Low versus high dose anticoagulation in patients with Coronavirus 2019 pneumonia at the time of admission to critical care units: A multicenter retrospective cohort study in the Beaumont healthcare system

Abstract

Purpose Coagulopathy is common in patients with COVID-19. The ideal approach to anticoagulation remains under debate. There is a significant variability in existing protocols for anticoagulation, and these are mostly based on sporadic reports, small studies, and expert opinion. Materials and methods This multicenter retrospective cohort study evaluated the association between anticoagulation dose and inpatient mortality among critically ill COVID-19 patients admitted to the intensive care units (ICUs) or step-down units (SDUs) of eight Beaumont Healthcare hospitals in Michigan, USA from March 10th to April 15th, 2020. Results Included were 578 patients with a median age of 64 years; among whom, 57.8% were males. Most patients (n = 447, 77.3%) received high dose and one in four (n = 131, 22.7%) received low dose anticoagulation. Overall mortality rate was 41.9% (n = 242). After adjusting for potential confounders (age, sex, race, BMI, ferritin level at hospital admission, intubation, comorbidities, mSOFA, and Padua score), administration of high anticoagulation doses at the time of ICU/SDU admission was associated with decreased inpatient mortality (OR 0.564, 95% CI 0.333–0.953, p = 0.032) compared to low dose. Conclusion Treatment with high dose anticoagulation at the time of ICU/SDU admission was associated with decreased adjusted mortality among critically ill adult patients with COVID-19.

The Comparison of Therapeutic With Prophylactic Anticoagulation on Mortality, Risk of Bleeding, and Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review

“…After adjusting for other characteristics associated with mortality, administering a high dose of anticoagulation was independently associated with decreased in-hospital mortality. The association remains consistent in sensitivity analyses, Cox regression analysis (Cox proportional hazards regression analysis), and 21-day mortality [5]. This result was in line with Ionescu et al, who said that anticoagulation therapy was correlated to lower mortality risk in the propensity score-weighted multivariate proportional hazard model.…”

“…These findings support the increased reports of venous thromboembolism (VTE) and pulmonary embolism (PE) in severe cases of COVID-19, which are considered poor prognostic indicators [2][3][4][5]. Consequently, elevated D-dimer, fibrinogen, and indicators of endothelial dysfunction (von Willebrand factor antigen and soluble thrombomodulin) have been associated with unfavorable prognoses, including death [5,6]. As a result, several clinical trials have emerged and initiated studies designed to improve COVID-19 prognosis with antithrombotic treatment [7].…”

“…In severe cases, over-accumulating pro-inflammatory cytokines promote hypercoagulation, vascular hyperpermeability, multiorgan failure, and even death. These findings support the increased reports of venous thromboembolism (VTE) and pulmonary embolism (PE) in severe cases of COVID-19, which are considered poor prognostic indicators [2][3][4][5]. Consequently, elevated D-dimer, fibrinogen, and indicators of endothelial dysfunction (von Willebrand factor antigen and soluble thrombomodulin) have been associated with unfavorable prognoses, including death [5,6].…”

“…The investigators published a report for 1,098 critically ill patients receiving intensive care unit (ICU)level support [18] and another report for 2,219 patients not initially receiving ICU-level support [19]. The latter study revealed that compared to prophylactic anticoagulation, therapeutic anticoagulation prolonged survival until hospital discharge, free from organ support in noncritically ill patients [5,19,22]. The trial stopped after the superiority of therapeutic anticoagulation was observed [19].…”

“…Despite the administration of thromboprophylaxis, COVID-19 patients are more likely to develop VTE than severely ill COVID-19-negative patients. This occurrence has prompted many experts to propose higher anticoagulant dosages, particularly in patients who are at increased risk of thromboembolism due to significantly elevated D-dimer results and/or other comorbidities [5]. Meanwhile, the most efficient thromboprophylactic strategies for a wide range of COVID-19 disease severity are still undetermined [11].…”