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.
Trial registration
<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://Clinicaltrials.gov">Clinicaltrials.gov</ext-link><ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04412304">NCT04412304</ext-link> June 2 2020, retrospectively registered
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