Method and apparatus for calculating a coagulation characteristic of a sample of blood a blood fraction or a control

• US 5,526,111 A
• Filed: 08/31/1993
• Issued: 06/11/1996
• Est. Priority Date: 08/31/1993
• Status: Expired due to Term

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Boehringer Mannheim Corporation (Roche Holding AG)
• Inventors: Weinert, Stefan, Maxwell, James L., Probst, Edna C., Heller, Zindel H., Vail, Loy M., Gerber, Martin T., Young, Morris J., Collins, Rick L.
• Primary Examiner(s): Hayes, Gail O.
• Assistant Examiner(s): Thomas, Joseph
• Application Number:
  US08/114,897
• Time in Patent Office: 1,015 Days
• Field of Search: 364/413.07, 364/413.08, 364/413.09, 364/413.02, 364/413.01, 73/64.41, 73/64.43, 73/53.01, 73/61.41, 73/61.43, 422/73, 422/61, 356/39, 356/40, 356/41, 356/42, 324/621, 324/613, 324/635, 324/647, 128/632, 128/633, 128/668, 128/635, 128/637, 128/DIG. 22, 210/645, 210/745, 436/69, 435/13
• US Class Current: 356/39
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56
• CPC Class Codes: Y10S 128/22 Blood coagulation

Abstract

A method for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control comprises generating an output signal indicative of coagulation of the sample, sampling the output signal at a sampling rate for a predetermined time to provide a plurality of sampled signal values, storing the sampled signal values, rectifying the stored sampled signal values to provide a plurality of envelope values, and storing the envelope values. The stored envelope values are examined in reverse time order to determine a slope of the envelope at each of the stored envelope values. All relative maxima in the stored envelope values are identified. A range of stored envelope values corresponding to each relative maximum is determined. The identified relative maxima are compared to locate an absolute maximum in the stored envelope values. The coagulation characteristic is then calculated from the stored envelope values within the predetermined range of envelope values corresponding to the absolute maximum.

Claims

1. A method for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control, the method comprising the steps of:

generating an output signal indicative of coagulation of the sample;

sampling the output signal at a sampling rate for a predetermined time interval to provide a plurality of sampled signal values;

storing the sampled signal values;

determining an envelope from the stored signal values;

storing the envelope; and

calculating the coagulation characteristic from the stored envelope based on the maximum signal value.

2. The method of claim 1 wherein the step of calculating the coagulation characteristic includes the steps of examining the stored envelope to locate a maximum value of the stored envelope and identifying a stored value in the envelope which is a predetermined percentage less than said maximum value, said coagulation characteristic being related to the number of stored samples between the beginning of the sampling interval and the thus-identified stored value.

3. The method of claim 2 wherein the predetermined percentage is about 5%.

4. The method of claim 2, further comprising the step of converting the number of stored samples between the beginning of the sampling interval and the thus-identified stored value into clinical units corresponding to the coagulation characteristic.

5. The method of claim 1, further comprising the step of filtering the stored sampled signal values to provide filtered stored sampled signal values before the step of calculating the envelope.

6. The method of claim 1, further comprising the step of filtering the stored envelope before the step of calculating the coagulation characteristic.

7. The method of claim 6 wherein the filtering step includes the steps of selecting a process point from among the stored sampled signal values, the process point having two nearest neighbor sampled signal values, calculating an average value of the two nearest neighbor sampled signal values, forming an absolute difference between the average value and the process point, establishing a noise tolerance value, comparing the absolute difference to the noise tolerance value, clearing a filter flag if the absolute difference is less than the noise tolerance value, checking the filter flag to determine if the filter flag is set if the absolute difference is greater than the noise tolerance value, forming a filtered signal value, replacing the process point with the filtered signal value only if the filter flag is set during the checking step, setting the filter flag if the filter flag is not set, and repeating the method with the next stored sampled signal value.

8. The method of claim 7 wherein the forming and replacing steps comprise the steps of forming a median sampled signal value from a plurality of stored sampled signal values neighboring the process point, and replacing the process point with the median sampled signal value.

9. The method of claim 7, further comprising the steps of establishing a noise threshold value, comparing the filtered signal value to the noise threshold value after the replacing step, providing a noise counter for storing a noise value, incrementing the noise value if the filtered signal value is greater than the noise threshold value, establishing a noise limit, comparing the noise value to the noise limit, and generating an error signal if the noise value is greater than the noise limit.

10. The method of claim 9, further comprising the steps of establishing a minimum time limit, establishing a time of the process point, comparing the time of the process point with the minimum time limit before the step of comparing the filtered signal value to the noise threshold value, and advancing to the repeating step if the time of the process point is less than the minimum time limit.

11. The method of claim 6 wherein the filtering step includes the steps of selecting a process point from among the stored sampled signal values, the process point having two nearest neighbor sampled signal values, calculating an average value of the two nearest neighbor sampled signal values, forming an absolute difference between the average value and the process point, establishing a noise tolerance value, comparing the absolute difference to the noise tolerance value to determine whether noise is present either at the process point or at one of the two nearest neighbor sampled signal values, determining whether the noise is at the process point or at one of the two nearest neighbor sampled signal values if the absolute difference is greater than the noise tolerance value, forming a filtered signal value, and replacing the process point with the filtered signal value only if the noise is located at the process point.

12. The method of claim 1, further comprising the step of recursively filtering the stored envelope for smoothing the stored envelope before the step of calculating the coagulation characteristic.

13. The method of claim 1, further comprising the step of examining stored envelope values in reverse time order to determine a slope of the envelope at each of the stored envelope values, identifying all relative maxima in the stored envelope values, determining a range of stored envelope values corresponding to each relative maximum, and comparing the identified relative maxima to identify an absolute maximum in the stored envelope values.

14. The method of claim 13, wherein the step of calculating the coagulation characteristic comprises the step of calculating the coagulation characteristic from the stored signal values within the determined range of envelope values corresponding to the identified absolute maximum.

15. The method of claim 13, further comprising the steps of establishing a minimum amplitude value, comparing each identified relative maximum to the minimum amplitude value, and disregarding each identified relative maximum having a value less than the minimum amplitude value.

16. The method of claim 13, further comprising the steps of establishing a minimum slope value, comparing the slope of the envelope at each identified relative maximum to the minimum slope value, and disregarding each identified relative maximum at which the slope is less than the minimum slope value.

17. The method of claim 13 wherein the step of identifying all relative maxima in the stored envelope values includes the steps of monitoring the slope at each of the stored envelope values to detect a change in slope from a negative slope to a positive slope, thereby indicating that a relative maximum has occurred in the stored envelope values.

18. The method of claim 13, further comprising the steps of establishing minimum and maximum time limits, determining a time at which each identified relative maximum occurred, comparing the time of each identified relative maximum to the minimum and maximum time limits, and disregarding each identified relative maximum which occurred before the minimum time limit or after the maximum time limit.

19. The method of claim 1, further comprising the steps of establishing positive and negative limits, comparing the sampled signal values to the positive and negative limits, and generating an error signal upon detection of a sampled signal value greater than the positive limit or less than the negative limit.

20. A method for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control, the method comprising the steps of:

generating an output signal indicative of coagulation of the sample;

sampling the output signal at a sampling rate for a predetermined time interval to provide a plurality of sampled signal values;

storing the sampled signal values;

determining an envelope from the stored signal values;

storing the envelope; and

calculating the coagulation characteristic from the stored envelope by locating a maximum value of the stored envelope; and

identifying a stored value in the envelope which is a predetermined percentage less than said maximum value, said coagulation characteristic being related to the number of stored samples between the beginning of the sampling interval and the thus-identified stored value.

21. The method of claim 20 wherein the predetermined percentage is about 5%.

22. The method of claim 20, further comprising the step of converting the number of stored samples between the beginning of the sampling interval and the thus-identified signal value into clinical units corresponding to the coagulation characteristic.

23. The method of claim 20, further comprising the step of filtering the stored sampled signal values to provide filtered stored sampled signal values after the step of storing the sample signal values and before the determining step.

24. The method of claim 20, further comprising the step of filtering the stored envelope before the locating step.

25. The method of claim 20, further comprising the step of recursively filtering the stored envelope for smoothing the stored envelope before the locating step.

26. A method for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control, the method comprising the steps of:

generating an output signal indicative of coagulation of the sample;

sampling the output signal at a sampling rate for a predetermined time interval to provide a plurality of sampled signal values;

storing the sampled signal values;

rectifying the stored sampled signal values to provide a plurality of envelope values;

storing the envelope values;

examining the stored envelope values in reverse time order to determine a slope of the envelope at each of the stored envelope values;

identifying all relative maxima in the stored envelope values and determining a range of stored envelope values corresponding to each relative maximum;

comparing the identified relative maxima to locate an absolute maximum in the stored envelope values; and

calculating the coagulation characteristic from the stored envelope values within the determined range of envelope values corresponding to the absolute maximum.

27. The method of claim 26, wherein the step of calculating the coagulation characteristic includes the steps of locating an absolute maximum signal value within the absolute maximum range and identifying a stored signal value which is a predetermined percentage less than said absolute maximum signal value, said coagulation characteristic being related to the number of stored samples between the beginning of the sampling interval and the thus-identified stored signal value.

28. The method of claim 27 wherein the predetermined percentage is about 5%.

29. The method of claim 27, further comprising the step of converting the number of stored samples between the beginning of the sampling interval and the thus-identified stored signal value into clinical units corresponding to the coagulation characteristic.

30. The method of claim 26, further comprising the step of filtering the stored signal values to provide filtered stored signal values before the rectifying step.

31. The method of claim 26, further comprising the step of filtering the stored envelope values before the examining step.

32. The method of claim 26, further comprising the step of recursively filtering the stored envelope values for smoothing the stored envelope after the comparing step.

33. An apparatus for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control, the apparatus comprising means for generating an output signal indicative of coagulation of the sample, and means for sampling the output signal at a sampling rate for a predetermined time interval to provide a plurality of sampled signal values, for storing the sampled signal values, for determining an envelope from the stored signal values, for storing the envelope, and for calculating the coagulation characteristic from the stored envelope based on the maximum signal value.

34. The apparatus of claim 33, wherein the means for calculating the coagulation characteristic also examines the stored envelope to locate a maximum value of the stored envelope and identifies a stored value in the envelope which is a predetermined percentage less than said maximum value, said coagulation characteristic being related to the number of stored samples between the beginning of the sampling interval and the thus-identified stored value.

35. The apparatus of claim 34 wherein the predetermined percentage is about 5%.

36. The apparatus of claim 35 wherein the means for sampling the output signal further comprises means for converting the number of stored samples between the beginning of the sampling interval and the thus-identified stored value into clinical units corresponding to the coagulation characteristic.

37. The apparatus of claim 33 wherein the means for sampling the output signal further comprises means for filtering the stored sampled signal values to provide filtered stored sampled signal values.

38. The apparatus of claim 33 wherein the means for sampling the output signal further comprises means for filtering the stored envelope

39. The apparatus of claim 33 wherein the means for sampling the output signal further comprises means for recursively filtering the stored envelope.

40. The apparatus of claim 33 wherein the means for sampling the output signal further comprises means for examining stored envelope values in reverse time order to determine a slope of the envelope at each of the stored envelope values, for identifying all relative maxima in the stored envelope values, for determining a range of stored envelope values corresponding to each relative maximum, and for comparing the identified relative maxima to identify an absolute maximum in the stored envelope values.

41. An apparatus for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control, the apparatus comprising means for generating an output signal indicative of coagulation of the sample, means for sampling the output signal at a sampling rate for a predetermined time interval to provide a plurality of sampled signal values, for storing the sampled signal values, for determining an envelope from the stored signal values, for storing the envelope, for calculating the coagulation characteristic from the stored envelope by identifying a maximum value from the stored envelope and for identifying a stored envelope value which is a predetermined percentage less than said maximum value, said coagulation characteristic being related to the number of stored samples between the beginning of the sampling interval and the thus-identified stored envelope value.

42. The apparatus of claim 41 wherein the predetermined percentage is about 5%.

43. The apparatus of claim 41 wherein the means for sampling the output signal further comprises means for converting the number of stored samples between the beginning of the sampling interval and the thus-identified envelope signal value into clinical units corresponding to the coagulation characteristic.

44. The apparatus of claim 41 wherein the means for sampling the output signal further comprises means for filtering the stored sampled signal values to provide filtered stored sampled signal values.

45. The apparatus of claim 41 wherein the means for sampling the output signal further comprises means for filtering the stored envelope.

46. The apparatus of claim 41 wherein the means for sampling the output signal further comprises means for recursively filtering the stored envelope.

47. An apparatus for calculating a coagulation characteristic of a sample of blood, a blood fraction, or a control, the apparatus comprising means for generating an output signal indicative of coagulation of the sample, means for sampling the output signal at a sampling rate for a predetermined time interval to provide a plurality of sampled signal values, for storing the sampled signal values, for rectifying the stored sampled signal values to provide a plurality of envelope values, for storing the envelope values, for examining the stored envelope values in reverse time order to determine a slope of the envelope at each of the stored envelope values, for identifying all relative maxima in the stored envelope values, for determining a range of stored envelope values corresponding to each relative maximum, for comparing the identified relative maxima to each other to locate an absolute maximum in the stored envelope values, and for calculating the coagulation characteristic from the stored signal values within the determined range of envelope values corresponding to the absolute maximum.

48. The apparatus of claim 47 wherein the means for sampling the output signal further includes means for locating a maximum signal value within the absolute maximum range and for identifying a stored signal value which is a predetermined percentage less than said maximum signal value, said coagulation characteristic being related to the number of stored samples between the beginning of the sampling interval and the thus-identified stored signal value.

49. The apparatus of claim 48 wherein the predetermined percentage is about 5%.

50. The apparatus of claim 48 wherein the means for sampling the output signal further comprises means for converting the number of stored samples between the beginning of the sampling interval and the thus-identified stored signal value into clinical units corresponding to the coagulation characteristic.

51. The apparatus of claim 47 wherein the means for sampling the output signal further comprises means for filtering the stored signal values.

52. The apparatus of claim 47 wherein the means for sampling the output signal further comprises means for filtering the stored envelope values.

53. The apparatus of claim 47, wherein the means for sampling the output signal further comprises means for recursively filtering the stored envelope values.