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Studies on severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) suggest a protective effect of anti-A antibodies against viral cell entry that may hold relevance for SARS-CoV-2 infection. Therefore, we aimed to determine whether ABO blood groups are associated with different severities of COVID-19. We conducted a multicenter retrospective analysis and nested prospective observational substudy of critically ill patients with COVID19. We collected data pertaining to age, sex, comorbidities, dates of symptom onset, hospital admission, intensive care unit (ICU) admission, mechanical ventilation, continuous renal replacement therapy (CRRT), standard laboratory parameters, and serum inflammatory cytokines. National (N 5 398 671; P 5 .38) and provincial (n 5 62 246; P 5 .60) ABO blood group distributions did not differ from our cohort (n 5 95). A higher proportion of COVID-19 patients with blood group A or AB required mechanical ventilation (P 5 .02) and CRRT (P 5 .004) and had a longer ICU stay (P 5 .03) compared with patients with blood group O or B. Blood group A or AB also had an increased probability of requiring mechanical ventilation and CRRT after adjusting for age, sex, and presence of $1 comorbidity. Inflammatory cytokines did not differ between patients with blood group A or AB (n 5 11) vs O or B (n 5 14; P . .10 for all cytokines). Collectively, our data indicate that critically ill COVID-19 patients with blood group A or AB are at increased risk for requiring mechanical ventilation, CRRT, and prolonged ICU admission compared with patients with blood group O or B. Further work is needed to understand the underlying mechanisms.

Objective To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. Design Randomised controlled, adaptive, open label clinical trial. Setting 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. Participants 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). Interventions Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. Main outcome measures The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. Results The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m 2 . At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). Conclusions In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. Trial registration ClinicalTrials.gov NCT04362085 .

Background: When bound to an anionic phospholipid-containing membrane, activated clotting factor X (FXa) is sequentially cleaved by plasmin from the intact form, FXaα, to FXaβ and then to Xa33/13. Tissue-type plasminogen activator (t-PA) produces plasmin and is the initiator of fibrinolysis. Both FXaβ and Xa33/13 enhance t-PA-mediated plasminogen activation. Although stable in experiments using purified proteins, Xa33/13 rapidly loses t-PA cofactor function in plasma. Bypassing this inhibition, covalent modification of the FXaβ active site prevents Xa33/13 formation by plasmin, and the persistent FXaβ enhances plasma fibrinolysis. As the direct oral anticoagulants (DOACs) rivaroxaban and apixaban bind to the FXa active site, we hypothesized that they similarly modulate FXa fibrinolytic function. Methods: DOAC effects on fibrinolysis and the t-PA cofactor function of FXa were studied in patient plasma, normal pooled plasma and purified protein experiments by the use of light scattering, chromogenic assays, and immunoblots. Results: The plasma of patients taking rivaroxaban showed enhanced fibrinolysis correlating with FXaβ. In normal pooled plasma, the addition of rivaroxaban or apixaban also shortened fibrinolysis times. This was related to the cleavage product, FXaβ, which increased plasmin production by t-PA. It was confirmed that these results were not caused by DOACs affecting activated FXIII-mediated fibrin crosslinking, clot ultrastructure and thrombin-activatable fibrinolysis inhibitor activation in plasma. Conclusion: The current study suggests a previously unknown effect of DOACs on FXa in addition to their well-documented anticoagulant role. By enabling the t-PA cofactor function of FXaβ in plasma, DOACs also enhance fibrinolysis. This effect may broaden their therapeutic indications.

Central venous catheters (CVCs) are used extensively in cancer patients for the administration of therapy and phlebotomy. An important complication of CVCs is the development of catheter-related thrombosis (CRT), which becomes symptomatic in approximately 5% of the patients. Several factors, such as insertion location and position of the catheter tip, increase the risk of CRT. Prevention of CRT with systemic anticoagulant prophylaxis has largely been ineffective. In addition, the optimal diagnostic strategy and anticoagulant treatment are unclear due to the lack of well-designed studies. The most recent American College of Chest Physicians guidelines recommend (color) Doppler ultrasound more than venography as the initial diagnostic test in patients with suspected arm thrombosis. Only if the ultrasound is negative and clinical suspicion is high is further testing with D-dimer, serial ultrasound, or venography advocated. In case of CRT, removal of the catheter is not necessary if it is functional and needed for chemotherapy. Anticoagulant treatment of CRT consists of treatment with low-molecular-weight heparin (LMWH) followed by vitamin K antagonists for at least 3 months. Whether long-term treatment with LMWH is more effective than vitamin K antagonists in cancer patients with CRT is unknown, but LMWH may be advocated following the recommendations in lower limb thrombosis and cancer. In addition, the effect of new anticoagulants in CRT has not been studied.