Thombosis, major bleeding, and survival in COVID-19 supported by veno-venous extracorporeal membrane oxygenation in the first vs second wave: a multicenter observational study in the United Kingdom

Background Bleeding and thrombosis are major complications of veno-venous (VV) extracorporeal membrane oxygenation (ECMO). Objectives To assess thrombosis, major bleeding (MB), and 180-day survival in patients supported by VV-ECMO between the first (March 1 to May 31, 2020) and second (June 1, 2020, to June 30, 2021) waves of the COVID-19 pandemic. Methods An observational study of 309 consecutive patients (aged ≥18years) with severe COVID-19 supported by VV-ECMO was performed in 4 nationally commissioned ECMO centers in the United Kingdom. Results Median age was 48 (19-75) years, and 70.6% were male. Probabilities of survival, thrombosis, and MB at 180 days in the overall cohort were 62.5% (193/309), 39.8% (123/309), and 30% (93/309), respectively. In multivariate analysis, an age of >55 years (hazard ratio [HR], 2.29; 95% CI, 1.33-3.93; P = .003) and an elevated creatinine level (HR, 1.91; 95% CI, 1.19-3.08; P = .008) were associated with increased mortality. Correction for duration of VV-ECMO support, arterial thrombosis alone (HR, 3.0; 95% CI, 1.5-5.9; P = .002) or circuit thrombosis alone (HR, 3.9; 95% CI, 2.4-6.3; P < .001) but not venous thrombosis increased mortality. MB during ECMO had a 3-fold risk (95% CI, 2.6-5.8, P < .001) of mortality. The first wave cohort had more males (76.7% vs 64%; P = .014), higher 180-day survival (71.1% vs 53.3%; P = .003), more venous thrombosis alone (46.4% vs 29.2%; P = .02), and lower circuit thrombosis (9.2% vs 28.1%; P < .001). The second wave cohort received more steroids (121/150 [80.6%] vs 86/159 [54.1%]; P < .0001) and tocilizumab (20/150 [13.3%] vs 4/159 [2.5%]; P = .005). Conclusion MB and thrombosis are frequent complications in patients on VV-ECMO and significantly increase mortality. Arterial thrombosis alone or circuit thrombosis alone increased mortality, while venous thrombosis alone had no effect. MB during ECMO support increased mortality by 3.9-fold. Keywords: COVID-19; extracorporeal membrane oxygenation; hemorrhage; mortality; thrombosi

Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial

Background Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation. Objectives The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations. Methods This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling. Conclusion Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials

Clinical and biological features of cerebral venous sinus thrombosis following ChAdOx1 nCov-19 vaccination

Vaccines for COVID-19were developed with unprecedented speedand since January 2021, the AstraZeneca/Oxford University ChAdOx1 nCoV-19 vaccine has been administered to over 400 million people globally1. In April 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA)reported a possible association between ChAdOx1 nCoV-19 and a rare syndrome of unusual site thrombosis combined with thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT).Frequency of VITT varies across age groups. Overall 411 cases of VITT have been reported to Medicine & Healthcare prodcuts Regulatory Agency (MHRA) by 21st of July 2021 with fatality rate of 17.76% (73/411)2

Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH: reply

We thank Dr Desborough and colleagues for their response to the recently published guidance from the SSC of the ISTH on the management of direct oral anticoagulants (DOACs) in women of childbearing potential [1,2]. We have carefully examined their view and seriously considered their proposal regarding the recommendation of this guidance as detailed below. We hereby, provide a detailed response to their letter. This article is protected by copyright. All rights reserve

Six month mortality in patients with COVID-19 and non-COVID-19 viral pneumonitis managed with veno-venous extracorporeal membrane oxygenation

A significant proportion of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) with high risk of death. The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) for COVID-19 on longer-term outcomes, unlike in other viral pneumonias, is unknown. In this study, we aimed to compare the 6 month mortality of patients receiving VV-ECMO support for COVID-19 with a historical viral ARDS cohort. Fifty-three consecutive patients with COVID-19 ARDS admitted for VV-ECMO to the Royal Brompton Hospital between March 17, 2020 and May 30, 2020 were identified. Mortality, patient characteristics, complications, and ECMO parameters were then compared to a historical cohort of patients with non-COVID-19 viral pneumonia. At 6 months survival was significantly higher in the COVID-19 than in the non-COVID-19 viral pneumonia cohort (84.9% vs. 66.0%, p = 0.040). Patients with COVID-19 had an increased Murray score (3.50 vs. 3.25, p = 0.005), a decreased burden of organ dysfunction (sequential organ failure score score [8.76 vs. 10.42, p = 0.004]), an increased incidence of pulmonary embolism (69.8% vs. 24.5%, p < 0.001) and in those who survived to decannulation longer ECMO runs (19 vs. 11 days, p = 0.001). Our results suggest that survival in patients supported with EMCO for COVID-19 are at least as good as those treated for non-COVID-19 viral ARDS