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Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan
Lubna Sato1,2, Noriko Iwamoto1,3, Yuko Kakumoto1
1Disease Control and Prevention Center, National Center for Global Health and Medicine.
Insights
Unfractionated heparin (UFH) use in COVID-19 patients showed a high incidence of major bleeding, particularly with therapeutic doses. Older age and critical illness are key risk factors for these bleeding complications.
Area of Science:
- Critical care medicine
- Pharmacology
- Infectious diseases
Background:
- Low-molecular-weight heparin (LMWH) efficacy in COVID-19 is established, but unfractionated heparin (UFH) safety remains under-investigated.
- Understanding UFH's bleeding risk in COVID-19 is crucial for patient management.
Purpose of the Study:
- To investigate bleeding complications during UFH administration in hospitalized COVID-19 patients.
- To determine the impact of UFH on mortality and identify risk factors for bleeding outcomes.
Main Methods:
- Retrospective cohort study at a single tertiary care hospital.
- Inclusion of hospitalized COVID-19 patients treated with UFH.
- Analysis of bleeding complications, thromboembolic events, and 60-day mortality using logistic regression and propensity score matching.
Main Results:
- 516 patients received UFH; 2.3% experienced major bleeding (9.2% with therapeutic doses).
- Major bleeding risk increased with age (≥60 years) and COVID-19 severity.
- No significant difference in 60-day mortality between UFH and non-UFH groups post-propensity score matching.
Conclusions:
- Therapeutic-dose UFH in COVID-19 patients is associated with a relatively high incidence of major bleeding.
- Critical COVID-19 illness and advanced age are significant risk factors for bleeding complications.
Aim:
Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH.
Methods:
This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality.
Results:
Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test).
Conclusions:
The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.
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