P1621: incidence, risk factors and mortality associated with major bleeding events in hospitalized covid-19 patients, tertiary center experience

Topic: 33. Bleeding disorders (congenital and acquired) Background: Thromboprophylaxis with low-molecular-weight-heparin (LMWH) is a mainstay of treatment of hospitalized COVID-19 patients due to high occurrence of thrombotic events and thromboinflammation playing active role in the pathophysiology of severe and critical COVID-19. On the opposite, there are scarce data on bleeding events, including major bleeding, associated risk factors and clinical significance in patients with severe and critical COVID-19. Aims: To evaluate incidence, predictors and outcomes associated with major bleeding in hospitalized COVID-19 patients. Methods: We retrospectively evaluated a cohort of 4014 consecutive hospitalized COVID-19 patients treated in a tertiary level institution University hospital Dubrava, Zagreb, Croatia, in period 3/2020-3/2021. Data used in the analysis were obtained by analysis of electronical and written medical records, and it is a part of a large hospital Registry project. Bleeding was considered as clinically significant if documented in medical records, whereas major bleeding was defined using the International Society on Thrombosis and Haemostasis (ISTH) criteria. Results: Among 4014 patients, 56.2% patients were of male sex. Severe or critical disease was present in 3359 (83.7%) patients at the time of admission. Median age was 74 years, median Charlson comorbidity index was 4 points. Bleeding of any kind was documented in 322 (8%) and major bleeding in 129 (3.2%) patients. For comparison, venous and arterial thrombotic events were recorded in 5.3% and 5.8% patients, respectively. Major bleeding events were similarly distributed at the time of and after admission (46.5% vs 53.5%). Median time of post-admission bleeding occurrence was day 7 of hospitalization. The most common localizations for documented bleeding of any kind were gastrointestinal tract in 131 (40.7% of all events), respiratory tract in 47 (14.6% of all events), urinary tract in 41 (12.7% of all events), intracranial in 36 (11.2% of all events), intramuscular in 16 (5% of all events), cutaneous in 6 (1.9% of all events), vaginal in 5 (1.6% of all events) and other (iatrogenic, postsurgical and internal bleeding events) in 40 (12.4% of all events). Major bleeding comprised 45.8% of gastrointestinal tract, 10.6% of respiratory tract, 9.8% of urinary tract, 100% of intracranial, 37.5% of intramuscular, none with cutaneous and vaginal bleeding and 45% of other types of bleeding as shown in a Figure. Parameters that were mutually independently associated with major bleeding events in the multivariate logistic regression were: atrial fibrillation (OR 2.21; P=0.048), higher white blood cell count (WBC, OR 1.03; P=0.049), lower hemoglobin (0.97; P=0.005), arterial thrombosis (3.15, P=0.022) and critical severity of COVID-19 on admission (OR 2.62; P=0.007). Major bleeding occurrence was significantly associated with increased in-hospital mortality (P<0.001), with especially higher risk if major bleeding occurred during hospitalization (mortality 48.3% for events at the time of and 69.6% for events after hospital admission). Death did not occur immediately adjacent to bleeding events but at median time of 5 days post major bleeding. Summary/Conclusion: Clinically significant bleeding and major bleeding events are frequent in mostly severe and critical hospitalized COVID-19 patients, with significant proportion of patients presenting at the time of hospital admission, and others almost universally exposed to anticoagulant and corticosteroid therapies. Major bleeding is associated with high mortality, especially if occurring during hospitalization. Figure 1: Incidence of major bleeding events among all documented bleeding events stratified to specific localizations.Keywords: COVID-19, Anticoagulation, Bleeding, Hemostasis