Association of aPTT-Guided Anticoagulation Monitoring with Thromboembolic Events in Patients Receiving V-A ECMO Support: A Systematic Review and Meta-Analysis

Abstract

Background: The initiation of extracorporeal membrane oxygenation (ECMO) is associated with complex inflammatory and coagulatory processes, raising the need for systemic anticoagulation. The balance of anticoagulatory and procoagulant factors is essential, as therapeutic anticoagulation confers a further risk of potentially life-threatening bleeding. Therefore, our study aims to systematize and analyze the most recent evidence regarding anticoagulation monitoring and the thromboembolic events in patients receiving veno-arterial ECMO support. Methods: Using the PRISMA guidelines, we systematically searched the Scopus and PubMed databases up to October 2022. A weighted effects model was employed for the meta-analytic portion of the study. Results: Six studies comprising 1728 patients were included in the final analysis. Unfractionated heparin was used for anticoagulation, with an activated partial thromboplastin time (aPTT) monitoring goal set between 45 and 80 s. The majority of studies aimed to investigate the incidence of adverse events and potential risk factors for thromboembolic and bleeding events. None of the authors found any association of aPTT levels with the occurrence of thromboembolic events. Finally, the most frequent adverse events were hemorrhage (pooled 43%, 95% CI 28.4; 59.5) and any kind of thrombosis (pooled 36%, 95% CI 21.7; 53.7), and more than one-half of patients did not survive to discharge (pooled 54%). Conclusions: Despite the tremendous development of critical care, aPTT-guided systemic anticoagulation is still the standard monitoring tool. We did not find any association of aPTT levels with thrombosis. Further evidence and new trials should clarify the true incidence of thromboembolic events, along with the best anticoagulation and monitoring strategy in veno-arterial ECMO patients.

Association of anti‐factor Xa‐guided anticoagulation with hemorrhage during ECMO support: A systematic review and meta‐analysis

“… 9 , 35 , 36 However, the true incidence of thrombosis remains uncertain due to potential underestimation in retrospective and observational studies. 37 , 38 …”

Extracorporeal Membrane Oxygenation (VA-ECMO) in Management of Cardiogenic Shock

“…There is currently no clear consensus on anticoagulation strategy and management differs significantly between patients, though current ELSO guidelines for anticoagulation during ECMO recommend an initial heparin infusion rate of 7.5-20.0 units/kg/h [88,89]. Furthermore, the conventional recommendation, based largely on expert opinion, is regular monitoring of coagulation studies and using unfractionated heparin to target an activated clotting time of 180 to 220 s, a partial thromboplastin time (aPPT) target in the 60-80 range, and anti-Xa level in the 0.3-0.7 IU/mL range [2,4,10,11,[89][90][91]. Although anticoagulation has been thought to be standard practice, a recent report demonstrated the safety and efficacy of VA-ECMO support without anticoagulation.…”

Subtypes and Mechanistic Advances of Extracorporeal Membrane Oxygenation-Related Acute Brain Injury

“…Although ischemic stroke is more common in VA ECMO (3.6–5.3%), it also occurs in VV ECMO patients (1.7–2%) [ 5 , 10 , 25 , 27 , 28 ]. However, one study reported that the true prevalence is also underestimated, and a rate of 11% was reported recently [ 29 ]. The pathology of ischemic stroke, occurring in the frontal neocortex, basal ganglia, anterior hypophysis, and cerebellum [ 2 ], is territorial, such that embolism may be the underlying mechanism [ 30 , 31 ].…”

“…Of these, a range of 1.5 to 2.5 times the patient’s baseline APTT (40–80 s) or a goal of 180–220 s for ACT is mostly used in cases of thromboembolism or bleeding risk [ 66 , 67 ]. However, the most appropriate anticoagulation monitoring tests is still missing, and recently, it was reported that the levels of APTT did not show any association with bleeding or thrombosis [ 29 , 68 ]. In addition, low-molecular-weight heparin (LMWH) is widely used to prevent and treat venous thromboembolism.…”