Anticoagulation Therapy in Patients With Coronavirus Disease 2019

Results From a Multicenter International Prospective Registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 (HOPE-COVID19))

Francesco Santoro, MD, PhD; Ivan J. Núñez-Gil, MD, PhD; María C. Viana-Llamas, MD; Charbel Maroun Eid, MD; Rodolfo Romero, MD; Inmaculada Fernández Rozas, MD; Alvaro Aparisi, MD; Victor Manuel Becerra-Muñoz, MD; Marcos García Aguado, MD; Jia Huang, MD; Ludovica Maltese, MD; Enrico Cerrato, MD; Emilio Alfonso-Rodriguez, MD; Alex Fernando Castro Mejía, MD; Francisco Marin, MD; Sergio Raposeiras Roubin, MD; Martino Pepe, MD; Victor H. Moreno Munguia, MD; Gisela Feltes, MD; Jesus Varas Navas, MD; Bernardo Cortese, MD; Luis Buzón, MD; Cristoph Liebetrau, MD; Raquel Ramos-Martinez, MD; Antonio Fernandez-Ortiz, MD; Vicente Estrada, MD; Natale Daniele Brunetti, MD, PhD


Crit Care Med. 2021;49(6):e624-e633. 

In This Article

Abstract and Introduction


Objectives: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival.

Design: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019).

Setting: Hospitalized patients with coronavirus disease 2019.

Patients: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients.

Interventions: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient.

Measurements and Main Results: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49–0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49–0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51–1.01) in noninvasive ventilation.

Conclusions: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation.


Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a newly discovered coronavirus, presenting mainly as a severe acute respiratory syndrome.[1] First, reported in China in December 2019, it has quickly spread all over the world becoming pandemic in few months. Actually, there is no standard therapy and no clear consensus from scientific societies in the absence of solid clinical data. Recent data from registries and autopsies suggested a potential role for coagulopathy in influencing outcome of COVID-19 patients.[2,3] The prevalence of pulmonary embolism (PE) among COVID-19 patients in ICU is about 20%.[4] Furthermore, Zhang et al[5] found in a cohort of 143 patients that 66 patients (46.1%) developed lower extremity deep vein thrombosis (DVT) (23 patients [34.8%] with proximal DVT and 43 [65.2%] with distal DVT). Patients with DVT were older and had a lower oxygenation index, a higher rate of cardiac injury and worse prognosis (mortality rate 23% vs 12%). However, ICU patients without COVID-19 have higher risk of DVT (about 12%) when compared with other hospitalized patients.[6]

Among COVID-19 patients, mainly those presenting with respiratory insufficiency, a combination of low-grade disseminated intravascular coagulation (DIC) and localized pulmonary thrombotic microangiopathy may be present.[7] Therefore, anticoagulation therapy could be theoretically useful in some COVID-19 patients. Aim of the study was therefore to evaluate the impact on survival through anticoagulation therapy in COVID-19 patients in an observational registry.