ANTICOAGULATION, BLEEDING, AND IMMUNOTHROMBOSIS IN CRITICALLY ILL PATIENTS WITH COVID-19

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: Coronavirus disease 2019 (COVID-19) carries hematological complications known as COVID-19 related coagulopathy. This association led to a modification of antithrombotic prophylaxis and the use of anticoagulation treatment, with indications and doses that remain controversial. The bleeding risk from this therapy escalation is recognized as a cause of morbidity, especially in critically ill patients. The prevalence of clinical thrombotic events has been widely reported and very variable. Besides, autopsy studies have found a significant presence of pulmonary microthrombosis due to local factors, also known as immunothrombosis. The effect of different doses of anticoagulation on immunothombosis is less known in comparison with clinical thrombotic events. METHODS: An observational study was done on COVID-19 critically ill patients in which post-mortem lung biopsies were carried. From March 1st to December 31st, 2020, biopsies were performed by percutaneous puncture using a 33mm/14G automatic gun at the bedside within the first hour of death. Data were collected from the electronic medical record, including transfusion requirements, presentation of bleeding events, and the type, dose, and duration of anticoagulation therapy. All patients received anticoagulation with LMWH (enoxaparin) following institutional protocol. Bleeding events were characterized using ISTH definitions of clinically relevant bleeding in studies of anticoagulants. Regarding anticoagulation dose received (in 24 hours), two groups were formed: group L for doses up to 100 mg of enoxaparin and group H for doses higher than 100 mg. Group L consisted of 10 patients with a mean dose of heparin of 80 mg. Group H consisted of 9 patients with a mean dose of heparin of 160 mg. RESULTS: A total of 19 patients were included, male in 100%. The median age was 64 years (RIQ 58-68). The median length of ICU stay was 27 days (RIQ 17-34). Microthrombosis was found in biopsies of 47% of all patients. For patients presenting with microthrombosis, 55% were from group L and 44% from group H (p=0,8). The mean of D-Dimer levels was 1111 μg/L in group L and 3860 μg/L in group H (p=0.02). Clinically relevant hemorrhagic events were seen in 20% of patients of group L and 44% of group H (p=0.25). Major bleeding represented 100% of bleeding events in group H and 50% in group L (p=0.08). No episodes of fatal bleeding were reported. Transfusions were required in 88% of group H and 23% of group L (p<0.001), with a relation of Units/mean days of heparin of 0.5 U/day for group L and 1.6 U/day for group H (p=0.09). CONCLUSIONS: No differences in the prevalence of microthombosis were found when analyzed according to anticoagulation dose. D-Dimer levels were higher in the high heparin group, probably due to an indication bias. There was a higher transfusion requirement in patients with higher heparin doses. CLINICAL IMPLICATIONS: Bleeding risk needs to be stratified in all patients, and anticoagulation should be revised on admission and periodically during ICU stay. Caution should be taken on the role of D-dimer in guiding therapy, as is not recommended by various societies. Microthrombosis could hold a key in the analysis of antithrombotic requirements, and more studies are needed on biomarkers that could better predict the presence of this phenomenon. DISCLOSURES: No relevant relationships by JAVIER FLANDES, source=Web Response No relevant relationships by José Fortes Alén, source=Web Response Scientific Medical Advisor relationship with Gilead Sciences Please note: 2020-2021 Added 04/26/2021 by Miguel Gorgolas, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Janssen Please note: 2020-2021 Added 04/26/2021 by Miguel Gorgolas, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with ViiV Healthcare Please note: 2020-2021 Added 04/30/2021 by Miguel Gorgolas, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Giliead Sciences Please note: 2020-2021 Added 04/30/2021 by Miguel Gorgolas, source=Web Response, value=Consulting fee Scientific Medical Advisor relationship with Jannssen Please note: 2020-2021 Added 04/30/2021 by Miguel Gorgolas, source=Web Response, value=Consulting fee No relevant relationships by pilar llamas, source=Web Response No relevant relationships by Juan Paez Vargas, source=Web Response No relevant relationships by CESAR PEREZ CALVO, source=Web Response No relevant relationships by Miguel Piris, source=Web Response No relevant relationships by Laura Prieto-Pérez, source=Web Response No relevant relationships by Denis Robaglia, source=Web Response No relevant relationships by Ánxela Vidal González, source=Web Response