A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.

BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Thrombosis and Bleeding After Implementation of an Intermediate-Dose Prophylactic Anticoagulation Protocol in ICU Patients With COVID-19: A Multicenter Screening Study.

Thrombosis and bleeding after implementation of an intermediate-dose prophylactic anticoagulation protocol in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19): a multicenter screening study Background: Venous thromboembolism (VTE) is common among critically ill patients with COVID-19. Information regarding VTE prevalence and bleeding complications after implementation of intermediate-dose prophylactic anticoagulation in such patients is, however, limited. Methods: We performed a prospective, observational study in 6 ICUs in 2 university-affiliated teaching hospitals in Sweden. After implementation of an intermediate-dose prophylactic anticoagulation protocol, we performed ultrasound screening for proximal lower-extremity deep vein thrombosis (DVT) and collected routine computed tomography pulmonary angiography exam results. Results: A total of 100 COVID-19 patients were included from June 21, 2020, through February 18, 2021. During a median follow-up of 120 (IQR, 89-134) days, we found VTE in 37 patients with the majority (78.4%) being diagnosed after ICU arrival. Overall, 20 patients had proximal lower-extremity DVT with 95% being detected on ultrasound screening; 22 patients had pulmonary vascular thrombosis; and 4 patients had venous thrombosis at other sites. A total of 6 patients had both proximal lower-extremity DVT and pulmonary vascular thrombosis. On univariate logistic regression analysis of 14 baseline characteristics, only pre-existing heart failure was associated with VTE (OR 4.67, 95% CI 1.13-19.34). Major and non-major bleeding occurred in 10 and 18 patients, respectively. Conclusions: In our cohort of ICU patients with COVID-19, we observed a high prevalence of VTE and bleeding complications after implementation of intermediate-dose anticoagulation. In approximately half of patients, VTE was identified on screening ultrasound.

The role of complement and extracellular vesicles in the development of pulmonary embolism in severe COVID-19 cases.

Complement and extracellular vesicles (EVs) association with thrombogenic tendencies is acknowledged, but limited evidence exists for their link to COVID-19 venous thromboembolism. This study aims to examine the relationship between pulmonary embolism and the expression of complement and other proteins related to thrombogenesis in severe Covid-19 patients. We included prospectively 207 severe COVID-19 patients and retrospectively screened for pulmonary embolism (PE). This analysis comprises 20 confirmed PE cases and 20 matched patients without PE. Blood samples taken at the admission in the intensive care unit were analyzed for complement using ELISA. EVs derived from neutrophils, endothelium, or platelets, as well carrying complement or tissue factor were analyzed using flow cytometry. Complement levels were markedly elevated, with a notable increase in C3a and Terminal Complement Complex. The most prevalent EV population was identified as tissue factor (TF)-carrying EVs which peaked in patients with PE during ICU days 4-9. However, for both the complement and analyzed EV populations, no statistically significant differences were found between the patients who developed pulmonary embolism and those who did not. In conclusion, complement factors and EVs expressing tissue factor, along with EVs derived from endothelial cells and platelets, are elevated in severe COVID-19 patients, regardless of the presence of pulmonary embolism. However, the involvement of complement and procoagulant EVs in peripheral plasma in the development of pulmonary embolism is still unclear and requires further investigation.