Method and apparatus for predicting the presence of haemostatic dysfunction in a patient sample

• US 20040248308A1
• Filed: 07/02/2004
• Published: 12/09/2004
• Est. Priority Date: 02/04/1999
• Status: Active Grant

• Current Assignee: Biomerieux Incorporated (Compagnie Merieux Alliance SAS)
• Original Assignee: Biomerieux Incorporated (Compagnie Merieux Alliance SAS)
• Inventors: Fischer, Timothy J., Downey, Colin, Toh, Cheng Hock
• Granted Patent: US 7,211,438 B2
• Time in Patent Office: Days
• US Class Current: 436/69
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

Methods for predicting the presence of haemostatic dysfunction in a patient from a time-dependent measurement profile include performing a time-dependent measurement on an unknown sample and measuring a respective property over time so as to derive a time-dependent measurement profile. The slope of the time-dependent measurement profile is computed prior to clot formation. A biphasic waveform is detected in the time-dependent measurement profile based on the computed slope. The presence of haemostatic dysfunction in the patient is predicted based on the detected biphasic waveform.

Claims

1. A method for predicting the presence of disseminated intravascular coagulation in a patient from a time-dependent measurement profile, comprising:

a) performing a time-dependent measurement on an unknown sample and measuring a respective property over time so as to derive a time-dependent measurement profile;

b) computing the slope of the time-dependent measurement profile prior to clot formation;

c) detecting a biphasic waveform in the time-dependent measurement profile based on the computed slope; and

d) predicting the presence of disseminated intravascular coagulation in the patient based on the detected biphasic waveform.

2. A method for predicting the presence of haemostatic dysfunction in a patient from at least one time-dependent measurement profile, comprising:

performing at least one time-dependent measurement on an unknown sample and measuring a respective property over time so as to derive a time-dependent measurement profile;

computing the slope of the time-dependent measurement profile prior to clot formation;

detecting a biphasic waveform in the time-dependent measurement profile based on the computed slope; and

predicting the presence of haemostatic dysfunction in the patient based on the biphasic waveform.

3. The method of claim 2 wherein the time-dependent measurement profile is at least one optical profile.

4. The method of claim 3 wherein the at least one optical profile is provided by an automated analyzer for thrombosis and wherein detecting a biphasic waveform comprises automatically detecting the biphasic waveform.

5. The method of claim 4 wherein the time-dependent measurement profile is of optical transmission through the unknown sample during an activated partial thromboplastin time (APTT) assay and wherein automatically detecting the biphasic waveform comprises automatically detecting the biphasic waveform when the slope is less than about −

0.0003.

6. The method of claim 4 wherein the time-dependent measurement profile is of optical transmission through the unknown sample during an activated partial thromboplastin time (APTT) assay and wherein automatically detecting the biphasic waveform comprises automatically detecting the biphasic waveform when the slope is less than about −

0.0005.

7. The method of claim 4 further comprising automatically generating a flag on an output device of the automated analyzer responsive to detecting a biphasic waveform and wherein predicting the presence of haemostatic dysfunction comprises predicting the presence of haemostatic dysfunction in the patient based on the flag.

8. The method of claim 4 wherein a plurality of optical measurements at one or more wavelengths are taken over time so as to derive the at least one optical profile, the plurality of optical measurements corresponding to changes in light transmission through the unknown sample.

9. The method of claim 8 wherein the optical measurements are normalized.

10. The method of claim 4 wherein the at least one optical profile is provided automatically by said automated analyzer based on optical transmission through the unknown sample, wherein the unknown sample is automatically removed by an automated probe from a sample container to a test well, one or more reagents are automatically added to the test well so as to initiate changes in the respective property within the unknown sample, and the development of the respective property over time is automatically optically monitored so as to derive the at least one optical profile.

11. The method of claim 2 wherein the time-dependent measurement profile is of optical transmission through the unknown sample during an activated partial thromboplastin time (APTT) assay.

12. The method of claim 2 wherein said time-dependent measurement profile is an optical transmission through the unknown sample during a prothrombin time (PT) assay.

13. The method of claim 12 wherein the prothrombin time (PT) assay includes adding to the unknown sample a PT reagent selected from the group consisting of Recombiplast™

and Thromborel™

.

14. The method of claim 2 wherein the slope of the time-dependent measurement profile is taken from an end of blank time up to immediately before the initiation of clot formation or a predetermined time period.

15. The method of claim 2 wherein the prediction of the presence of haemostatic dysfunction includes flagging the presence of the haemostatic dysfunction and wherein predicting the presence of the haemostatic dysfunction comprises predicting the presence of the haemostatic dysfunction based on the flagging.

16. The method of claim 2 wherein the predicted haemostatic dysfunction is due to one or more of infection, trauma, major surgery, malignancy, hepatic disease, pregnancy and/or child birth, hypoxia, acidosis, lithium overdose, and graft rejection.

17. The method of claim 16 wherein performing at least one time-dependent measurement, computing the slope and detecting a biphasic waveform are performed on an automated or semi-automated analyzer and wherein predicting the presence of haemostatic dysfunction further comprises flagging the presence or likelihood of the haemostatic dysfunction and wherein said flagging is an alert to at least one of an individual operating said automated or semi-automated analyzer or an individual reading or evaluating the results of a test run on said automated or semi-automated analyzer, that there is a possibility and/or probability of haemostatic dysfunction of a patient whose test sample has been run on the automated or semi-automated analyzer and flagged.

18. The method of claim 17 wherein a slope of less than about −

0.0003 causes flagging of the unknown sample and wherein an increase in steepness of the slope from test to test corresponds to disease progression.

19. The method of claim 2 wherein the unknown sample comprises whole blood or a portion thereof.

20. The method of claim 2 wherein the unknown sample comprises a plasma sample.

21. A method for predicting the presence of haemostatic dysfunction in a patient utilizing an automated or semi-automated optical analyzer comprising:

conducting a prothrombin time (PT) clot time assay on an unknown patient sample to provide a time-dependent optical measurement profile;

detecting a biphasic waveform in the time-dependent optical measurement profile; and

predicting the presence of haemostatic dysfunction in the patient based on the biphasic waveform.

22. The method of claim 21 further comprising computing a slope of the time-dependent measurement profile prior to clot formation and wherein detecting a biphasic waveform comprises detecting the biphasic waveform based on the computed slope.

23. The method of claim 22 further comprising automatically generating a flag on an output device of the analyzer responsive to detecting a biphasic waveform and wherein predicting the presence of haemostatic dysfunction comprises predicting the presence of haemostatic dysfunction in the patient based on the flag.

24. The method of claim 23 wherein the output device comprises at least one of a monitor or a printer.

25. The method of claim 22 wherein the haemostatic dysfunction comprises disseminated intravascular coagulation.

26. The method of claim 21 wherein conducting a prothrombin time (PT) clot time assay on an unknown patient sample to provide a time-dependent optical measurement profile includes adding to the unknown sample a PT reagent selected from the group consisting of RECOMBIPLAST™

and THROMBOREL™

.

41. The analyzer of claim 22 further comprising means for alerting an operator of the possible presence of haemostatic dysfunction in the patient responsive to detecting a biphasic waveform.

42. The analyzer of claim 41 wherein the means for alerting comprises at least one of a monitor or a printer.

27. A method for predicting the presence of disseminated intravascular coagulation in a patient utilizing an automated or semi-automated analyzer comprising:

a) conducting an activated partial thromboplastin time (APTT) clot time assay on an unknown patient sample utilizing said analyzer;

b) profiling said APTT clot time assay results utilizing an optical time dependent measurement profile;

c) causing said analyzer to distinguish between a normal sigmoidal appearance from a normal APTT clot time assay profile and an abnormal biphasic waveform associated with an abnormal APTT clot time assay profile associated with disseminated intravascular coagulation to produce a flag on a monitor or print out of the analyzer; and

d) utilizing the flag to predict the presence of disseminated intravascular coagulation by alerting an operator of the analyzer.

28. The method of claim 27 wherein the flag is produced on the monitor.

29. The method of claim 27 wherein the flag is produced on the print out of the analyzer.

30. A method for predicting the presence of disseminated intravascular coagulation in a patient utilizing an automated or semi-automated analyzer comprising:

a) conducting an prothrombin time (PT) clot time assay on an unknown patient sample utilizing said analyzer;

b) profiling the PT clot time assay results utilizing an optical time dependent measurement profile;

c) causing the analyzer to distinguish between a normal sigmoidal appearance from a normal PT clot time assay profile and an abnormal biphasic waveform associated with an abnormal PT clot time assay profile associated with disseminated intravascular coagulation to produce a flag on a monitor or print out of the analyzer; and

d) utilizing the flag to predict the presence of disseminated intravascular coagulation.

31. The method of claim 30 wherein the PT assay is performed utilizing a reagent comprising thromboplastin.

32. An automated analyzer for predicting the presence of haemostatic dysfunction in a patient from at least one time-dependent measurement profile, comprising:

means for performing at least one time-dependent measurement on an unknown sample and measuring a respective property over time so as to derive a time-dependent measurement profile;

means for computing the slope of the time-dependent measurement profile prior to clot formation;

means for detecting a biphasic waveform in the time-dependent measurement profile based on the computed slope; and

means for alerting an operator that a haemostatic dysfunction may be present in the patient responsive to detection of a biphasic waveform.

33. The analyzer of claim 32 wherein the means for performing at least one time-dependent measurement comprises a means for measuring optical transmission through the unknown sample during an activated partial thromboplastin time (APTT) assay and wherein the means for detecting the biphasic waveform comprises means for detecting the biphasic waveform when the slope is less than about −

0.0003.

34. The analyzer of claim 32 wherein the means for performing at least one time-dependent measurement comprises a means for measuring optical transmission through the unknown sample during an activated partial thromboplastin time (APTT) assay and wherein the means for detecting the biphasic waveform comprises means for detecting the biphasic waveform when the slope is less than about −

0.0005.

35. The analyzer of claim 32 wherein the means for performing at least one time-dependent measurement comprises a means for measuring optical transmission through the unknown sample including:

means for automatically removing the unknown sample by an automated probe from a sample container to a test well;

means for automatically adding one or more reagents to the test well so as to initiate changes in the respective property within the unknown sample; and

means for automatically optically monitoring the development of the respective property over time so as to derive at least one optical profile.

36. The analyzer of claim 32 wherein the means for computing the slope comprises means for computing the slope of the time-dependent measurement profile from an end of blank time up to immediately before the initiation of clot formation or a predetermined time period.

37. The analyzer of claim 32 wherein the means for alerting comprises at least one of a monitor or a printer.

38. The analyzer of claim 32 wherein the haemostatic dysfunction comprises disseminated intravascular coagulation.

39. An automated analyzer for predicting the presence of haemostatic dysfunction in a patient comprising:

means for conducting a prothrombin time (PT) clot time assay on an unknown patient sample to provide a time-dependent optical measurement profile;

means for detecting a biphasic waveform in the time-dependent optical measurement profile; and

means for predicting the presence of haemostatic dysfunction in the patient based on the biphasic waveform.

40. The analyzer of claim 39 further comprising means for computing a slope of the time-dependent measurement profile prior to clot formation and wherein the means for detecting a biphasic waveform comprises means for detecting the biphasic waveform based on the computed slope.

43. The analyzer of claim 39 wherein the haemostatic dysfunction comprises disseminated intravascular coagulation.

44. The analyzer of claim 39 wherein the means for conducting a prothrombin time (PT) clot time assay on an unknown patient sample to provide a time-dependent optical measurement profile includes means for adding to the sample a PT reagent selected from the group consisting of RECOMBIPLAST™

and THROMBOREL™

.