Evaluation of a heparin monitoring protocol for extracorporeal membrane oxygenation and review of the literature

Abstract

Background: Bleeding complications are common with extracorporeal membrane oxygenation (ECMO).We investigated whether a heparin monitoring protocol using activated partial thromboplastin time (aPTT) and thromboelastography (TEG) affected clinical outcomes. Methods: This retrospective chart review stratified cohorts by study interval: pre-protocol (January 2016-March 2017) or post-protocol (March 2017-December 2017. The protocol defined therapeutic anticoagulation as aPTT of 60-80 seconds and a TEG reaction (TEG-R) time of 2-4× baseline; pre-protocol management used aPTT alone. The primary endpoints were the rates of bleeding and thrombotic events (clinical/device thrombosis) as defined by Extracorporeal Life Support Organization (ELSO) guidelines.Secondary endpoints included time in therapeutic aPTT range, rate of physician compliance with the protocol, time to heparin initiation, intensive care unit length of stay, mortality, and antithrombin III (ATIII) supplementation.Results: The pre-protocol (n=72) and post-protocol (n=51) groups (age 60±12 years; 80% on venoarterial ECMO; average ECMO duration of 6 days) showed no difference in baseline characteristics. Major bleeding events occurred in 69% of pre-protocol patients, versus 67% of post-protocol patients (P=0.85). The post-protocol group had fewer retroperitoneal bleeds (P=0.01) and had a non-significantly lower rate of pulmonary or central nervous system (CNS) bleeding (P=0.07). Thrombotic events occurred in 21% of the pre-protocol group, versus 28% of the post-protocol group (P=0.39). Mortality during ECMO support was significantly lower in the post-protocol group (56.9% vs. 33.3%, P=0.01). The thrombosis rate was higher in patients who received ATIII than in those who did not (48.2% vs. 15.9%, P<0.01). Conclusions: Major bleeding did not differ between the treatment groups. However, we observed significantly less mortality and retroperitoneal bleeding in the post-protocol group, suggesting an important gain from the intervention. Further study of the value of ATIII supplementation in ECMO patients is needed since we observed that a lower baseline ATIII level may indicate higher risk for thrombosis.

Hemostasis, coagulation and thrombin in venoarterial and venovenous extracorporeal membrane oxygenation: the HECTIC study

“…In our study only about one half of aPTT values were within prescribed range. This number is lower than documented in previous prospective randomised studies 41 but higher than other cohort studies 42 and reflects the difficulty in accurately titrating heparin in ECMO patients. VA patients had a higher proportion of aPTTs above the therapeutic range despite lower total heparin dosage and anti-FXa levels.…”

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

“…Besides potential differences in treatment algorithms, these variations are most likely due to differing definitions and methods for assessing bleeding [ 5 , 18 , 21 ]. In our study, the rate of bleeding complications was numerically relatively high but was mainly related to the chosen definition of bleeding according to the ELSO classification [ 5 ] that is liberal compared to other definitions [ 22 , 23 ]. Considering only patients with either a drop in hemoglobin of ≥ 2 g/dl/day or a transfusion of ≥ 2 RBC/day, the incidence of major bleeding in our study was below 30%.…”

Thromboelastography-Guided Anticoagulant Therapy for the Double Hazard of Thrombohemorrhagic Events in COVID-19: A Report of 3 Cases

“…The effect of this cytokine storm on the endothelial surface may cause a pathophysiologic milieu like that found in patients on ECMO, as well as in patients who are post-resuscitative and recovering from trauma [ 11 , 28 ]. The persistence of fibrinolytic shutdown in all patients with COVID-19, regardless of whether the patient bled, reflects one of the interesting pathophysio-logic moments that defines the hypercoagulopathy of this novel disease [ 19 , 24 ].…”

“…As the storm abates, so too does the requirement of higher levels of anticoagulation, suggesting the need for intense hemostatic monitoring not just with the aPTT, but also with adjunctive TEG analysis. We have drawn from the experience of ECMO, whereby frequent monitoring by a specialized coagulation team follows the clinical pattern of aPTT, anti-factor Xa levels, and TEG to guide anticoagulation therapy [ 11 ]. For patients with COVID-19, we utilized the same strategy by following biochemical inflammatory markers, D-dimer, fibrinogen, aPTT, and TEG to guide anticoagulation.…”