is typically a polyurethane material. The cylindrical housing may have one or two access ports. One port is for the hemofiltration filter, and two ports allow dialysate to flow through the housing contacting the exterior surface of the membrane for hemodialysis or hemodiafiltration. In one embodiment, the open fibers at the end of the cylindrical housing are covered at both ends with a cap. One cap is the blood entry cap, the other is the blood exit cap. In other embodiments, the housing includes end plates at one or both ends, the end plates integral with the housing.  
           [0006]    The exit cap is attached to the housing, in some cases removably attached, and generally at a position opposite the inlet cap. The exit cap has an outlet for blood and a port adjacent the outlet for receiving replacement fluid. In certain embodiments, the blood outlet, the replacement fluid port, the blood inlet, and/or the waste outlet of the filter assembly communicate with bond sockets adapted to receive flexible tubing.  
           [0007]    In another embodiment, the filter has an outlet or exit cap for blood at one end and an inlet or inlet cap at the other end, the cap having an inlet for blood and a port adjacent to the inlet for receiving dilution fluid, such as saline, Ringer&#39;s lactate, or other physiological solutions. The housing also includes access ports for waste and ultrafiltrate.  
           [0008]    In still another embodiment, the housing includes first and second caps at opposite ends and an outlet for waste and ultrafiltrate. The first cap has an inlet for blood and a port adjacent to the inlet for receiving dilution fluid. The second cap has an outlet for blood and a port adjacent to the outlet for receiving dilution fluid.  
           [0009]    In use, blood is passed through the blood inlet of the entry cap, through the filter membrane fibers, and through the blood outlet of the exit cap. Replacement fluid or dilution fluid, such as saline, Ringer&#39;s lactate, or other physiological solutions, is infused into the port adjacent the blood outlet to produce hemodilution at the blood outlet. Alternatively, the fluid is infused into the port adjacent the blood inlet of the entry cap to produce hemodilution at the inlet. In still another alternative method, fluid is infused into the port adjacent the blood inlet of the entry cap and into the port adjacent the blood outlet of the exit cap to produce hemodilution as blood enters and exits the filter housing. In certain constructions the replacement fluid swirls in a circular pattern in a headspace that is defined by the gap between the filter and the cap. Swirling of the replacement fluid facilitates mixing of the fluid and the blood, thereby preventing hemoconcentration and stasis of blood, and sweeping any particles of thrombus away from the filter.  
           [0010]    The advantages associated with the hemodilution cap described herein include (1) preventing coagulation during blood processing procedures, (2) manufacturing efficiency, i.e., reducing plastic used in disposable components, (3) eliminating up to two bonds and up to two components, (4) less expense in materials costs and manufacturing costs, (5) more robust system, not subject to tolerances like bonding two rigid parts, and (6) integration of parts saves labor, materials, and precious resources. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0011]    [0011]FIG. 1A depicts a filter within a housing for hemofiltration.  
         [0012]    [0012]FIG. 1B depicts a filter within a housing having a replacement fluid port adjacent the blood outlet port for hemofiltration.  
         [0013]    [0013]FIG. 1C depicts a filter within a housing having a replacement fluid port adjacent the blood inlet port for hemofiltration.  
         [0014]    [0014]FIG. 1D depicts a filter within a housing having replacement fluid ports adjacent both the blood inlet port and the blood outlet port for hemofiltration.  
         [0015]    [0015]FIG. 1E depicts a filter within a housing for hemodiafiltration having dialysate inlet and outlet ports.  
         [0016]    [0016]FIG. 1F depicts a filter within a housing for hemodiafiltration having a replacement fluid port adjacent the blood outlet port.  
         [0017]    [0017]FIG. 2 depicts a filter-housing cap having a replacement fluid port adjacent the blood outlet port for hemofiltration.  
         [0018]    [0018]FIG. 3A depicts a cross-sectional view of a filter housing cap having a replacement fluid port adjacent the blood outlet port for hemofiltration.  
         [0019]    [0019]FIG. 3B depicts another cross-sectional view of a filter housing cap having a replacement fluid port adjacent the blood outlet port for hemofiltration.  
         [0020]    [0020]FIG. 3C depicts another cross-sectional view of a filter housing cap having a replacement fluid port adjacent the blood outlet port and a headspace for hemofiltration.  
         [0021]    [0021]FIG. 4A depicts a fluid bond socket communicating with the blood outlet.  
         [0022]    [0022]FIG. 4B depicts a fluid bond socket communicating with the replacement fluid port.  
         [0023]    [0023]FIG. 5 depicts a filter-housing cap removably mounted on a filter housing for hemofiltration.  
         [0024]    [0024]FIG. 6 depicts a filter-housing cap for hemofiltration, the cap being made of flexible PVC and having ribs for stability. 
     
    
     DETAILED DESCRIPTION  
       [0025]    During blood-processing procedures, such as hemofiltration, hemodialysis, and hemodiafiltration, blood has a tendency to clot as it passes through processing equipment, particularly where it exits the outlet of a filter, due to hemoconcentration. In FIG. 1A, the hemofiltration device includes cylindrical housing  10  which contains filter fibers  20  that remove waste from blood passing through the fibers. It will be understood that any other suitable shape can be used for the housing. Housing  10  is equipped with entry cap  13  having blood inlet  11 . Waste and ultrafiltrate that are removed from the blood exits the housing through waste outlet  12 . Exit cap  30  is mounted on housing  10  opposite blood entry cap  13 . Headspace  31  is formed in the gap between filter fibers  20  and cap  30  and between filters  20  and cap  13 . Headspace  31  communicates with blood outlet  32 . Each of the inlet  11  waste outlet  12  and blood outlet  32  are adapted for attachment to flexible tubing sections that connect with a blood processing system.  
         [0026]    In FIG. 1B, cap  30  further includes replacement fluid inlet port  33  that communicates with headspace  31 . Replacement fluid is infused through port  33  to effect hemodilution of blood exiting filter  20 . The system thereby reconstitutes blood as close as possible to the exit from the filter fibers. In this way hemodilution is accomplished with one part (cap  30 ) and two bonds (one between tubing and port  32 , and another between tubing and port  33 ).  
         [0027]    In FIG. 1C, housing  10  includes cap  13  having blood inlet  11  and dilution fluid inlet port  15  that communicates with headspace  31 . Blood is diluted as it enters housing  10 , thereby helping to prevent coagulation.  
         [0028]    In FIG. 1D, housing  10  includes cap  13  having blood inlet and dilution fluid inlet port  15  that communicates with headspace  31 . The housing also includes cap  30  having blood outlet  32  and fluid inlet port  33  that communicates with headspace  31 . Dilution fluid is infused through port  33  and port  15  to effect hemodilution of blood entering and exiting filter  20 .  
         [0029]    [0029]FIG. 1E shows a housing  10  designed for hemodiafiltration. Housing  10  includes dialysate inlet  16  and dialysate outlet  12  to establish countercurrent dialysate flow. Filter fiber membrane  20  is mounted within potting material  21  at both ends, where the potting material typically is a polyurethane material. In FIG. 1F, cap  30  further includes replacement fluid inlet port  33  that communicates with headspace  31 . Replacement fluid is infused through port  33  to effect hemodilution of blood exiting filter  20  as described for other embodiments above. It will be understood that for hemodiafiltration, a hemodilution cap may be included alternatively on the inlet to effect pre-dilution of blood, and/or on both the inlet and outlet.  
         [0030]    [0030]FIG. 2 shows a top view of cap  30  having blood outlet  32  and replacement fluid infusion port  33 . In use, replacement fluid, such as saline, Ringer&#39;s lactate, sterile filtered dialysate, or other physiological solutions, enters through port  33  and establishes a swirling current within headspace  31 . This current has the beneficial effect of sweeping thrombus particles that may have accumulated in the headspace and flushing the particle through outlet  32 . Inlet blood flow rate will typically be 50-1000 mL/min, preferably 350-600 mL/min. Infusion of dilution fluid at the exit cap will generally be 1-50% of inlet blood flow, preferably 20-30% in order to establish swirling. The foregoing ranges are set forth solely for the purpose of illustrating typical operating parameters. The actual parameters for operation of a device constructed according to the principles of the present invention may obviously vary outside of the listed ranges without departing from those basic principles.  
         [0031]    Infusion port  33  includes bond socket  34 , and outlet  32  includes bond socket  35 . Each bond socket is adapted to receive flexible tubing. Where the tubing is generally constructed of PVC and the bond socket is constructed of any one of a number of thermoplastic resins including PVC, polycarbonate, ABS, etc., PVC being preferable as it is solvent bonded to the housing, the tubing may be fused to the bond socket by brief immersion in cyclohexanone or other suitable organic solvent before inserting the tubing in the bond socket. Soft PVC is flexible, allowing the cap to have an interference fit when solvent bonded. This makes it less susceptible to tolerance problems.  
         [0032]    [0032]FIG. 3A depicts a side view of an embodiment of cap  30  with blood outlet  32  and bond socket  35 . FIG. 3B depicts a side view of another embodiment of cap  30  having blood outlet  32  and bond socket  35 . FIG. 3C depicts a side view of still another embodiment of cap  30  having blood outlet  32  and bond socket  35 . Filter housing  10  is slideably received within the opening in cap  30  when fully inserted, housing  10  rests against annular ridge  36 . Headspace  31  is defined by the gap between filter  20  and cap  30 .  
         [0033]    [0033]FIG. 4A shows the details of bond socket  35  communicating with the blood outlet designed for interference fit with appropriately sized tubing. Passage  41  has a dimension of approximately 0.185 inches in diameter. Surface  43  is approximately 0.248 inches in diameter. Annular member  42  has a height of approximately 0.35 inches. Surface  45  is approximately 0.252 inches in diameter. Thus, blood outlet  32  communicates with a quarter inch bond socket. Replacement fluid infusion port  33  communicates with bond socket  34  shown in details in FIG. 4B. Passage  41  has a dimension of approximately 0.098 inches in diameter. Surface  43  is approximately 0.142 inches in diameter. Annular member  42  has a height of approximately 0.31 inches. Surface  45  is approximately 0.147 inches in diameter. The foregoing ranges are set forth solely for the purpose of illustrating typical device dimensions. The actual dimensions of a device constructed according to the principles of the present invention may obviously vary outside of the listed ranges without departing from those basic principles.  
         [0034]    [0034]FIG. 5 depicts housing  10  inserted within cap  30 . Headspace  31  communicates with outlet  32 , which in turn communicates with bond socket  35 . Headspace  31  ranges from approximately 1.5 mm at the outer edge to approximately 3 mm in the center of the dome-like region. In use, the pressure in headspace  31  can reach 40 PSI (2000 mmHg), resulting in 25 lbs force pushing the cap off. The cap  30  may therefore need to be bonded, threaded, or snapped on, or attached by other suitable means, to withstand pressure. Solvent bonding and use of a threaded cap are two suitable means to accomplish attachment. It will again be understood that these device dimension are merely illustrative as stated above. FIG. 6 depicts a top view of another embodiment of cap  30  having ribs  37 .  
         [0035]    Although the foregoing invention has, for the purposes of clarity and understanding, been described in some detail by way of illustration and example, it will be obvious that certain changes and modifications may be practiced which will still fall within the scope of the appended claims. For example, it will be understood that any feature of any device or method disclosed herein can be used with any of the other devices or methods, even though any given figure might depict only a particular combination.