Subcutaneous Enoxaparin for Systemic Anticoagulation of COVID-19 Patients During Extracorporeal Life Support

Abstract

BackgroundExtracorporeal membrane oxygenation, with an inherent requirement for anticoagulation to avoid circuit thrombosis, is a key element in the treatment of respiratory failure associated with COVID-19. Anticoagulation remains challenging, the standard of care being intravenous continuous administration of unfractionated heparin. Yet regimens vary. Some intensive care units in our center have successfully used enoxaparin subcutaneously in recent years and throughout the pandemic.MethodsWe retrospectively analyzed adult COVID-19 patients with respiratory failure who had been systemically anticoagulated using either enoxaparin or unfractionated heparin. The choice of anticoagulant therapy was based on the standard of the intensive care unit. Defined thromboembolic and hemorrhagic events were analyzed as study endpoints.ResultsOf 98 patients, 62 had received enoxaparin and 36 unfractionated heparin. All hazard ratios for the thromboembolic (3.43; 95% CI: 1.08–10.87; p = 0.04), hemorrhagic (2.58; 95% CI: 1.03–6.48; p = 0.04), and composite (2.86; 95% CI: 1.41–5.92; p = 0.007) endpoints favored enoxaparin, whose efficient administration was verified by peak levels of anti-factor Xa (median: 0.45 IU ml−1; IQR: 0.38; 0.56). Activated partial thromboplastin time as well as thrombin time differed significantly (both p<0.001) between groups mirroring the effect of unfractionated heparin.ConclusionsThis study demonstrates the successful use of subcutaneous enoxaparin for systemic anticoagulation in patients with COVID-19 during extracorporeal membrane oxygenation. Our findings are to be confirmed by future prospective, randomized, controlled trials.

Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium

“…Subcutaneous administration of anticoagulation was associated with thrombotic complications (both combined and individual), suggesting that this route might not be suitable for preventing thrombosis in COVID-19 ECMO patients. This finding contrasts with Wiegele et al 's single-center study, where ECMO patients treated with subcutaneous enoxaparin experienced fewer thrombotic or major bleeding events than those receiving unfractionated heparin [20].…”

Efficacy and Safety of Direct Oral Anticoagulants Compared With Heparin for Preventing Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis

“…Recently, although heparin, especially LMWH, seemed to perform well in anticoagulation and has been recommended in hospitalized COVID-19 patients. 17 , 30 – 34 However, early evidence demonstrates that COVID-19 patients are at high risk for thrombosis, even those receiving standard or intensified thromboprophylaxis doses with LMWH or UFH. 35 In addition, heparin tolerance or resistance has become an ongoing problem in anticoagulation therapy for COVID-19, which makes it more difficult to monitor.…”

Anticoagulation Strategies during Extracorporeal Membrane Oxygenation: A Narrative Review

“…The risk of life-threatening hemorrhage, blood product transfusion, and the risk of thromboembolic events should be taken into consideration when initiating systemic anticoagulation. In well-selected patients, the use of reduced anticoagulation by using low-dose heparin only or different dosages of LMWH is being investigated [ 75 , 76 , 77 , 78 ].…”

“…Moreover, patients receiving LMWH had a lower risk of thromboembolic events [ 77 ]. Finally, Wiegele et al compared the use of heparin and enoxaparin (2 × 4000 IU, anti-Xa level monitored) in COVID-19 patients and concluded that the subcutaneously administered enoxaparin is superior (given the rate of adverse events) when compared to UFH, and may be seen as a possible anticoagulation strategy in COVID-19 patients requiring ECMO support [ 78 ].…”