Claims
- 1. A method for predicting that an individual has an increased likelihood of having antiphospholipid syndrome, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam at the test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; d) determining if a value or a slope at or over a particular time in the time-dependent measurement profile is beyond a corresponding predetermined value or slope threshold; and if the value or slope in the time-dependent measurement profile is beyond the predetermined threshold, then determining that the individual has an increased likelihood of antiphospholipid syndrome.
- 2. The method according to claim 1, wherein the time-dependent measurement is an optical measure of changes in absorbance and/or transmittance through the sample over time.
- 3. The method according to claim 1, wherein the sample is a whole blood or plasma sample from the individual.
- 4. The method according to claim 1, wherein the phospholipids are added as part of a coagulation reagent that comprises thromboplastin.
- 5. The method according to claim 4, wherein the coagulation reagent is a prothrombin time reagent.
- 6. The method according to claim 1, wherein the phospholipids are a heterogenous mixture of phospholipids of varying structures, including non-bilayer arrangements.
- 7. The method according to claim 1 wherein the phospholipids are from natural sources.
- 8. The method according to claim 4, wherein the coagulation reagent comprises tissue factor, a halide salt and a mixture of phospholipids.
- 9. The method according to claim 1, further comprising adding a divalent metal cation or a salt of a divalent metal cation along with the phospholipids.
- 10. The method according to claim 1, further comprising performing at least one confirmatory assay to determine the existence of antiphospholipid antibodies.
- 11. The method according to claim 10, wherein the at least one confirmatory assay is a latex immunoassay or an ELISA.
- 12. The method according to claim 10, wherein the at least one immunoassay comprises an assay for at least one of anti-β2 glycoprotein, anti-prothrombin and anticardiolipin antibodies.
- 13. The method according to claim 1, wherein the individual is a person taking an oral anticoagulant.
- 14. The method according to claim 10, further comprising initiating oral anticoagulant therapy if antiphospholipid antibodies are found in the confirmatory assay.
- 15. The method according to claim 1, wherein the time-dependent measurement profile is an optical transmittance profile.
- 16. The method according to claim 15, wherein the optical transmittance profile is generated on a photo-optical coagulation analyzer.
- 17. The method according to claim 1, wherein the individual is one who has experienced spontaneous miscarriage or a thromboembolic event.
- 18. The method according to claim 1, further comprising performing an APTT assay on a sample from the individual to determine whether the APTT exhibits a prolonged clot time.
- 19. The method according to claim 10, wherein the at least one confirmatory assay is confirmatory assay for identifying APLA according to the criteria: a) prolongation of a phospholipid-dependent screening assay; b) lack of correction of the prolonged assay with a 1:1 mix with pooled normal plasma; and c) correction of the prolonged assay by the addition of excess phospholipid.
- 20. The method according to claim 1, wherein the phospholipids are not added as part of a coagulation reagent.
- 21. The method according to claim 1, wherein a confirmatory assay is run which comprises deriving a time-dependent measurement profile with an APTT reagent and determining if there is a negative slope 1 in the time-dependent measurement.
- 22. The method according to claim 1, wherein a confirmatory assay is run that is a platelet neutralization test.
- 23. The method of claim 21, wherein if there is no slope 1 in the APTT time-dependent measurement beyond a predetermined value or threshold, then performing an additional confirmatory assay which is an immunoassay.
- 24. The method of claim 23, wherein the immunoassay is an ELISA for anti-β2 glycoprotein, anti-prothrombin and anticardiolipin antibodies.
- 25. The method of claim 1, wherein the vesicles or liposomes are part of a DRVVTDRVVT reagent that comprises Russel's Viper Venom.
- 26. The method of claim 1, wherein if the value or slope is beyond a predetermined threshold, then determining if the test sample comprises C-reactive protein or LC-CRP.
- 27. The method of claim 26, wherein determining if the test sample comprises C-reactive protein comprises performing an APTT assay in the presence and absence of phosphorylcholine.
- 28. The method of claim 27, wherein if there is a negative APTT slope and this is inhibited by phosphorylcholine, performing a confirmatory test for APLA.
- 29. The method of claim 1, wherein the phospholipids are phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine and/or phosphatidylinositol.
- 30. The method of claim 29, further comprising adding a metal cation in the form of a metal salt prior to determining the slope or value.
- 31. The method of claim 29, wherein a plurality of phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine and phosphatidylinositol are added to the test sample.
- 32. The method of claim 1, wherein the test sample is purified IgG from the individual.
- 33. The method of claim 32, further comprising adding a phospholipid binding protein to the test sample prior to determining the value or slope.
- 34. The method of claim 33, wherein the phospholipid binding protein is 2 glycoprotein I, cardiolipin or prothrombin.
- 35. The method of claim 33, further comprising adding a coagulation reagent to the test sample prior to determining the value or slope.
- 36. The method of claim 1, wherein the individual is not a disseminated intravascular coagulation patient.
- 37. The method of claim 1, wherein the phospholipids are part of a reagent derived from mammal tissue.
- 38. The method of claim 37, wherein the tissue is brain or placenta.
- 39. The method of claim 1, wherein the phospholipids are added in the absence of a source of metal cation.
- 40. The method of claim 1, wherein the phospholipids are part of a prothrombin time reagent.
- 41. The method of claim 1, further comprising performing the method of claim 1 again with phospholipids more sensitive to APLA.
- 42. The method of claim wherein the at least one immunoassay comprises an assay for anti-β2 glycoprotein.
- 43. The method of claim 12, wherein the at least one immunoassay comprises an assay for anti-prothrombin.
- 44. The method of claim 12, wherein the at least one immunoassay comprises an assay for anti-β2 glycoprotein and anti-prothrombin.
- 45. The method of claim 12, wherein the at least one immunoassay comprises an assay for anticardiolipin antibodies.
- 46. The method of claim 1, wherein the test sample is from an individual on oral anticoagulant, and wherein prothrombin is added to the test sample along with phospholipids.
- 47. The method according to claim 1, further comprising performing a confirmatory assay to determine the existence of phospholipid binding proteins.
- 48. The method of claim 47, wherein the confirmatory assay is an assay for β2 glycoprotein, prothrombin or anticardiolipin.
- 49. The method of claim 1, wherein a test sample is combined with phospholipids and a time dependent measurement profile is obtained in the absence of adding a coagulation reagent to the test sample.
- 50. The method of claim 1, wherein a confirmatory assay is performed after determining an increased likelihood of the presence of antiphospholipid antibodies, the confirmatory assay comprising a) prolongation of a phospholipid-dependent screening assay; b) lack of correction of the prolonged assay with a 1:1 mix with pooled normal plasma; and c) correction of the prolonged assay by the addition of excess phospholipid.
- 51. The method of claim 1, wherein if a slope—1 beyond a predetermined threshold is detected, a confirmatory assay is performed after determining an increased likelihood of the presence of antiphospholipid antibodies, the confirmatory assay comprising adding phospholipids to a test sample from the individual along with at least one prothrombin binding protein, performing a time dependent measurement profile on the sample, and determining whether there is an increase or not in the slope—1 compared to the initial slope—1 detected.
- 52. The method of claim 1, wherein the phospholipids added are not part of a PT or APTT reagent.
- 53. The method of claim 1, further comprising, if a slope—1 is detected as being beyond a predetermined threshold, performing the method of claim 1 again with the addition of one phospholipid binding protein and performing the method of claim 1 yet again with the addition of another phospholipid binding protein, and determining whether there is an increase in the slope—1 for each additional test.
- 54. The method of claim 1, further comprising, if a slope—1 is detected as being beyond a predetermined threshold, performing a DRVVT test as a confirmatory test.
- 55. The method of claim 1, wherein the phospholipids comprise PC and PS.
- 56. The method of claim 55, wherein the phospholipids further comprise PE.
- 57. The method of claim 56, wherein PS is 10% or more of the total phospholipids.
- 58. The method of claim 54, wherein the PS is 15% or more of the total phospholipids.
- 59. The method of claim 58, wherein the PS is 25% or more of the total phospholipids.
- 60. The method of claim 56, wherein the PC is at least 40% of the total phospholipids.
- 61. The method of claim 60, wherein the PC is at least 60% of the total phospholipids.
- 62. The method of claim 61, wherein the PC is from 40% to 70% of the total phospholipids.
- 63. The method of claim 56, wherein the PE is at least 5% of the total phospholipids.
- 64. The method of claim 63, wherein the PE is at least 15% of the total phospholipids.
- 65. The method of claim 63, wherein the PE is from 5 to 50% of the total phospholipids.
- 66. The method of claim 65, wherein the PE is from 5 to 30% of the total phospholipids.
- 67. The method of claim 56, wherein the PS is from 10% to 30%, PC is from 40% to 70% and PE is from 5% to 50% of the total phospholipids.
- 68. The method according to claim 4, wherein the coagulation reagent is a thrombin time reagent.
- 69. The method according to claim 4, wherein the coagulation reagent is a dilute Russel's Viper Venom reagent.
- 70. The method according to claim 4, wherein the coagulation reagent is a activated partial thromboplastin time reagent.
- 71. The method according to claim 4, wherein the coagulation reagent is a reagent comprising snake venom and phospholipids.
- 72. The method of claim 1, wherein the phospholipids are phospholipids sufficient to cause a slope—1 beyond a predetermined threshold in a majority of patients with antiphospholipid syndrome.
- 73. The method of claim 1, wherein if it is determined that a value or a slope at or over a particular time in the time-dependent measurement profile is beyond a corresponding predetermined value or slope threshold, then the test sample is flagged as being a sample from an individual with an increased likelihood of having antiphospholipid syndrome.
- 74. The method of claim 73, wherein the flagging is performed by printing an alert on a printer in communication with an analyzer on which the method is performed.
- 75. The method of claim 73, wherein the flagging is performed by displaying an alert on a monitor in communication with an analyzer on which the method is performed.
- 76. A method for predicting that an individual is at an increased likelihood for having antiphospholipid syndrome, comprising:
a) providing a test sample from an individual; b) combining the test sample with a coagulation reagent comprising phospholipids; c) monitoring the formation of fibrin polymerization over time so as to provide a time-dependent measurement profile; d) defining a set of one or more predictor variables which sufficiently define the data of the time-dependent measurement profile; e) deriving a model that represents the relationship between the antiphospholipid syndrome and the one or more predictor variables; and f) utilizing the model of step e) to predict the increased likelihood of antiphospholipid syndrome in the individual.
- 77. The method according to claim 76, wherein the coagulation reagent is a PT reagent.
- 78. The method according to claim 77, further comprising repeating steps a) to e) with an APTT reagent.
- 79. The method according to claim 78, wherein when the PT reagent is used the one or more predictor variables includes slope prior to clot initiation, slope post coagulation and time of initiation of clot formation.
- 80. The method according to claim 79, wherein when the APTT reagent is used, the one or more predictor variable include one or more of time corresponding to coagulation onset, time corresponding to midpoint of coagulation, time corresponding to end of coagulation, and value or slope prior to clot initiation.
- 81. The method according to claim 76, wherein the predictor variables include clot time or INR, and slope prior to initiation of clot formation.
- 82. The method of claim 76, wherein the coagulation reagent comprising the phospholipids is a prothrombin time reagent.
- 83. The method of claim 82, wherein the one or more parameters are slope 1, tmin2, tmin1, tmax2, slope 3 and delta.
- 84. The method of claim 83, wherein the individual is an individual not on oral anticoagulant therapy.
- 85. The method of claim 82, wherein the one or more parameters are slope 1, tmin2, tmin1 and tmax2.
- 86. The method of claim 82, wherein the one or more parameters are slope 1, tmin2, min2, tmin1, tmax2, max2, slope 3 and delta.
- 87. The method of claim 86, wherein the individual is an individual on oral anticoagulant therapy.
- 88. The method of claim 76, wherein the time dependent measurement profile is at least one optical profile.
- 89. The method of claim 88, wherein the optical profile is provided by an automated analyzer for thrombosis and hemostasis testing.
- 90. The method of claim 76, wherein after step f, one or more assays for confirming the predicted antiphospholipid syndrome are performed.
- 91. The method of claim 90, wherein the one or more confirmatory assays are one or more immunoassays for antiphospholipid antibodies.
- 92. The method of claim 76, wherein the model is a neural network.
- 93. The method of claim 76, wherein the phospholipids are phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine and/or phosphatidylinositol.
- 94. The method of claim 93, further comprising adding a metal cation in the form of a metal salt prior to determining the slope or value.
- 95. The method of claim 93, wherein a plurality of phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine and phosphatidylinositol are added to the test sample.
- 96. The method of claim 76, wherein the test sample is purified IgG from the individual.
- 97. The method of claim 96, further comprising adding a phospholipid binding protein to the test sample prior to determining the value or slope.
- 98. The method of claim 97, wherein the phospholipid binding protein is 2 glycoprotein I, cardiolipin or prothrombin.
- 99. The method of claim 97, wherein the phospholipids are added to the test sample as part of a coagulation reagent prior to determining the value or slope.
- 100. The method of claim 76, wherein the individual is not a disseminated intravascular coagulation patient.
- 101. The method of claim 76, wherein the phospholipids are part of a reagent derived from mammal tissue.
- 102. The method of claim 101, wherein the tissue is brain or placenta.
- 103. The method of claim 76, wherein the phospholipids are added in the absence of a source of metal cation.
- 104. The method of claim 76, wherein the phospholipids are part of a prothrombin time reagent.
- 105. The method of claim 91, wherein the one or more immunoassays are immunoassays for anti-β2 glycoprotein, anti-prothrombin and/or anticardiolipin antibodies.
- 106. The method of claim 1, further comprising performing a second assay on those test samples that indicate that an individual is at an increased likelihood of having antiphospholipid syndrome, wherein the results of the second assay are capable of increasing the likelihood of the individual having antiphospholipid syndrome.
- 107. A method for predicting antiphospholipid syndrome in an individual from at least one time-dependent measurement profile, comprising:
a) combining a test sample from an individual with phospholipids and directing a light beam at a test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; b) defining a set of one or more predictor variables which sufficiently define the data of the time-dependent measurement profile; c) deriving a model that represents the relationship between the antiphospholipid syndrome and the one or more predictor variables; and d) utilizing the model of step c) to predict the existence of antiphospholipid syndrome in the individual.
- 108. The method according to claim 107, wherein the one or more predictor variables includes a decrease in value or a slope of the profile prior to clot initiation.
- 109. The method according to claim 108, wherein the one or more predictor variables is a plurality of variables that further includes one or more of: a minimum of the first derivative of the profile, a time index of the minimum of the first derivative, a minimum of the second derivative of the profile, a time index of the minimum of the second derivative, a maximum of the second derivative of the profile, a time index of the maximum of the second derivative, an overall change in the coagulation parameter during the time-dependent measurement on the unknown sample, a clotting time, and a slope of the profile after clot formation.
- 110. The method according to claim 109, wherein said at least one time-dependent measurement profile is at least one optical profile.
- 111. The method according to claim 110, wherein said at least one optical profile is provided by an automated analyzer for thrombosis and hemostasis testing.
- 112. The method according to claim 111, wherein a plurality of optical measurements at one or more wavelengths are taken over time so as to derive said at least one optical profile, said optical measurements corresponding to changes in light scattering and/or light absorption in the unknown sample.
- 113. The method according to claim 112, wherein a plurality of optical measurements are taken over time so as to derive said at least one optical profile, and wherein said plurality of optical measurements are each normalized to a first optical measurement.
- 114. The method according to claim 110, wherein in step a) said at least one optical profile is provided automatically by said analyzer, whereby said sample is automatically removed by an automated probe from a sample container to a test well, one or more reagents are automatically added to said test well so as to initiate said property changes within said sample, and the development of said property over time is automatically optically monitored so as to derive said optical data profile.
- 115. The method according to claim 114, wherein after step d), a predicted antiphospholipid syndrome is automatically stored in a memory of said automated analyzer and/or displayed on said automated analyzer.
- 116. The method according to claim 114, wherein after step d), one or more assays for confirming the predicted antiphospholipid syndrome are performed.
- 117. The method according to claim 116, wherein the one or more confirmatory assays comprise one or more immunoassays for antiphospholipid antibodies.
- 118. The method according to claim 107, wherein said model of step c) is a neural network.
- 119. The method according to claim 107, wherein said relationship in step c) is determined via at least one automated algorithm.
- 120. The method according to claim 119, wherein said model is a multilayer perceptron, and wherein said at least one algorithm is a back propagation learning algorithm.
- 121. The method according to claim 107, wherein in step a), a plurality of time-dependent measurement profiles are derived for use in step b).
- 122. The method according to claim 121, wherein said plurality of time dependent measurement profiles includes at least two profiles from assays initiated with PT reagents, APTT reagents, fibrinogen reagents and TT reagents.
- 123. The method according to claim 107, wherein the sample is a sample from a medical patient, and wherein in step d), both said model and additional patient medical data are utilized for predicting antiphospholipid syndrome in the individual.
- 124. The method according to claim 116, wherein the one or more confirmatory assays is a confirmatory assay for identifying APLA according to the criteria: a) prolongation of a phospholipid-dependent screening assay; b) lack of correction of the prolonged assay with a 1:1 mix with pooled normal plasma; and c) correction of the prolonged assay by the addition of excess phospholipid.
- 125. A method for predicting an increased risk of thrombosis in a test subject, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam through the test sample and monitoring the transmittance of light through the sample over time so as to provide a time-dependent measurement profile; d) determining if a value or slope in the time-dependent measurement profile at a particular time is beyond a corresponding predetermined value or slope threshold; and if the value or slope in the time-dependent measurement profile is beyond the predetermined threshold, then determining an increased risk of thrombosis in the test subject.
- 126. The method according to claim 125, wherein the light beam is from a monochromatic light source in an automated coagulometer.
- 127. The method according to claim 125, wherein the sample is a whole blood or plasma sample from the individual.
- 128. The method according to claim 125, wherein the phospholipids are part of a coagulation reagent comprising thromboplastin.
- 129. The method according to claim 128, wherein the coagulation reagent is a PT reagent.
- 130. The method according to claim 129, wherein the phospholipids are vesicles or liposomes.
- 131. The method according to claim 125, wherein the phospholipids are not added to the test sample as part of a coagulation reagent.
- 132. The method according to claim 125, wherein the phospholipids are part of a coagulation reagent that comprises thromboplastin, and a halide salt.
- 133. The method according to claim 129, further comprising adding a metal cation or a salt of a metal cation.
- 134. The method according to claim 125, further comprising performing at least one confirmatory assay to determine the existence of antiphospholipid antibodies.
- 135. The method according to claim 134, wherein the at least one assay is a latex immunoassay or an ELISA.
- 136. The method according to claim 134, wherein the at least one confirmatory assay is an assay for anti-β2 glycoprotein, anti-prothrombin and anticardiolipin antibodies.
- 137. The method according to claim 125, wherein the individual is a patient taking an oral anticoagulant.
- 138. The method according to claim 134, further comprising treating the individual with an oral anticoagulant if antiphospholipid antibodies are determined.
- 139. The method according to claim 125, wherein the time-dependent measurement profile is an optical transmittance profile.
- 140. The method according to claim 139, wherein the optical transmittance profile is generated on a photo-optical coagulation analyzer.
- 141. The method according to claim 125, wherein the individual is one who has experienced spontaneous miscarriage or a thromboembolic event.
- 142. The method according to claim 125, further comprising performing an APTT assay on a sample from the individual to determine whether the APTT exhibits a prolonged clot time.
- 143. A method for monitoring the therapy of an individual having antiphospholipid syndrome, comprising:
a) providing a test sample from an individual with APS; b) combining the test sample with phospholipids; c) directing light at the test sample and monitoring light reflectance from or transmittance through the test sample over time so as to provide a time-dependent measurement profile; d) determining a value or slope in the time-dependent measurement profile; e) administering therapy to the individual; f) repeating steps a) to d); and g) comparing the values or slopes to each other in order to determine the efficacy of said therapy.
- 144. The method according to claim 143, wherein the therapy is the administration of an oral anticoagualant.
- 145. The method according to claim 143, wherein if the value decreases overtime or the slope increases over time, then it is determined that the individual's condition is worsening, and if the value increases over time or the slope decreases over time, then it is determined that the individual's condition is improving.
- 146. The method according to claim 143, wherein the vesicles or liposomes are added as part of a coagulation reagent.
- 147. The method according to claim 146, wherein the coagulation reagent is a DRVVT or PT reagent.
- 148. The method according to claim 146, wherein the INR of the sample is determined.
- 149. The method according to claim 148, wherein the value or slope and the INR are used to manage the therapy of the individual.
- 150. The method of claim 143, wherein the therapy is directed at reducing APLA antibodies.
- 151. A method for monitoring the therapy of an individual having antiphospholipid syndrome, comprising:
a) providing a test sample from an individual with APS; b) combining the test sample with a coagulation reagent, and added phospholipids c) monitoring the formation of fibrin polymerization over time so as to provide a time-dependent measurement profile; d) determining a value or slope in the time-dependent measurement profile prior to initiation of clot formation; e) administering therapy to the individual based on the value or slope determined.
- 152. The method according to claim 151, wherein the further the value or slope is beyond threshold, the greater the therapy provided to the individual.
- 153. The method according to claim 152, wherein the therapy is the administration of oral anticoagulant, and wherein the dosage of the oral anticoagulant is increased or decreased depending upon the value or slope determined.
- 154. A method for categorizing an individual as an acute risk individual within a population of APS individuals, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam at the test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; d) determining if a value or slope at a particular time in the time-dependent measurement profile is beyond a corresponding predetermined value or slope threshold; and if the value or slope in the time-dependent measurement profile is beyond the predetermined threshold, then determining that the APS individual is an acute risk individual.
- 155. The method according to claim 154, wherein the acute risk is an acute risk of a thrombotic event.
- 156. The method according to claim 154, wherein the acute risk is an acute risk of a miscarriage, SLE or autoimmune disorder.
- 157. The method according to claim 156, wherein the acute risk is an acute risk of SLE.
- 158. The method of claim 154, wherein the acute risk is an acute risk of thrombocytopenia.
- 159. A method for indirectly measuring a level of antiphospholipid antibodies in a test sample from a test subject with antiphospholipid syndrome, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam at the test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; d) determining the value or slope at a particular time in the time-dependent measurement profile; and correlating the value or slope to a level of antiphospholipid antibodies in the test sample.
- 160. The method of claim 159, wherein the antiphospholipid antibodies are anti-β2 glycoprotein, anti-prothrombin and/or anticardiolipin antibody.
- 161. The method of claim 160, wherein the level of anti-β2 glycoprotein or anticardiolipin is determined.
- 162. A method for predicting that an individual is at an increased likelihood for having antiphospholipid syndrome, comprising:
a) providing a test sample from an individual; b) combining the test sample with an APTT reagent; c) monitoring the formation of fibrin polymerization over time so as to provide a time-dependent measurement profile; d) defining a set of one or more predictor variables which sufficiently define the data of the time-dependent measurement profile; e) deriving a model that represents the relationship between the antiphospholipid syndrome and the one or more predictor variables; and f) utilizing the model of step e) to predict the increased likelihood of antiphospholipid syndrome in the individual.
- 163. The method of claim 162, wherein the time dependent measurement profile is at least one optical profile.
- 164. The method of claim 163, wherein the optical profile is provided by an automated analyzer for thrombosis and hemostasis testing.
- 165. The method of claim 162, wherein after step f, one or more assays for confirming the predicted antiphospholipid syndrome are performed.
- 166. The method of claim 165, wherein the one or more confirmatory assays are one or more immunoassays for antiphospholipid antibodies.
- 167. The method of claim 162, wherein the model is a neural network.
- 168. The method of claim 162, wherein the one or more parameters are selected from slope 1, clot time, tmin2, min2, tmin1, min1, tmax2, max2, slope 3 and delta.
- 169. The method of claim 168, wherein a plurality of parameters are used and are selected from slope 1, clot time, tmin2, tmin1, tmax2, max2, slope 3 and delta.
- 170. The method of claim 169, wherein the individual is not on oral anticoagulant therapy.
- 171. The method of claim 168, wherein a plurality of parameters are used, at least two of which are slope 1 and slope 3.
- 172. The method of claim 162, further comprising performing one or more confirmatory assays.
- 173. The method of claim 172, wherein the one or more confirmatory assays included assaying for C reactive protein or LC-CRP.
- 174. The method of claim 173, wherein the one or more confirmatory assays comprises an immunoassay for at least one antiphospholipid antibody.
- 175. The method of claim 174, wherein the antiphospholipid antibody is anti-β2 glycoprotein, anti-prothrombin and/or anticardiolipin antibody.
- 176. The method of claim 162, wherein the individual is on oral anticoagulant therapy.
- 177. The method of claim 162, further comprising performing a PT assay on a test sample from the individual and determining whether there is a slope 1 beyond a predetermined threshold.
- 178. The method of claim 168 further comprising running a second assay with an APTT reagent and phophorylcholine to determine whether slope 1 is inhibited.
- 179. The method of claim 162, wherein a single parameter is used and the model is a threshold.
- 180. A method for determining an increased risk of antiphospholipid syndrome, comprising:
a) adding an APTT reagent to an individual's test sample, b) performing a time dependent measurement profile on the test sample, c) determining whether the profile exhibits a slope or value beyond a predetermined threshhold prior to initiation of clot formation, and if so, d) repeating steps (a) to (c) except with an APTT reagent not comprising calcium so as to confirm the determination of antiphospholipid syndrome (or an increased likelihood of antiphospholipid syndrome) is the profile again exhibits a slope or value beyond a predetermined threshold.
- 181. A method for monitoring an individual, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam at the test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; d) determining if a value or a slope at or over a particular time in the time-dependent measurement profile is beyond a corresponding predetermined value or slope threshold; and if the value or slope in the time-dependent measurement profile is beyond the predetermined threshold, then determining that the individual has antiphospholipid syndrome or an increased risk of antiphospholipid syndrome.
- 182. A method for detecting antiphospholipid antibodies in a test sample, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam at the test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; d) determining if a value or a slope at or over a particular time in the time-dependent measurement profile is beyond a corresponding predetermined value or slope threshold; and if the value or slope in the time-dependent measurement profile is beyond the predetermined threshold, then determining that the individual has antiphospholipid antibodies.
- 183. A method for determining an increased likelihood that an individual will experience a clinical event due to an underlying APS, comprising:
a) providing a test sample from an individual; b) combining the test sample with phospholipids; c) directing a light beam at the test sample and monitoring light scattering or transmittance over time so as to provide a time-dependent measurement profile; d) determining if a value or a slope at or over a particular time in the time-dependent measurement profile is beyond a corresponding predetermined value or slope threshold; and if the value or slope in the time-dependent measurement profile is beyond the predetermined threshold, then determining that the individual has an increased likelihood of experiencing a clinical event due to underlying APS.
- 184. The method of claim 183, wherein the clinical event is SLE, miscarriage, thrombosis or an autoimmune disorder.
Parent Case Info
[0001] This application claims priority from U.S. Provisional Application No. 60/302,261 to Ortel, et al. filed Jun. 29, 2001 and to U.S. Provisional Application No. 60/318,755 to Ortel, et al. filed Sep. 11, 2001, each incorporated herein by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60302261 |
Jun 2001 |
US |
|
60318755 |
Sep 2001 |
US |