anticoagulation in severe covid-19 patients

Conditions: Severe COVID-19 Pneumonia

Summary: coronavirus disease 2019 (covid-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), may predispose patients to thrombotic disease due to a state of profound inflammation, platelet activation, and endothelial dysfunction leading to respiratory distress and increased mortality. the incidence of macrovascular thrombotic events varies from 10 to 30% in covid-19 hospitalized patients depending on the type of arterial or vein thrombosis captured and severity of illness . observational results in patients receiving routine low-dose prophylactic anticoagulation (ld-pa), several institutions have recently released guidance statement to prevent macrovascular thrombotic events with dose escalation anticoagulation. in these recommendations, high-dose prophylactic anticoagulation (hd-pa) and therapeutic anticoagulation (ta) can be employed either empirically or based on the body mass index and increased d-dimer values. no randomized trial has validated this approach, and other recent recommendations challenge this approach. microvascular thrombotic events are also of major concern in critically ill patients with covid-19, even in the absence of obvious macrovascular thrombotic events. a large review of autopsy findings in covid-19-related deaths reported micro thrombi in small pulmonary vessels. more generally, covid-19-induced endothelitis and coagulopathy across vascular beds of different organs lead to widespread microvascular thrombosis with microangiopathy and occlusion of capillaries. thus, in severe covid-19 patients requiring oxygen therapy without initial macrovascular thrombotic event, a hd-pa or a ta could be beneficial by limiting the extension of microvascular thrombosis and the evolution of the lung and multi-organ microcirculatory dysfunction. in a large observational cohort of 2,773 covid-19 patients, a lower in-hospital mortality in ventilated patients receiving ta as compared to those receiving pa (29.1% vs. 62.7%). our hypothesis is dual: i) first, that ta and hd-pa strategies mitigate microthrombosis and each limit the progression of covid-19, including respiratory failure and multi-organ dysfunction, with in fine a decreased mortality and duration of disease, as compared to a low-dose pa; ii) second, that ta outperforms hd-pa in this setting.


Eligibility criteria:
inclusion criteria: * age ≥ 18 years ; * severe covid-19 pneumonia, defined by: * a newly-appeared pulmonary parenchymal infiltrate; and * a positive rt-pcr (either upper or lower respiratory tract) for covid-19 (sars-cov-2); and * who progression scale ≥ 5 (on the who ordinal scale) * written informed consent (patient, next of skin or emergency situation). * in view of the exceptional and urgent situation, affiliation to a social security scheme will not be a criterion for inclusion. exclusion criteria: * pregnancy and breast feeding woman; * postpartum (6 weeks); * extreme weights (\ 100 kg); * patients admitted since more than 72 hours to the hospital (if the who ordinal scale is 5 at time of inclusion) or since more than 72 hours to the intensive care unit (if the who ordinal scale is 6 or more at time of inclusion); * need for therapeutic anticoagulation (except for covid-related pulmonary thrombosis); * bleeding event related to hemostasis disorders, acute clinically significant bleed, current gastrointestinal ulcer or any organic lesion with high risk for bleeding * platelet count \< 50 g/l; * within 15 days of recent surgery, within 24 hours of spinal or epidural anesthesia; * any prior intracranial hemorrhage, enlarged acute ischemic stroke, known intracranial malformation or neoplasm, acute infectious endocarditis; * severe renal failure (creatinine clearance \<30 ml/min); * iodine allergy; * hypersensitivity to heparin or its derivatives including low-molecular-weight heparin; * history of type ii heparin-induced thrombocytopenia; * chronic oxygen supplementation; * moribund patient or death expected from underlying disease during the current admission; * patient deprived of liberty and persons subject to institutional psychiatric care; * patients under guardianship or curatorship; * participation to another interventional research on anticoagulation.

Keywords: covid-19 anticoagulation