Detection of a blood coagulation activity marker in a body fluid sample

• US 20020132370A1
• Filed: 02/23/2001
• Published: 09/19/2002
• Est. Priority Date: 02/23/2000
• Status: Abandoned Application

• Current Assignee: Besst-Test APS
• Original Assignee: Besst-Test APS
• Inventors: Borris, Lars C., Lassen, Michael Rud
• Application Number:
  US09/791,384
• Publication Number:
  US 20020132370A1
• Time in Patent Office: Days
• US Class Current: 436/512
• CPC Class Codes: C07K 16/36 against blood coagulation factors
• CPC Class Codes: C12Q 1/56 involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• CPC Class Codes: G01N 2800/224 Haemostasis or coagulation
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors

Abstract

The invention relates to a method for detecting in a body fluid sample at least one blood coagulation activity marker that reflects e blood coagulation activity of an individual. By correlating the amount or concentration of the blood coagulation activity marker present e.g. in a urine sample, it is possible to monitor the blood coagulation activity of a patient following surgery without having to obtain a blood sample from said patient.

Claims

1. Method of correlating a predetermined amount of at least one blood coagulation activity marker comprised in a sample with the amount of at least one quantifiably detectable reporter species capable of being operably linked to said blood coagulation activity marker, said method comprising the steps of

i) obtaining a test sample comprising a predetermined amount of at least one blood coagulation activity marker:

ii) obtaining at least one quantifiably detectable reporter species capable of being operably linked to said blood coagulation activity marker,

iii) contacting said test sample comprising said predetermined amount of at least one blood coagulation activity marker with said at least one quantifiably detectable reporter species,

iv) operably linking said predetermined amount of said blood coagulation activity marker comprised in said test sample to said at least one quantifiably detectable reporter species,

v) detecting said at least one quantifiably detectable reporter species operably linked to said predetermined amount of said blood coagulation activity marker comprised in said test sample,

vi) determining the amount of said at least one quantifiably detectable reporter species operably linked to said predetermined amount of said blood coagulation activity marker comprised in said test sample, and

vii) correlating said predetermined amount of said blood coagulation activity marker comprised in said test sample with said determined amount of said at least one quanffiably detectable reporter species.

2. Method according to claim 1, wherein said sample is contacted with at least one target species prior to step iv).

5. Method of claim 3, wherein said correlation in step vi) is performed by using data obtainable by the method of correlating a predetermined amount of at least one blood coagulation activity marker with the amount of at least one quantifiably detectable reporter species as described in claim 1.

9. Method of claim 6, wherein said determination of said amount of said blood coagulation activity marker as described in claim 3 is obtainable by the method of correlating a predetermined amount of at least one blood coagulation activity marker with the amount of at least one quantifiably detectable reporter species as described in claim 1.

12. Method of claim 10, wherein said determination of said amount of said blood coagulation activity marker as described in claim 3 is obtainable by the method of correlating a predetermined amount of at least one blood coagulation activity marker with the amount of at least one quantifiably detectable reporter species as described in claim 1.

15. Method of claim 14, wherein said determination of said amount of said blood coagulation activity marker as described in claim 3 is obtainable by the method of correlating a predetermined amount of at least one blood coagulation activity marker with the amount of at least one quanffiably detectable reporter species as described in claim 1.

23. Method of claim 22, wherein said determination of said amount of said blood coagulation activity marker as described in claim 3 is obtainable by the method of correlating a predetermined amount of at least one blood coagulation activity marker with the amount of at least one quantifiably detectable reporter species as described in claim 1.

24. Method of claim 2, wherein said body fluid sample is a urine sample.

25. Method of determining the amount of at least one blood coagulation activity marker of claim 2, wherein such determination is based on a cut-off point, above which one visible colour indicates the presence of the marker and below which cut-off point another visible colour or no colour change indicates that the marker is present in an amount less than that indicated cut-off point.

29. Method of claim 1, wherein said blood coagulation activity marker is selected from the group consisting of peptides comprising a fragment of pro-thrombin.

41. Method of claim 1, wherein said marker is detectable by a reporter species capable of detecting any of pro-thrombin Fragment 1+2 (F₁₊₂), pro-thrombin Fragment 1 (F₁), and pro-thrombin Fragment 2 (F₂).

42. Method of claim 1, wherein, said blood coagulation activity marker is selected from the group consisting of peptides comprising a fragment of fibrinogen.

43. Method of claim 42, wherein said marker is selected from the group consisting of peptides comprising fibrinopeptide A (FpA).

44. Method of claim 42, wherein said marker essentially consists of fibrinopeptide A (FpA).

45. Method of claim 42, wherein said marker is fibrinopeptide A (FpA).

46. Method of claim 1, wherein said marker is detectable by a reporter species capable of detecting fibrinopeptide A (FpA).

47. Method of claim 1, wherein said marker is selected from the group consisting of peptides comprising the carboxy-terminal 17 amino acid residues of the heavy chain of Factor X_a.

48. Method of claim 47, wherein said marker essentially consists of the carboxy-terminal 17 amino acid residues of the heavy chain of Factor X_a.

49. Method of claim 47, wherein said marker is the carboxy-terminal 17 residues of the heavy chain of Factor X_a.

50. Method claim 1, wherein said reporter species comprises at least one targeting species.

51. Method of claim 1, wherein said reporter species comprises more than one targeting species.

52. Method according to 50, wherein said targeting species comprises at least one antibody, or a binding fragment thereof, capable of detecting at least one blood coagulation marker defined by an antibody against F₂.

53. Method of claim 52, wherein said targeting species comprises the F₁₊₂ antibody deposited with the ATCC under the Accession No. HB 10291, or a binding fragment thereof, capable of detecting said blood coagulation marker.

54. Method according to 50, wherein said targeting species comprises at least one antibody, or a binding fragment thereof, capable of detecting at least one blood coagulation marker defined by an antibody against F₁.

55. Method of claim 54, wherein said targeting species comprises the antibody against F₁ disclosed by Bezeaud and Guillin in British Journal of Haematology (1984), vol. 58, pages 597-606, or a binding fragment thereof, capable of detecting said blood coagulation marker.

56. Method according to 50, wherein said reporter species comprises at least one antibody, or a binding fragment thereof, capable of detecting at least one blood coagulation marker defined by an antibody against F₂.

57. Method of claim 56, wherein said targeting species comprises the antibody against F₂ deposited with the ATCC under the Accession No. HB 10291, or a binding fragment thereof, capable of detecting said blood coagulation marker.

58. Method according to 50, wherein said, targeting species comprises at least one antibody capable of detecting at least one blood coagulation marker defined by an antibody against FpA.

59. Method of claim 58, wherein said targeting species comprises a binding fragment of said FpA antibody capable of detecting said blood coagulation marker.

60. Method according to claim 50, wherein said targeting species comprises at least one antibody capable of detecting at least one blood coagulation marker defined by an antibody against X_a.

61. Method of claim 60, wherein said targeting species comprises a binding fragment of said X_a antibody capable of detecting said blood coagulation marker.

62. Method according to claim 52, wherein the targeting species is immobilised on a solid surface.

63. Method according to claim 62, wherein said solid surface is comprised within a lateral flow device.

64. Method according to claim 62, wherein said solid surface is a dipstick or part thereof.

65. Method according to claim 62, wherein said solid surface is nitrocellulose.

66. Method according to claim 62, wherein said solid surface is comprised within a micro fluid device.

67. Method of claim 41, wherein said at least one antibody comprises a polyclonal antibody.

68. Method of claim 41, wherein said at least one antibody comprises a monoclonal antibody.

69. Method according to claim 50, wherein said reporter species further comprises at least one polypeptide operably linked to said at least one targeting species.

70. Method of claim 69, wherein said polypeptide comprises an enzyme

71. Method of claim 70, wherein said enzyme comprises a peroxidase activity.

72. Method according to claim 50, wherein said reporter species further comprises at least one fluorochrome.

73. Method according to claim 50, wherein said reporter species further comprises at least one radio label.

74. Method according claim 50, wherein said reporter species further comprises at least one coloured dye molecule.

75. Method according to claim 74, wherein said at least one coloured dye molecule is rhodamine.

76. Method according to claim 50, wherein said reporter species comprises two antibodies.

77. Method according to claim 50, wherein said boo antibodies are selected from a polyclonal antibody and a monoclonal antibody.

78. Method according to claim 50, wherein said reporter species comprises a polymeric carrier molecule.

79. Method according to 78, wherein the polymeric carrier molecule has a hydrophilic sugar chain backbone.

80. Method according to 78, wherein the polymeric carrier molecule has a polymeric dextran backbone.

107. System of claim 95,1 wherein said marker is fibrinopeptide A (FpA).

3. Method of determining the amount of at least one blood coagulation activity marker comprised in a body fluid sample, said method comprising the steps of

i) obtaining a body fluid sample comprising at least one blood coagulation activity marker,

ii) contacting said body fluid sample comprising said blood coagulation activity marker with at least one quantifiably detectable reporter species,

iii) operably linking said blood coagulation activity marker comprised in said body fluid sample to said at least one quantifiably detectable reporter species,

iv) detecting said at least one quantifiably detectable reporter species operably linked to said blood coagulation activity marker comprised in said body fluid sample,

v) determining the amount of said at least one quantifiably detectable reporter species operably linked to said blood coagulation activity marker comprised in said body fluid sample,

vi) correlating the determined amount of said at least one quantifiably detectable reporter species with the amount of said blood coagulation activity marker comprised in said body fluid sample, and based on the correlation of step vi), determining said amount of said blood coagulation activity marker comprised in said body fluid sample.

4. Method according to claim 3, wherein said body fluid sample is contacted with at least one targeting species prior to step iii).

8. Method of claim 6, wherein said determination in step iii) is obtainable by the method of determining the amount of at least one blood coagulation activity marker as described in claim 3.

6. Method of correlating the blood coagulation activity of a blood sample obtained from an individual with the amount of at least one blood coagulation activity marker comprised in a body fluid sample obtained from said individual, said method comprising the steps of

i) obtaining a blood sample from said individual,

ii) obtaining a body fluid sample comprising at least one blood coagulation activity marker from said individual,

iii) determining the amount of at least one blood coagulation activity marker present in said body fluid sample obtained from said individual, and

iv) correlating said amount of said at least one blood coagulation activity marker present in said body fluid sample obtained from said individual with said blood coagulation activity of said individual,

7. Method of claim 6 wherein the correlation of the blood coagulation activity of said blood sample obtained from an individual with said amount of at least one blood coagulation activity marker comprised in a body fluid sample obtained from said individual is obtainable by correlating the determined blood coagulation time and the determined amount of said at least one blood coagulation activity marker comprised in said body fluid sample.

81. Method of treatment of a clinical condition in a human or animal body by therapy or surgery, said method comprising the steps of

i) determining the amount of at least one blood coagulation activity marker comprised in a body fluid sample according to the method of claim 6,

ii) correlating said amount of said blood coagulation activity marker in said body fluid sample determined in step i) to said clinical condition,

iii) confirming said correlation of said blood coagulation activity marker in said body fluid sample determined in step 1) to said clinical condition by diagnosing said clinical condition,

iv) based on the diagnosis of step iii) treating said clinical condition in said human or animal body.

83. Diagnostic method practised on the human or animal body, said method comprising the steps of

i) determining the amount of at least one blood coagulation activity marker comprised in a body fluid sample according to the method of claim 6,

ii) correlating said amount of said blood coagulation activity marker in said body fluid sample determined in step i) to said clinical condition,

iii) based on the correlation of step ii), diagnosing said clinical condition in said human or animal body.

85. Method of claim 81, wherein said clinical condition in said individual is an acute clinical condition.

86. Method of claim 81, wherein said clinical condition in said individual is a condition developing into an acute clinical condition unless treated.

87. Method of claim 81, wherein said clinical condition in said individual is selected from the group consisting of cardiovascular diseases.

88. Method of claim 87, wherein said cardiovascular disease is selected from venous thromboembolism, pulmonary embolism, myocardial infarction, angina pectoris, coronary heart disease, disseminated intravascular coagulation,

89. Method of claim 81, wherein said clinical condition in said individual is selected from the group consisting of a liver disease, a malignant disease, acute pro-myelocytic leukaemia, diabetes, respiratory distress syndrome, and cerebral infarction.

10. Method of correlating the blood coagulation activity of a blood sample obtained from an individual with the amount of at least one blood coagulation activity marker comprised in a body fluid sample obtained from said individual, said method comprising the steps of

i) obtaining a blood sample from said individual,

ii) obtaining a body fluid sample comprising at least one blood coagulation activity marker from said individual,

iii) determining the amount of at least one quantifiably detectable biological species present in said blood sample obtained from said individual, said at least one quantifiably detectable biological species being correlatable to said blood coagulation activity in said blood sample obtained from said individual,

iv) determining the amount of at least one blood coagulation activity marker present in said body fluid sample obtained from said individual, said blood coagulation activity marker being correlatable with said at least one quantifiably detectable biological species present in said blood sample obtained from said individual,

v) correlating said amount of said at least one blood coagulation activity marker present in said body fluid sample obtained from said individual with the amount of at least one quantifiably detectable biological species present in said blood sample obtained from said individual,

vi) correlating said amount of said at least quantifiably detectable biological species present in said blood sample obtained from said individual with the blood coagulation activity of said individual, and

vii) based on the correlations of steps v) and vi), correlating said amount of at least one blood coagulation activity marker present in said body fluid sample obtained from said individual with said blood coagulation activity of said individual.

11. Method of claim 10, wherein said determination in step iv) is obtainable by the method of determining the amount of at least one blood coagulation activity marker as described in claim 3.

14. Method of claim 13, wherein said determination in step ii) is obtainable by the method of determining the amount of at least one blood coagulation activity marker as described in claim 3.

16. Method of claim 13, wherein said correlation in step iii) is obtainable by the method of correlating the blood coagulation activity of a blood sample with the amount of at least one blood coagulation activity marker comprised in a body fluid sample as described in claim 6.

17. Method of claim 11, wherein said correlation in step iii) is obtainable by the method of correlating the blood coagulation activity of a blood sample with the amount of at least one blood coagulation activity marker comprised in a body fluid sample as described in claim 10.

18. Method of monitoring the blood coagulation activity of an individual, said method comprising obtaining a plurality of individual determinations of said blood coagulation activity of said individual, wherein each determination of said blood coagulation activity is obtainable by the method of claim 13.

19. Method of monitoring the blood coagulation activity of an individual, said method comprising obtaining a plurality of individual determinations of said blood coagulation activity of said individual, wherein each determination of said blood coagulation activity is obtainable by the method of claim 14.

20. Method of monitoring the blood coagulation activity of an individual, said method comprising obtaining a plurality of individual determinations of said blood coagulation activity of said individual, wherein each determination of said blood coagulation activity is obtainable by the method of claim 16.

28. Method of claim 10, wherein said biological, species is selected from the group consisting of pro-thrombin, thrombin, thrombin antithrombin III complex (TAT), fibrinogen, fibrin, fibrin/fibrinogen degradation products D-dimer (FDP D-dimer), and alpha 2PI plasmin complex (PIC).

82. Method of treatment of a clinical condition in a human or animal body by therapy or surgery, said method comprising the steps of

i) determining the blood coagulation activity of an individual according to the method of claim 13,

ii) correlating said blood coagulation activity of said individual determined in step i) to said clinical condition,

iii) confirming said correlation of said blood coagulation activity of said individual determined in step i) to said clinical condition by diagnosing said clinical condition,

iv) based on the diagnosis of step iii), treating said clinical condition in said human or animal body.

84. Diagnostic method practised on the human or animal body, said method comprising the steps of

i) determining the blood coagulation activity of an individual according to the method of claim 13,

ii) correlating said blood coagulation activity of said individual determined in step i) said clinical condition, and

iii) based on the correlation of step ii), diagnosing said clinical condition in said human or animal body.

13. Method of determining the blood coagulation activity of an individual, said method comprising the steps of

i) obtaining a body fluid sample comprising at least one blood coagulation activity marker from said individual,

ii) determining the amount of said at least one blood coagulation activity marker present in said body fluid sample,

iii) correlating said determined amount of said at least one blood coagulation activity marker present in said body fluid sample with said blood coagulation activity of said individual, and

iv) based on the correlation of step iii), determining said blood coagulation activity of said individual.

21. Method of monitoring a clinical condition in an individual, said clinical condition affecting the blood coagulation activity in said individual, said method comprising the steps of

i) obtaining over a predetermined period of time a plurality of body fluid samples comprising at least one blood coagulation activity marker from said individual,

ii) determining the amounts of said at least one blood coagulation activity marker present in said plurality of body fluid samples,

iii) correlating said determined amounts of said at least one blood coagulation activity marker present in said plurality of body fluid samples obtained over a predetermined period of time with said clinical condition affecting said blood coagulation activity in said individual, and

iv) based on said correlation of step iii), monitoring said clinical condition in said individual.

22. Method of claim 21, wherein said determination of said amounts of said at least one blood coagulation activity marker present in said plurality of body fluid samples obtained over a predetermined period of time is obtainable by the method of claim 3.

26. Method of claim 25 wherein said cut-off point is at least 0.1 nM, for example at least 0.15 nM, such as at least 0.20 nM, for example at least 0.25 nM, such as at least 0.30 nM, for example between 0.1 and 2.0 nM, for example between 0.20 and 1.5 nM, such as between 0.30 and 1.0 nM of said marker.

27. Method of claim 25 wherein said cutoff point is around 0.30 nM of said marker.

30. Method of claim 28, wherein said marker is selected from the group consisting of peptides comprising pro-thrombin Fragment 1+2 (F₁₊₂), peptides comprising pro-thrombin Fragment 1 (F₁), and peptides comprising pro-thrombin Fragment 2 (F₂).

31. Method of claim 28, wherein said marker is selected from peptides comprising pro-thrombin Fragment 1+2 (F₁₊₂)

32. Method of claim 28, wherein said marker is selected from peptides comprising pro-thrombin Fragment 1 (F₁)

33. Method of claim 28, wherein said marker is selected from peptides comprising prothrombin Fragment 2 (F₂).

34. Method of claim 28, wherein said marker is selected from the group consisting of pro-thrombin Fragment 1+2 (F₁₊₂), pro-thrombin Fragment 1 (F₁), and pro-thrombin Fragment 2 (F₂).

35. Method of claim 28, wherein said marker essentially consists of pro-thrombin Fragment 1+2 (F1+2).

36. Method of claim 28, wherein said marker essentially consists of pro-thrombin Fragment 1 (F₁).

37. Method of claim 28, wherein said marker essentially consists of pro-thrombin Fragment 2 (F₂).

38. Method of claim 28, wherein said marker is pro-thrombin Fragment 1+2 (F₊₂) comprising amino acid residues 1 to 271 of pro-thrombin, including any functional variant thereof being at least 95% identical to said sequence, said functional variant being obtained by deletion, insertion or substitution of at least one amino acid.

39. Method of claim 28, wherein said marker is pro-thrombin Fragment 1 (F₁) comprising amino acid residues 1 to 155 of prothrombin, including any functional variant thereof being at least 95% identical to said sequence, said functional variant being obtained by deletion:

insertion or substitution of at least one amino acid.

40. Method of claim 28, wherein said marker is pro-thrombin Fragment 2 (F₂) comprising amino acid residues 156 to 271 of pro-thrombin, including any functional variant thereof being at least 95% identical to said sequence, said variant being obtained by deletion, insertion or substitution of at least one amino acid.

102. System of claim 24, wherein said marker essentially consists of pro thrombin Fragment 1+2 (F1).

90. System for and quantification of at least one blood coagulation activity marker present in a body fluid sample, and information linking said determined amount of said blood coagulation activity marker to the blood coagulation activity of an individual, comprising

i) a zone for applying a body fluid sample comprising a blood coagulation activity marker, said zone comprising at least one movable reporter species capable of binding said marker, said application zone being in liquid contact with

ii) a zone for detecting the presence, amount or concentration of said at least one reporter species bound to said marker, said zone further comprising a binding species for immobilizing onto said detection zone at least a substantial amount of said marker comprised in said body fluid sample, and optionally

iii) a positive control zone generating a positive control confirming the transfer of at least part of said body fluid sample from said application zone to said detection zone.

91. System according to claim 90, wherein the at least one reporter species comprises at least one antibody.

92. System according to claim 90, comprising

i) a hollow casing having a body fluid sample application aperture and a test result observation aperture,

ii) a bibulous body fluid sample receiving member within said hollow casing to receive said body fluid sample applied to said sample application aperture,

iii) a test strip comprising a dry porous carrier such as nitrocellulose within said casing and extending from said bibulous body fluid sample receiving member to and beyond said test result observation aperture, said dry porous carrier having a test result zone observable through said observation aperture,

iv) at least one of said bibulous body fluid sample receiving member and said test strip containing upstream from said test result zone a detectable reporter species capable of specifically binding said marker to form a first complex,

v) said reporter species comprising ad least one particulate label, such as a dye sol, a metallic sol or a coloured latex particle, and optionally also at least one fluorescently detectable label, said label being released into a mobile form by said body fluid sample,

wherein mobility of said label within said test strip is facilitated by either coating at least a portion of said test strip upstream from said test result zone with a material comprising a polysaccharide, or drying said label onto a portion of said test strip upstream frog said test zone in the presence of a material comprising a polysaccharide, in an amount effective to reduce interaction between said test strip and said label, and

wherein said dry porous carrier contains in said test result zone a means for binding said first complex, said means for binding comprising specific binding means immobilized in said test result zone, and

wherein migration of said body fluid sample from said bibulous sample receiving member into and through said dry porous carrier conveying by capillarity said first complex to said test result zone of said dry porous carrier whereat said binding means binds said first complex thereby to form a second complex, and

vi) determining the presence, amount or concentration of said second complex being observable through said test result observation aperture.

93. System according to claim 90, wherein such determination is based on a cut-off point, above which one visible colour indicates the presence of the marker and below which cutoff point another visible colour indicates that the marker is present in an amount less than that indicated cut-off point.

94. System of claim 93, wherein said cut-off point is at least 0.1 nM, for example at least 0.15 nM, such as at least 0.20 nM, for example at least 0.25 nM, such as at least 0.30 nM, for example between 0.1 and 2.0 nM, for example between 0.20 and 1.5 nM, such as between 0.30 and 1.0 nM.

95. System of claim 93, wherein said cut-off point is around 0.30 nM.

96. System of claim 90, wherein said biological species is selected from the group consisting of pro-thrombin, thrombin, thrombin antithrombin II complex (TAT), fibrinogen, fibrin, fibrin/fibrinogen degradation products D-dimer (FDP D-dimer), and alpha 2PI plasmin complex (PIC).

97. System of claim 96, wherein said blood coagulation activity marker is selected from the group consisting of peptides comprising a fragment of pro-thrombin.

98. System of claim 97, wherein said marker is selected from the group consisting of peptides comprising prothrombin Fragment 1+2 (F₁+₂), peptides comprising pro-thrombin Fragment 1 (F₁), and peptides comprising pro-thrombin Fragment 2 (F₂).

99. System of claim 97, wherein said marker is selected from peptides comprising pro-thrombin Fragment 1+2 (F₁)

100. System of claim 97, wherein said marker is selected from peptides comprising pro-thrombin Fragment 1 (F₂).

101. System of claim 97, wherein said marker is selected from peptides comprising pro-thrombin Fragment 1 (F₂).

103. System of claim 90, wherein said marker is detectable by a reporter species capable of detecting any of pro-thrombin Fragment 1+2 (F₁₊₂), pro-thrombin Fragment 1 (F₁), and pro-thrombin Fragment 2 (F₂).

104. System of claim 90, wherein said blood coagulation activity marker is selected from the group consisting of peptides comprising a fragment of fibrinogen.

105. System of claim 95, wherein said marker is selected from the group consisting of peptides comprising fibrinopeptide A (FpA).

106. System of claim 95, wherein said marker essentially consists of fibrinopeptide A (FpA).

108. System of claim 95, wherein said marker is detectable by a reporter species capable of detecting fibrinopeptide A (FpA).

109. System of claim 90, wherein said marker is selected from the group consisting of peptides comprising the carboxy-terminal 17 amino acid residues of the heavy chain of Factor X_a.

110. System of claim 90, wherein said reporter species comprises at least one targeting species,

111. System according to claim 90, wherein said targeting species comprises at least one antibody, or a binding fragment thereof, capable of detecting at least one blood coagulation marker defined by an antibody against F₁₊₂.

112. System of claim 111, wherein said targeting species comprises the F₁₊₂ antibody deposited with the ATCC under the Accession No. HB 10291, or a binding fragment thereof, capable of detecting said blood coagulation marker.

113. System according to 90, wherein said targeting species comprises at least one antibody, or a binding fragment thereof, capable of detecting at least one blood coagulation marker defined by an antibody against F₁.

114. System of claim 113, wherein said targeting species comprises the antibody against F₁ disclosed by Bezeaud and Guillin in British Journal of Haematology (1984), vol. 58, pages 597-606, on, a binding fragment thereof, capable of detecting said blood coagulation marker.

115. System according to 90, wherein said reporter species comprises at least one antibody, or a binding fragment thereof, capable of detecting at least one blood coagulation marker defined by an antibody against F₂.

116. System of claim 115, wherein said targeting species comprises the antibody against F₂ deposited with the ATCC under the Accession No. HB 10291, or a binding fragment thereof, capable of detecting said blood coagulation marker.

117. System according to 90, wherein said targeting species comprises at least one antibody capable of detecting at least one blood coagulation marker defined by an antibody against FpA.

118. System of claim 117, wherein said targeting species comprises a binding fragment of said FpA antibody capable of detecting said blood coagulation marker.

119. System according to claim 90, wherein said targeting species comprises at least one antibody capable of detecting at least one blood coagulation marker defined by an antibody against X_a.

120. System of claim 119, wherein said targeting species comprises a binding fragment of said X_a antibody capable of detecting said blood coagulation marker.

121. System according to any of the claims 90, wherein the targeting species is immobilised on a solid surface.

122. System according to claim 121, wherein said solid surface is comprised within a lateral flow device.

123. System according to claim 121, wherein said solid surface is a dipstick or part thereof.

124. System according to claim 121, wherein said solid surface is nitrocellulose.

125. System according to claim 121, wherein said solid surface is comprised within a micro fluid device,

126. System according to claim 90, wherein said reporter species further comprises at least one polypeptide operably linked to said at least one targeting species.

127. System of claim 126, wherein said polypeptide comprises an enzyme.

128. System of claim 127, where said enzyme comprises a peroxidase activity.

129. System according to claim !90, wherein said reporter species further comprises at least one fluorochrome.

130. System according to claim 90 wherein said reporter species further comprises at least one radio label.

131. System according claim 90, wherein said reporter species further comprises at least one coloured dye molecule.

132. System according to claim 90, wherein said reporter species comprises two antibodies.

133. System according to claim 90, wherein said two antibodies are selected from a polyclonal antibody and a monoclonal antibody.

134. System according to claim 90, wherein said reporter species comprises a polymeric carrier molecule.

135. System according to 134, wherein the polymeric carrier molecule has a hydrophilic sugar chain backbone.

136. System according to 134, wherein the polymeric carrier molecule has a polymeric dextran backbone.