Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry – a prospectively controlled randomized double-blind clinical trial

Abstract

BackgroundArgatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population.Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients.MethodsThis study was part of the double-blind randomized trial “Argatroban versus Lepirudin in critically ill patients (ALicia)”, which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor.ResultsTo reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01–1.2] μg/ml argatroban and 0.17 [0.1–0.32] μg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs.Conclusion In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT.Trial registrationClinicalTrials.gov, NCT00798525, registered on 25 Nov 2008Electronic supplementary materialThe online version of this article (10.1186/s12871-018-0475-y) contains supplementary material, which is available to authorized users.

Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19

“…So in critically ill patients, TEG parameters may provide better correlation to argatroban plasma concentrations than aPTT. 18 The concentration of unfractionated heparin is best correlated with the level of anti-Xa and the R time of TEG. 19 The R time in TEG corresponds to the CT of the EX test in ClotPro.…”

The role of rotational thromboelastometry during the COVID-19 pandemic: a narrative review

“…The argatroban plasma concentrations needed for therapeutic anticoagulation range from 0.2 IU/ml to 0.5 IU/ml of anti-IIa activity. Here, EXTEM CT correlated better with argatroban plasma concentrations than aPTT (r = 0.71; P < 0.001 and r = 0.214; P = 0.117, respectively) [ 73 , 74 ]. Furthermore, the importance of VET in patients treated with direct thrombin inhibitors was highlighted by Ranucci et al [ 75 ] and Maier et al [ 76 ].…”

“…Accordingly, close monitoring of all hematologic parameters, including VET and personalized antithrombotic therapy, is recommended in patients with severe COVID-19, particularly during ECMO support [ 29 ]. The degree of anticoagulation can be assessed based on the anti-Xa activity or INTEM/HEPTEM CT-ratio for UFH, anti-Xa activity or NATEM/NAHEPTEM CT-ratio for LMWH, and anti-IIa activity, EXTEM CT, or ECATEM/ECA-test CT for IV direct thrombin inhibitors such as argatroban and bivalirudin [ 65 , 73 , 74 , 85 – 90 ]. Furthermore, the hemostatic phenotype of COVID-19 patients may change from hyper- to hypocoagulability and from hypo- to hyperfibrinolysis during advanced stages of COVID-19 in case of DIC [ 21 , 55 ].…”

Case Report: Hypergranular Platelets in Vaccine-Induced Thrombotic Thrombocytopenia After ChAdOx1 nCov-19 Vaccination

“…Dabigatran (univalent DTI) and fondaparinux (indirect Factor Xa inhibitor) were used in the treatment of our patient and their effects, coupled with IVIg, were immediate with platelet count and D-dimer levels resolving drastically over the first several days post admission. Dabigatran was administered rather than argatroban to deliver robust anticoagulation—unhampered by argatroban monitoring challenges ( 22 )—and due to dabigatran's reversibility while platelet count was reduced and bleeding risk high.…”