Chemistry: analytical and immunological testing – Hemoglobin – myoglobin – or occult blood
Reexamination Certificate
2001-05-18
2003-09-23
Wallenhorst, Maureen M. (Department: 1743)
Chemistry: analytical and immunological testing
Hemoglobin, myoglobin, or occult blood
C436S063000, C436S164000, C435S002000
Reexamination Certificate
active
06623972
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to new methods and systems for detecting, quantifying and monitoring extracellular or exogenously added hemoglobin, including hemoglobin substitutes, in a blood sample, particularly a whole blood sample, as well as in plasma and serum samples. The present invention further relates to the use of automated hematology analyzers to determine and quantify the concentration of extracellular and exogenous hemoglobin, including cell-free hemoglobin substitutes, in a blood, plasma, or serum sample, and is particularly advantageous for medical use during patient trauma or surgery, as well as for monitoring hemoglobin levels during recovery.
BACKGROUND OF THE INVENTION
Whole blood substitutes have long been sought after as alternatives to whole blood for use in the medical field, particularly following trauma and/or surgery where transfusions are needed. Motivated by the need to supply large quantities of blood to the military on the battlefield, but limited by the resources to insure the safety of the blood supply in the face of contamination by human pathogens and viruses, notably hepatitis viruses and HIV, blood banks abandoned their whole blood supply programs in the early 1980s. However, the search for blood substitutes, e.g., synthetic blood substitutes, that are free of contaminants and that can be used in patient treatment has continued.
Currently, there is a renewed interest to produce and/or isolate a blood substitute. However, because of the complexity of blood and the various components that comprise whole blood, as well as the stringent federal regulations governing the testing and use of such synthetic products, industry has focused its research efforts on the development of products which temporarily deliver oxygen, rather than on the development of a variety of different products having other functions that transfused blood provides.
Hemoglobin (HGB) isolated from human or animal blood, or a synthetically produced oxygen carrier, such as perfluorocarbon, are two types of hemoglobin substitutes that are currently in clinical trials. Other red blood cell substitutes, i.e., oxygen-carrying hemoglobin substitutes, have also been developed and characterized for use in patients. (See, for example,
Red Blood Cell Substitutes,
1998, (Eds.) A. S. Rudolph, R. Rabinovici, and G. Z. Feuerstein, Dekker, New York, N.Y.). Such oxygen-carrying hemoglobin substitutes may be used in conjunction with standard medical therapies, such as transfused blood or blood products.
As a specific but nonlimiting example, Enzon, Inc. (Piscataway, N.J.), has developed a polyethylene glycol (PEG)-modified bovine hemoglobin, abbreviated PEG-HGB. PEG-HGB is produced by a process in which strands of PEG are crosslinked to the surfaces of HGB molecules, for example, as disclosed in U.S. Pat. Nos. 5,386,014 and 5,234,903 to Nho et al.). Other specific, yet nonlimiting, examples include Hemopure® and Oxyglobin (Biopure, Cambridge, Mass.).
The first generation HGB substitutes were generally intended for short term treatment of blood/oxygen loss during surgery or following trauma. One disadvantage of HGB substitutes is the short circulation half-life attributed to these products. For example, HGB substitutes that are added to blood have a circulation half-life of up to 36 hours compared with a circulation half-life of up to 30 days for transfused blood. However, this relatively short half-life is typically not a serious problem associated with the use of such blood substitutes, because these products are predominantly indicated for short-term treatment objectives.
In determining whether or not to transfuse a patient who has a low blood hemoglobin concentration, the transfusion “trigger” is between about 6 and 8 g/dL of hemoglobin in whole blood and depends on a number of specific factors, such as blood volume status, pulmonary, cardiac and cerebrovascular status, chronicity or severity of anemia, patient symptoms relating to blood loss, expected blood loss for a particular procedure, risk of re-bleeding from surgery, high risk patients (i.e., the elderly), and thrombocytopenia.
In general, the measurement of hemoglobin in whole blood samples is performed by commercially available automated hematology analyzers. To date, with the exception of certain hematology analyzers, such as those available from Bayer Corporation, e.g., the ADVIA 120® hematology analyzer system, other commercially-available blood analyzers are able to measure only total hemoglobin, which includes not only exogenously added hemoglobin, but also intracellular hemoglobin that is derived from the red blood cells in a blood sample. The present invention provides the ability to determine and measure exogenous hemoglobin in a whole blood, plasma, or serum sample in a reliable, reproducible and automated way.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide automated methods and hematology systems to specifically and accurately detect, quantify and monitor different types of hemoglobin in a blood, plasma, or serum sample, preferably a whole blood sample, undergoing analysis, namely, (i) hemoglobin derived from red blood cells (i.e., intracellular hemoglobin, or cellular hemoglobin, as used herein); (ii) extracellular hemoglobin, or a hemoglobin product or substitute, particularly, a cell-free hemoglobin derivative, e.g., PEG-HGB, or a synthetic form of hemoglobin, e.g., Hemopure®, (Biopure, Cambridge, Mass.); Oxyglobin, (Biopure, Cambridge, Mass.), which has been transfused into a patient requiring added HGB, or otherwise added to a blood, plasma, or serum sample (i.e., exogenous hemoglobin); and (iii) total hemoglobin (i.e., the combination of intracellular and exogenous hemoglobin).
It is another object of the present invention to provide the ability to monitor, during a course or regimen of treatment, hemoglobin or a hemoglobin product, derivative or substitute, such as a cell-free hemoglobin derivative, that has been added to blood of a patient or individual in need thereof. Also, in accordance with the present invention, hemoglobin, or a hemoglobin product, derivative or substitute, such as a cell-free hemoglobin derivative, can be monitored, determined or quantified as exogenous hemoglobin in a patient's blood, plasma, or serum, after the patient has been transfused with such a hemoglobin product, or a substance containing the product (e.g., a physiologically acceptable solution or composition, and the like).
It is yet another object of the present invention to provide a system to differentiate and accurately measure the contribution of an added or exogenous hemoglobin product or blood substitute, e.g., PEG-HGB, separately and distinctly from the contribution of cellular HGB which derives from a patient's red blood cells. In accordance with the present invention, the automated analytical method and system as described calculate a specific concentration of the extracellular hemoglobin in a blood sample which has been transfused with a hemoglobin product, or in a blood, plasma, or serum sample which contains extracellular hemoglobin to be detected. Thus, the invention allows the detection and monitoring of an extracellular hemoglobin component, even in the presence of a cellular hemoglobin component derived from the red blood cells in a given sample. In addition, through the present method, as little as about 0.5 g/dL of hemoglobin is detectable in a total of approximately 6.0 g/dL of extracellular hemoglobin. Experiments were performed in the HGB concentration range which is relevant to transfusions, i.e., a decision point of about 6-7 g/dL of total HGB in blood. Moreover, hemoglobin was recoverable and quantified in blood samples that were 24 hours old, and which had been stored at temperatures of 2° C. to 8° C.
Further objects and advantages afforded by the present invention will be apparent from the detailed description hereinbelow.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides automated methods and hematology systems
Malin Michael J.
Shapiro Phyllis
Bayer Corporation
Morgan & Finnegan , LLP
Wallenhorst Maureen M.
LandOfFree
Automated method for detecting, quantifying and monitoring... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Automated method for detecting, quantifying and monitoring..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Automated method for detecting, quantifying and monitoring... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3041782