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William J. Martone - One of the best experts on this subject based on the ideXlab platform.
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Interaction of daptomycin with two Recombinant Thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 2008Co-Authors: Peggy S Webster, Frederick B Oleson, David L. Paterson, Charles F Arkin, Alexandra Mangili, Donald E. Craven, Dorothy M Adcock, Kimberly C. Lindfield, Andrew. G. Knapp, William J. MartoneAbstract:A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the Thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available Thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial Thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two Recombinant Thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial Thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.
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interaction of daptomycin with two Recombinant Thromboplastin reagents leads to falsely prolonged patient prothrombin time international normalized ratio results
Blood Coagulation & Fibrinolysis, 2008Co-Authors: Peggy S Webster, Frederick B Oleson, David L. Paterson, Charles F Arkin, Alexandra Mangili, Donald E. Craven, Dorothy M Adcock, Kimberly C. Lindfield, Andrew. G. Knapp, William J. MartoneAbstract:A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the Thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available Thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial Thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two Recombinant Thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial Thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.
James H Morrissey - One of the best experts on this subject based on the ideXlab platform.
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Thromboplastin composition affects the sensitivity of prothrombin time pt clotting tests to direct factor xa inhibitors
Blood, 2007Co-Authors: Stephanie A Smith, James H MorrisseyAbstract:Abstract Introduction: Thromboplastin reagents used for prothrombin time (PT) clotting assays vary in their sensitivity to anticoagulant drugs that directly inhibit Factor Xa (FXa). The International Sensitivity Index (ISI)/International Normalized Ratio (INR) system was introduced for monitoring warfarin, and corrects for differences in PT assay sensitivity. However, it does not adequately correct for differences in assay sensitivity to direct FXa inhibitors. The objective of this study was to determine how the composition of Thromboplastin reagents affects PT sensitivity to the novel oral, direct FXa inhibitor rivaroxaban and how this correlates with the INR. Methods: Several Recombinant Thromboplastin reagents were prepared using different concentrations of NaCl, tissue factor and phospholipids (PL). They also contained different % of phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). These locally prepared Thromboplastin reagents and five commercial Thromboplastin assays were evaluated. PT ratios (PTR = PT with drug/PT without drug) were measured using normal human plasma to which rivaroxaban 1 μg/mL was added in vitro. Some PTRs were converted to INRs using locally determined ISI. Results: PT obtained with commercial Thromboplastins was prolonged by rivaroxaban (Table), but the magnitude varied more than 3-fold, depending on the Thromboplastin. Converting PTR to INR failed to normalize these results and made discrepancies more pronounced. Using locally prepared Thromboplastin reagents, the PT sensitivity toward rivaroxaban was found to increase by decreasing the concentration of tissue factor or by increasing the concentration of PL or NaCl. Increasing the % PS generally decreased rivaroxaban sensitivity, while including PE generally increased rivaroxaban sensitivity. There was also a trend toward higher rivaroxaban sensitivity as the baseline PT increased. As with commercial Thromboplastins, converting these PTR values to INR frequently made the discrepancies more pronounced. Conclusions: Changing the composition of Thromboplastin reagents had disparate effects on the sensitivity of PT clotting tests to rivaroxaban. Furthermore, converting PTR values to INR failed to eliminate, and in some cases even exacerbated, the apparent differences in assay sensitivity of these PT clotting tests to rivaroxaban. This study sheds new light on the shortfall of the ISI/INR system to adequately correct for variation in the sensitivity of PT tests to direct FXa inhibitors. However, data show that other global clotting tests, such as PT, can be used to assess the efficacy of direct FXa inhibitors. Table 1: . PT results for normal plasma spiked with 1 μg/ml rivaroxaban using commercial Thromboplastins Commercial Thromboplastins ISI PTR INR Recombiplastin 0.94 5.07 4.60 Innovin 0.98 2.25 2.22 Thromborel S 1.07 2.37 2.52 Neoplastine CL+ 1.09 7.32 8.76 Thromboplastin C+ 1.50 3.77 7.31 INR, International Normalized Ratio; ISI, International Sensitivity Index; PTR, prothrombin time ratio
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Thromboplastin composition affects the sensitivity of prothrombin time pt clotting tests to direct factor xa inhibitors
Blood, 2007Co-Authors: Stephanie A Smith, James H MorrisseyAbstract:Introduction: Thromboplastin reagents used for prothrombin time (PT) clotting assays vary in their sensitivity to anticoagulant drugs that directly inhibit Factor Xa (FXa). The International Sensitivity Index (ISI)/International Normalized Ratio (INR) system was introduced for monitoring warfarin, and corrects for differences in PT assay sensitivity. However, it does not adequately correct for differences in assay sensitivity to direct FXa inhibitors. The objective of this study was to determine how the composition of Thromboplastin reagents affects PT sensitivity to the novel oral, direct FXa inhibitor rivaroxaban and how this correlates with the INR. Methods: Several Recombinant Thromboplastin reagents were prepared using different concentrations of NaCl, tissue factor and phospholipids (PL). They also contained different % of phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). These locally prepared Thromboplastin reagents and five commercial Thromboplastin assays were evaluated. PT ratios (PTR = PT with drug/PT without drug) were measured using normal human plasma to which rivaroxaban 1 μg/mL was added in vitro. Some PTRs were converted to INRs using locally determined ISI. Results: PT obtained with commercial Thromboplastins was prolonged by rivaroxaban (Table), but the magnitude varied more than 3-fold, depending on the Thromboplastin. Converting PTR to INR failed to normalize these results and made discrepancies more pronounced. Using locally prepared Thromboplastin reagents, the PT sensitivity toward rivaroxaban was found to increase by decreasing the concentration of tissue factor or by increasing the concentration of PL or NaCl. Increasing the % PS generally decreased rivaroxaban sensitivity, while including PE generally increased rivaroxaban sensitivity. There was also a trend toward higher rivaroxaban sensitivity as the baseline PT increased. As with commercial Thromboplastins, converting these PTR values to INR frequently made the discrepancies more pronounced. Conclusions: Changing the composition of Thromboplastin reagents had disparate effects on the sensitivity of PT clotting tests to rivaroxaban. Furthermore, converting PTR values to INR failed to eliminate, and in some cases even exacerbated, the apparent differences in assay sensitivity of these PT clotting tests to rivaroxaban. This study sheds new light on the shortfall of the ISI/INR system to adequately correct for variation in the sensitivity of PT tests to direct FXa inhibitors. However, data show that other global clotting tests, such as PT, can be used to assess the efficacy of direct FXa inhibitors.
Peggy S Webster - One of the best experts on this subject based on the ideXlab platform.
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Interaction of daptomycin with two Recombinant Thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 2008Co-Authors: Peggy S Webster, Frederick B Oleson, David L. Paterson, Charles F Arkin, Alexandra Mangili, Donald E. Craven, Dorothy M Adcock, Kimberly C. Lindfield, Andrew. G. Knapp, William J. MartoneAbstract:A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the Thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available Thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial Thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two Recombinant Thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial Thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.
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interaction of daptomycin with two Recombinant Thromboplastin reagents leads to falsely prolonged patient prothrombin time international normalized ratio results
Blood Coagulation & Fibrinolysis, 2008Co-Authors: Peggy S Webster, Frederick B Oleson, David L. Paterson, Charles F Arkin, Alexandra Mangili, Donald E. Craven, Dorothy M Adcock, Kimberly C. Lindfield, Andrew. G. Knapp, William J. MartoneAbstract:A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the Thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available Thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial Thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two Recombinant Thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial Thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.
P Sie - One of the best experts on this subject based on the ideXlab platform.
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control of oral anticoagulation in patients with the antiphospholipid syndrome influence of the lupus anticoagulant on international normalized ratio
Thrombosis and Haemostasis, 1998Co-Authors: A Robert, Le A Querrec, B Delahousse, C Caron, L Houbouyan, B Boutiere, M H Horellou, Guido Reber, P SieAbstract:The recommended therapeutic range of International Normalized Ratio (INR) for oral anticoagulant treatment in patients with the antiphospholipid syndrome remains controversial. As a part of this controversy, it has been suggested that lupus anticoagulants (LA) could interfere with the determination of prothrombin time, thus questioning the validity of monitoring the treatment of these patients using INR. To clarify this point, we compared the values of INR obtained in the plasmas of two groups of patients, one without LA (n = 47), and the other with LA (n = 43). INR were determined using 8 different Thromboplastin reagents on the same automated coagulation instrument. Chromogenic factor X, which is supposed to be insensitive to the presence of LA, was also measured. The results are the following: provided INR was calculated using calibrated reference plasmas, there was no significant difference between INR values obtained with the 8 reagents, both in the non-LA and in the LA groups (CV: 5.9 and 6.7%, respectively). Closer examination revealed that INR results obtained with one reagent (the Recombinant Thromboplastin Innovin) diverged from those of the 7 others, leading to an overestimation of INR, to a very large extent in some instances. However this effect was restricted to a subset of the patient population with LA (6 out of 43). Finally, the relationship between INR (average value obtained using the 8 reagents) and factor X was identical in non-LA and in LA patient groups. We conclude that, provided the reagents which display the LA interference are identified and excluded for this purpose, the INR system is valid for monitoring oral anticoagulant treatment in patients with LA.
David L. Paterson - One of the best experts on this subject based on the ideXlab platform.
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Interaction of daptomycin with two Recombinant Thromboplastin reagents leads to falsely prolonged patient prothrombin time/International Normalized Ratio results.
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 2008Co-Authors: Peggy S Webster, Frederick B Oleson, David L. Paterson, Charles F Arkin, Alexandra Mangili, Donald E. Craven, Dorothy M Adcock, Kimberly C. Lindfield, Andrew. G. Knapp, William J. MartoneAbstract:A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the Thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available Thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial Thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two Recombinant Thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial Thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.
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interaction of daptomycin with two Recombinant Thromboplastin reagents leads to falsely prolonged patient prothrombin time international normalized ratio results
Blood Coagulation & Fibrinolysis, 2008Co-Authors: Peggy S Webster, Frederick B Oleson, David L. Paterson, Charles F Arkin, Alexandra Mangili, Donald E. Craven, Dorothy M Adcock, Kimberly C. Lindfield, Andrew. G. Knapp, William J. MartoneAbstract:A cluster of patients experiencing elevations of International Normalized Ratio without clinical bleeding in temporal association with daptomycin therapy was identified during postmarketing safety surveillance. A common element was the Thromboplastin reagent used for the laboratory assay. The present study evaluated the effect of daptomycin on measured prothrombin time using commercially available Thromboplastin reagent kits commonly used in the United States. Thirty reagent kits were obtained. Daptomycin was added to pooled normal human plasma samples to achieve final concentrations of 0-200 μg/ml. Quality control ranges were established for each reagent kit using normal and abnormal control plasmas. Triplicate assays of the prothrombin time were performed on the daptomycin-spiked plasma samples using each of the 30 kits. The activated partial Thromboplastin time and thrombin time were also assessed. Statistical comparisons of interest were performed using analysis of variance with the Bonferroni t-test for multiple comparisons; α = 0.05 was used. Addition of daptomycin to human plasma samples dose-dependently prolonged measured prothrombin times when two Recombinant Thromboplastin reagents were utilized. The findings were statistically and clinically significant. No clinically meaningful effect was observed with the other reagents. The activated partial Thromboplastin time and thrombin time were not affected. Prolonged International Normalized Ratio patient values were an artifact caused by the interaction of daptomycin with the in-vitro prothrombin time test reagent; an in-vivo anticoagulant effect was not observed. Healthcare providers should consider a possible drug-laboratory test interaction if prolonged prothrombin time or elevated International Normalized Ratio values are observed in patients receiving daptomycin.