US 12,716,902 B2 · Method for measuring titer of coagulation factor inhibitor

Abstract

A method for measuring a titer of a coagulation factor inhibitor. The-method includes: preparing a mixed specimen containing a-subject blood specimen and a normal blood specimen; heating the mixed specimen and acquiring a coagulation reaction-curve for the heated mixed specimen; acquiring a-coagulation reaction curve for the mixed specimen that has-not been heated; calculating a parameter related to the-coagulation reaction curve of the mixed specimen that has-not been heated as a first parameter; calculating a-parameter related to the coagulation reaction curve of the-heated mixed specimen as a second parameter; and-calculating a titer of a coagulation factor inhibitor in-the subject blood specimen on the basis of the ratio or the difference between the first parameter and the second-parameter.

A method for electronically measuring a titer of a coagulation factor inhibitor in a subject blood specimen using a processor, comprising:

obtaining, from a subject, the subject blood specimen;
preparing a mixed specimen containing the subject blood specimen and a reference blood specimen;
heating, with a heater, the mixed specimen and acquiring, with a first clotting time test, a first coagulation reaction curve for the heated mixed specimen;
preparing a second mixed specimen containing the subject blood specimen and the reference blood specimen;
acquiring, with a second clotting time test, a second coagulation reaction curve for the second mixed specimen, the second mixed specimen having not been subjected to the heating;
calculating, using the processor, a first parameter related to the second coagulation reaction curve of the second mixed specimen that has not been subjected to the heating;
calculating, using the processor, a second parameter related to the first coagulation reaction curve of the heated mixed specimen;
and
determining a measurement of the titer of the coagulation factor inhibitor in the subject blood specimen on a basis of a ratio or a difference between the first parameter and the second parameter, wherein
the first parameter related to the second coagulation reaction curve is at least one parameter selected from the group consisting of:
a parameter related to a primary differential curve of the second coagulation reaction curve, and a parameter related to a secondary differential curve of the second coagulation reaction curve,
the second parameter related to the first coagulation reaction curve is at least one parameter selected from the group consisting of:
a parameter related to a primary differential curve of the first coagulation reaction curve, and a parameter related to a secondary differential curve of the first coagulation reaction curve,
the first parameter and the second parameter are each a parameter related to a weighted average point in a predetermined area of the primary differential curve or the secondary differential curve, and wherein
the weighted average point is a weighted average point of the primary differential curve represented by coordinates (vT, vH) defined by a weighted average time vT and a weighted average height vH, wherein
when the primary differential curve is defined as F(t) (t represents time) and a time when F(t) is a predetermined value X is defined as t1, t2 (t1<t2), the vT and the vH are represented by the following formulas, respectively:
vT
=
M
∑
i
=
t
⁢
1
t
⁢
2
F
⁡
(
i
)
(
3
)
vH
=
M
∑
i
=
t
⁢
1
t
⁢
2
i
(
4
)
wherein
M
=
∑
i
=
t
⁢
1
t
⁢
2
⁢
(
i
×
F
⁡
(
i
)
)
,
(
2
)
the parameter related to the weighted average point includes one or more parameters selected from the group consisting of the vT, the vH, a peak width vB, a weighted average peak width vW, a flattening vAB, a time rate vTB, a flattening vAW, a time rate vTW, an average time vTa, an average height vHa, vTm, vABa, and vAWa,
wherein
the peak width vB is a length of time satisfying F(t)≥X from the t1 to t2,
the weighted average peak width vW is a length of time satisfying F(t)≥vH from the t1 to t2,
the vAB represents a ratio between the vH and the vB,
the vTB represents a ratio between the vT and the vB,
the vAW represents a ratio between the vH and the vW,
the vTW represents a ratio between the vT and the vW,
when F(t), t1 and t2 have the same definitions as described above, and a number of data points from F(t1) to F(t2) is defined as n, the vTa, the vHa, and the vTm are represented by the following formulas, respectively:
v
⁢
Ta
=
∑
i
=
t
⁢
1
t
⁢
2
i
n
(
5
)
v
⁢
Ha
=
∑
i
=
t
⁢
1
t
⁢
2
F
⁡
(
i
)
n
(
6
)
v
⁢
Tm
=
t
⁢
1
+
t
⁢
2
2
(
7
)
the vABa represents a ratio between the vHa and the vB, and
the vAWa represents a ratio between the vHa and the vW, or
the weighted average point is a weighted average point of a plus peak of the secondary differential curve represented by coordinates (pT, pH) defined by a weighted average time pT and a weighted average height pH, wherein
when the secondary differential curve is defined as F′(t) (t represents time) and a time when F′(t) is a predetermined value X is defined as t1, t2 (t1<t2), the pT and the pH are represented by the following formulas, respectively:
pT
=
M
∑
i
=
t
⁢
1
t
⁢
2
F
′
(
i
)
(
3
)
′
p
⁢
H
=
M
∑
i
=
t
⁢
1
t
⁢
2
i
(
4
)
′
wherein
M
=
∑
i
=
t
⁢
1
t
⁢
2
⁢
(
i
×
F
′
(
i
)
)
,
(
2
)
′
the parameter related to the weighted average point includes one or more parameters selected from the group consisting of the pT, the pH, a peak width pB, a weighted average peak width pW, a flattening pAB, a time rate pTB, a flattening pAW, and a time rate pTW,
wherein
the peak width pB is a length of time satisfying F′(t)≥X from the t1 to t2,
the weighted average peak width pW is a length of time satisfying F′(t)≥pH from the t1 to t2,
the pAB represents a ratio between the pH and the pB,
the pTB represents a ratio between the pT and the pB,
the pAW represents a ratio between the pH and the pW, and
the pTW represents a ratio between the pT and the pW, or
the weighted average point is a weighted average point of a minus peak of the secondary differential curve represented by coordinates (mT, mH) defined by a weighted average time mT and a weighted average height mH, wherein
when the secondary differential curve is defined as F′(t) (t represents time) and a time when F′(t) is a predetermined value X is defined as t1, t2 (t1<t2), the mT and the mH are represented by the following formulas, respectively:
m
⁢
T
=
M
∑
i
=
t
⁢
1
t
⁢
2
F
′
(
i
)
(
3
)
″
m
⁢
H
=
M
∑
i
=
t
⁢
1
t
⁢
2
i
(
4
)
″
wherein
M
=
∑
i
=
t
⁢
1
t
⁢
2
⁢
(
i
×
F
′
(
i
)
)
,
(
2
)
′
the parameter related to the weighted average point includes one or more parameters selected from the group consisting of the mT, the mH, a peak width mB, a weighted average peak width mW, a flattening mAB, a time rate mTB, a flattening mAW, and a time rate mTW,
wherein
the peak width mB is a length of time satisfying F′(t)≤X from the t1 to t2, the weighted average peak width mW is a length of time satisfying F′(t)≤mH from the t1 to t2,
the mAB represents a ratio between the mH and the mB,
the mTB represents a ratio between the mT and the mB,
the mAW represents a ratio between the mH and the mW, and
the mTW represents a ratio between the mT and the mW.

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Method for measuring titer of coagulation factor inhibitor

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Method for measuring titer of coagulation factor inhibitor

Life of this patent

Abstract

Claims8