COMPOSITION FOR THE DETERMINATION OF COAGULATION CHARACTERISTICS OF A TEST LIQUID
The present invention is directed to a diagnostic composition for use in the viscoelastic analysis of a test liquid, and to a container ( 1 ) comprising same. The composition comprises at least an activator of coagulation, and at least one further constituent selected from CaCl2 and from one or more inhibitors and/or coagulation components, wherein the composition is present in essentially dry form of all constituents and in an amount sufficient for performing one single viscoelastic analysis of a specified blood or plasma sample and wherein the constituents are not present in a substance mixture, but in a spatially separated form. The present invention is further directed to a method of performing a viscoelastic analysis on a test liquid, and to the use of the diagnostic composition in such a method.
1 . A diagnostic composition for use in the viscoelastic analysis of a test liquid, comprising at least two of the following constituents:
a) one activator of coagulation; and
b) a calcium salt in an amount sufficient to ensure recalcification of the test liquid; or
c) one inhibitors or other coagulation components or factors;
characterized in that
the constituents are present in an essentially dry,
and wherein the constituents are not present in a substance mixture, but in a spatially separated form.
2 . The composition according to claim 1 , where the spatial separation of the constituents is realized by incorporating each constituent into a separate carrier material.
3 . The composition according to claim 2 , where the carrier material comprises at least a carbohydrate.
4 . The composition according to claim 3 , where the carrier material shows no significant influence on the clotting behaviour, the clot formation behaviour, or the clot lysis behaviour.
5 . The diagnostic composition of claim 1 , wherein the activator of coagulation is an intrinsic or extrinsic activator.
6 . The diagnostic composition of claim 5 , wherein the extrinsic activator of coagulation is the Tissue Factor (TF).
7 . The diagnostic composition of claim 6 , wherein the Tissue Factor is lipidated TF or rTF.
8 . The diagnostic composition of claim 5 , wherein the intrinsic activator of coagulation is celite, ellagic acid, sulfatit, kaolin, silica, or RNA.
9 . The diagnostic composition of claim 1 , wherein the inhibitor is a platelet inhibitor, fibrinolysis inhibitor, or heparin inhibitor.
10 . The diagnostic composition of claim 9 , wherein platelet inhibitor is a cytoskeleton inhibitor or a GPIIb/IIIa antagonist.
11 . The diagnostic composition of claim 9 , wherein the fibrinolysis inhibitor is aprotinine, tranexamic acid, or eaca.
12 . The diagnostic composition of claim 9 , wherein the heparin inhibitor is selected from heparinase, protamine or protamine-related peptides.
13 . The diagnostic composition of claim 1 , wherein the coagulation factor is a coagulation factor or activated coagulation factor.
14 . (canceled)
15 . The diagnostic composition of claim 1 , wherein the dry form is a lyophilized form.
16 . The diagnostic composition of claim 1 , which further comprises a stabilizer.
17 . The diagnostic composition of claim 16 , wherein the stabilizer is albumin or gelatine.
18 . A container, comprising the diagnostic composition of claim 1 , having an inner portion shaped in a manner that it can be attached to a device for performing viscoelastic measurements.
19 . (canceled)
20 . (canceled)
21 . (canceled)
22 . (canceled)
23 . A method of performing a viscoelastic analysis on a test liquid, comprising the steps of:
a) adding the test liquid into a container comprising the diagnostic composition of claim 1 , thereby dissolving the diagnostic composition contained therein in the test liquid to form a mixture;
b) optionally transferring the mixture of said test liquid and said diagnostic composition into an apparatus suitable for performing a viscolelastic analysis;
or
putting the container into an apparatus suitable for performing a viscolelastic analysis; and
c) performing the viscoelastic analysis of said mixture.
24 . The method of claim 23 , wherein the test liquid is a blood sample.
25 . The method of claim 23 , wherein the blood sample is whole blood or blood plasma.
26 . The method of claim 23 , wherein step c) takes about 1-60 sec., preferably about 2-10 sec., more preferably about 5 sec.
27 . The method of claim 23 , wherein the mixture is transferred in step b) by manually or automatically pipetting the mixture from the container and by transferring it thereby to the apparatus.
28 . The method of claim 23 , wherein the mixture is transferred to a measuring cup of the apparatus.
29 . The method of claim 23 , wherein the apparatus is a thromboelastometer or a thrombelastograph.
30 . The method of claim 23 , wherein the analysis comprises the determination of the clotting time, the clot formation time, the firmness of the clot over time and/or fibrinolysis.
31 . (canceled)
32 . (canceled)
33 . The diagnostic composition according to claim 1 , wherein the calcium salt is CaCl 2 .
34 . The diagnostic composition of claim 33 , wherein CaCl 2 is present in an amount of about 1-100 μmol/ml of the test liquid.
35 . The composition of claim 3 , where the carrier material comprises saccharose or cellulose.
36 . The diagnostic composition of claim 1 , wherein the coagulation factor is FXa or FVa or activated protein C or FVIIa.
37 . The method of claim 23 , wherein the test liquid is a mammalian blood sample.
38 . The method of claim 23 , wherein the test liquid is a human blood sample.