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Higher Dose Anticoagulation Cannot Prevent Disease Progression in COVID-19 Patients: A Systematic Review and
Emőke Henrietta Kovács1,2,3, Krisztián Tánczos2, László Szabó1,4
1Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary.
Insights
Higher dose (HD) thromboprophylaxis in coronavirus disease 2019 (COVID-19) patients reduced thrombosis risk but increased bleeding. HD showed no mortality benefit and limited effect in patients with low D-dimer levels.
Area of Science:
- Medical research
- Infectious diseases
- Cardiovascular medicine
Background:
- Coronavirus disease 2019 (COVID-19) is associated with a high risk of thrombotic events.
- Higher dose (HD) thromboprophylaxis has been explored as a strategy to mitigate this risk.
Purpose of the Study:
- To compare the efficacy and safety of HD versus standard dose (SD) thromboprophylaxis in COVID-19 patients.
- To analyze outcomes including mortality, thrombotic events, bleeding, and disease progression.
Main Methods:
- Systematic review and meta-analysis of randomized controlled studies.
- Searched CENTRAL, Embase, Medline, and medRxiv databases.
- Analyzed data using a random effects model for 14 included articles (6253 patients).
Main Results:
- HD thromboprophylaxis did not significantly reduce mortality compared to SD (OR 0.83).
- HD was associated with a decreased risk of thrombosis (OR 0.58) but an increased risk of major bleeding (OR 1.64).
- A tendency towards lower thrombotic risk with HD was observed in patients with D-dimer > 1 mg/mL (OR 0.56).
Conclusions:
- HD thromboprophylaxis cannot be recommended for all COVID-19 patients due to increased bleeding risk.
- HD may offer some nonsignificant benefits in disease progression for patients with elevated D-dimer who do not require ICU admission.
Abstract:
Implementation of higher dose (HD) thromboprophylaxis has been considered in patients infected with coronavirus disease 2019 (COVID-19). Our aim was to compare HD to standard dose (SD) thromboprophylaxis in COVID-19 patients. The protocol is registered on PROSPERO (CRD42021284808). We searched for randomised controlled studies (CENTRAL, Embase, Medline and medRxviv) that compared HD to SD anticoagulation in COVID-19 and analysed outcomes such as mortality, thrombotic events, bleedings, and disease progression. The statistical analyses were made using the random effects model. Fourteen articles were included (6253 patients). HD compared with SD showed no difference in mortality (OR 0.83 [95% CI 0.54−1.28]). The use of HD was associated with a decreased risk of thrombosis (OR 0.58 [95% CI 0.44−0.76]), although with an increased risk of major bleeding (OR 1.64 [95% CI 1.25−2.16]). The cohort with D-dimer < 1 mg/mL showed no effect (OR 1.19 [95% CI 0.67−2.11]), but in the case of D-dimer > 1 mg/mL, a tendency of lower risk in the HD group was observed (OR 0.56 [95% CI 0.31−1.00]). The need for intubation in moderately ill patients showed a nonsignificant lower likelihood in the HD group (OR 0.82 [95% CI 0.63−1.08]). We cannot advocate for HD in all COVID-19 patients, although it shows some nonsignificant benefits on disease progression in those with elevated D-dimer who do not need ICU admission.
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