Dosing Of Thromboprophylaxis And Mortality In Critically Ill Covid-19 Patients

Abstract

Background: A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association of initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding. Method: All critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500−4500 IU tinzaparin or 2500−5000 IU dalteparin), medium (>4500 IU but <175 IU/kilogram, kg, of body weight tinzaparin or >5000 IU but <200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body-mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis. Results: A total of 152 patients were included; 67 received low, 48 medium, and 37 high dose thromboprophylaxis. Baseline characteristics did not differ between groups. Mortality was lower in high (13.5%) vs medium (25.0%) and low dose thromboprophylaxis (38.8%) groups, p≡0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13 − 0.87) among those who received high dose, respectively 0.88 (95% confidence intervals 0.43 − 1.83) among those who received medium dose, as compared with those who received low dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low dose thromboprophylaxis (17.9%) groups, p≡0.04, but no difference in the proportion of bleeding events, p≡0.16. Conclusions: Among critically ill COVID-19 patients with respiratory failure, high dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses.

Cardiac Dysfunction in Critically Ill patients with COVID-19 – A Multicentre Observational Study

“…The incidence of cardiac dysfunction was in line with other studies of patients hospitalized, whose COVID-19 disease severities ranged from mild to severe, and where LV dysfunction was found in 10 to 42% and RV dysfunction in 14 to 39% [15,23,24]. One reason for the relatively low incidence of RV dysfunction may have been the liberal use of thromboprophylaxis that was introduced early in the study period [25], leading to less pulmonary embolism than in many earlier studies [15,26]. We did not assess patients with tissue doppler or strain analysis, modalities that are more sensitive for the detection of ventricular dysfunction, which could explain a comparative low incidence of cardiac dysfunction in our study.…”

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

“…Importantly, there was no difference in the development of bleeding events among the three groups. 27 Similar findings were identified in a retrospective study from Abu Dhabi albeit finding that therapeutic anticoagulation, rather than enhanced chemoprophylaxis, was associated with major bleeding. 28 Another retrospective observational study of 468 hospitalized patients in the United States found that initial use of enhanced dosing thromboprophylaxis correlated with a downtrend in D-dimer levels and was associated with improved 30-day mortality without a significant increased rate of bleeding.…”

RETRACTED: Clinical and Scientific Rationale for the “MATH+” Hospital Treatment Protocol for COVID-19

“…Jonmarker et al compared the outcomes of COVID-19 ICU patients treated with standard, intermediate, and full dose anti-coagulation. 100 They found that mortality was lower in high dose (13.5%) vs medium dose (25.0%) and low dose thromboprophylaxis (38.8%) groups, p ¼ 0.02.…”