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David J. Moliterno - One of the best experts on this subject based on the ideXlab platform.
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relationship between Activated Clotting Time and ischemic or hemorrhagic complications analysis of 4 recent randomized clinical trials of percutaneous coronary intervention
Circulation, 2004Co-Authors: Sorin J Brener, Michael A Lincoff, David J. Moliterno, Steven R Steinhubl, Katherine Wolski, Eric J TopolAbstract:Background— Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal Activated Clotting Time (ACT) for prevention of ischemic or hemorrhagic complications. Methods and Results— We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with hig...
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point of care ecarin Clotting Time versus Activated Clotting Time in correlation with bivalirudin concentration
Thrombosis Research, 2004Co-Authors: Ivan P. Casserly, Joel P Reginelli, Paul H Gibson, William A. Gray, Michael A. Lauer, Dean J Kereiakes, David J. MoliternoAbstract:Abstract Introduction: A thrombin inhibitor management (TIM) point-of-care test based upon the ecarin Clotting Time (ECT) has been developed. The ECT has been suggested to more accurately reflect the anti-coagulant effect of direct thrombin inhibitors compared with the Activated Clotting Time (ACT). We sought to examine the correlation of the TIM-ECT test with bivalirudin concentration in patients undergoing percutaneous coronary intervention (PCI), and to compare the performance of this test with the current standard (i.e., ACT). Materials and methods: In a multicenter study, blood samples were obtained at six pre-defined Time-points in 170 consecutive patients undergoing PCI using bivalirudin. For each sample, the TIM-ECT (citrated and non-citrated), ACT, and bivalirudin concentration was determined. Results: Considering samples from all Time-points (n=784), the correlations of TIM-ECT citrated, TIM-ECT non-citrated, and ACT with bivalirudin concentration were 0.96, 0.93, and 0.90, respectively. For samples collected at therapeutic levels of bivalirudin (n=353), the correlations of TIM-ECT citrated, TIM-ECT non-citrated, and ACT with bivalirudin concentration were lower, and showed a greater disparity between methods, with correlation coefficients of 0.75, 0.59, and 0.37, respectively. Prediction models based on the measured bivalirudin concentration were developed for TIM-ECT and ACT, and the coefficients of determination (r2) of actual versus predicted TIM-ECT and ACT were 0.91 and 0.81, respectively. Conclusions: In this PCI population, the TIM-ECT point-of-care test and ACT demonstrated a strong correlation with bivalirudin concentration. The TIM-ECT test had a higher correlation with bivalirudin concentration at therapeutic levels of the drug, and for individual samples appears to more consistently reflect the bivalirudin concentration compared with the ACT.
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correlation of point of care ecarin Clotting Time versus Activated Clotting Time with bivalirudin concentrations
American Journal of Cardiology, 2003Co-Authors: Kandice Kottkemarchant, Joel P Reginelli, Theresa Kaldus, Michael A Lincoff, Marco Roffi, David J. MoliternoAbstract:To rapidly and specifically monitor the anticoagulant effect of direct thrombin inhibitors, a thrombin inhibitor management (TIM) point-of-care test was developed (PharmaNetics, Inc., Morrisville, North Carolina), based upon the ecarin Clotting Time (ECT). This method utilizes the enzyme ecarin (from the venom of Echis carinatus) to convert prothrombin to meizothrombin. Meizothrombin catalyzes the conversion of fibrinogen to fibrin and is rapidly inhibited by direct thrombin inhibitors, such as bivalirudin. This assay has the particular advantage of being relatively specific for the effect of direct thrombin inhibitors, because heparins are poor inhibitors of meizothrombin. 1,2 The TIM-ECT test card may provide a more accurate measurement of direct thrombin inhibitor activity than current point-of-care assays. The purpose of this study was to compare the TIM-ECT test and 2 available Activated Clotting Time (ACT) methods with a central laboratory anti-Factor IIa assay for monitoring bivalirudin-mediated anticoagulation. ••• Consecutive patients who underwent non-emergency percutaneous coronary intervention (PCI) with bivalirudin at The Cleveland Clinic Foundation were enrolled into the study. The protocol was approved by the institutional review board, and all patients gave written informed consent. Patients were not allowed to receive lepirudin, argatroban, abciximab, epti fibatide, or tirofiban 72 hours before PCI. All unfractionated heparin was discontinued 12 hours before PCI and all fractionated heparins 24 hours before PCI. All patients received preprocedural aspirin. Information regarding patient demographics, laboratory data, procedural details, and serial postprocedural creatine kinase (CK, CK-MB) was prospectively collected. Clinical outcomes were assessed to 30-day follow-up. Arterial blood samples were collected at baseline (sample 1), after bivalirudin bolus and infusion initiation (sample 2), after glycoprotein IIb/IIIa inhibitor bolus and infusion initiation (sample 3), during the procedure (sample 4), and before sheath removal (sample 5). Samples were procured from a nonheparinized arterial sheath and were placed into a noncitrated tube (3 ml) and a 3.2% sodium citrate tube (2.7 ml). Immediately at collection, the noncitrated whole blood samples were tested with the Hemochron ACT (International Technidyne, Edison, New Jersey), CoaguChek Pro/DM ACT (Roche Diagnostics, Indianapolis, Indiana), and the TIM-ECT. After this, the citrated whole blood was tested with the TIM-ECT. The remaining citrated blood was promptly centrifuged, and the plasma was aliquoted into cryovials and frozen at 70°C for the bivalirudin concentration assay. The ACT measures the Time for whole blood to clot in the presence of an activating substance. 3,4 The Hemochron tube-based system uses a magnet in a rotating glass specimen tube that contains diatomaceous earth.5 As the blood clots, the magnet is displaced from the tube’ s bottom, thereby activating a proximity switch. Hemochron ACT values were truncated at a maximum of 999 seconds. The Pro/DM ACT is a cartridge-based system that uses tissue factor and sulfatides as activating substances. 6 The blood sample is drawn by capillary action into the reagent chamber, where it mixes with the chemical activators. The Time from application of blood to cessation of flow within the chamber is detected by an optical system and converted to an ACT equivalent. Pro/DM Clotting Times were truncated at a maximum of 500 seconds.
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effect of platelet glycoprotein iib iiia integrin blockade on Activated Clotting Time during percutaneous transluminal coronary angioplasty or directional atherectomy the epic trial
American Journal of Cardiology, 1995Co-Authors: David J. Moliterno, Robert M Califf, Frank V Aguirre, Keaven M Anderson, Kristina N Sigmon, Harlan F Weisman, Eric J TopolAbstract:Abstract The Activated Clotting Time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti-coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (>14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p
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effect of platelet glycoprotein iib iiia integrin blockade on Activated Clotting Time during percutaneous transluminal coronary angioplasty or directional atherectomy the epic trial
American Journal of Cardiology, 1995Co-Authors: David J. Moliterno, Robert M Califf, Frank V Aguirre, Keaven M Anderson, Kristina N Sigmon, Harlan F Weisman, Eric J TopolAbstract:The Activated Clotting Time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti-coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (> 14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p < 0.001) ACT when corrected for body weight. The ACT is increased approximately 35 seconds by the platelet IIb/IIIa receptor antagonist c7E3 Fab. This has important implications for dosing conjunctive heparin therapy and performing PTCA or directional coronary atherectomy in the setting of IIb/IIIa-directed therapy.
Eric J Topol - One of the best experts on this subject based on the ideXlab platform.
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relationship between Activated Clotting Time and ischemic or hemorrhagic complications analysis of 4 recent randomized clinical trials of percutaneous coronary intervention
Circulation, 2004Co-Authors: Sorin J Brener, Michael A Lincoff, David J. Moliterno, Steven R Steinhubl, Katherine Wolski, Eric J TopolAbstract:Background— Unfractionated heparin (UFH) is the most widely used antithrombin during percutaneous coronary intervention (PCI). Despite significant pharmacological and mechanical advancements in PCI, uncertainty remains about the optimal Activated Clotting Time (ACT) for prevention of ischemic or hemorrhagic complications. Methods and Results— We analyzed the outcome of all UFH-treated patients enrolled in 4 large, contemporary PCI trials with independent adjudication of ischemic and bleeding events. Of 9974 eligible patients, maximum ACT was available in 8369 (84%). The median ACT was 297 seconds (interquartile range 256 to 348 seconds). The incidence of death, myocardial infarction, or revascularization at 48 hours, by ACT quartile, was 6.2%, 6.8%, 6.0%, and 5.7%, respectively (P=0.40 for trend). Covariate-adjusted rate of ischemic complications was not correlated with maximal procedural ACT (continuous value, P=0.29). Higher doses of UFH (>5000 U, or up to 90 U/kg) were independently associated with hig...
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effect of abciximab versus tirofiban on Activated Clotting Time during percutaneous intervention and its relation to clinical outcomes observations from the target trial
American Journal of Cardiology, 2003Co-Authors: Ivan P. Casserly, Eric J Topol, Peter M Dibattiste, Richard A Lange, Christian W Hamm, Bernhard Meier, Nasser Lakkis, Derek P Chew, Gregg W Stone, David J CohenAbstract:Abstract Previous evidence suggests that the monoclonal antibody abciximab may have a more potent anticoagulant effect than small-molecule glycoprotein (GP) IIb/IIIa inhibitors. We prospectively reviewed collected heparin dose, Activated Clotting Time (ACT), and corresponding clinical outcome data from The Do Tirofiban and ReoPro Give Similar Efficacy Outcome Trial (TARGET), a direct comparison of tirofiban versus abciximab in patients who underwent percutaneous intervention. Of the 4,809 patients enrolled in the trial, 3,739 patients (78%) had an ACT measured after the administration of GP IIb/IIIa and heparin (peak procedural ACT); this formed the population for the present study. Mean total heparin dose was 75 ± 32 and 76 ± 31 U/kg in the tirofiban and abciximab groups, respectively. The resultant mean peak ACTs were 296 ± 91 and 299 ± 89 seconds (p = 0.09). In a subset of patients with both baseline ACT (before any heparin or GP IIb/IIIa therapy) and peak procedural ACT measurements, the difference in ACT between these Time points was 80 ± 97 vs 82 ± 101 seconds (p = 0.44) for the tirofiban and abciximab groups, respectively. After adjusting for patients’ weight, weight-adjusted heparin dose, and method of ACT measurement in a multiple linear regression analysis, the type of GP IIb/IIIa inhibitor was not predictive of the peak ACT (p = 0.24). When stratified by ACT quartile, no statistically significant difference in bleeding or ischemic end points between the tirofiban and abciximab cohorts was observed. In this large contemporary percutaneous coronary intervention trial, there was no observed difference in the anticoagulant effect of tirofiban and abciximab, as measured by the ACT, or in the incidence of bleeding or ischemic complications in each ACT quartile.
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effect of platelet glycoprotein iib iiia integrin blockade on Activated Clotting Time during percutaneous transluminal coronary angioplasty or directional atherectomy the epic trial
American Journal of Cardiology, 1995Co-Authors: David J. Moliterno, Robert M Califf, Frank V Aguirre, Keaven M Anderson, Kristina N Sigmon, Harlan F Weisman, Eric J TopolAbstract:Abstract The Activated Clotting Time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti-coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (>14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p
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effect of platelet glycoprotein iib iiia integrin blockade on Activated Clotting Time during percutaneous transluminal coronary angioplasty or directional atherectomy the epic trial
American Journal of Cardiology, 1995Co-Authors: David J. Moliterno, Robert M Califf, Frank V Aguirre, Keaven M Anderson, Kristina N Sigmon, Harlan F Weisman, Eric J TopolAbstract:The Activated Clotting Time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti-coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (> 14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p < 0.001) ACT when corrected for body weight. The ACT is increased approximately 35 seconds by the platelet IIb/IIIa receptor antagonist c7E3 Fab. This has important implications for dosing conjunctive heparin therapy and performing PTCA or directional coronary atherectomy in the setting of IIb/IIIa-directed therapy.
Robert M Califf - One of the best experts on this subject based on the ideXlab platform.
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relationship between Activated Clotting Time during percutaneous intervention and subsequent bleeding complications
American Heart Journal, 2002Co-Authors: William B Hillegass, James E Tcheng, Harry R Phillips, Richard S Stack, Brigitta C Brott, Gregory D Chapman, Robert M CaliffAbstract:Background Approximately 50% of percutaneous coronary interventions in the United States are performed with unfractionated heparin and no IIb/IIIa agent. The operator must weigh the risks and benefits of more intensive anticoagulation during these percutaneous interventions. This study helps clarify the relationship between patient and procedural factors, such as the intensity of heparin anticoagulation as measured by Activated Clotting Time (ACT), and the risk of blood loss and bleeding complications. Methods Four hundred twenty-nine patients undergoing elective or urgent percutaneous coronary intervention were followed up prospectively for 72 hours after intervention for clinical bleeding complications. Blood loss, defined as the difference between preprocedural and nadir postprocedural hematocrit adjusted for interval transfusions, was also tracked. In-laboratory ACTs, as well as other potential clinical and procedural predictors of blood loss and bleeding risk, were collected and analyzed. Results Maximum in-laboratory ACT was significantly related to blood loss as measured by the change in hematocrit (P =.017) and to the risk of major bleeding complications (P =.002). In multivariate analysis, patient age (P =.004), sex (P =.014), procedure length (P <.001), and additional interventions (P <.001) were significant, independent predictors of blood loss. Major bleeding complications were significantly, independently predicted by patient age (P <.001), additional interventions (P =.015), and maximum in-laboratory ACT (P <.001). Conclusions Compared with the other clinical and procedural predictors of bleeding complications, maximum in-laboratory ACT was second only to patient age in significance as a multivariate predictor of postprocedural bleeding complications. Maximum in-laboratory ACT was found to be the most significant modifiable univariate and multivariate predictor of clinical bleeding complications after percutaneous coronary intervention. Particularly in patients with nonmodifiable risk factors for blood loss and bleeding complications such as advanced age, female sex, and multiple and prolonged procedures, avoiding high intensity anticoagulation with unfractionated heparin is associated with lower bleeding risk. (Am Heart J 2002;144:501-7.)
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relation between Activated Clotting Time during angioplasty and abrupt closure
Circulation, 1996Co-Authors: Craig R Narins, William B Hillegass, Charlotte L Nelson, James E Tcheng, Robert A Harrington, Harry R Phillips, Richard S Stack, Robert M CaliffAbstract:Background The purpose of this study was to determine whether the degree of heparin anticoagulation during coronary angioplasty, as measured by the Activated Clotting Time, is related to the risk of abrupt vessel closure. Methods and Results Sixty-two cases of in- and out-of-laboratory abrupt closure in patients in whom intraprocedure Activated Clotting Times were measured were identified from a population of 1290 consecutive patients who underwent nonemergency coronary angioplasty. This group was compared with a matched control population of 124 patients who did not experience abrupt closure. Relative to the control population, patients who experienced abrupt closure had significantly lower initial (median, 350 seconds [25th to 75th percentile, 309 to 401 seconds] versus 380 seconds [335 to 423 seconds], P=.004) and minimum (345 seconds [287 to 387 seconds] versus 370 seconds [321 to 417 seconds], P=.014) Activated Clotting Times. Higher Activated Clotting Times were not associated with an increased like...
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effect of platelet glycoprotein iib iiia integrin blockade on Activated Clotting Time during percutaneous transluminal coronary angioplasty or directional atherectomy the epic trial
American Journal of Cardiology, 1995Co-Authors: David J. Moliterno, Robert M Califf, Frank V Aguirre, Keaven M Anderson, Kristina N Sigmon, Harlan F Weisman, Eric J TopolAbstract:Abstract The Activated Clotting Time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti-coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (>14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p
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effect of platelet glycoprotein iib iiia integrin blockade on Activated Clotting Time during percutaneous transluminal coronary angioplasty or directional atherectomy the epic trial
American Journal of Cardiology, 1995Co-Authors: David J. Moliterno, Robert M Califf, Frank V Aguirre, Keaven M Anderson, Kristina N Sigmon, Harlan F Weisman, Eric J TopolAbstract:The Activated Clotting Time (ACT) has been used during percutaneous transluminal coronary angioplasty (PTCA) to monitor the extent of thrombin inhibition and anti-coagulation from heparin in an attempt to minimize untoward thrombotic events and hemorrhagic complications. With the introduction of potent platelet inhibitors, such as the chimeric monoclonal antibody c7E3, to interventional cardiology, the utility of measuring and regulating procedural ACT has not been examined. To investigate the possible influence of platelet IIb/IIIa antagonism on procedural ACT, we reviewed data from the Evaluation of c7E3 Fab in the Prevention of Ischemic Complications (EPIC) trial. In the EPIC trial, 2,099 patients undergoing PTCA with a high risk of abrupt vessel closure were randomized to receive placebo (n = 696) or the IIb/IIIa platelet receptor antagonist c7E3 Fab (n = 1,403). Despite receiving less procedural heparin, and fewer patients receiving very high heparin doses (> 14,000 U) than the placebo group, those receiving c7E3 had a higher mean (401 vs 367 seconds, p < 0.001) ACT when corrected for body weight. The ACT is increased approximately 35 seconds by the platelet IIb/IIIa receptor antagonist c7E3 Fab. This has important implications for dosing conjunctive heparin therapy and performing PTCA or directional coronary atherectomy in the setting of IIb/IIIa-directed therapy.
George J Despotis - One of the best experts on this subject based on the ideXlab platform.
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heparin concentration based anticoagulation for cardiac surgery fails to reliably predict heparin bolus dose requirements
Anesthesia & Analgesia, 2009Co-Authors: Sean Garvin, George J Despotis, Daniel C Fitzgerald, Prem Shekar, Simon C BodyAbstract:BACKGROUND Hemostasis management has evolved to include sophisticated point-of-care systems that provide individualized dosing through heparin concentration–based anticoagulation. The Hepcon HMS Plus system (Medtronic, Minneapolis, MN) estimates heparin dose, Activated Clotting Time (ACT), and heparin dose response (HDR). However, the accuracy of this test has not been systematically evaluated in large cohorts.
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the plasma supplemented modified Activated Clotting Time for monitoring of heparinization during cardiopulmonary bypass a pilot investigation
Anesthesia & Analgesia, 2002Co-Authors: Andreas Koster, George J Despotis, Marcus Gruendel, Thomas Fischer, Michael Praus, Herman Kuppe, Jerrold H LevyAbstract:UNLABELLED: The standard celite or kaolin Activated Clotting Time (ACT) correlates poorly with heparin levels during cardiopulmonary bypass (CPB). We compared a modified kaolin ACT, in which plasma was supplemented, to a standard undiluted kaolin ACT for monitoring heparin levels during CPB. Fifteen patients undergoing normothermic CPB were enrolled in this prospective study. Heparin management was performed according to the Hepcon HMS results (Medtronic, Minneapolis, MN). The ACTs were performed with the ACT II device (Medtronic). Hepcon HMS calculations, standard kaolin ACTs, and plasma supplemented modified ACTs (mACTs), prepared by diluting blood samples 1:1 with human plasma (Behring, Marburg, Germany), were measured every 30 min during CPB. The data obtained were correlated to the plasma chromogenic anti-Xa activity as a reference assay for heparin levels. A total of 64 samples were evaluated. The chromogenic anti-Xa activity ranged from 0.2 to 5.5 IU/mL. The Hepcon HMS calculations ranged from 2.7-8.2 IU/mL of heparin, the standard ACT ranged from 424 to >999 s, and the mACT ranged from 210 to 801 s. The correlation to the chromogenic anti-Xa method was r = 0.43 for the standard kaolin ACT and r = 0.69 for the plasma mACT. The plasma mACT provided an improved correlation to chromogenically measured levels of anti-Xa activity during CPB. The improved correlation most likely results from a correction of the effects of the impairment of the coagulation system caused by hemodilution and consumption of procoagulants on extracorporeal surfaces. IMPLICATIONS: During cardiopulmonary bypass, the plasma modified kaolin Activated Clotting Time (ACT) provides a better correlation with heparin levels than the standard kaolin ACT.
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antithrombin iii concentrate to treat heparin resistance in patients undergoing cardiac surgery
The Journal of Thoracic and Cardiovascular Surgery, 2002Co-Authors: John H Lemmer, George J DespotisAbstract:Abstract Objective: The purpose of this report is to describe the clinical use of antithrombin III concentrate in 53 patients who were found, in the operating room before cardiopulmonary bypass, to be heparin resistant. Method: Resistance to heparin was determined to be present when greater than 600 U/kg body weight of heparin failed to prolong the kaolin-Activated Clotting Time to more than 600 seconds in 53 aprotinin-treated patients. Blood samples were obtained for subsequent antithrombin III activity determination. Patients were then administered 500 U of antithrombin III concentrate, and the Activated Clotting Time was remeasured. If the Activated Clotting Time remained less than 600 seconds, a second 500-U dose was given. Results: Of the 53 patients, 45 (85%) had subnormal measured antithrombin III activity, and the mean plasma antithrombin III activity level for the entire group was 67% (normal 80%-120%). Administration of antithrombin III concentrate (500 U in 45 patients and 1000 U in 8 patients) resulted in prolongation of the mean Activated Clotting Time from 492 to 789 seconds without additional heparin. The mean heparin dose response increased from 36.5 to 69.3 s·U –1 ·mL –1 with antithrombin III treatment. Only one patient did not achieve the target Activated Clotting Time, despite administration of greater than 600 U/kg heparin and 1000 U of antithrombin III concentrate, and was treated with fresh-frozen plasma. Conclusions: On the basis of the criterion used in this report, most of the patients defined as being heparin resistant had subnormal plasma antithrombin III activity. Treatment with antithrombin III concentrate resulted in potentiation of the heparin effect to meet predetermined Activated Clotting Time thresholds and allow for cardiopulmonary bypass.
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the relationship between hirudin and Activated Clotting Time implications for patients with heparin induced thrombocytopenia undergoing cardiac surgery
Anesthesia & Analgesia, 2001Co-Authors: George J Despotis, Charles W Hogue, Rao Saleem, Matthew Bigham, Nicholas Skubas, Ioanna Apostolidou, Assad Qayum, Heinrich J JoistAbstract:UNLABELLED: Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified Activated coagulation Time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r(2) = 0.83) linear relationships between ACT values and r-hirudin concentrations ( 999 s) at hirudin concentrations >2 microg/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4 microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 microg/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB. IMPLICATIONS: A modified Activated Clotting Time test system that may be helpful in monitoring hirudin anticoagulation in patients with heparin-induced thrombocytopenia during cardiac surgery with cardiopulmonary bypass is described.
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antithrombin iii during cardiac surgery effect on response of Activated Clotting Time to heparin and relationship to markers of hemostatic activation
Anesthesia & Analgesia, 1997Co-Authors: George J Despotis, Heinrich J Joist, Diane Joinermaier, Vladimir Levine, Edward L SpitznagelAbstract:This study was designed to determine if, and to what extent, antithrombin III (AT) levels affect the response of the Activated Clotting Time (ACT) to heparin in concentrations used during cardiac surgery, and to characterize the relationship between AT levels and markers of activation of coagulation during cardiopulmonary bypass (CPB).After informed consent, blood specimens obtained from eight normal volunteers (Phase I) were used to measure the response of the kaolin and celite ACT to heparin after in vitro addition of AT (200 U/dL) and after dilution with AT-deficient plasma to yield AT concentrations of 20, 40, 60, 80, and 100 U/dL. In Phase II, blood specimens collected before the administration of heparin and prior to discontinuation of CPB, were used to measure the response of the kaolin ACT to heparin (preheparin only), AT concentration, and a battery of coagulation assays in 31 patients undergoing repeat or combined cardiac surgical procedures. In Phase I, strong linear relationships were observed between kaolin (slope = 1.04 AT - 2, r2 = 0.78) and celite (slope = 1.36 AT + 6, r2 = 0.77) ACT slopes and AT concentrations below 100 U/dL. In the pre-CPB period of Phase II, only factors V (partial r = -0.49) and VIII (partial r = -0.63) were independently associated with heparin-derived slope using multivariate analysis; an inverse relationship was observed between AT and fibrinopeptide A levels (r = -0.41) at the end of CPB. Our findings indicate that the responsiveness of whole blood (ACT) to heparin at the high concentrations used with CPB is progressively reduced when the AT concentration decreases below 80 U/dL. Because AT is variably, and someTimes extensively, reduced in many patients before and during CPB, AT supplementation in these patients might be useful in reducing excessive thrombin-mediated consumption of labile hemostatic blood components, excessive microvascular bleeding, and transfusion of blood products. Implications: Heparin, a drug with anticoagulant properties, is routinely given to patients undergoing cardiac surgery to prevent clot formation within the cardiopulmonary bypass circuit. However, when levels are reduced, heparin is not as effective. Findings within this study indicate that administration of antithrombin III may help to preserve the hemostatic system during cardiopulmonary bypass. (Anesth Analg 1997;85:498-506)
Christoph K Hofer - One of the best experts on this subject based on the ideXlab platform.
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monitoring Activated Clotting Time for combined heparin and aprotinin application in vivo evaluation of a new aprotinin insensitive test using sonoclot
European Journal of Cardio-Thoracic Surgery, 2006Co-Authors: Michael T Ganter, Richard Klaghofer, Antoinette Monn, Reza Tavakoli, Michele Genoni, Lukas Furrer, Hanspeter Honegger, Christoph K HoferAbstract:Objective: Kaolin-based Activated Clotting Time assessed by HEMOCHRON (HkACT) is a clinical standard for heparin monitoring alone and combinedwithaprotininduringcardiopulmonarybypass(CPB).However,aprotininisknowntoprolongnotonlycelite-basedbut alsokaolin-based Activated Clotting Time. Overestimation of Activated Clotting Times implies a potential hazardous risk of subtherapeutic heparin anticoagulation. Recently, a novel ‘aprotinin-insensitive’ Activated Clotting Time test has been developed for the SONOCLOTanalyzer (SaiACT). The aim of our study was to evaluate SaiACT in patients undergoing CPB in presence of heparin and aprotinin. Methods: Blood samples were taken from 44 elective cardiac surgery patients at the following measurement Time points: baseline (T0); before CPB after heparinization (T1 and T2); on CPB, before administration of aprotinin (T3); 15, 30, and 60 min on CPB after administration of aprotinin (T4, T5, and T6); after protamine infusion (T7). On each measurement Time point, Activated Clotting Time was assessed with HkACTand SaiACT, both in duplicate. Furthermore, the rate of factor Xa inhibition and antithrombin concentration were measured. Statistical analysis was done using Bland and Altman analysis, Pearson’s correlation, and ANOVA with post hoc Bonferroni—Dunn correction. Results: Monitoring anticoagulation with SaiACTshowed reliable readings. Compared to the established HkACT, SaiACT values were lower at all measurement Time points. On CPB but before administration of aprotinin (T3), SaiACT values (mean SD) were 44 118 s lower compared to HkACT. However, the difference between the two measurement techniques increased significantly on CPB after aprotinin administration (T4—T6; 89 152 s, P= 0.032). Correlation of ACT measurements with anti-Xa activity was unchanged for SaiACT before and after aprotinin administration (r 2 = 0.473 and 0.487, respectively; P = 0.794), but was lower for HkACT after aprotinin administration (r 2 = 0.481 and 0.361, respectively; P = 0.041). On CPB after administration of aprotinin, 96% of all ACT values were classified as therapeutic by HkACT, but only 86% of all values were classified therapeutic if ACT was determined by SaiACT. Test variability was comparable for SaiACTand HkACT. Conclusions: The use of SaiACT may result in more consistent heparin management that is less affected by aprotinin and a corresponding increase in heparin administration for patients receiving aprotinin.
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effects of heparin haemodilution and aprotinin on kaolin based Activated Clotting Time in vitro comparison of two different point of care devices
Acta Anaesthesiologica Scandinavica, 2006Co-Authors: Seraina Dalbert, Andreas Zollinger, Michael T Ganter, Richard Klaghofer, L Furrer, Christoph K HoferAbstract:Background: During cardiopulmonary bypass (CPB), measurement of kaolin-based Activated Clotting Time (kACT) is a standard practice in monitoring heparin-induced anticoagulation. Despite the fact that the kACT test from the Sonoclot Analyzer (SkACT) has been commercially available for several years, no published data on the performance of SkACT are available. Thus, the aim of this in vitro study was to compare SkACT with an established kACT from Hemochron (HkACT). Methods: Blood was withdrawn from 25 patients before elective cardiac surgery. SkACT and HkACT were measured in duplicate after in vitro administration of heparin (0, 1, 2 and 3 U/ml), calcium-free lactated Ringer's solution (25% and 50% haemodilution) and aprotinin (200 kIU/ml). Results: A total of 600 duplicate kACT measurements were obtained from 25 cardiac surgery patients. Overall, mean bias ± SD between SkACT and HkACT was 7 ± 70 s (1.3% ± 14.1%). Administration of heparin, haemodilution and aprotinin induced a comparable effect on both Activated Clotting Time (ACT) tests. Mean bias ranged from −4 ± 39 s (−1.7% ± 12.9%) to 4 ± 78 s (3.2% ± 15.6%) for heparinzed blood samples after haemodilution or aprotinin application and increased after combined aprotinin administration and haemodilution. After haemodilution and administration of aprotinin, both ACT tests were less reliable for values >480 s in heparinized blood samples. Conclusion: Accuracy and performance of SkACT and HkACT were comparable after in vitro administration of heparin, aprotinin and haemodilution. Both ACT tests were considerably affected by aprotinin and haemodilution.
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monitoring Activated Clotting Time for combined heparin and aprotinin application an in vitro evaluation of a new aprotinin insensitive test using sonoclot
Anesthesia & Analgesia, 2005Co-Authors: Michael T Ganter, Seraina Dalbert, K Graves, Richard Klaghofer, Christoph K HoferAbstract:The kaolin-based Activated Clotting Time (ACT) is commonly used for monitoring heparin-induced anticoagulation alone and combined with aprotinin during cardiopulmonary bypass. However, aprotinin prolongs ACT measurements. Recently, a new so-called ‘aprotinin-insensitive‘ ACT test (SaiACT) has been d
