Methods for coagulation monitoring

• US 4,720,787 A
• Filed: 10/11/1985
• Issued: 01/19/1988
• Est. Priority Date: 10/15/1984
• Status: Expired due to Term

• Current Assignee: Innovative Medical Systems Corp. (GT Biopharma, Inc.), Ortho Diagnostic Systems, Inc. (The Carlyle Group LP (Corporate Private Equity))
• Original Assignee: Innovative Medical Systems Corp. (GT Biopharma, Inc.), Ortho Diagnostic Systems, Inc. (The Carlyle Group LP (Corporate Private Equity))
• Inventors: Lipscomb, Myatt S.
• Primary Examiner(s): Smith, Jerry
• Assistant Examiner(s): Tbui, Kim Thanh
• Application Number:
  US06/786,925
• Time in Patent Office: 830 Days
• Field of Search: 364/416, 128/632, 128/637, 422/73, 356/39, 436/69, 435/13
• US Class Current: 600/369
• CPC Class Codes: G01N 21/82 producing a precipitate or turbidity
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

Improved methods for the determination of clotting times of fibrinogen. APTT and PT are provided. Surprising and unexpected accuracy is obtained by combining a backward-looking approach to determine a desired range of values over times T1 and T2, selected in accordance with predetermined percentages of the observed Vmax, thereby avoiding early false positives due to noise and other inhomogeneities from reagent sample mixing. Thereafter, a regression analysis is performed over the time period T1 and T2 and from the derived function, the coagulation time is determined by calculating the time associated with the predetermined percentage of Vmax.

Claims

1. In a system for monitoring the presence of a coagulation component in a mixture of coagulation reagent and patient sample by measuring component clotting detection time, and employing a sensor for determining increases in optical density and providing a signal in coordination therewith, a method comprising:

(a) measuring and subsequently storing the values of the signal proportional to the optical property of the mixture at a plurality of times during a predetermined interval after formation of the mixture;

(b) determining the last stored value of the signal at the end of the predetermined interval;

(c) scanning all stored signal values starting with the last stored signal value to determine a time T1 when the measured signal is more than or equal to a fraction X times the last stored signal value;

(d) further scanning the stored signal values starting with the last stored signal value to determine a time T2 when the measured signal is less than or equal to a fraction Y times the last stored signal value, wherein 1>

Y>

X>

0;

(e) producing a function relating the stored signal values to the plurality of times by performing a curve fitting analysis of the stored signal values for the times bounded by times T1 and T2; and

(f) determining from the function the time at which the value of the signal is equal to Z times the last stored signal value, wherein 1>

Z>

0, whereby the component clotting detection time is determined.

2. The method as provided in claim 1 where the stored signal values are normalized by a method selected from the group of following:

(a) adjusting the lowest stored signal value to zero and reducing all the other stored signal values by an amount equal to the lowest stored signal value, prior to the step of determining the last stored value of the signal; and

(b) prior to storing the signal values, reducing the measured values by the lowest measured signal value.

3. The method as provided in claim 2 wherein the curve fitting analysis comprises a polynomial regression analysis of the first order.

4. The method as provided in claim 3 wherein the detection time is correlated with a standard curve to obtain the concentration of the coagulant component in the sample.

5. The method as provided in claim 4 wherein the method is employed to a determination selected from the group consisting of fibrinogen, PT, APTT, and factor assays.

6. A method for determining a fibrinogen, PT, APTT, or factor coagulation time by monitoring the optical density of a mixture of patient sample and coagulation reagent with a sensor capable of supplying a continuous signal, comprising the steps of:

(a) measuring and storing the signal values proportional to an optical property of the mixture at a plurality of times during a predetermined time interval during which the coagulation time is to be determined;

(b) normalizing the measured signal values by setting the lowest measured signal value to zero and reducing all other measured signal values by the value of the lowest measured signal value;

(c) determining the value of the signal last measured at the end of the predetermined interval;

(d) scanning the measured values of the signal starting with the last measured signal to determine the time T1 of the first measured signal, the value of which is equal to or more than the fraction X times the last measured signal value and T2 of the first signal, the value of which is less than or equal to the fraction Y times the last measured signal value, wherein 1>

Y>

X>

0;

(e) performing a polynomial regression analysis of order P of the measured values of the signal over a time period bounded by times T1 and T2 to form a function, wherein P is greater than or equal to tow; and

(f) determining from the function the time at which the value of the signal is equal to the fraction Z times the last measured value of the signal, wherein 1>

Z>

0 and whereby fibrinogen, partial thromboplastin or prothrombin coagulation time is determined.

7. The method as provided in claim 6 wherein the value of the last measured signal of the predetermined interval is determined by averaging the last five measured values of the signal.

8. The method as provided in claim 7 further comprising the step of correlating the detection time with a standard curve to obtain the concentration of the coagulant component in the sample.