Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study

Abstract

Background: There is no consensus on the management of anticoagulation during extracorporeal membrane oxygenation (ECMO). ECMO is currently burdened by a high rate of hemostatic complications, possibly associated with inadequate monitoring of heparin anticoagulation. This study aims to assess the safety and feasibility of an anticoagulation protocol for patients undergoing ECMO based on thromboelastography (TEG) as opposed to an activated partial thromboplastin time (aPTT)-based protocol.

Methods: We performed a multicenter, randomized, controlled trial in two academic tertiary care centers. Adult patients with acute respiratory failure treated with veno-venous ECMO were randomized to manage heparin anticoagulation using a TEG-based protocol (target 16-24 min of the R parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5-2 of aPTT ratio, aPTT group). Primary outcomes were safety and feasibility of the study protocol.

Results: Forty-two patients were enrolled: 21 were randomized to the TEG group and 21 to the aPTT group. Duration of ECMO was similar in the two groups (9 (7-16) days in the TEG group and 11 (4-17) days in the aPTT group, p = 0.74). Heparin dosing was lower in the TEG group compared to the aPTT group (11.7 (9.5-15.3) IU/kg/h vs. 15.7 (10.9-21.3) IU/kg/h, respectively, p = 0.03). Safety parameters, assessed as number of hemorrhagic or thrombotic events and transfusions given, were not different between the two study groups. As for the feasibility, the TEG-based protocol triggered heparin infusion rate adjustments more frequently (p < 0.01) and results were less frequently in the target range compared to the aPTT-based protocol (p < 0.001). Number of prescribed TEG or aPTT controls (according to study groups) and protocol violations were not different between the study groups.

Conclusions: TEG seems to be safely used to guide anticoagulation management during ECMO. Its use was associated with the administration of lower heparin doses compared to a standard of care aPTT-based protocol. Trial registration ClinicalTrials.gov, October 22,2014. Identifier: NCT02271126.

Keywords: Anticoagulation; Extracorporeal membrane oxygenation; Hemorrhage; Heparin; Thromboelastography; Thrombosis.

Fig. 1

During the first 12 h after ECMO cannulation, the algorithm was identical in the two study groups. After the first 12 h according to randomization, the anticoagulation management was modified according to the assigned study group: In the TEG group (intervention group), heparin infusion was titrated to reach a target TEG-K reaction time (R-K) of 16–24 min (normal values: 4–8 min); in the aPTT group (standard of care–control group), heparin infusion was titrated to reach a target aPTT ratio value of 1.5–2. Under-target levels of anticoagulation were corrected with either heparin bolus plus increase in infusion or with increase in infusion only; similarly, over-target levels of anticoagulation were corrected with either heparin infusion stop for 30 or 60 min and restart with a reduced dose or with decrease in infusion only. Time to the next control varied according to the degree of derangement from target values of anticoagulation. In case of surgery, minimal levels of anticoagulation (i.e., R-K of 8–12 min and aPTT ratio of 1.2–1.3, in the study and control group, respectively) were tolerated during the first 24 h after the operation. In case of bleeding, heparin infusion was reduced to the lower value of the target range or interrupted based on the severity of bleeding

Fig. 2

Flow diagram. We assessed 64 patients for eligibility. Of these, patients 22 were excluded. We enrolled and randomly assigned the remaining 42 to the aPTT or TEG arm. Thirty-one patients were enrolled in the Fondazione Ca’ Granda (Milan, Italy) center and 11 patients in the ISMETT (Palermo, Italy) center

Fig. 3

aPTT ratio and R-K values during study days in patients randomized to the aPTT group (panel A) and to the TEG group (panel B). Lines are lowess smoothing. Reference lines: 1.5–2 for the aPTT ratio and 16–24 min for the R time. 56.5% of the analysis was in range in the aPTT group compared to 29.8% in the TEG group (p < 0.001). aPTT activated partial thromboplastin time ratio, R-K TEG reaction time, TEG thromboelastography