Identification of novel disease states using viscoelastic analysis in the presence of a thrombolytic agent

Patent metadata

Field	Value
Publication number	US-11137409-B2
Application number	US-201515524095-A
Country	US
Kind code	B2
Filing date	Nov 5, 2015
Priority date	Nov 6, 2014
Publication date	Oct 5, 2021
Grant date	Oct 5, 2021

Abstract

In some embodiments, the invention provides methods for detecting an aberrant fibrinolysis condition in a patient. The method includes subjecting a blood sample from the patient to a viscoelastic analysis in the presence of a known amount of a thrombolytic agent, to obtain a coagulation characteristic value of the patient; and comparing the coagulation characteristic value of the patient to a coagulation characteristic value of a healthy individual, the coagulation characteristic value of the healthy individual obtained by subjecting a blood sample from a healthy individual to the viscoelastic analysis in the presence of the known amount of the thrombolytic agent, wherein a difference in the coagulation characteristic value of the patient as compared to the coagulation characteristic value of the healthy individual identifies the patent as having aberrant fibrinolysis. In some embodiments, the invention also provides a container adapted for detecting an aberrant fibrinolysis condition in a blood sample using viscoelastic analysis comprising an interior having a coating comprising a thrombolytic agent.

First claim

What is claimed is:

1. A method for detecting latent hyperfibrinolysis or fibrinolysis shutdown in a patient, the method comprising
a) subjecting a first whole blood sample from the patient to a viscoelastic assay in the presence of a low amount of between about 1 ng/ml to about 100 ng/ml of a thrombolytic agent to obtain a low coagulation characteristic value of the patient, wherein the viscoelastic assay measures mechanical strength of a blood clot in the first whole blood sample over time, wherein the viscoelastic assay is selected from the group consisting of a thromboelastographic (TEG) assay and a thromboelastometry (TEM) assay, wherein the low coagulation characteristic value is selected from the group consisting of an LY30 value or a derivative thereof and an LI30 value or a derivative thereof, and wherein the thrombolytic agent is human single chain tissue plasminogen activator (tPA), human double chain tPA, tPA from a non-human mammalian species, alteplase, reteplase, tenecteplase, anistreplase, serokinase, streptokinase, urokinase, or kallikrein;
b) subjecting a second whole blood sample from the patient to a viscoelastic assay in the presence of a high amount of between about 110 ng/ml to about 1200 ng/ml of the thrombolytic agent to obtain a high coagulation characteristic value of the patient, wherein the viscoelastic assay measures mechanical strength of a blood clot in the first whole blood sample over time, wherein the viscoelastic assay is selected from the group consisting of a TEG assay and a TEM assay, wherein the high coagulation characteristic value is selected from the group consisting of an LY30 value or a derivative thereof and an LI30 value or a derivative thereof;
c) comparing the low coagulation characteristic value of the patient to a low coagulation characteristic value of a healthy individual or an averaged low coagulation characteristic value of a group of healthy individuals, the low coagulation characteristic value of the healthy individual obtained by subjecting a blood sample from a healthy individual to the viscoelastic assay in the presence of the low amount of the thrombolytic agent and the averaged low coagulation characteristic value of the group of healthy individuals obtained by subjecting blood samples from healthy individuals to the viscoelastic assay in the presence of the low amount of the thrombolytic agent, and
d) comparing the high coagulation characteristic value of the patient to a high coagulation characteristic value of a healthy individual or an averaged high coagulation characteristic value of a group of healthy individuals, the high coagulation characteristic value of the healthy individual obtained by subjecting a blood sample from a healthy individual to the viscoelastic assay in the presence of the high amount of the thrombolytic agent and the averaged high coagulation characteristic value of the group of healthy individuals obtained by subjecting blood samples from healthy individuals to the viscoelastic assay in the presence of the high amount of the thrombolytic agent, and

wherein an increase in the low coagulation characteristic value of the patient as compared to the low coagulation characteristic value of the healthy individual or to the averaged low coagulation characteristic value of the group of healthy individuals identifies the patent as having latent hyperfibrinolysis and wherein a decrease in the high coagulation characteristic value of the patient as compared to the high coagulation characteristic value of the healthy individual or to the averaged high coagulation characteristic value of the group of healthy individuals identifies the patent as having fibrinolysis shutdown.

2. The method of claim 1 , wherein the thrombolytic agent is human single chain tissue plasminogen activator (tPA).

3. The method of claim 1 , wherein the thrombolytic agent is human single chain tissue plasminogen activator (tPA) and the low amount is about 75 ng/ml.

4. The method of claim 1 , wherein the thrombolytic agent is human single chain tissue plasminogen activator (tPA) and the high amount is about 150 ng/ml.

5. The method of claim 1 , wherein the viscoelastic assay is performed using a container containing the thrombolytic agent on an interior of the container.

6. The method of claim 5 , wherein the assay is performed using the container and a pin, wherein the pin moves relative to the container or wherein the container moves relative to the pin.

7. The method of claim 1 , wherein the coagulation characteristic value is a LY30 value.

8. The method of claim 1 , wherein the patient is a human or a non-human animal.

9. The method of claim 1 , wherein the patient has or is undergoing a condition selected from the group consisting of surgery, a disease condition, a critical illness, trauma, bleeding, and a thromboembolic event.

10. The method of claim 1 , wherein the patient identified as having hyperfibrinolysis is administered a therapeutically relevant amount of a therapeutic agent that strengthens a blood clot or slows the dissolution of a blood clot.

11. The method of claim 10 , wherein the therapeutic agent that strengthens a blood clot or slows the dissolution of a blood clot is selected from the group consisting of an antifibrinolytic agent, whole blood, blood plasma, cryoprecipitate, factor XIII, fibrinogen and other specific clotting factor concentrates.

12. The method of claim 1 , wherein the patient identified as having fibrinolysis shutdown is administered a therapeutically relevant amount of a therapeutic agent that weakens a blood clot or speeds the dissolution of a blood clot.

13. The method of claim 12 , wherein the therapeutic agent that weakens a blood clot or speeds the dissolution of a blood clot is selected from the group consisting of aspirin, heparin, clopidogrel, warfarin, a direct thrombin inhibitor, a Factor Xa inhibitor, tPA, an anticoagulant, a thrombolytic agent, an antifibrinogen agent, an anti-Factor XIII agent, a glycoprotein IIb/IIIa inhibitor, and an antiplatelet agent.

14. The method of claim 11 , wherein the antifibrinolytic agent is selected from the group consisting of tranexamic acid, aminocaproic acid and aprotinin.

15. The method of claim 1 , wherein the coagulation characteristic value is a LI30 value.

Assignees

• Univ Colorado Regents

Inventors

• Chapman Michael P
• Moore Hunter B
• Barreda Eduardo Gonzalez
• Moore Ernest E

Classifications

• G01N2800/226

  Thrombotic disorders, i.e. thrombo-embolism irrespective of location/organ involved, e.g. renal vein thrombosis, venous thrombosis · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• G01N33/86 Primary

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

• A61K38/36

  Blood coagulation or fibrinolysis factors · CPC title

• C12Q1/56

  involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen · CPC title