Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial

Abstract

IntroductionCritically 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.MethodsFollowing 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.ResultsWe 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.ConclusionsThis 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.Trial registrationClinical Trials.gov NCT00798525. Registered 25 November 2008Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0588-8) contains supplementary material, which is available to authorized users.

Citrate Formulation Determines Filter Lifespan during Continuous Veno-Venous Hemofiltration: A Prospective Cohort Study

“…Regional citrate anticoagulation for CRRT was first described by Mehta et al [11] . Before, systemic UFH was the anticoagulant of choice; yet it was associated with suboptimal FLS, bleeding, and heparin-induced thrombocytopenia and thrombosis (HITT) [15,20,[22][23][24] . Premature mechanical filter failure due to clotting was also often observed and contributed to increased bedside workload and costs [2] .…”

“…Premature mechanical filter failure due to clotting was also often observed and contributed to increased bedside workload and costs [2] . Recent evidence suggests that anticoagulation with citrate maintains filter patency during CRRT better than heparin with less bleeding risk and no HITT development [12,18,24] . To date, citrate anticoagulation practice relies on local protocols, customization of citrate replacement solutions, or regional pharmacy compounding.…”

Anticoagulants in children and adolescents

“…There are no prospective studies evaluating lepirudin in children, and this drug appears to cause more bleeding than the others. 35,36 Furthermore, it is no longer marketed and thus not a therapeutic option.…”

Spontaneous Left Renal Subcapsular Hematoma and Right Hip Hematoma in a Hemodialysis Patient: A Case Report and Review of the Literature

“…Anticoagulants for hemodialysis used in China are as follows: (1) common heparin is cheap but can cause bleeding, (2) low molecular weight heparin can reduce the risk of bleeding, but still has potential risk of bleeding because of its long half-life and is difficult to be cleared through dialysis [13] , (3) regional citrate anticoagulation, although studies have shown that the proportion of bleeding complications is less than that of common heparin, as ordinary dialysate contains calcium ions, it only applies to CRRT which dialysate composition can be regulated [14] and (4) recently, some new anticoagulant drugs (such as argatroban and lepirudin) are used for hemodialysis in exceptional circumstances such as thrombocytopenia [15] . A meta-analysis showed that argatroban can significantly reduce the incidence of thrombosis and coagulation in pipeline without increasing mortality and risk of bleeding [16] .…”