Chemistry: analytical and immunological testing – Sedimentation rate or hematocrit
Reexamination Certificate
2001-07-25
2003-02-04
Warden, Jill (Department: 1743)
Chemistry: analytical and immunological testing
Sedimentation rate or hematocrit
C436S069000
Reexamination Certificate
active
06514766
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to an improved whole-blood or isolated red blood cell diagnostic test for diagnosing or predicting various inflammatory and other conditions.
BACKGROUND OF THE INVENTION
Erythrocyte sedimentation rate (ESR) is a simple diagnostic test which determines the distance red blood cells in a sample of anticoagulated whole blood settle in one hour, and is expressed in units of mm per hour. This test measures the acute phase response to inflammatory disease. The current ESR test is similar to that described by Fahraeus (1921, The suspension-stability of the blood. Acta Med Scand 55:1-228) and Westergren (1921, Studies of the suspension stability of the blood in pulmonary tuberculosis. Acta Med Scand 54:247-282) in 1921, and has changed little since that time. The International Council for Standardization in Hematology (ICSH) has more recently put forth its description for the Erythrocyte Sedimentation Rate (ESR; Bull B S, Caswell M, Ernst E et al. ISCH recommendations for measurement of erythrocyte sedimentation rate. J Clin Path 1993, 46:198-203). The standardization method describes blood sample collection, anticoagulation, dilution of sample, sedimentation pipette and holding device specifications, calculating result and verification. The anticoagulant blood is drawn into a long tube with a narrow uniform bore. After placement of blood in the tube, the lower end is sealed, the tube placed in a vertical position and the distance (usually mm) the erythrocytes settle in 1 hour recorded as the ESR. Normal values are considered to be 15 mm or less. Automatically-zeroing ESR tubes are available as well as automatic instrumental determination of ESR values.
The ESR is a nonspecific marker of the inflammatory process and appears simplistic in concept. That is, cells and plasma interact under the influence of gravity and the final sedimentation distance of cells at one hour can be measured by simply reading the graduated tube. Beyond diagnosis of inflammatory diseases per se, reports describe the use of ESR in monitoring sickle cell disease, osteomyelitis, stroke, myocardial infarction, cancer, pregnancy, infection, atherosclerosis, rheumatoid arthritis, ischemic heart disease and trauma.
However, the major problems with the ESR are that it (1) is a nonspecific marker for disease; (2) it has lack of sensitivity in some disease states, and (3) it is rarely elevated in asymptomatic individuals, who may have occult disease. It is towards improving the value and utility of the ESR test and increasing its sensitivity for the diagnosis, monitoring and prognostication of various conditions and diseases that the present invention is directed.
The citation of any reference herein should not be construed as an admission that such reference is available as “Prior Art” to the instant application.
SUMMARY OF THE INVENTION
In its broadest aspect, the present invention is directed to a method for determining the health status of an animal, preferably a human, by carrying out the sequential steps of: (i) obtaining an anticoagulated sample of whole blood from the animal; (ii) determining at least one erythrocyte sedimentation rate (ESR) of the sample in the presence of at least one ESR-modulating agent; and (iii) correlating the at least one ESR in the presence of the at least one ESR-modulating agent with the health status of the animal. The health status may indicate presence or extent of a condition or disease, propensity for the development of a condition or disease, or effect of therapy on a condition or disease, such as, but not limited to, inflammation, sickle cell disease, osteomyelitis, stroke, myocardial infarction, cancer, pregnancy, infection, atherosclerosis, rheumatoid arthritis, ischemic heart disease and trauma. It may also help decide on the course of therapy of a particular disease or condition, such as whether the cardiac patient is a candidate for an angioplastic procedure or will need a more invasive surgery such as a bypass operation.
The foregoing modified ESR determination may also be performed in combination with at least one other assay, such as but not limited to clotting time or a metal- or polymer-modified clotting time, to provide data of additional diagnostic or prognostic utility. Other additional tests include red blood cell deformability and any other clotting parameter, as traditionally done or as modified by the addition to the blood sample of a modifying agent such as a metal ion, polymer, or other agent as described herein.
By way of non-limiting examples, the ESR-modulating agent may be a metal ion, such as silver, mercuric or lanthanum ion; a polymer, such as methylcellulose or polyvinylpyrrolidone; epinephrine; an oxidant such as hydrogen peroxide; a procoagulant such as but not limited to a snake venom, such as Russell's viper venom; an endotoxin; or collagen.
In a further embodiment, the above method may be carried out with an additional ESR determination is performed on the sample in the absence of an ESR-modulating agent. In another embodiment, an additional ESR determination is made on the sample in the presence of a second ESR-modulating agent. All of the foregoing methods may be performed on washed erythrocytes (red blood cells) rather than anticoagulated whole blood. They may be washed or isolated in plasma, albumin solution, normal saline, etc.
The anticoagulated sample of whole blood may be anticoagulated with, for example, citrate, isocitrate, heparin or EDTA.
The prognostic value of the present invention includes, among other uses, determining from a sample of blood whether a cardiac patient will be a candidate for an angioplastic procedure, or may need more extensive surgery such as a bypass operation. This may be achieved from the modified ESR determination, optionally in combination with at least one additional determination, such as a modified clotting time. In one embodiment, a whole blood sample is drawn, anticoagulated, and a modulator such as a silver (I) or mercury (II) salt, or a polymer such as methyl cellulose, is added to the sample. The sample is divided into two aliquots. With one aliquot, a gravity erythrocyte sedimentation rate is determined. With the other sample, a calcium salt is added and the clotting time is determined. From the results of the modified ESR and modified clotting time, prognosis as to the likelihood or risk of acute or chronic coronary heart disease may be made. In a patient presenting with acute chest pain, the test aids in determining whether an angioplastic procedure may be useful or whether the patient should be prepared for a coronary artery bypass graft procedure.
Therefore, it is an object of the invention to improve the diagnostic specificity of an erythrocyte sedimentation rate (ESR) determination by performing the ESR determination in the presence of an ESR-modulating agent, optionally along with at least one additional whole blood test.
These and other aspects of the present invention will be better appreciated by reference to the following Detailed Description.
DETAILED DESCRIPTION OF THE INVENTION
Improvements have been made herein in the methodology of performing the erythrocyte sedimentation rate (ESR) so that many of its defects can be removed, and moreover its sensitivity may be increased to expand its diagnostic and prognostic value. The test is extremely simple to perform, and can be done on an anticoagulated whole blood sample present in a capillary or other similar tube, wherever a source of gravity is present. While instruments can help automate the determination and perhaps increase the speed of the test (from the usual prescribed one hour of settling), the basic test is applicable to a wide variety of conditions and locations, including medical facilities with minimal equipment and personnel, military or battlefield conditions, as well as in space. Alternate gravity conditions will of course require recalibrating the ESR, but the improvements described herein are applicable to the ESR test wherever and however it is normally performed. The variou
Khalil Marcelle
Spillert Charles R.
Cole Monique T.
Klauber & Jackson
Spillert Charles R.
Warden Jill
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