Thromboembolic and bleeding events in intensive care unit patients with COVID-19: results from a Brazilian tertiary hospital.

OBJECTIVES: To describe the incidence of thromboembolic events in adult patients with severe COVID-19 and identify clinical and laboratory factors associated with these events. DESIGN: Observational retrospective cohort study of 243 adult patients with severe COVID-19 admitted to an intensive care unit (ICU) at a Brazilian tertiary hospital. RESULTS: The incidence of all thromboembolic events was 14.8%, in which 3.8% developed deep vein thrombosis, 7.8% pulmonary embolism, 2.5% acute myocardial infarction, 1.2% stroke, and 1.2% peripheral artery occlusion. Risk factors identified were D-dimer at admission >3000 ng/mL (P=<0.0013) and major bleeding (P=0.001). The cumulative risk of developing thromboembolic events at day 28 after ICU admission was 16.0%. The rate of major bleeding was 4.1%. After receiver operating characteristic curve analysis, the D-dimer cut-off at admission correlating with thromboembolic events was 1140.5 ng/mL. CONCLUSIONS: The rate of thromboembolic events in our study was lower than previously described. High D-dimer level at admission was the leading risk factor; the optimal cut-off was 1140.5 ng/mL. The occurrence of thromboembolic events did not have an impact on the median overall survival rate. The optimal anticoagulant strategy in this context still needs to be established.

Real-world analysis of treatment patterns and clinical outcomes in patients with newly diagnosed chronic lymphocytic leukemia from seven Latin American countries.

OBJECTIVE: To describe chronic lymphocytic leukemia (CLL) treatment patterns and patient outcomes in Latin America. METHODS: This chart review study (NCT02559583; 2008-2015)evaluated time to progression (TTP) and overall survival (OS) outcomes among patients with CLL who initiate done (n = 261) to two (n = 96) lines of therapy (LOT) since diagnosis. Differences in TTP and OS were assessed by Kaplan-Meier analysis, with a log-rank test for statistical significance. Association between therapeutic regimen and risk for disease progression or death was estimated using Cox proportional hazard regression. RESULTS: The most commonly prescribed therapies in both LOTs were chlorambucil-, followed by fludarabine- and cyclophosphamide (C)/CHOP-based therapies. Chlorambucil- and C/CHOP-based therapies were largely prescribed to elderly patients (≥65 years) while fludarabine-based therapy was predominantly used by younger patients (≤65 years). In LOT1, relative to chlorambucil-administered patients, those prescribed fludarabine-based therapies had lower risk of disease progression (hazard ratio [HR] and 95% confidence interval [CI] 0.32 [0.19-0.54]), whereas C/CHOP-prescribed patients had higher risk (HR 95%CI 1.88 [1.17-3.04]). Similar results were observed in LOT2. There was no difference in OS between treatments in both LOTs. DISCUSSION: Novel therapies such as kinase inhibitors were rarely prescribed in LOT1 or LOT2in Latin America. The greater TTP observed forfludarabine-based therapies could be attributed to the fact that fludarabine-based therapies are predominantly administered to young and healthy patients. CONCLUSION: Chlorambucil-based therapy, which has limited benefits, is frequently prescribed in Latin America. Prescribing novel agents for fludarabine-based therapy-ineligible patients with CLL is the need of the hour. Trial registration: ClinicalTrials.gov identifier: NCT02559583.

The influence of MTHFR C677T polymorphism in chronic lymphocytic leukemia.

Some factors have been associated with the etiology of chronic lymphocytic leukemia (CLL), among them the Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. The aim of this study was to evaluate the role of MTHFR C677T polymorphism in CLL. A case-control study was conducted with 219 individuals from Brazilian central population. MTHFR C677T polymorphism was determined through PCR-RFLP followed by PAGE. The T allele frequence was higher in patients diagnosed with CLL than healthy subjects. However, when stratified by gender, the TT genotype was exclusively found in men diagnosed with CLL (p < 0.05). Adjusted multiple logistic regression analysis demonstrated that age was significantly linked to CLL predisposition (odds ratio = 1.08; p < 0.001). Studies evaluating the influence of genetic factors may provide insights on susceptibility for CLL.