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Andreas Greinacher - One of the best experts on this subject based on the ideXlab platform.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
2016Co-Authors: Petra Eichler, Norbert Lubenow, Heinz-juergen Friesen, Bernd Jaeger, Andreas GreinacherAbstract:Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with Lepirudin: incidence, effects on aPTT, and clinical relevanc
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Lubenow N. Recombinant hirudin in clinical practice: focus on Lepirudin. Circulation 2001;103:1479–84
2016Co-Authors: Andreas Greinacher, Md Norbert LubenowAbstract:Abstract—Clinical applications for recombinant hirudins have been investigated for the past 10 years. The first indication for which a hirudin—Lepirudin—has been approved is treatment of heparin-induced thrombocytopenia (HIT). Also, the recently completed trials for use of Lepirudin in unstable angina indicate a potentially new indication. This review describes pharmacology and clinical applications of Lepirudin with an emphasis on HIT and unstable angina. An overview of usage of Lepirudin in acute coronary syndromes is given, as well as a summary of rare indications for Lepirudin, such as extracorporeal circulation, for which comprehensive data are lacking. (Circulation. 2001;103:1479-1484.) Key Words: recombinant hirudin n platelets n thrombosis n cardiovascular diseases n heparin Hirudin was used for the first parenteral anticoagulation inhumans in 19091 and as the anticoagulant for the first hemodialysis in humans.2 Soon after, heparin became avail-able and has since become the most widely used drug for parenteral anticoagulation. Heparin, however, can induce a life-threatening adverse immune reaction, heparin-induced thrombocytopenia (HIT), which up to 3 % of patients receiv-ing unfractionated heparin (UFH) for.5 days will develop.
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argatroban versus Lepirudin in critically ill patients alicia a randomized controlled trial
Critical Care, 2014Co-Authors: Tanja Treschan, Andreas Greinacher, Patrick Werner, Astrid Bahlmann, Tobias Brezina, Maximilian S Schaefer, Johann Geib, Elisabeth Golla, B Pannen, Detlef KindgenmillesAbstract:Introduction: Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and Lepirudin in critically ill surgical patients. Methods: Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or Lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events. Results: We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus Lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI −13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven Lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P =0 .040). In the argatroban-group, three thromboembolic events occurred compared to two in the Lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population. Conclusions: This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.
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Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial
Critical care (London England), 2014Co-Authors: Tanja Treschan, Andreas Greinacher, Patrick Werner, Astrid Bahlmann, Tobias Brezina, Maximilian S Schaefer, Johann Geib, Elisabeth Golla, B Pannen, Detlef Kindgen-millesAbstract:Introduction Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and Lepirudin in critically ill surgical patients.
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differences in the clinically effective molar concentrations of four direct thrombin inhibitors explain their variable prothrombin time prolongation
Thrombosis and Haemostasis, 2005Co-Authors: Theodore E. Warkentin, Andreas Greinacher, S Craven, Lori Dewar, Joann I Sheppard, F A OfosuAbstract:Four direct thrombin inhibitors (DTIs), Lepirudin, bivalirudin, argatroban, and melagatran, differ in their ability to prolong the prothrombin time (PT).Paradoxically,the DTI in clinical use with the lowest affinity for thrombin (argatroban) causes the greatest PT prolongation.We compared the effects of these DTIs on various clotting assays and on inhibition of human and bovine factor Xa (FXa). On a mole-for-mole basis, Lepirudin was most able to prolong the PT, activated partial thromboplastin time (APTT), and thrombin clotting time (TCT), whereas argatroban had the least effect.At concentrations that doubled the APTT (argatroban, 1 µ mol/l; melagatran, 0.5 µ mol/l; bivalirudin, 0.25 µ mol/l; Lepirudin, 0.06 µ mol/l), the rank order for PT prolongation was: argatroban > melagatran > bivalirudin > Lepirudin.Although the Ki’s associated with inhibition of human FXa by melagatran (1.4 µ mol/l) and argatroban (3.2 µ mol/l) approach their therapeutic concentrations, inhibition of FXa did not appear to be a major contributor to PT prolongation, since argatroban also prolonged the PT of bovine plasma (despite a Ki for bovine FXa of 2,600 µ mol/l). Only melagatran inhibited prothrombinase-bound FXa. We conclude that the differing effects of the DTIs on PT prolongation are primarily driven by their respective molar plasma concentrations required for clinical effect. DTIs with a relatively low affinity for thrombin require high plasma concentrations to double the APTT; these higher plasma concentrations, in turn, quench more of the thrombin generated in the PT,thereby more greatly prolonging the PT.
John T Owings - One of the best experts on this subject based on the ideXlab platform.
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effects of pentasaccharide fondaparinux and direct thrombin inhibitors on coagulation testing
Archives of Pathology & Laboratory Medicine, 2004Co-Authors: Robert C Gosselin, Jeffrey H King, Edward C Larkin, Kim A Janatpur, William H Dager, John T OwingsAbstract:Abstract Context.—Direct thrombin inhibitors (DTIs) and fondaparinux represent a new class of anticoagulants. The effects of DTIs on activated partial thromboplastin time and prothrombin time measurements have been reported previously, but there are limited data on the impact of these anticoagulants on other coagulation tests. Objective.—To determine the effects of fondaparinux and 3 DTIs (argatroban, bivalirudin, and Lepirudin) on miscellaneous coagulation tests. Design.—Bivalirudin, Lepirudin, argatroban, and fondaparinux were added to pooled normal plasma and tested for fibrinogen, antithrombin (thrombin and Xa substrate methods), plasminogen, protein C (clot and chromogenic methods), protein S, von Willebrand factor, D-dimer, lupus anticoagulant testing (dilute Russell viper venom test [DRVVT] with ratio), and factors II, IX, and X activities. Results.—We found no drug interference on antithrombin, plasminogen, chromogenic protein C, von Willebrand factor, or D-dimer results. All DTIs falsely decrease...
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effect of direct thrombin inhibitors bivalirudin Lepirudin and argatroban on prothrombin time and inr values
American Journal of Clinical Pathology, 2004Co-Authors: Robert C Gosselin, William E. Dager, Jeffrey H King, Kim A Janatpour, Kathleen Mahackian, Edward C Larkin, John T OwingsAbstract:Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. Unfortunately, DTIs not only prolong the activated partial thromboplastin time but also can affect international normalized ratio (INR) values. We approximated the DTI effect on INRs by each drug to pooled plasma at concentrations between 0.1 and 1.2 microg/mL. We then concurrently tested these samples using 14 prothrombin time (PT) reagents. By using repeated measures analysis of variance, we found significant differences (P < .05) between the median INRs for Lepirudin and argatroban for all PT reagents, between Lepirudin and bivalirudin for all reagents except PT-Fibrinogen HS Plus (P = .07), and between bivalirudin and argatroban for all reagents except Thromborel S (P = .05). The DTI effect on INRs was dependent on drug, drug concentration, and reagent. Argatroban had the most effect on INRs, while Lepirudin had the least effect. Reagents with a lower international sensitivity index were less affected by DTI; ThromboMax HS was the least sensitive PT reagent to any DTI.
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Lepirudin in Heparin-Induced Thrombocytopenia and Extracorporeal Membranous Oxygenation
The Annals of pharmacotherapy, 2004Co-Authors: William E. Dager, Robert C Gosselin, Richard Yoshikawa, John T OwingsAbstract:OBJECTIVETo report a case of intermediate-probability suspected heparin-induced thrombocytopenia (HIT) treated with Lepirudin in a patient requiring continuous extracorporeal membranous oxygenation (ECMO).CASE SUMMARYA 17-year-old girl was admitted with multiple traumatic injuries including severe bilateral pulmonary contusions. Within 48 hours, she developed progressive pulmonary failure despite mechanical ventilation, and was placed on ECMO. Anticoagulation of the ECMO circuit was facilitated by unfractionated heparin (UFH). The platelet count of 116 × 103/mm3 after initiation of ECMO gradually decreased over 5 days to 44 × 103/mm3. On ECMO day 5, a highly positive enzyme-linked immunosorbent assay for HIT antibodies was reported, and the UFH infusion was discontinued. Lepirudin was immediately started with a bolus of 0.1 mg/kg, followed by an infusion of 0.12 mg/kg/h, with a target activated partial thromboplastin time (aPTT) ratio approximately 2 times control. The ECMO circuit was maintained without ...
Job Harenberg - One of the best experts on this subject based on the ideXlab platform.
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Lepirudin bei heparininduzierter Thrombozytopenie - Grundlagen und aktueller Erkenntnisstand zur klinischen Anwendung
Hämostaseologie, 2004Co-Authors: Job Harenberg, I. Jörg, S. Koch, Tivadar FenyvesiAbstract:Heparin-induced thrombocytopenia (HIT) type II is an antibody mediated severe adverse event to heparin with a paradoxical decrease of platelet count and an increased risk for thromboembolic complications. The antibodies are directed against a neoepitop of platelet factor 4 after its binding to heparin. The incidence of HIT type II is lower with low-molecular-weight heparin compared to unfractionated heparin and lower in not operated patients compared to those after major surgery. In patients with HIT type II alternative anticoagulation has to be performed immediately due to the high thrombogenicity of the antibodies. The recombinant hirudin Lepirudin (Refludan®) is the anticoagulant drug of choice. A long-term anticoagulation has to be performed depending on the concomitant risk factors, intravenous administration followed by subcutaneous Lepirudin overlapping with vitamin K antagonists.
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Lepirudin for therapeutic use in heparin-induced thrombocytopenia
Hamostaseologie, 2004Co-Authors: Job Harenberg, I. Jörg, S. Koch, Tivadar FenyvesiAbstract:Heparin-induced thrombocytopenia (HIT) type II is an antibody mediated severe adverse event to heparin with a paradoxical decrease of platelet count and an increased risk for thromboembolic complications. The antibodies are directed against a neoepitop of platelet factor 4 after its binding to heparin. The incidence of HIT type II is lower with low-molecular-weight heparin compared to unfractionated heparin and lower in not operated patients compared to those after major surgery. In patients with HIT type II alternative anticoagulation has to be performed immediately due to the high thrombogenicity of the antibodies. The recombinant hirudin Lepirudin (Refludan) is the anticoagulant drug of choice. A long-term anticoagulation has to be performed depending on the concomitant risk factors, intravenous administration followed by subcutaneous Lepirudin overlapping with vitamin K antagonists.
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effects of Lepirudin argatroban and melagatran and additional influence of phenprocoumon on ecarin clotting time
Thrombosis Research, 2003Co-Authors: Tivadar Fenyvesi, Ingrid Jorg, Christel Weiß, Job HarenbergAbstract:Introduction: Direct thrombin inhibitors (DTI) prolong the ecarin clotting time (ECT). Oral anticoagulants (OA) decrease prothrombin levels and thus interact with actions of DTIs on the ECT method during concomitant therapy. Materials and methods: Actions of Lepirudin, argatroban and melagatran on ECT were investigated in normal plasma (NP) and in plasma of patients (n=23 each) on stable therapy with phenprocoumon (OACP). Individual line characteristics were tested statistically. Results: Control ECT in OACP was prolonged compared to NP (50.1F0.9 vs. 45.7F0.8 s; p<0.001). Lepirudin prolonged the ECT linearly. Argatroban and melagatran delivered biphasic dose– response curves. OA showed additive effects on the ECT of Lepirudin but not of argatroban and melagatran. Both in NP and OACP, the first and second slopes of melagatran were steeper compared to argatroban (primary analysis; p<0.001). When using the same drug, slopes in OACP were steeper than in NP (secondary analysis; p<0.001). At similar molar concentrations, the crossing points of both slopes were significantly higher with melagatran (323.1F11.0 s in NP and 333.2F8.2 s in OACP) than with argatroban (219.6F14.7 and 248.4F15.2 s) corresponding to ratios of 7.1F0.2 and 6.7F0.2 (melagatran) vs. 4.8F0.3 and 4.9F03 with argatroban (p<0.0001). Discussion: The patterns of interactions between vitamin K antagonists and DTI effects are different for bivalent (increase of slope without affecting linearity) and monovalent inhibitors (slight increase or alteration of nonlinear slopes), but there are also differences between the two monovalent inhibitors on thrombin inhibition as determined by ECT. D 2003 Elsevier Ltd. All rights reserved.
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Effects of Lepirudin, argatroban and melagatran and additional influence of phenprocoumon on ecarin clotting time.
Thrombosis research, 2003Co-Authors: Tivadar Fenyvesi, Ingrid Jorg, Christel Weiß, Job HarenbergAbstract:Direct thrombin inhibitors (DTI) prolong the ecarin clotting time (ECT). Oral anticoagulants (OA) decrease prothrombin levels and thus interact with actions of DTIs on the ECT method during concomitant therapy. Actions of Lepirudin, argatroban and melagatran on ECT were investigated in normal plasma (NP) and in plasma of patients (n=23 each) on stable therapy with phenprocoumon (OACP). Individual line characteristics were tested statistically. Control ECT in OACP was prolonged compared to NP (50.1+/-0.9 vs. 45.7+/-0.8 s; p<0.001). Lepirudin prolonged the ECT linearly. Argatroban and melagatran delivered biphasic dose-response curves. OA showed additive effects on the ECT of Lepirudin but not of argatroban and melagatran. Both in NP and OACP, the first and second slopes of melagatran were steeper compared to argatroban (primary analysis; p<0.001). When using the same drug, slopes in OACP were steeper than in NP (secondary analysis; p<0.001). At similar molar concentrations, the crossing points of both slopes were significantly higher with melagatran (323.1+/-11.0 s in NP and 333.2+/-8.2 s in OACP) than with argatroban (219.6+/-14.7 and 248.4+/-15.2 s) corresponding to ratios of 7.1+/-0.2 and 6.7+/-0.2 (melagatran) vs. 4.8+/-0.3 and 4.9+/-03 with argatroban (p<0.0001). The patterns of interactions between vitamin K antagonists and DTI effects are different for bivalent (increase of slope without affecting linearity) and monovalent inhibitors (slight increase or alteration of nonlinear slopes), but there are also differences between the two monovalent inhibitors on thrombin inhibition as determined by ECT.
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effect of phenprocoumon on monitoring of Lepirudin argatroban melagatran and unfractionated heparin with the pict method
Pathophysiology of Haemostasis and Thrombosis, 2002Co-Authors: Tivadar Fenyvesi, Ingrid Jorg, Job HarenbergAbstract:Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors Lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.
Steven R. Deitcher - One of the best experts on this subject based on the ideXlab platform.
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Risk of anaphylaxis after reexposure to intravenous Lepirudin in patients with current or past heparin-induced thrombocytopenia.
Mayo Clinic proceedings, 2005Co-Authors: Gustavo A. Cardenas, Steven R. DeitcherAbstract:OBJECTIVE To retrospectively assess the signs and symptoms indicative of adverse reactions to repeated exposures to Lepirudin in patients with heparin-induced thrombocytopenia who received at least 2 courses of Lepirudin therapy. PATIENTS AND METHODS Medical records were retrospectively assessed from adult patients who received at least 2 courses of Lepirudin therapy separated by at least 1 week between January 1999 and June 2002 at The Cleveland Clinic, Cleveland, Ohio. We evaluated the list of 289 low-level terms for possible signs and symptoms of anaphylactic reactions in the medical dictionary for regulatory activities as well as patient vital signs to detect manifestations of immediate hypersensitivity reactions. Vital signs from the day before initiation of Lepirudin therapy were compared with those from days 1 and 2 after exposure. RESULTS No cases of anaphylaxis or allergic reaction related to Lepirudin administration were identified among 43 adult patients. On day 1 of Lepirudin, 10 patients had lower systolic blood pressures (by =20 mm Hg) than pre-Lepirudin values, and 4 patients had systolic blood pressures of less than 100 mm Hg. CONCLUSIONS Isolated asymptomatic decreases in blood pressure after patient reexposure to Lepirudin most likely do not reflect anaphylaxis due to Lepirudin. We believe that isolated and uncommon cases of anaphylaxis temporally related to Lepirudin exposure should not preclude its use in patients with heparin-induced thrombocytopenia and past Lepirudin exposure.
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Lepirudin anticoagulation for heparin-induced thrombocytopenia
The Journal of pediatrics, 2002Co-Authors: Steven R. Deitcher, Arthur P. Topoulos, John R. Bartholomew, Maryanne R. Kichuk-chrisantAbstract:Abstract Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT). We describe 2 cases of HIT and thrombosis in children with heart disease, including one that required extracorporeal membrane oxygenation. Lepirudin, dosed in the recommended adult weight–based fashion, was an effective antithrombotic agent in pediatric patients with HIT. (J Pediatr 2002;140:264-6)
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Outpatient management of venous thromboembolic disease with subcutaneous Lepirudin: a case report.
Journal of thrombosis and thrombolysis, 2002Co-Authors: Susan M. Begelman, Steven R. DeitcherAbstract:Outpatient treatment of deep venous thrombosis has gained widespread acceptance and is facilitated by the use of subcutaneous low molecular weight heparins (LMWH). We report two patients in whom subcutaneous Lepirudin was used for long term anticoagulation after heart transplant or surgical pulmonary embolectomy because treatment with LMWH or warfarin was contraindicated, unsuccessful, or impractical. Neither bleeding complications nor recurrent thromboses developed. Subcutaneous Lepirudin may be safely and effectively employed for the outpatient treatment of venous thrombosis in selected cases including patients with heparin-induced thrombocytopenia and in those who fail LMWH.
Tivadar Fenyvesi - One of the best experts on this subject based on the ideXlab platform.
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Lepirudin bei heparininduzierter Thrombozytopenie - Grundlagen und aktueller Erkenntnisstand zur klinischen Anwendung
Hämostaseologie, 2004Co-Authors: Job Harenberg, I. Jörg, S. Koch, Tivadar FenyvesiAbstract:Heparin-induced thrombocytopenia (HIT) type II is an antibody mediated severe adverse event to heparin with a paradoxical decrease of platelet count and an increased risk for thromboembolic complications. The antibodies are directed against a neoepitop of platelet factor 4 after its binding to heparin. The incidence of HIT type II is lower with low-molecular-weight heparin compared to unfractionated heparin and lower in not operated patients compared to those after major surgery. In patients with HIT type II alternative anticoagulation has to be performed immediately due to the high thrombogenicity of the antibodies. The recombinant hirudin Lepirudin (Refludan®) is the anticoagulant drug of choice. A long-term anticoagulation has to be performed depending on the concomitant risk factors, intravenous administration followed by subcutaneous Lepirudin overlapping with vitamin K antagonists.
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Lepirudin for therapeutic use in heparin-induced thrombocytopenia
Hamostaseologie, 2004Co-Authors: Job Harenberg, I. Jörg, S. Koch, Tivadar FenyvesiAbstract:Heparin-induced thrombocytopenia (HIT) type II is an antibody mediated severe adverse event to heparin with a paradoxical decrease of platelet count and an increased risk for thromboembolic complications. The antibodies are directed against a neoepitop of platelet factor 4 after its binding to heparin. The incidence of HIT type II is lower with low-molecular-weight heparin compared to unfractionated heparin and lower in not operated patients compared to those after major surgery. In patients with HIT type II alternative anticoagulation has to be performed immediately due to the high thrombogenicity of the antibodies. The recombinant hirudin Lepirudin (Refludan) is the anticoagulant drug of choice. A long-term anticoagulation has to be performed depending on the concomitant risk factors, intravenous administration followed by subcutaneous Lepirudin overlapping with vitamin K antagonists.
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effects of Lepirudin argatroban and melagatran and additional influence of phenprocoumon on ecarin clotting time
Thrombosis Research, 2003Co-Authors: Tivadar Fenyvesi, Ingrid Jorg, Christel Weiß, Job HarenbergAbstract:Introduction: Direct thrombin inhibitors (DTI) prolong the ecarin clotting time (ECT). Oral anticoagulants (OA) decrease prothrombin levels and thus interact with actions of DTIs on the ECT method during concomitant therapy. Materials and methods: Actions of Lepirudin, argatroban and melagatran on ECT were investigated in normal plasma (NP) and in plasma of patients (n=23 each) on stable therapy with phenprocoumon (OACP). Individual line characteristics were tested statistically. Results: Control ECT in OACP was prolonged compared to NP (50.1F0.9 vs. 45.7F0.8 s; p<0.001). Lepirudin prolonged the ECT linearly. Argatroban and melagatran delivered biphasic dose– response curves. OA showed additive effects on the ECT of Lepirudin but not of argatroban and melagatran. Both in NP and OACP, the first and second slopes of melagatran were steeper compared to argatroban (primary analysis; p<0.001). When using the same drug, slopes in OACP were steeper than in NP (secondary analysis; p<0.001). At similar molar concentrations, the crossing points of both slopes were significantly higher with melagatran (323.1F11.0 s in NP and 333.2F8.2 s in OACP) than with argatroban (219.6F14.7 and 248.4F15.2 s) corresponding to ratios of 7.1F0.2 and 6.7F0.2 (melagatran) vs. 4.8F0.3 and 4.9F03 with argatroban (p<0.0001). Discussion: The patterns of interactions between vitamin K antagonists and DTI effects are different for bivalent (increase of slope without affecting linearity) and monovalent inhibitors (slight increase or alteration of nonlinear slopes), but there are also differences between the two monovalent inhibitors on thrombin inhibition as determined by ECT. D 2003 Elsevier Ltd. All rights reserved.
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Effects of Lepirudin, argatroban and melagatran and additional influence of phenprocoumon on ecarin clotting time.
Thrombosis research, 2003Co-Authors: Tivadar Fenyvesi, Ingrid Jorg, Christel Weiß, Job HarenbergAbstract:Direct thrombin inhibitors (DTI) prolong the ecarin clotting time (ECT). Oral anticoagulants (OA) decrease prothrombin levels and thus interact with actions of DTIs on the ECT method during concomitant therapy. Actions of Lepirudin, argatroban and melagatran on ECT were investigated in normal plasma (NP) and in plasma of patients (n=23 each) on stable therapy with phenprocoumon (OACP). Individual line characteristics were tested statistically. Control ECT in OACP was prolonged compared to NP (50.1+/-0.9 vs. 45.7+/-0.8 s; p<0.001). Lepirudin prolonged the ECT linearly. Argatroban and melagatran delivered biphasic dose-response curves. OA showed additive effects on the ECT of Lepirudin but not of argatroban and melagatran. Both in NP and OACP, the first and second slopes of melagatran were steeper compared to argatroban (primary analysis; p<0.001). When using the same drug, slopes in OACP were steeper than in NP (secondary analysis; p<0.001). At similar molar concentrations, the crossing points of both slopes were significantly higher with melagatran (323.1+/-11.0 s in NP and 333.2+/-8.2 s in OACP) than with argatroban (219.6+/-14.7 and 248.4+/-15.2 s) corresponding to ratios of 7.1+/-0.2 and 6.7+/-0.2 (melagatran) vs. 4.8+/-0.3 and 4.9+/-03 with argatroban (p<0.0001). The patterns of interactions between vitamin K antagonists and DTI effects are different for bivalent (increase of slope without affecting linearity) and monovalent inhibitors (slight increase or alteration of nonlinear slopes), but there are also differences between the two monovalent inhibitors on thrombin inhibition as determined by ECT.
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effect of phenprocoumon on monitoring of Lepirudin argatroban melagatran and unfractionated heparin with the pict method
Pathophysiology of Haemostasis and Thrombosis, 2002Co-Authors: Tivadar Fenyvesi, Ingrid Jorg, Job HarenbergAbstract:Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors Lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.