Coagulation testing in underfilled patient samples

Patent metadata

Field	Value
Publication number	US-10976305-B2
Application number	US-201815965343-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	Apr 27, 2017
Publication date	Apr 13, 2021
Grant date	Apr 13, 2021

Abstract

Provided herein are methods for generating an estimated coagulation test result from an underfilled sample tube.

First claim

The invention claimed is:

1. A method for calculating an estimated coagulation test value for an underfilled blood sample with an actual volume that is less than a target volume, comprising:
(a) determining a percent fill of the sample, wherein the percent fill is equal to the actual volume divided by the target volume;
(b) correcting the actual volume to produce a corrected sample with a volume equal to the target volume;
(c) performing a coagulation test to obtain a determined coagulation test value;
(d) applying a percent-fill-dependent correction factor to the determined coagulation test value to generate the estimated coagulation test value.

2. The method of claim 1 , wherein the percent fill is less than 90%.

3. The method of claim 2 , wherein the percent fill is 50% to 90%.

4. The method of claim 1 , wherein correcting the sample volume comprises adding aqueous buffer or other diluent to the sample.

5. The method of claim 4 , wherein correcting the sample volume comprises adding imidazole buffered saline to the sample.

6. The method of claim 5 , wherein the imidazole buffered saline comprises about 0.34 g imidazole and about 0.585 g of NaCl per 100 mL of distilled water and is at about pH 7.3.

7. The method of claim 1 , wherein correcting the sample volume comprises bringing to volume of the sample to 90-110% fill.

8. The method of claim 7 , wherein correcting the sample volume comprises bringing to volume of the sample to 99-101% fill.

9. The method of claim 8 , wherein correcting the sample volume comprises bringing to volume of the sample to 100% fill.

10. The method of claim 1 , wherein performing the coagulation test comprises determining one or more of prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen level, and international normalized ratio (INR).

11. The method of claim 1 , wherein the determined coagulation test value is the result obtained by performing the coagulation test as if the corrected sample were a properly filled sample.

12. The method of claim 1 , wherein the percent-fill-dependent correction factor is a multiplier/divider that is selected based on the percent fill of the original sample and generates an estimated coagulation test value that is an estimate of the coagulation test value that would have been obtained for a properly filled sample.

13. The method of claim 12 , wherein the percent-fill-dependent correction factor for any particular percent fill is derived from a population average of coagulation test values at the particular percent fill normalized to coagulation test values or properly-filled samples.

14. The method of claim 13 , wherein the percent-fill-dependent correction factor is skewed to reduce the likelihood that a subject at risk of excessive or prolonged bleeding will be determined to be a normal coagulator.

15. The method of claim 13 , wherein the percent-fill-dependent correction factor is multiplied by the determined coagulation test value to generate the estimated coagulation test value.

16. The method of claim 13 , wherein the determined coagulation test value is divided by the percent-fill-dependent correction factor to generate the estimated coagulation test value.

17. The method of claim 16 , wherein the prothombin time percent-fill-dependent correction factor is:
(i) about 1.42 for a 50% full sample tube;
(ii) about 1.25 for a 60% full sample tube;
(iii) about 1.15 for a 70% full sample tube;
(iv) about 1.08 for a 80% full sample tube; and/or
(v) about 1.02 for a 90% full sample tube.

18. The method of claim 16 , wherein the activated partial thromboplastin time percent-fill-dependent correction factor is:
(i) about 1.58 for a 50% full sample tube;
(ii) about 1.35 for a 60% full sample tube;
(iii) about 1.20 for a 70% full sample tube;
(iv) about 1.10 for a 80% full sample tube; and/or
(v) about 1.03 for a 90% full sample tube.

19. The method of claim 16 , wherein the fibrinogen level percent-fill-dependent correction factor is:
(i) about 0.41 for a 50% full sample tube;
(ii) about 0.50 for a 60% full sample tube;
(iii) about 0.66 for a 70% full sample tube;
(iv) about 0.72 for a 80% full sample tube; and/or
(v) about 0.84 for a 90% full sample tube.

20. The method of claim 1 , wherein the blood sample is obtained from a human subject.

21. The method of claim 20 , wherein the human subject is a candidate for treatment with an anticoagulant agent.

22. The method of claim 21 , wherein the anticoagulant agent is selected from heparin, low molecular weight heparin, warfarin, an inhibitor of factor Xa, a directly acting oral anticoagulants, and a direct thrombin inhibitor.

23. The method of claim 19 , wherein the human subject presents with acute stroke symptoms.

Assignees

• Univ Chicago

Inventors

• Miller Jonathan
• Cloe Adam
• Mikrut Krzysztof

Classifications

• G01N33/86

  involving blood coagulating time {or factors, or their receptors} · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N33/96

  involving blood or serum control standard · CPC title

• G01N33/4905 Primary

  Determining clotting time of blood (by chemical methods G01N33/86, C12Q1/56) · CPC title