To the Editor,
We read with extreme interest the updated Extracorporeal Life Support (ELSO) guidelines for anticoagulation during extracorporeal membrane anticoagulation (ECMO)1 and would like to integrate this valuable document with a potential alternative therapeutic anticoagulation strategy for patients requiring veno-venous ECMO.
This approach is based on subcutaneous administration of low-molecular-weight heparin (LMWH) 3 times a day, paired with antifactor Xa (anti-Xa) assay monitoring, 3 times a day, each sample equidistant between two administrations of LMWH. Anticoagulation monitoring is integrated on a regular schedule with additional blood tests, including hemoglobin and hematocrit, platelets count, Fibrinogen, D-dimers, haptoglobin levels, and with full coagulation tests and point-of-care viscoelastic testing on an as needed basis.
We designed and started implementing an algorithmic protocol (detailed in Figure, Supplemental Digital Content 1, https://links.lww.com/ASAIO/A838) to standardize dosage adjustment based on anti-Xa value, potential evidence of clinically significant bleeding or prothrombotic states, and eventual need for surgical interventions or other invasive procedures.
Despite paucity of literature related to anticoagulation management based on LMWH only during ECMO support,2–4 we decided to introduce this approach since the second wave of Coronavirus disease 2019 (COVID-19) pandemic, to simplify and standardize anticoagulation management, reducing the strain on the team members, particularly on most recently recruited, and less experienced ones, involved to expand ECMO capacity.
The rationale for the off-label three-daily dosing (despite the commonly recommended once/twice daily dosing) is to achieve and constantly maintain a therapeutic level of anticoagulation, avoiding excessive peaks and minimizing peak-to-trough variability, with the aim of effective prevention of thrombosis without increasing bleeding risk.5
The rationale for anti-Xa assessment 4 hours after LMWH administration is to thoroughly evaluate its effect, including peak, occurring 3–5 hours after subcutaneous administration, being able to properly adapt subsequent dosing.
During the run, the protocol anticipates some conditions which demand to modify LMWH administration (dose or timing):
- need for invasive elective or emergent procedures; we do not consider percutaneuos central venous catheter, pulmonary artery catheter and arterial line placement, nor percutaneous tracheostomy among procedures requiring dosing adjustment;
- evidence of clinically significant bleeding defined (as per ELSO Registry definition);
- evidence of thrombotic complications (both intracircuit or patient complications).
Since the implementation of this protocol, we did not notice increased ratio of thrombotic events; no patient required the circuit to be replaced more than once during the run (mean duration 19 days [6–52]). No cannula thrombosis, nor thrombosis involving the cannula or cannulated vessels have been observed, despite the high risk profile of this patient population. No brain hemorrhages, nor GI or cannulation site bleedings requiring more than medical approach were observed; and increased incidence of pulmonary hemorrhages was noticed: clinical evidence suggested these as presumably disease, rather than anticoagulation, related.
We recognize that such an algorithm significantly deviates from conventional clinical practice and from guidelines, but in our limited, single center experience, its application in a population of COVID-19 patients requiring V-V ECMO was feasible and safe (unpublished data, manuscript in preparation), and easy to be implemented at bedside, in selected settings.
1. McMichael ABV, Ryerson LM, Ratano D, Fan E, Faraoni D, Annich GM. 2021 ELSO Adult and Pediatric Anticoagulation Guidelines. ASAIO J. 268:303-310, 2020.
2. Gratz J, Pausch A, Schaden E, et al.: Low molecular weight heparin versus unfractioned heparin for anticoagulation during perioperative extracorporeal membrane oxygenation: A single center experience in 102 lung transplant patients. Artif Organs 44: 638–646, 2020.
3. Piwowarczyk P, Borys M, Kutnik P, et al.: Unfractionated heparin versus subcutaneous nadroparin in adults supported with venovenous extracorporeal membrane oxygenation: A Retrospective, Multicenter Study. ASAIO J 67: 104–111, 2021.
4. Krueger K, Schmutz A, Zieger B, Kalbhenn J: Venovenous extracorporeal membrane oxygenation with prophylactic subcutaneous anticoagulation only: An observational study in more than 60 patients. Artif Organs 41: 186–192, 2017.
5. Frydman AM, Bara L, Le Roux Y, Woler M, Chauliac F, Samama MM: The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80 mg. J Clin Pharmacol 28: 609–618, 1988.