ABSTRACT
Objectives: Unfractionated heparin (UFH) remains the anticoagulation of choice at most centres for patients receiving extracorporeal membrane oxygenation (ECMO). One disadvantage of UFH relies on its individual dosing requirement to achieve target values. In this context heparin resistance has been described, defined as doses exceeding 35,000 IU UFH/d. However, the incidence of heparin resistance and its association with thromboembolic complications despite anticoagulation within target ranges remains unknown. Method(s): This retrospective study included adults receiving venovenous (VV) and venoarterial (VA) ECMO, or extracorporeal CO2-removal (ECCO2R) between 2010 and May 2022. The primary outcome was the incidence of heparin resistance (>35,000 IU of UFH/d). Secondary outcomes were heparin failure (thromboembolic complications despite anticoagulation within target ranges) and survival. A multivariable poisson regression model was fitted to analyse the effect of heparin resistance, COVID-19 and ECMO type on the incidence rate of thromboembolic events. Result(s): Of 197 included patients, 33 (16.8%) had heparin resistance. Patients with COVID-19 (n=51) had a higher rate of heparin resistance compared to nonCOVID-19 patients (37% vs. 9.6%, P<0.001). Thromboembolic complications occurred at a rate of 5.89/100 ECMO days. There was a significant effect of COVID-19 (incidence rate ratio (IRR) 2.12, 95% confidence interval (CI) 1.4 to 3.3, P<0.001) and ECMO type (VA ECMO: IRR 2.35;95% CI 1.43 to 3.87, P<0.001;ECCO2R: IRR 2.63, 95% CI 1.37 to 4.9, P=0.003;reference VV ECMO) on incidence rate of thromboembolic events, but not of heparin resistance (IRR 1.11, 95% CI 0.7 to 1.76, P=0.7). ECMO duration was longer (25d (IQR 11-33) vs. 8d (IQR 4-18), P<0.001) in patients with heparin resistance, but hospital survival did not differ (23 (70%) vs. 91 (57%), P=0.2). Conclusion(s): The study revealed a high incidence of heparin failure in ECMO patients, especially in those with COVID-19. Heparin resistance had no effect on the incidence rate of thromboembolic events, whereas our data suggest an increased risk in patients with COVID19, VA ECMO and ECCO2R.
ABSTRACT
Objectives: At the beginning of the pandemic, it was believed that severe SARS-CoV2 infection would induce lifelong immunity and that reinfections would be unlikely. However, several cases of reinfection were documented in previously infected patient and the waning humoral immunity has raised significant concerns. Accordingly, long-term and durable vaccineinduce antibody protection against infection have also become a challenge, as several breakthroughs of COVID-19 have been identified in individuals partially or fully vaccinated. This study describes the incidence, the characteristics of severe COVID-19 infections requiring ECMO occurred after vaccination and the presence of side effects related to the vaccine. Method(s): EuroECMO COVID is a prospective, multicenter, observational study, developed by the EuroELSO, based on data from patients aged >=16 years who received ECMO support for refractory COVID-19 during the pandemic in 204 centers. The analysis investigates the survival of vaccinated patient, the associations between management-related variables, the incidence of vaccination during the different pandemic phases, the type of vaccines and the possible side effects. Result(s): Immunosuppressed patients are susceptible to reinfection even after being naturally infected or receiving a full vaccination. Ineffective antibody production, due to relatively ineffective vaccines, inadequate number of doses or the time after vaccination are involved in the pathogenesis of postvaccination infections. This population was found to have a partial immunity due to an inadequate number of doses and an overlapped time from vaccination and SARS-CoV2 incubation with PCR results after being vaccinated. Several manifestations of SARS-CoV2 infection are similar to vaccine-induce side effects and mild symptoms can be presented both as an adverse reaction after vaccination and a result of infection. In this subgroup no side effects were attributable to the vaccine. Conclusion(s): Vaccination does not entirely prevent SARS-CoV2 but will lead to less morbidity and mortality, as demonstrated by less need of ICU and ECMO care. In addition, the partial immunity for inadequate doses of vaccine or through the evolution of new variants demonstrated the importance of further analysis to differentiate the possible causes of waning humoral immunity.
ABSTRACT
Background : Pulmonary thrombus formation is a hallmark of COVID-19. A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear. Aims : To evaluate the role of extracellular vesicles (EV) and citrullinated histone H3 (citH3) as markers of coagulopathy and inflammation. Methods : We studied 41 adult COVID-19 patients with a positive result on a reverse-transcriptase polymerase-chain-reaction assay and 37 sex-and age-matched healthy controls. Number and surface characteristics of EV and citH3 levels were determined in plasma upon admission by flowcytometry and immunoassay, respectively. Values are given as median (25 th , 75 th percentile) and differences by geometric mean ratios (GMR [95% CI]) or mean differences (ΔsMean [95% CI]). Results : 20 patients had severe and 21 mild disease. Patients exhibited significantly higher numbers of total EV, and of EV derived from platelets, endothelial cells, leukocytes, or neutrophils than controls (Table 1). EV from alveolar-macrophages and alveolar-epithelial-cells were detectable in plasma and were significantly higher in patients. ICAM-1 positive EV levels were higher in patients while no difference between TF-positive and ACE-positive EV was seen between the two groups. Levels of EV did not differ between patients with severe and mild COVID-19. citH3 levels were higher in patients than in controls [1.42 (0.6, 3.37) vs 0.31 (0.14, 0.6), GMR 4.44 (2.57, 7.66);P < 0.001], and were significantly lower in patients with mild disease compared to those with severe disease. Conclusions : EV and citH3 are associated with COVID-19. They provide information regarding pathophysiology and could be explored as markers of the disease.