Thrombosis and bleeding in patients with COVID-19 requiring extracorporeal membrane oxygenation: a systematic review and meta-analysis

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact the coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in patients with COVID-19 supported with ECMO, summarize anticoagulation regimens, and guide future research. METHODS: Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in patients with COVID-19 requiring ECMO. The primary outcomes were the prevalences of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes. RESULTS: Twenty-three peer-reviewed studies involving 6878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%-27.6%; 1532 patients), that of ischemic stroke was 2.6% (95% CI: 1.5%-3.7%; 5926 patients), and that of pulmonary embolism (PE) was 11.8% (95% CI: 6.8%-16.8%; 5853 patients). For bleeding events, 37.4% of the patients experienced major hemorrhage (95% CI: 28.1%-46.8%; 1558 patients) and 9.9% experienced intracranial hemorrhage (ICH; 95% CI: 7.8%-12.1%; 6348 patients). COVID-19 cases on ECMO were complicated with more ICH than patients without COVID-19 on respiratory ECMO [RR = 2.23 (95% CI: 1.32-3.75)]. Anticoagulation strategies varied among centers. CONCLUSIONS: Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice, and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double “hit” of COVID-19 and ECMO.