scholarly journals Evaluation of Bivalirudin’s Effect on International Normalized Ratio to Determine an Appropriate Strategy for Transitioning to Warfarin

2018 ◽  
Vol 34 (3) ◽  
pp. 117-122
Author(s):  
Andrea Fetea ◽  
Brian E. Gulbis ◽  
Andrea C. Hall
Keyword(s):  
Primary Endpoint ◽  
Major Bleeding ◽  
Partial Thromboplastin Time ◽  
International Normalized Ratio ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Limited Data ◽  
Heparin Induced Thrombocytopenia ◽  
Secondary Endpoints

Background: Direct thrombin inhibitors are recommended in confirmed or suspected heparin-induced thrombocytopenia. False elevation of the international normalized ratio (INR) occurs with these agents making bridging to warfarin challenging. There is limited data regarding bivalirudin’s effect on INR. Objective: To evaluate bivalirudin’s effect on the INR and determine a strategy for transitioning to warfarin. Methods: This was a retrospective observational study. Included patients were >18 years old receiving primary bridging therapy with overlapping bivalirudin and warfarin for at least 72 hours. Patients with administration of alternate anticoagulants during the transition interval or active major bleeding within 48 hours prior to bivalirudin initiation were excluded. The primary endpoint was to determine the effect on INR at first therapeutic activated partial thromboplastin time after bivalirudin initiation and prior to warfarin initiation. Secondary endpoints included change in INR 12 and 24 hours after bivalirudin initiation, change in INR 4 hours after bivalirudin cessation, and incidence of major bleeding or new thrombotic events. Results: Thirty-four patients met study criteria. For the primary endpoint, the change in INR at first therapeutic activated partial thromboplastin time was 0.37 (range = 0.28-0.48), which occurred at 8.4 hours (range = 4.6-14.2; n = 14). INR increased at 12 and 24 hours by a median of 0.55 and 0.5 from baseline, respectively. Median change in INR 4 to 8 hours post-bivalirudin cessation was −0.48. Conclusion: Targeting an INR > 2.5 when bridging to warfarin will account for this false elevation and maintain an INR above 2.0 on bivalirudin discontinuation.

scholarly journals Direct Thrombin Inhibitor Resistance and Possible Mechanisms

2016 ◽  
Vol 51 (11) ◽  
pp. 922-927 ◽  
Author(s):  
Maria Cardinale ◽  
Michael Ha ◽  
Michael H. Liu ◽  
David P. Reardon
Keyword(s):  
International Normalized Ratio ◽  
Resistance Mechanisms ◽  
Direct Thrombin Inhibitor ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Heparin Induced Thrombocytopenia ◽  
Vein Thrombosis ◽  
Inhibitor Resistance ◽  
Deep Vein

Objective To report 3 cases in which doses of bivalirudin higher than commonly used in clinical practice were required in order to achieve therapeutic anticoagulation as monitored by the activated partial thromboplastin time (aPTT). Case Summary The medical records of 3 patients who required large doses of bivalirudin to remain therapeutic were thoroughly reviewed. In all 3 patients, bivalirudin was initiated at a rate appropriate for the patients' renal function and titrated using a nurse-driven protocol with recommended dose adjustments based on aPTT. Indications for bivalirudin were anticoagulation in intra-aortic balloon pump, treatment of deep vein thrombosis, and heparin-induced thrombocytopenia with thrombosis. Target aPTT was achieved between 25.5 and 134 hours after initiation despite appropriate titration intervals per protocol. Discussion Bivalirudin is a direct thrombin inhibitor frequently used off-label for the medical management of heparin-induced thrombocytopenia. It typically exhibits predictable, dose-dependent anticoagulation. Heparin-induced thrombocytopenia was suspected in 2 of the 3 cases and confirmed in 1. In all 3 patients, target aPTT was initially achieved with doses between 0.456 and 1.0 mg/kg/h after a median of 30.7 hours; up to 1.8 mg/kg/h was required to maintain therapeutic aPTT. In 2 of the cases, the international normalized ratio also increased unexpectedly upon achievement of therapeutic aPTT values. Conclusion Direct thrombin inhibitors may be subject to resistance mechanisms similar to those previously described in patients receiving heparin. The anticoagulation status of these patients remains unknown.

Transition from argatroban to oral anticoagulation with phenprocoumon or acenocoumarol: effects on prothrombin time, activated partial thromboplastin time, and Ecarin Clotting Time

2004 ◽  
Vol 91 (06) ◽  
pp. 1137-1145 ◽  
Author(s):  
Jochen Graff ◽  
Ute Klinkhardt ◽  
Nils von Hentig ◽  
Jeanine Walenga ◽  
Hikari Watanabe ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Combined Treatment ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Sensitivity Index ◽  
Clotting Time ◽  
Ecarin Clotting Time

SummaryTreatment with the direct thrombin inhibitor argatroban (ARG) is often followed by vitamin K-antagonist treatment (VKA). Phenprocoumon (PC) and acenocoumarol (AC) are frequently used in Europe. The standard monitoring test for VKA, prothrombin time (PT), is prolonged by direct thrombin inhibitors. Therefore the International Normalized Ratio (INR) obtained during combined treatment does not reflect the true effect of the VKA. A similar interference of the VKA on the activated partial thromboplastin time (aPTT), a monitoring assay for direct thrombin inhibitors, can occur. In 39 healthy volunteers the effect of ARG alone or combined with PC or AC on PT, INR, aPTT, and Ecarin Clotting Time (ECT) was investigated. 6 groups each of 6-8 volunteers received a 5-hour infusion of either 1.0, 2.0 or 3.0 µg/kg/min ARG (days 1, 3, 4 and 5) before initiation of either PC or AC (day 1) and during continued VKA dosing (target INR 2-3). A linear relationship (INR ARG+VKA = intercept + slope * INR VKA alone) was observed between the INR measured “on” and “off” ARG.The slope depended on the argatroban dose and on the International Sensitivity Index (ISI) of the PT reagent, the steepest slope (i.e., the largest difference between INR ARG+VKA and INR VKA alone) was seen with the highest ARG dose and the PT reagent with an ISI of 2.13.There was a close correlation between plasma levels of ARG and aPTT or ECT. Under VKA the ARG-aPTT relationship indicated an increased sensitivity of the aPTT to ARG, VKA treatment had no effect on the prolongation of the ECT induced by argatroban. In conclusion, ARG at doses up to 2 µg/kg/min can be discontinued at an INR of 4.0 on combined therapy with VKA, as this would correspond to an INR between 2.2 and 3.7 for the VKA. If it is necessary to monitor ARG in the critical transition period, the ECT which is not influenced by VKA can be used as an alternative to the aPTT.

scholarly journals Transitioning from Argatroban to Warfarin Therapy in Patients with Heparin-induced Thrombocytopenia

2005 ◽  
Vol 11 (3) ◽  
pp. 279-287 ◽  
Author(s):  
Marcie J. Hursting ◽  
Bruce E. Lewis ◽  
Donald E. Macfarlane
Keyword(s):  
Major Bleeding ◽  
Warfarin Therapy ◽  
International Normalized Ratio ◽  
Activated Partial Thromboplastin Time ◽  
Adverse Outcomes ◽  
Thrombin Inhibitor ◽  
Complication Rates ◽  
Median Dose ◽  
Heparin Induced Thrombocytopenia ◽  
Baseline Platelet Count

Argatroban, a direct thrombin inhibitor used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT), is routinely monitored using the activated partial thromboplastin time (aPTT) yet also prolongs the international normalized ratio (INR). Peritransitional INRs, aPTTs, anticoagulant dosing patterns, and outcomes were evaluated in 165 HIT patients who were transitioned, without guidelines, from argatroban to warfarin therapy. Argatroban (median doses: 1.5-2.0 mcg/kg/min) and warfarin (median dose: 5 mg initially with 3.8 mg/day thereafter) overlapped a median 4 days. Median (5-95th percentile) aPTTs (in seconds) and INRs, respectively, were 59.8 (38.8-82.9) and 3.2 (1.7-7.0) during argatroban monotherapy, 68.6 (44.5-104) and 5.3 (2.4-16) maximally during cotherapy, 59.9 (38.7-92.2) and 4.0 (2.2-11.6) immediately before argatroban cessation during cotherapy, and 36.0 (25.6-60.2) and 2.3 (1.3-7.3) within a median 10-12 hours after argatroban cessation. Major bleeding occurred in 1 (0.6%) patient pretransitionally and no patient during or after cotherapy. Eighteen (10.9%) patients experienced 19 peritransitional adverse outcomes (one death, two amputations, 16 new thromboses); these patients had more severe HIT than event-free patients (median baseline platelet count, 39 vs. 83 × 109/L). Of 108 patients with post-transitional INR data, 43 achieved a therapeutic INR (prospectively defined as 1.9-3.5), 34 were subtherapeutic, and 31 were supratherapeutic, with no across-group trend in new thrombosis. Hence in the absence of guidelines, physicians transfer patients from argatroban to warfarin therapy with acceptably low complication rates in HIT, without systematically over- or under-dosing warfarin. Furthermore, INRs greater than 5 commonly occur in HIT patients during argatroban monotherapy and argatroban/warfarin cotherapy, without major bleeding.

Abstract 15944: Fondaparinux: A Low-hanging Fruit in Heparin-induced Thrombocytopenia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
José P Sousa ◽  
rogerio teixeira ◽  
Carolina Lourenço ◽  
Lino Gonçalves
Keyword(s):  
Primary Endpoint ◽  
Retrospective Studies ◽  
Meta Analysis ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Bleeding Events ◽  
Heparin Induced Thrombocytopenia ◽  
Life Threatening ◽  
Thrombotic Complications ◽  
Related Mortality

Introduction: Heparin-induced thrombocytopenia (HIT) is a life-threatening disease associated with thromboembolic complications. Therefore, its treatment should comprise non-heparin anticoagulants. As opposed to direct thrombin inhibitors (DTI) and danaparoid, fondaparinux use is generally regarded as off-label. Purpose: To perform a meta-analysis to appraise fondaparinux efficacy and safety in the setting of HIT. Methods: We systematically searched Embase, MEDLINE, Web of Science, Cochrane CENTRAL and Google Scholar databases, using the terms “heparin-induced thrombocytopenia” and “fondaparinux”, form inception to June 1, 2020. Studies targeting thrombotic complications, bleeding events, platelet count and mortality were included. The primary endpoint was a composite of arterial and venous thromboembolism, amputation, gangrene and HIT-related mortality. Therapeutic arms were those of fondaparinux and a standard non-heparin anticoagulant. A random-effects model with Mantel-Haenszel method was performed to calculate pooled odds ratios (OR) and their 95% confidence interval (CI). Results: We encompassed 7 retrospective studies, which accounted for 630 patients, of which 302 were under fondaparinux. The remaining were treated with danaparoid, argatroban, lepirudin or bivalirudin. There were 109 primary endpoint events, 80 hemorrhages, 13 persistent or recurring thrombocytopenia cases and 98 deaths. Fondaparinux was found not only to numerically reduce thromboembolism (6 studies, OR 0.28, 95% CI 0.06-1.20, P 0.09, i 2 45%) but also to significantly lessen primary endpoint events (7 studies, OR 0.26, 95% CI 0.10-0.67, P 0.006, i 2 66%). In parallel, a tendency towards a lower rate of bleeding with fondaparinux use was also unveiled (7 studies, OR 0.78, 95% CI 0.50-1.21, P 0.27, i 2 0%). Likewise, thrombocytopenia cases were less common in the fondaparinux arm (4 studies, OR 0.16, 95% IC 0.05-0.57, P 0.004, i 2 0%). Finally, fondaparinux use was also associated with a survival benefit (6 studies, OR 0.26, 95% IC 0.08-0.90, P 0.03, i 2 54%). Conclusions: Fondaparinux seems to be at least as safe and more effective than other non-heparin anticoagulants, in the setting of HIT. Prospective studies are needed to demonstrate this hypothesis.

scholarly journals Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Christoph Fisser ◽  
Maren Winkler ◽  
Maximilian V. Malfertheiner ◽  
Alois Philipp ◽  
Maik Foltan ◽  
...  
Keyword(s):  
Propensity Score ◽  
Extracorporeal Membrane Oxygenation ◽  
Major Bleeding ◽  
University Hospital ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Heparin Induced Thrombocytopenia ◽  
Membrane Oxygenation ◽  
Technical Complications ◽  
Venovenous Extracorporeal Membrane Oxygenation

Abstract Background During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. Methods We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). Results Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). Conclusion In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

Sign in / Sign up

Export Citation Format

Share Document