Blood platelet concentrate in a plasma-free medium. Method for storage of blood platelets in a plasma-free medium which comprises centrifuging plasma to obtain a platelet pellet, removing the supernatant plasma, and resuspending the platelet pellet in a balanced salt medium. The balanced salt medium in an isotonic solution and may be selected from well known physiologically tolerable salt mediums. Additives to enhance platelet storage can be added to the salt medium.
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18. A An essentially plasma-free platelet concentrate composition for administration to animals comprising blood platelets suspended in a medium consisting essentially of:
a balanced, physiologically compatible, saline solution; an anticoagulant; and one or more additives to enhance stability of the platelets selected from (a) nutrients to improve the storage life of the platelets, (b) reversible inhibitors for platelet activation, (c) substances to raise cyclic adenosine monophosphate levels which have reversible effects on platelets, and (d) buffering agents which are physiologically compatible.
1. A method for the preparation of a an essentially plasma-free blood platelet concentrate for administration to animals which comprises
centrifuging plasma to obtain a platelet pellet, removing the supernatant plasma, and resuspending the platelet pellet in a medium consisting essentially of: a balanced, physiological compatible, saline solution; an anticoagulant; and one or more additives to enhance stability of the platelets selected from (a) nutrients to improve the storage life of the platelets, (b) reversible inhibitors for platelet activation, (c) substances to raise cyclic adenosine monophosphate levels which have reversible effects on platelets, and (d) buffering agents which are physiologically compatible.
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29. An essentially plasma-free storage-stable package of blood platelets, which comprises a concentrate of blood platelets suspended in a volume of physiologically acceptable salt solution, said suspension being sealedly enclosed within a blood storage member. 30. The storage-stable package as defined by
7. The storage-stable package as defined by
saline-citrate-buffer-nutrient. 44. A composition of matter comprising an essentially plasma-free storage-stable concentrate of blood platelets suspended in a volume of physiologically acceptable salt solution, said composition exhibiting no worse than normal platelet aggregation. 45. The composition of matter as defined by claim 44, further comprising an additive adopted to enhance platelet function under conditions of storage, or to prolong the storage life thereof. 46. The composition of matter as defined by claim 45, which said additive is a buffering agent. 47. The composition of matter as defined by claim 44, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. 48. The composition of matter as defined by claim 47, wherein the physiologically compatible salt solution is Tyrode's solution. 49. The composition of matter as defined by claim 48, wherein Tyrode's solution contains a phosphate buffer or a histidine buffer. 50. The composition of matter as defined by claim 44, wherein the blood platelets are human blood platelets. 51. The composition of matter as defined by claim 50, wherein the blood platelets are derived from platelet-rich plasma from whole blood or by apheresis on a human donor. 52. The composition of matter as defined by claim 44, further comprising an anticoagulant. 53. The composition of matter as defined by claim 44, further comprising saline-citrate-buffer. 54. The composition of matter as defined by claim 44, further comprising saline-citrate-buffer-nutrient. 55. A method for the storage of essentially plasma-free blood platelets, which comprises confining a concentrate of said blood platelets suspended in a volume of physiologically acceptable salt solution within a blood storage member, for a period of time of at least 72 hours. 56. The method as defined by claim 55, comprising confining the suspension within said blood storage member under conditions of agitation. 57. The method as defined by claim 55, wherein a buffering agent is contained in the storage member. 58. The method as defined by claim 55, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. 59. The method as defined by claim 58, wherein the physiologically compatible salt solution is Tyrode's solution. 60. The method as defined by claim 59, wherein Tyrode's solution contains a phosphate buffer or a histidine buffer. 61. The method as defined by claim 55, wherein the plasma is human plasma. 62. The method as defined by claim 61, wherein the plasma is derived from human whole blood or by apheresis on a human donor. 63. The method as defined by claim 55, wherein the storage member is highly permeable. 64. The method as defined by claim 55, wherein an anticoagulant is contained in the storage member. 65. The method as defined by claim 55, wherein saline-citrate-buffer is present within the storage member. 66. The method as defined by claim 55, wherein saline-citrate-buffer-nutrient is present within the storage member. 67. A method for the treatment of thrombocytopenia in a patient in need of such treatment, which comprises infusing into such patient an effective amount of an essentially plasma-free concentrate of blood platelets suspended in a volume of physiologically compatible salt solution. 68. The method as defined by claim 67, wherein the physiologically compatible salt solution is selected from the group consisting of Spinner salt solution, Tyrode's solution, Seligmann balanced salt solution, Earle's balanced salt solutions, Dulbecco's phosphate buffered saline, Hank's balanced salt solutions, Gey's balanced salt solution or Puck's saline. 69. The method as defined by claim 68, wherein the physiologically compatible salt solution is Tyrode's solution. 70. The method as defined by claim 69, wherein Tyrode's solution contains a phosphate buffer or histidine buffer. |
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This invention is concerned with a method for the storage of blood platelets in a plasma-free medium. Also described is a platelet concentrate obtained by this method.
Thrombocytopenia means low platelet counts in the circulatory system. Persons with this disease have a tendency to bleed as do hemophiliacs, except that the bleeding is usually from many small capillaries rather than from large vessels as in hemophilia. Such persons suffer small punctate hemorrhages throughout all the body tissues. The skin of such a person will exhibit many small, purplish blotches. Platelets are especially important for repair of minute breaks in capillaries and other small vessels. Platelets aglutinate to fill such ruptures without actually causing clots.
Normally, excessive bleeding does not occur until the number of platelets in the blood falls below a value of approximately 70,000 per cubic millimeter rather than the normal of 150,000 to 350,000.
At the present time, persons who have low platelet counts are supported by infusion of platelet concentrates. Platelet concentrates contain on average 6×1010 platelets suspended in a volume of 50-60 ml of plasma. Larger platelet concentrates can be obtained using apheresis machinery, in which case the concentration is in the range of 4×1011 and the plasma volume may reach 200-300 ml. Platelet concentrates can be kept for 3, 5 or even 7 days, depending on the type of bag and mode of rotation used.
There are generally speaking two types of blood collection and storage bags available. One type permits storage of platelets in plasma for up to 3 days while another type permits storage of platelets in plasma for up to 5 days and sometimes up to 7 days. The latter type is generally used for research purposes. In addition it should be noted that platelet storage bags must not contain the plasticizer di-2-ethyl-hexylphthalate and they should be highly permeable. While stored, all bags are subjected to rotation on a continuous basis which can be rotational about a transverse axis or horizontal and reciprocal or horizontal and circular.
The present inventors have developed a method whereby platelets can be stored in a medium other than plasma while still retaining the functional characteristics of platelets stored in plasma. The technique involves centrifugation of the plasma to obtain a platelet pellet, removal of the supernatant plasma, and subsequent resuspension of the platelet pellet in a balanced salt medium.
Thus, the present invention provides a method for the preparation of a platelet concentrate which comprises centrifuging plasma to obtain a platelet pellet, removing supernatant plasma and resuspending the platelet pellet in a balanced salt medium.
The plasma can be derived from freshly collected while blood or may be collected using apheresis machinery, i.e. apheresis platelets. The blood or plasma is preferably collected from humans.
The balanced salt medium or isotonic solution is designed to provide the basic nutrients required for platelet support during storage and, as well, to enhance the environment above that obtained under plasma (physiological) conditions. More specifically, the isotonic solution or balanced salt medium comprises a conventional, physiologically tolerable isotonic solution to which various additional additives may be added to enhance platelet stability.
Examples of conventional balanced salt mediums or isotonic solutions which can be used for this purpose are Spinner salt solution (Eagle H, Science, 130:432 (1959)), Tyrode's (Tyrode, M. V., Arch. Intern. Pharmacodyn., 20:205 (1910)), Seligmann balanced salt solution (formula below), Earle's balanced salt solutions (Natl. Cancer. Inst. 4:167 (1943)), Dulbecco's phosphate buffered saline (J. Exp. Med., 98:167 (1954)), Hanks' balanced salt solutions (Proc. Soc. Exp. Biol. Med., 71:196 (1949)), modification-National Institutes of Health) Gey's balanced salt solutions (Amer. J. of Cancer, 27:55 (1936)), Puck's saline (Puck, T. T., Cieciura, S. J. and Robinson, A. J. Exp. Med., 108:945 (1958)).
The formula for Seligmann balanced salt solution is as follows:
| ______________________________________ |
| Component mg/L |
| ______________________________________ |
| NaCl 7650.00 |
| KCl 200.00 |
| NaCO2.CH3 |
| 1500.00 |
| NaH2 PO4.H2 O |
| 50.00 |
| KH2 PO4 |
| 100.00 |
| D-Glucose 1000.00 |
| NaHCO3 700.00 |
| Ascorbic Acid 3.00 |
| ______________________________________ |
There are several advantages to using a balanced salt solution in place of plasma and these are as follows. The plasma can be recovered and can be used for other purposes involving protein fractionation or transfusion to patients. Plasma is an expensive commodity and generally in short supply. Replacement of the plasma as a supernatant for platelet storage would result in considerable saving of plasma (estimated 14,000 liters in Canada alone in 1982) throughout the world.
Another advantage is the possibility of enhancing the storage environment above that generally found for plasma. Platelets are collected into an anticoagulant solution whose pH and biochemical constituents are chosen to enhance red cell preservation and which therefore may not be of optimal composition for platelet storage.
Beside the economic advantages, there are considerable theoretical medical advantages to removal of plasma and resuspension of platelets in a plasma free medium:
i. Removal of plasma components that are potentially harmful to platelets such as glycolytic and proteolytic enzymes that remove membrane glycoproteins and thus cause premature clearance from the circulation;
ii. Reduce the risk of exposure to infectious agent;
iii. Reduced risk of immediate and delayed allergic responses of recipients;
iv. Greater control over environmental conditions, especially pH, ion concentration and volume;
v. Reduced variations in platelet concentrates that would enhance the confidence of physicians in platelet concentrates perhaps leading to therapeutic regimes requiring fewer platelet concentrates per treatment; and
vi. The addition of agents to the storage medium may further improve platelet function after storage or prolong the storage life of platelets.
The agents which can be added to the storage medium can include one or more of the following. Nutrients may be added to the medium, and may be selected from fructose and other sugars, adenine or acetyl CoA. These nutrients are substrates for the glycolytic or proteolytic enzymes on the platelet surface and prevent these enzymes from altering the platelet surface.
Another approach is to inhibit the above and other enzymes with reversible inhibitors that are diluted upon infusion into the circulatory system and hence no longer inhibitory. Examples of these compounds are indomethacin, quinacrine or vitamin E, all of which inhibit platelet activation during storage and perhaps increase storage life.
Yet another method to control platelet activation during storage is to raise cyclic adenosine monophosphate with exogenous prostaglandins E1, D2 or I2 which again have a short half-life in vivo and reversible effects on platelets.
Finally, the artificial medium can be buffered by addition to the medium of a number of agents all of which can safely be infused into patients. These include phosphate and the amino acids: histidine, cysteine, tyrosine, lysine or arginine. These amino acids have the ability to buffer at an alkaline pH of 9 while phosphate precipitates at this pH.
Thus, in summary the isotonic solution may contain nutrients to improve the storage life of the platelets, reversible inhibitors for platelet activation, substances to raise cyclic adenosine monophosphate levels and which have reversible effects on platelets, and buffering agents which can be safely infused into patients. Generally these additives are used in physiological salt concentrations.
By the present method, the storage of platelet concentrates in a plasma free medium can be effected for at least 72 hours and results can be obtained which are similar to or better than those currently found using standard conditions of storage in plasma.
In another aspect, this invention provides a platelet concentrate in a plasma-free medium, which medium is a balanced salt medium which is an isotonic solution. The solution may be modified with the previously described agents. The present platelet concentrates can be stored for the same amount of time as presently available plasma concentrates can be stored. Further the platelet concentrates in the non-plasma medium are about the same as for the plasma medium, that is, about 109 ml or 1012 /L.
The following examples are used to illustrate the present invention. All parts and percentages are by weight unless otherwise specified.
Two series of experiments were carried out to show the effects of storing platelets in a non-plasma medium. The first series (A) uses extraction and a washing step to remove plasma from platelets prior to final suspension in a Tyrode's solution. The second series (B) uses only extraction of plasma and final suspension in a modified Tyrode's solution containing either extra phosphate buffer or histidine buffer.
PAC Series AMethod:
Preparation of Platelet Concentrates: Platelet concentrates were prepared by acidification of a pool of platelet-rich plasma using 35 ml acid-citrate-dextrose anticoagulant to 230 ml of platelet-rich plasma, to yield a final pH of 6.4. This lower pH allows immediate resuspension of platelets concentrated by the normal centrifugation procedure of 3000 g for 5.5 minutes. The plasma was extracted and the platelets resuspended in a washing solution containing 0.5 mM EDTA in calcium and magnesium-free Tyrode's buffer, pH 6.4. After centrifugation at 3000 g for 5.5 minutes and extraction of supernatant, the platelets were resuspended in (Citrate-Phosphate-Dextrose anticoagulant) CPD Tyrode's solution or CPD-plasma at a final volume of 60 ml in P1-146 (plastic) bags (a trademark of Fenwall Company, Deerfield, Ill. 60015). The composition of the CPD-Tyrode's balanced salt solution is given in Table 1. These concentrates were stored at 22°C in a horizontal shaker for testing after 3 days.
Platelet Aggregation: Aliquots from the platelet concentrates were diluted in pooled plasma containing CPD to a final concentration of 3×108 platelets/μl. After incubating for one hour at 37° the platelet suspensions were aggregated by addition of one stimulus or simultaneous addition of pairs of stimuli. The stimuli and concentrations used were adenosine diphosphate (ADP) at 10-5 M, epinephrine at 5×10-5 M, collagen at 2.4 μg/ml, arachidonic acid at 10-4 M, and calcium ionophore A23187 at 5×10-6 M. All these are final concentrations in the platelet suspensions.
Results:
The results for the platelets washed and resuspended in CPD-Tyrode's (Table 2) and CPD-plasma (Table 3) and for unwashed normal platelet concentrates (Table 4) are presented. The reported values are means and standard errors of at least three determinations except for those aggregations using arachidonate. The platelets stored in CPD-Tyrode's had slightly reduced aggregation responses when compared to the two control preparations stored in CPD-plasma. All three preparations lost the ability to aggregate to collagen, epinephrine or ADP while retaining aggregation response to pairs of stimuli or ionophore. The response to all three preparations were identical when tested before storage, indicating the washing procedure did not acutely alter the platelets (data not shown).
PAC Series BMethod:
Preparation of Platelet Concentrates: Platelet concentrates were prepared by the normal centrifugation procedure of 3000 g for 5.5 minutes (no ACD was added). The plasma was extracted and the platelets resuspended in CPD-Tyrode's-phosphate solution, CPD-Tyrode's-Histidine (see Table 1 for recipes) or CPD-plasma at a final volume of 60 ml in PL 145 bags. These concentrates were stored at 22°C in a horizontal shaker for testing after 3 days.
Platelet Aggregation: All aggregations were performed as in Series A.
Results:
The results for the platelets washed and resuspended in CPD-Tyrode's-phosphate (Table 5), and CPD-Tyrode's-Histidine (Table 6) and for unwashed normal platelet concentrates (Table 4) are presented and show values equal to or better than for platelets stored in the usual way in plasma. The reported values are means and standard errors of at least three determinations except for those aggregations using arachidonate. There was no difference between the platelets stored in CPD-Tyrode's-Histidine, CPD-Tyrode's-phosphate and the preparations stored in CPD-plasma. As in Series A, all three preparations lost the ability to aggregate to collagen, epinephrine or ADP while retaining aggregation response to pairs to stimuli or ionophore. The responses of all three preparations were identical when tested before storage, indicating the washing procedure did not significantly alter the platelets (data not shown).
| TABLE 1 |
| ______________________________________ |
| Composition of Some Artificial Mediums Used |
| CPD- CPD-Tyrode's- |
| CPD-Tyrode's- |
| Tyrode's Phosphate Histidine |
| ______________________________________ |
| NaCl 120 mM 102 mM 102 mM |
| KCl 2.4 mM 2.4 mM 2.4 mM |
| NaHCO3 |
| 22.0 mM 10.0 mM 10.0 mM |
| NaH2 PO4 |
| 0.4 mM 22.0 mM -- |
| CaCl2 |
| 1.8 mM 1.8 mM 1.8 mM |
| MgCl2 |
| 0.9 mM 0.9 mM 0.9 mM |
| Glucose 22.0 mM 22.0 mM 22.0 mM |
| Citrate 1.0 mM 1.9 mM 1.9 mM |
| Trisodium |
| 10.8 mM 10.8 mM 10.8 mM |
| Citrate |
| Na2 HPO4 |
| 1.9 mM 1.9 mM -- |
| Histindine |
| -- -- 22.0 mM |
| pH 7.4 mM 7.4 mM 7.4 mM |
| Osmolarity |
| 298 mOsm 303 mOsm 313 mOsm |
| ______________________________________ |
| TABLE 2 |
| ______________________________________ |
| Percent Platelet Aggregation After Storage of Washed Platelets |
| at 22°C for 72 hours in CPD-Tyrode's. |
| First Stimulus |
| Second Arach- |
| Stimulus Saline ADP Epinephrine |
| Collagen |
| idonate |
| ______________________________________ |
| Saline 0 |
| ADP 5(2)* |
| Epinephrine |
| 2(3) 24(8) |
| Collagen 1(2) 26(2) 22(18) |
| Arachidonate |
| 18(5) -- 34 -- |
| Ionophore 31(8) 29(8) 27(7) 31(9) -- |
| ______________________________________ |
| *mean (S.E.) of at least 3 determinations except for aggregations using |
| arachidonate |
| TABLE 3 |
| ______________________________________ |
| Percent Platelet Aggregation After Storage of Washed Platelets |
| at 22°C for 72 hours in CPD-Plasma. |
| First Stimulus |
| Second Arach- |
| Stimulus Saline ADP Epinephrine |
| Collagen |
| idonate |
| ______________________________________ |
| Saline 0 |
| ADP 8(5)* |
| Epinephrine |
| 1(1) 40(4) |
| Collagen 2(2) 43(3) 47(6) |
| Arachidonate |
| 21(2) 48 46 -- |
| Ionophore 40(2) 45(6) 40(4) 47(10) 46 |
| ______________________________________ |
| *mean (S.E.) of at least 3 determintions except for aggregations using |
| arachidonate |
| TABLE 4 |
| ______________________________________ |
| Percent Platelet Aggregation After Storage of Unwashed |
| Platelets at 22°C for 72 hours in CPD-Plasma |
| First Stimulus |
| Second Arach- |
| Stimulus Saline ADP Epinephrine |
| Collagen |
| idonate |
| ______________________________________ |
| Saline 0 |
| ADP 14(5)* |
| Epinephrine |
| 0(1) 40(2) |
| Collagen 2(1) 43(2) 41(2) |
| Arachidonate |
| 27(3) 44(2) 43(5) -- |
| Ionophore 47(5) 46(2) 39(2) 46(2) 44 |
| ______________________________________ |
| *mean (S.E.) of at least 7 determinations except for aggregations using |
| arachidonate which are means of 3 determinations. |
| TABLE 5 |
| ______________________________________ |
| Percent Platelet Aggregation After Storage of Washed Platelets |
| at 22°C for 72 hours in CPD-Tyrode's-Phosphate. |
| First Stimulus |
| Second Arach- |
| Stimulus Saline ADP Epinephrine |
| Collagen |
| idonate |
| ______________________________________ |
| Saline 0 |
| ADP 7 |
| Epinephrine |
| 0 38 |
| Collagen 2 47 41 |
| Arachidonate |
| 28 40 39 38* |
| Ionophore 40 45 42 46 38* |
| ______________________________________ |
| TABLE 6 |
| ______________________________________ |
| Percent Platelet Aggregation After Storage of Washed Platelets |
| at 22°C for 72 Hours in CPD-Tyrode's-Histidine. |
| First Stimulus |
| Second Arach- |
| Stimulus Saline ADP Epinephrine |
| Collagen |
| idonate |
| ______________________________________ |
| Saline 0 |
| ADP 11 |
| Epinephrine |
| 1 35 |
| Collagen 5 |
| 43 33 |
| Arachidonate |
| 24* 42* 38* 33* |
| Ionophore + 48 37 43 30* |
| A23187 |
| ______________________________________ |
| *mean (S.E.) of at least 3 determinations except for aggregation using |
| arachidonate + 2 experiments gave no aggregation with ionophore A23187 |
| while one gave 36% aggregation. Normal platelet aggregation to ionophore |
| A23187 were found in CPDTyrod' sPhosphate. |
Rock, Gail A., Adams, George A.
| Patent | Priority | Assignee | Title |
| 10273456, | Apr 07 2011 | Fenwal, Inc | Automated methods and systems for washing platelet concentrates |
| 10358627, | Dec 20 2007 | Fenwal, Inc. | Medium and methods for the storage of platelets |
| 10897891, | Apr 10 2015 | Board of Regents, The University of Texas System | Compositions and methods for prolonged cell storage |
| 5147776, | Feb 26 1990 | University of Iowa Research Foundation | Use of 2,5-anhydromannitol for control of pH during blood storage |
| 5234808, | Oct 30 1991 | Thomas Jefferson University | Acetate addition to platelets stored in plasma |
| 5344752, | Oct 30 1991 | Thomas Jefferson University | Plasma-based platelet concentrate preparations |
| 5376524, | Apr 01 1991 | Thomas Jefferson University | Platelet storage medium containing acetate and phosphate |
| 5378601, | Jul 24 1992 | Montefiore Medical Center | Method of preserving platelets with apyrase and an antioxidant |
| 5459030, | Mar 02 1992 | Cerus Corporation | Synthetic media compositions for inactivating bacteria and viruses in blood preparations with 8-methoxypsoralen |
| 5466573, | Apr 01 1991 | Thomas Jefferson University | Platelet storage method in a medium containing acetate and phosphate |
| 5474891, | Oct 30 1991 | Thomas Jefferson University | Plasma-based platelet concentrate preparations with additive |
| 5482828, | Mar 02 1992 | Cerus Corporation | Synthetic media compositions and methods for inactivating bacteria and viruses in blood preparations with 8-methoxypsoralen |
| 5569579, | Apr 01 1991 | Thomas Jefferson University | Synthetic-based platelet storage media |
| 5589395, | Dec 20 1989 | Dade Behring Marburg GmbH | Method for stabilizing annexins |
| 5618662, | Mar 02 1992 | Cerus Corporation | Intravenous administration of psoralen |
| 5709991, | Mar 02 1992 | Cerus Corporation | Proralen inactivation of microorganisms and psoralen removal |
| 5906915, | Nov 07 1990 | Fenwal, Inc | Method for storing red cells using reduced citrate anticoagulant and a solution containing sodium, citrate, phosphate, adenine and mannitol |
| 5908742, | Mar 02 1992 | Fenwal, Inc | Synthetic media for blood components |
| 5965349, | Mar 02 1992 | Cerus Corporation | Methods of photodecontamination using synthetic media |
| 6063624, | Jun 09 1997 | Fenwal, Inc | Platelet suspensions and methods for resuspending platelets |
| 6251580, | Mar 02 1992 | Fenwal, Inc | Synthetic media for blood components |
| 6258577, | Jul 21 1998 | Terumo BCT Biotechnologies, LLC | Method and apparatus for inactivation of biological contaminants using endogenous alloxazine or isoalloxazine photosensitizers |
| 6268120, | Oct 19 1999 | Terumo BCT Biotechnologies, LLC | Isoalloxazine derivatives to neutralize biological contaminants |
| 6277337, | Jul 21 1998 | Terumo BCT Biotechnologies, LLC | Method and apparatus for inactivation of biological contaminants using photosensitizers |
| 6277556, | Dec 16 1994 | Baxter International Inc. | Controlling donor blood characteristics |
| 6326197, | Jun 09 1997 | Fenwal, Inc | Platelet suspensions and methods for resuspending platelets |
| 6413713, | Oct 30 1998 | Human Biosystems | Method for preserving blood platelets |
| 6548241, | Nov 28 2000 | Terumo BCT Biotechnologies, LLC | Storage solution containing photosensitizer for inactivation of biological contaminants |
| 6566046, | Mar 02 1992 | Fenwal, Inc | Synthetic media for blood components |
| 6613566, | Jun 09 1997 | Fenwal, Inc | Platelet suspensions and methods for resuspending platelets |
| 6828323, | Oct 19 1999 | Terumo BCT Biotechnologies, LLC | Isoalloxazine derivatives to neutralize biological contaminants |
| 6866992, | Mar 02 1992 | Fenwal, Inc | Synthetic platelet storage media formulation |
| 7029839, | Apr 23 2003 | Human Biosystems | Methods and solutions for storing donor organs |
| 7049110, | Jul 21 1998 | Terumo BCT Biotechnologies, LLC | Inactivation of West Nile virus and malaria using photosensitizers |
| 7094378, | Jun 15 2000 | Terumo BCT Biotechnologies, LLC | Method and apparatus for inactivation of biological contaminants using photosensitizers |
| 7183045, | Apr 24 2002 | Terumo BCT Biotechnologies, LLC | Removal of adenine during a pathogen reduction process in whole blood or red blood cell by dilution |
| 7202020, | Oct 30 1998 | Human Biosystems | Compositions, methods and apparatuses for preserving platelets |
| 7220747, | Jul 21 1998 | Terumo BCT Biotechnologies, LLC | Method for preventing damage to or rejuvenating a cellular blood component using mitochondrial enhancer |
| 7498156, | Jul 21 1998 | Terumo BCT Biotechnologies, LLC | Use of visible light at wavelengths of 500 to 550 nm to reduce the number of pathogens in blood and blood components |
| 7648699, | Jun 02 2000 | Terumo BCT Biotechnologies, LLC | Preventing transfusion related complications in a recipient of a blood transfusion |
| 7892535, | Jun 02 2000 | Terumo BCT Biotechnologies, LLC | Preventing transfusion related complications in a recipient of a blood transfusion |
| 7901673, | Jun 02 2000 | Terumo BCT Biotechnologies, LLC | Induction of and maintenance of nucleic acid damage in pathogens using riboflavin and light |
| 7985588, | Jun 02 2000 | Terumo BCT Biotechnologies, LLC | Induction of and maintenance of nucleic acid damage in pathogens using riboflavin and light |
| 8679736, | Apr 24 2002 | Terumo BCT Biotechnologies, LLC | Removal of adenine during a pathogen reduction process in whole blood or red blood cells by dilution |
| 8835104, | Dec 20 2007 | Fenwal, Inc | Medium and methods for the storage of platelets |
| 9044523, | Jun 15 2000 | Terumo BCT Biotechnologies, LLC | Reduction of contaminants in blood and blood products using photosensitizers and peak wavelengths of light |
| 9168281, | Mar 09 2011 | WORDEN IP HOLDING COMPANY, LLC | Kit for treating a wound |
| 9402866, | Apr 07 2011 | Fenwal, Inc | Automated methods and systems for providing platelet concentrates with reduced residual plasma volumes and storage media for such platelet concentrates |
| Patent | Priority | Assignee | Title |
| 2786014, | |||
| 3629071, | |||
| 3729947, | |||
| 3735005, | |||
| 3753357, | |||
| 3814687, | |||
| 3850174, | |||
| 4014993, | Mar 17 1972 | The Upjohn Company | Inhibition of platelet aggregation with substituted phenylhydratropic acid compounds |
| 4061537, | Jul 18 1975 | Behringwerke Aktiengesellschaft | Polyionic isotonic salt solution |
| 4148879, | Dec 23 1977 | WHITBY RESEARCH, INC | Inhibition of platelet aggregation with selected phosphonic and phosphinic acid esters |
| 4152208, | Mar 29 1977 | Hoffmann-La Roche Inc. | Stabilized leucocytes |
| 4267269, | Feb 05 1980 | Baxter Travenol Laboratories, Inc. | Red cell storage solution |
| 4269718, | May 05 1980 | Medical Research Institute | Process and device for centrifugal separation of platelets |
| 4387031, | Jul 22 1980 | Compositions able to separate the erythrocytes from the serum or plasma in blood analysis samples, and the method which uses them | |
| 4390619, | Sep 28 1981 | HAIGHT, JAMES CLIFFORD | Leukocyte or platelet storage using ion-exchange resins |
| 4405719, | May 29 1981 | Coulter Electronics, Inc. | Method of stabilizing platelets for determining multiple platelet parameters in reference control and calibrator compositions; diluents therefor; and combination stabilization procedures |
| 4455299, | Nov 20 1981 | BAXTER TRAVENOL LABORATORIES, INC , A CORP OF DE | Storage of blood platelets |
| GB1014712, | |||
| GB1283273, |
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