Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

To the Editor: Patients with coronavirus disease 2019 have a profound hypercoagulable state, and complicating venous thrombotic events are common. [1][2][3] Abnormalities in coagulation screening measures, including a prolonged activated partial-thromboplastin time (aPTT), have been reported in patients with This finding could be seen as a reason to avoid the use of anticoagulation at both therapeutic and prophylactic doses.A prolonged aPTT may indicate a clottingfactor deficiency or the presence of an inhibitor of coagulation that is either specific (e.g., antibody to factor VIII) or nonspecific (e.g., lupus anticoagulant). Lupus anticoagulant can affect in vitro tests of blood coagulation but typically is not associated with bleeding. As part of the antiphospholipid syndrome, lupus anticoagulant is associated with a thrombotic risk. We investigated the cause of prolonged aPTT in patients with Covid-19.Blood specimens obtained from 216 patients who were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were received for coagulation screening, and 44 (20%) were found to have a prolonged aPTT. The specimens from 9 patients were excluded, and those from 35 patients were investigated further. (Details of the methods are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.)A summary of the results is provided in Table 1. The median age was 57 years, and 24 patients were male. Pulmonary embolism was confirmed in 1 patient, and clinically suspected thrombosis was present in 1 patient. No clinically significant bleeding or arterial thromboses were reported.No patients were found to have deficiencies in factor VIII or factor IX. In 5 patients, marginal reductions in factor XI were found that were un-