Dabigatran plasma levels, aPTT and thromboelastography in patients with AF: implications for allowing early non-elective surgical procedures

Abstract

According to current recommendations, patients on dabigatran should stop the drug 24-96 h before scheduled surgery. This may seem too long for non-elective cases. The aim of our study was to assess the number of patients on dabigatran who could theoretically undergo surgery 12 h post last drug dosing. We measured dabigatran plasma trough concentration by Hemoclot assay in 75 consecutive patients receiving dabigatran. Coagulation was assessed by aPTT and thromboelastography (TEG). Plasma levels ≤30 ng/ml were considered low. TEG parameters measured were clot reaction time (R), clot growth index (k), angle (α), maximal amplitude (MA) and the percentage of clot lysed after 30 min (LY30). Twelve patients (16%) had low plasma dabigatran levels 11.6 ± 0.9 h post last dosing. These patients compared to those with higher levels had significantly different aPTT (37.7 ± 4.4 vs. 49.6 ± 9.2 s; p < 0.001) and TEG R (6.7 ± 1.3 vs. 8.4 ± 2.6 min; p = 0.002). Only three of the patients with low levels had an aPTT >40 s. Within those with levels >30 ng/ml, four patients (6.4%) had plasma dabigatran levels ≥200 ng/ml, all with aPTT >65 s and TEG R >11 min. When the analysis was restricted to patients with creatinine clearance >80 ml/min, six (27.3%) had low plasma dabigatran levels. In this theoretical study, with a low risk population, it is suggested that one-sixth of patients receiving dabigatran have low drug concentrations at 12 h. Further studies are needed to confirm that such patients with low trough levels can actually undergo safely early surgery if necessary.

In vitro investigation of the effects of exogenous sugammadex on coagulation in orthopedic surgical patients

“…R time, k time, α angle, MRTG, and TMRTG were statistically different in factor Xa inhibitor or direct thrombin inhibitors when compared with the control. Pipilis and co-workers found that among 75 patients with atrial fibrillation, those with high plasma dabigatran concentrations exhibited an r time > 11 min and an aPTT > 65 s, with a correlation between the r time and aPTT [ 5 ]. In patients receiving warfarin, TEG and ROTEM showed an acceptable diagnostic value [ 13 ]; in addition, the PT-INR and TEG r times correlated with thrombin generation and were corrected after prothrombin complex administration in patients with intracranial bleeding who were treated with warfarin [ 14 ].…”

“…Thromboelastography (TEG) provides a real-time viscoelastic profile of patients, from the initial thrombin activation to fibrinolysis, and yields information not available through conventional coagulation studies. TEG is also used as a tool to assess the anticoagulation action of oral anticoagulant drugs [ 4 ] and to assist in clinical decisions for patients taking oral anticoagulants requiring urgent surgery [ 5 , 6 ]. The evaluation of the potential effects of drugs on coagulation variables is important because a combination of more than two drugs that affect coagulation may substantially increase a patient’s risk of bleeding [ 7 ].…”

Dabigatran Reversal With Idarucizumab in 2 Patients With Portal Vein Thrombosis Undergoing Orthotopic Liver Transplantation

“…The abnormalities seen in TEG on donated blood from healthy volunteers dabigatran showed a prolonged R time, decreased angle, and a decreased maximum amplitude, 47 while other studies have shown only a prolonged R time. 48 Reversal of dabigatran was difficult prior to the advent of targeted monoclonal therapies. Hemodialysis or the administration of prothrombin complex concentrate (PCC) were the most viable options.…”

Diagnostic performance of coagulation indices for direct oral anticoagulant concentration

“…Thromboelastography (TEG) is also a global coagulation assay since it measures the formation time of a fibrin clot [36]. The correlation of dabigatran levels with the TEG parameters is not significant except for reaction time-thromboelastography (R-TEG) [37]. Overall, it is less valuable due to low sensitivity, specificity, and high cost.…”