Introduction
Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID‐19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown.
Methods
We performed a cohort study of patients hospitalized for COVID‐19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding.
Results
During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate‐ and 618 (31%) therapeutic‐dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non‐major bleeding. The 30‐day all‐cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%‐54%) and for non‐major bleeding 32% (95% CI: 24%‐40%). Multivariable analysis showed increased risk for in‐hospital major bleeding associated with D‐dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38–3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02–3.95), critical illness (HR, 1.91; 95% CI, 1.14–3.18), and therapeutic‐intensity anticoagulation (HR, 1.43; 95% CI, 1.01–1.97).
Conclusions
Among patients hospitalized with COVID‐19 receiving intermediate‐ or therapeutic‐intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic‐intensity anticoagulation, critical illness, and elevated D‐dimer or ferritin levels at admission were associated with increased risk for major bleeding.
extend to a greater number of patients and include other drugs with adjustment to renal function. In order to validate the estimated renal function and understand which formula is closest to reality, it would be important to determine the measured GFR. Controversy remains as to whether adoption of eGFR for drug dosing is appropriate given that dosing recommendations for many available drugs are based on CG estimates of kidney function. Using the same kidney function estimate for management of kidney disease, drug development and dosing would harmonise all clinical areas.
BackgroundNon-vitamin K oral antagonists are being increasingly used. However, broad clinical experience with them is lacking.ObjectivesTo review guidelines and evidence for the use of non-vitamin K oral antagonists in the periprocedural environment.ResultsDespite the clear advantages of vitamin K oral antagonists, their use can entail risks owing to the scarcity of reversal agents. Consensus has been reached about postoperative resumption, which is recommended at 24 hours and 48–72 hours, respectively, after low-risk and high-risk bleeding surgery. Bridging with heparin is recommended in patients with a high risk of thrombosis. Urgent interventions should ideally take place 24 hours after the last dose intake. Major discrepancies exist between the American and the European recommendations for neuraxial procedures. The American proposals recommend suspending the drug for five half-lives, whereas the European approaches suggest suspension of just two half-lives. Suggestions for perioperative discontinuation vary widely. Some authors recommend a longer time of resumption for patients with renal impairment. All agree that there should be an increase in the number of days of interruption in high-risk bleeding procedures versus low-risk bleeding procedures.ConclusionsA diverse number of approaches have been suggested for perioperative management of novel oral antagonists. American recommendations tend to be more rigorous than those of Europe. A need for more studies that measure health outcomes after the use of these drugs would be indispensable.
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