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 between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding. Method In this retrospective study, 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. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13–0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43–1.83) among those who received medium dose, as compared to 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. 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 Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.

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.…”

Characteristics of viral pneumonia in the COVID-19 era: an update

“…A retrospective study comparing patients with COVID-19 to those with Influenza A evaluated the effects of different thromboprophylaxis strategies on 152 patients admitted to 2 intensive care units. An association between high dose (200 UI x kg per day) dalteparin and reduction of mortality in respect to those receiving low or middle dose of heparin was reported (hazard ratio of death 0.33; 95% confidence intervals 0.13–0.87) [ 69 , 70 ]. Although the majority of the studies report a favorable effect of anticoagulant therapy, no consensus exists about the timing and dosage of heparins in patients with COVID-19 [ 71 ].…”

The Potency of Seaweed Sulfated Polysaccharides for the Correction of Hemostasis Disorders in COVID-19

“…Despite the data on the effectiveness of heparin drugs in reducing mortality in severe COVID-19 patients, and despite thromboprophylaxis [ 7 , 8 ], the development of venous and arterial thromboembolic complications has been reported. There is also a problem with the optimal dosage of anticoagulant agent [ 5 , 9 , 10 , 11 ]. Thus, there are a number of unresolved issues regarding the use of these drugs.…”