Coagulopathy monitoring and anticoagulation management in COVID-19 patients on ECMO: Advantages of a heparin anti-Xa-based titration strategy

Rhoades, Ruben; Leong, Ron; Kopenitz, Jason; Thoma, Brandi; McDermott, Lydia; Dovidio, Joseph; Barletti, Shannon; Gong, Jerald Z.; Massey, H. Todd; McKenzie, Steven E.; Rame, J. Eduardo; Al-Rawas, Nawar

doi:10.1016/j.thromres.2021.04.008

Cited by 9 publications

(14 citation statements)

References 13 publications

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“…1 , Additional file 1 : Table S4) [ 3 , 5 , 16 – 65 ]. All studies were retrospective and observational in nature; 22 studies were conducted by studies centres from Europe [ 5 , 17 , 19 , 23 , 27 , 29 , 31 – 34 , 36 , 39 , 42 , 43 , 45 , 46 , 50 , 55 , 56 , 60 , 63 , 65 ], 17 from North America [ 16 , 18 , 20 – 22 , 24 , 25 , 37 , 40 , 47 , 48 , 52 – 54 , 57 , 58 , 61 ], 6 from the Asia–Pacific [ 26 , 28 , 35 , 38 , 41 , 44 ], 2 from South-West Asia and Africa,[ 51 , 62 ] 2 from Latin America [ 30 , 64 ], and 3 were studies conducted by centres from multiple ELSO regions [ 3 , 49 , 59 ], of which 2 were based on registry data [ 3 , 49 ]. The pooled age was 52.5 years (95% CI 50.7 to 54.3), and the majority of patients were male (75.0%, 95% CI 72.4% to 77.4%) and obese (BMI: 31.0, 95% CI 30.2 to 31.8).…”

Section: Resultsmentioning

confidence: 99%

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis

et al. 2022

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Background Extracorporeal membrane oxygenation (ECMO) has been used extensively for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). Reports early in the pandemic suggested that mortality in patients with COVID-19 receiving ECMO was comparable to non-COVID-19-related ARDS. However, subsequent reports suggested that mortality appeared to be increasing over time. Therefore, we conducted an updated systematic review and meta-analysis, to characterise changes in mortality over time and elucidate risk factors for poor outcomes. Methods We conducted a meta-analysis (CRD42021271202), searching MEDLINE, Embase, Cochrane, and Scopus databases, from 1 December 2019 to 26 January 2022, for studies reporting on mortality among adults with COVID-19 receiving ECMO. We also captured hospital and intensive care unit lengths of stay, duration of mechanical ventilation and ECMO, as well as complications of ECMO. We conducted random-effects meta-analyses, assessed risk of bias of included studies using the Joanna Briggs Institute checklist and evaluated certainty of pooled estimates using GRADE methodology. Results Of 4522 citations, we included 52 studies comprising 18,211 patients in the meta-analysis. The pooled mortality rate among patients with COVID-19 requiring ECMO was 48.8% (95% confidence interval 44.8–52.9%, high certainty). Mortality was higher among studies which enrolled patients later in the pandemic as opposed to earlier (1st half 2020: 41.2%, 2nd half 2020: 46.4%, 1st half 2021: 62.0%, 2nd half 2021: 46.5%, interaction p value = 0.0014). Predictors of increased mortality included age, the time of final patient enrolment from 1 January 2020, and the proportion of patients receiving corticosteroids, and reduced duration of ECMO run. Conclusions The mortality rate for patients receiving ECMO for COVID-19-related ARDS has increased as the pandemic has progressed. The reasons for this are likely multifactorial; however, as outcomes for these patients evolve, the decision to initiate ECMO should include the best contextual estimate of mortality at the time of ECMO initiation.

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Section: Resultsmentioning

confidence: 99%

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis

et al. 2022

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“…Of course, reduced APTT values may correspond to a number of clinical situations, each with differing implications on outcomes. For example, APTT measurements may simply fail to accurately reflect the level of anticoagulation during ECMO, and for this reason, AntiXa levels are increasingly relied upon instead [ 69 , 70 , 71 , 72 , 73 ]. The APTT may also be reduced in the setting of heparin resistance due to an antithrombin III (ATIII) deficiency.…”

Section: Discussionmentioning

confidence: 99%

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study

Worku

Win

Parmar

et al. 2023

JCM

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The temporal trends in haematological parameters and their associations with blood product transfusion requirements in patients supported with extracorporeal membrane oxygenation (ECMO) are poorly understood. We performed a retrospective data analysis to better understand the behaviour of haematological and coagulation parameters and their associations with transfusion requirements during ECMO. Methods: Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. Results: Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5–13) days and 13 (8–23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. Conclusion: ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.

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“…[46][47][48] The partial prothrombin time can be affected by an increased factor VIII level, making the patient appear to be therapeutically anticoagulated while failing to achieve inhibition of activated factor X. 49 Anti-Xa monitoring improves heparin effectiveness when used in critically ill patients and should be considered in the COVID-19 population in particular. 50 The CHEST guideline and expert panel report recommends anticoagulation therapy for a minimum duration of 3 months for patients with COVID-19 diagnosed with a proximal DVT or PE, although there are no randomized studies to support this.…”

Section: Opportunistic Infectionmentioning

confidence: 99%

Complications of Critical COVID-19

Maslove

Sibley

Boyd

et al. 2022

Chest

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Patients admitted to the intensive care unit with critical COVID-19 often require prolonged periods of mechanical ventilation. Difficulty weaning, lack of progress, and clinical deterioration are commonly encountered. These conditions should prompt a thorough evaluation for persistent or untreated manifestations of COVID-19, as well as complications from COVID-19 and its various treatments. Inflammation may persist and lead to fibroproliferative changes in the lungs. Infectious complications may arise including bacterial superinfection in the earlier stages of disease. Use of immunosuppressants may lead to the dissemination of latent infections, and to opportunistic infections. Venous thromboembolic disease is common, as are certain neurologic manifestations of COVID-19 including delirium and stroke. High levels of ventilatory support may lead to ventilator-induced injury to the lungs and diaphragm. We present diagnostic and therapeutic considerations for the mechanically ventilated COVID-19 patient who shows persistent or worsening signs of critical illness, and we offer an approach to managing this complex but common scenario.

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Coagulopathy monitoring and anticoagulation management in COVID-19 patients on ECMO: Advantages of a heparin anti-Xa-based titration strategy

Cited by 9 publications

References 13 publications

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study

Complications of Critical COVID-19

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