Blood factor monitoring assay and uses thereof
First Claim
Patent Images
1. A method of treating a bleeding disorder in a patient in need thereof comprising:
- a) measuring the time between contacting of a sample obtained from the patient with an activation mixture dried on a solid substrate and the onset of clotting, thereby calculating the clotting time (Ct),wherein the activation mixture comprises (i) an activated Factor IX (FIXa) and (ii) a phospholipid mixture,wherein the Ct is used to determine a pharmacokinetic (PK) parameter of a coagulation factor, wherein the coagulation factor comprises a Factor VIII (FVIII),wherein the PK parameter is a terminal half-life (HL) or a time to trough (T),wherein the HL is calculated according to the following formula;
HL=−
0.693×
(T2−
T1)×
A/(Ct1−
Ct2),wherein A is a constant value corresponding to the slope of a Ct versus coagulation factor concentration dose-response, T1 and T2 are times at which Ct is measured, and Ct1 and Ct2 are Ct values measured at T1 and T2, respectively,wherein the T is calculated according to the following formula;
T=−
1.44×
HL/(A×
(Ctmeasured−
Cttrough),wherein A is a constant value corresponding to the slope of a Ct versus coagulation factor concentration dose-response, and HL is the terminal half-life, Ctmeasured is Ct measured at certain time point, and Cttrough is patient-specific clot time at trough, andb) administering an effective amount of the coagulation factor at a dosing interval based on the PK parameter.
3 Assignments
0 Petitions
Accused Products
Abstract
The present disclosure provides methods and compositions for diagnosing and treating subject having a bleeding disorder. The disclosed methods comprise contacting a sample, e.g., a blood or plasma sample obtained from the patient, with an activation mixture comprising an activated coagulation factor and a phospholipid mixture, wherein the activation mixture is dried onto a solid substrate. Also provided is a global hemostasis test based on the integration of clotting time (Ct) and pharmacokinetics data. The methods and compositions presented can be applied to point-of-care diagnostic systems.
-
Citations
22 Claims
-
1. A method of treating a bleeding disorder in a patient in need thereof comprising:
-
a) measuring the time between contacting of a sample obtained from the patient with an activation mixture dried on a solid substrate and the onset of clotting, thereby calculating the clotting time (Ct), wherein the activation mixture comprises (i) an activated Factor IX (FIXa) and (ii) a phospholipid mixture, wherein the Ct is used to determine a pharmacokinetic (PK) parameter of a coagulation factor, wherein the coagulation factor comprises a Factor VIII (FVIII), wherein the PK parameter is a terminal half-life (HL) or a time to trough (T), wherein the HL is calculated according to the following formula;
HL=−
0.693×
(T2−
T1)×
A/(Ct1−
Ct2),wherein A is a constant value corresponding to the slope of a Ct versus coagulation factor concentration dose-response, T1 and T2 are times at which Ct is measured, and Ct1 and Ct2 are Ct values measured at T1 and T2, respectively, wherein the T is calculated according to the following formula;
T=−
1.44×
HL/(A×
(Ctmeasured−
Cttrough),wherein A is a constant value corresponding to the slope of a Ct versus coagulation factor concentration dose-response, and HL is the terminal half-life, Ctmeasured is Ct measured at certain time point, and Cttrough is patient-specific clot time at trough, and b) administering an effective amount of the coagulation factor at a dosing interval based on the PK parameter. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 13)
-
-
2. A method of treating a bleeding disorder in a patient in need thereof comprising:
-
a) measuring the time between contacting of a sample obtained from the patient with an activation mixture dried on a solid substrate and the onset of clotting, thereby calculating the clotting time (Ct), wherein the activation mixture comprises (i) an activated Factor XI (FXIa) and (ii) a phospholipid mixture, wherein the Ct is used to determine a pharmacokinetic (PK) parameter of a coagulation factor, wherein the coagulation factor comprises a Factor IX (FIX), wherein the PK parameter is a terminal half-life (HL) or a time to trough (T), wherein the HL is calculated according to the following formula;
HL=−
0.693×
(T2−
T1)×
A/(Ct1−
Ct2),wherein, for each coagulation factor, A is a constant value corresponding to the slope of a Ct versus coagulation factor concentration dose-response, T1 and T2 are times at which Ct is measured, and Ct1 and Ct2 are Ct values measured at T1 and T2, respectively, wherein the T is calculated according to the following formula;
T=−
1.44×
HL/(A×
(Ctmeasured−
Cttrough),wherein for each coagulation factor, A is a constant value corresponding to the slope of a Ct versus coagulation factor concentration dose-response, and HL is the terminal half-life, Ctmeasured is Ct measured at certain time point, and Cttrough is patient-specific clot time at trough, and b) administering an effective amount of the coagulation factor at a dosing interval based on the PK parameter. - View Dependent Claims (12, 14, 15, 16, 17, 18, 19, 20, 21, 22)
-
Specification