Method for determining the fibrinogen level of a blood sample

• US 5,156,974 A
• Filed: 05/27/1988
• Issued: 10/20/1992
• Est. Priority Date: 05/27/1988
• Status: Expired due to Term

• Current Assignee: Biodata SPA
• Original Assignee: Biodata SPA
• Inventors: Rausch, Michael, Grossman, Hyman
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Redding, David
• Application Number:
  US07/199,551
• Time in Patent Office: 1,607 Days
• Field of Search: 436/63, 436/69, 436/86, 436/164, 436/171, 436/805, 435/4, 435/13, 73/64.1, 364/413.09, 356/39
• US Class Current: 436/69
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

A method for determining the fibrinogen level of a patient blood plasma in an optical density based prothrombin time test. The method and apparatus utilize a novel parameter DELTA which factors out statistical inaccuracies associated with prior art test methods. The patient fibrinogen level is determined using DELTA points calculated from blood samples having known fibrinogen levels in the low, normal and high ranges. A piece wise function is then constructed around the DELTA points and the fibrinogen level of a patient blood sample is calculated using four equations pre-stored in a non-volatile memory.

Claims

1. A method for determining fibrinogen level of a blood plasma sample, comprising the steps of:

(a) obtaining reference samples of blood plasmas having known fibrinogen levels in respective low, normal and high ranges;

(b) sequentially performing a blood coagulation test on each reference sample so as to determine a value of a parameter, said parameter equalling an initial optical density of the reference sample under test, minus a special end of reaction term corresponding to an optical density at a point in time when differential change of optical density with respect to time of said reference sample under test decreases to a fraction of its previous maximum value, the difference between the initial optical density of the reference sample and the end of reaction term of the reference sample being divided by the initial optical density of each said reference sample under test;

(c) performing a blood coagulation time test on a patient blood sample having an unknown fibrinogen level in order to determine a value of a parameter for said patient sample, said parameter equalling an initial optical density of said patient sample minus a special end of reaction term corresponding to an optical density of said patient sample at a point when the differential change of optical density with respect to time of said patient sample decreases to a fraction of its previous maximum value, the difference between the initial optical density of the patient sample and the end of reaction term of the patient sample being divided by the initial optical density of said patient sample; and

(d) determining a fibrinogen level of said patient sample using a first linear equation if the value of the parameter of the unknown patient sample is less than or equal to the value of the parameter of the reference sample having a known fibrinogen level in the low range, a second linear equation if the value of the parameter of the unknown sample is less than or equal to the value of the parameter of the reference sample having a known fibrinogen level in the normal range, a third linear equation if the value of the parameter of the unknown sample is less than or equal to the value of the parameter of the reference sample having a known fibrinogen level in the high range, or a fourth non-linear equation if the value of the parameter of the unknown sample is greater than the value of the parameter for the reference sample having a fibrinogen level in the high range;

said first linear equation being a function of the value of the parameter of said unknown patient sample the fibrinogen level of said reference sample having a known fibrinogen level in the low range, and the value of the parameter for the reference sample having a fibrinogen level in the low range, and having the form ##EQU6## said second linear equation being a function of the fibrinogen value of the reference sample having a known fibrinogen value in the low range, the value of the parameter of the unknown patient sample, the value of the parameter of the reference sample having a low fibrinogen level, the value of the parameter for the reference sample having a normal fibrinogen level, and the fibrinogen value of the reference sample having a known fibrinogen level in the normal range, and having the form ##EQU7## said third linear equation being a function of the fibrinogen level of the reference sample having a known fibrinogen level in the normal range, the value of the parameter of the unknown patient sample, the value of the parameter for the reference sample having a normal fibrinogen level, the value of the parameter for the reference sample having a high fibrinogen level, and the fibrinogen level of the reference sample having a known fibrinogen level in the high range, and having the form ##EQU8## said fourth non-linear equation being a function of a constant having a value between zero and one, a linear extrapolation term, the value of the parameter of the unknown patient sample, the value of the parameter for the reference sample having a high fibrinogen level, and the fibrinogen value of the reference sample having a known fibrinogen level in the high range, and having the form ##EQU9##

2. A method for determining fibrinogen level of a blood plasma sample, comprising the steps of:

(a) obtaining reference samples of blood plasmas having known fibrinogen levels in low, normal and high ranges;

(b) sequentially performing a blood coagulation time test on each of said reference samples having respective known low, normal and high fibrinogen levels in order to determine a value of a parameter for each of said samples, said parameter equalling an initial optical density of said reference sample under test minus a special end of reaction term corresponding to an optical density of said reference sample under test when differential rate of change of optical density with respect to time of said reference sample decreases to a fraction of its previous maximum value, the difference between the initial optical density of the reference sample and the end of reaction term of the reference sample being divided by the initial optical density of said reference sample under test;

(c) performing a blood coagulation time test on a sample of patient blood plasma having an unknown fibrinogen level in order to determine a value of a parameter for said sample, said parameter equalling an initial optical density of said sample minus a special end of reaction term corresponding to an optical density of said patient sample at a point when the differential change of optical density with respect to time of said patient sample decreases to a fraction of its previous maximum value, the difference between the initial optical density of the patient sample and the end of reaction term of the patient sample then being divided by the initial optical density of said patient sample; and

(d) determining a fibrinogen level of said patient sample using a first linear equation having a zero intercept if the value of the parameter of the unknown sample is less than the value of the parameter of the reference sample having a known fibrinogen level in the low range, a second linear equation having a non-zero intercept if the value of the parameter of the unknown sample is less than the value of the parameter of the reference sample having a known fibrinogen level in the normal range, a third linear equation having a non-zero intercept if the value of the parameter of the unknown sample is less than the value of the parameter of the reference sample having a known fibrinogen level in the high range, or a fourth non-linear equation if the value of the parameter of the unknown sample is greater than the value of the parameter for the reference sample having a fibrinogen level in the high range;

said first linear equation being a function of the value of the parameter of said unknown patient sample, the fibrinogen level of said reference sample having a known fibrinogen level in the low range, and the value of the parameter for the reference sample having a fibrinogen level in the low range, and having the form ##EQU10## said second linear equation being a function of the fibrinogen value of the reference sample having a known fibrinogen value in the low range, the value of the parameter of the unknown patient sample, the value of the parameter of the reference sample having a low fibrinogen level, the value of the parameter of the reference sample having a normal fibrinogen level, and the fibrinogen value of the reference sample having a known fibrinogen level in the normal range, and having the form ##EQU11## said third linear equation being a function of the fibrinogen level of the reference sample having a known fibrinogen level in the normal range, the value of the parameter of the unknown patient sample, the value of the parameter for reference sample having a normal fibrinogen level, the value of the parameter for the reference sample having a high fibrinogen level, and the fibrinogen level of the reference sample having a known fibrinogen level in the high range, and having the form ##EQU12## said fourth non-linear equation being a function of a constant having a value between zero and one, a linear extrapolation term, the value of the parameter of the unknown patient sample, the value of the parameter for the reference sample having a high fibrinogen level, and the fibrinogen value of the reference sample having a known fibrinogen level in the high range, and having the form ##EQU13##

3. A method for determining fibrinogen level of a blood sample comprising the steps of:

(a) electronically storing values representing known fibrinogen levels of referenced blood samples having respective low, normal and high fibrinogen levels;

(b) electronically determining and storing a value of a parameter for each said reference sample in accordance with a blood coagulation time test, said parameter equalling a voltage corresponding to an optical density of said reference blood sample under test prior to the initiation of clotting minus a voltage corresponding to a special end of reaction term corresponding to an optical density when the differential change of optical density with respect to time of said reference sample decreases to a fraction of its previous maximum value, the difference between the voltage corresponding to an optical density of the reference sample and the voltage corresponding to the end of reaction term of the reference sample being divided by the voltage corresponding to optical density of the referenced blood sample under test prior to the initiation of clotting;

(c) electronically determining and storing a value of a parameter for a patient blood sample in accordance with a blood coagulation time test, said parameter equalling a voltage corresponding to an optical density of said patient blood sample prior to the initiation of clotting minus voltage corresponding to a special end of reaction term corresponding to an optical density of said patient sample when the differential change of optical density with respect of time of aid patient sample decreases to a fraction of its previous maximum value, the difference between the voltage corresponding to an optical density of the patient sample and the voltage corresponding to the end of reaction term of the patient sample being divided by the voltage corresponding to the optical density of said patient sample prior to the initiation of clotting; and

(d) determining a fibrinogen level of said patient sample using a first linear equation if the value of the parameter of the patient blood sample is less than the value of the parameter of the reference sample having a known fibrinogen level in the low range, a second linear equation if the value of the parameter of the unknown sample is less than the value of the parameter of the reference sample having a known fibrinogen level in the normal range, a third linear equation if the value of the parameter of the patient blood sample is less than the value of the parameter of the reference sample having a known fibrinogen level in the high range, and a fourth non-linear equation the value of the parameter of the unknown sample is greater than the value of the parameter for the reference sample having a fibrinogen level in the high range;

said first linear equation being a function of the value of the parameter of said unknown patient sample, the fibrinogen level of said reference sample having a known fibrinogen level in the low range, and the value of the parameter for the reference sample having a fibrinogen level in the low range, and having the form ##EQU14## said second equation being a function of the fibrinogen value of the reference sample having a known fibrinogen value in the low range, the value of the parameter of the unknown patient sample, the value of the parameter of the reference sample having a low fibrinogen level, the value of the parameter of the reference sample having a normal fibrinogen level, and the fibrinogen value of the reference sample having a known fibrinogen level in the normal range, and having the form ##EQU15## said third linear equation being a function of the fibrinogen level of the reference sample having a known fibrinogen level in the normal range, the value of the parameter of the unknown patient sample, the value of the parameter for reference sample having a normal fibrinogen level, the value of the parameter for the reference sample having a high fibrinogen level, and the fibrinogen level of the reference sample having a known fibrinogen level in the high range, and having the form ##EQU16## said fourth non-linear equation being a function of a constant having a value between zero and one, a linear extrapolation term, the value of the parameter of the unknown patient sample, the value of the parameter for the reference sample having a high fibrinogen level, and the fibrinogen value of the reference sample having a known fibrinogen level in the high range, and having the form ##EQU17##