Background Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. Methods In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d -dimer level. Results The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d -dimer cohort, 92.9% in the low d -dimer cohort, and 97.3% in the unknown d -dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. Conclusions In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589 , NCT04505774 , NCT04359277 , and NCT02735707 .)

Background Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID‐19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID‐19. We did a systematic review and meta‐analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID‐19. Methods We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel‐Haenszel fixed‐effect meta‐analysis was used to combine odds ratios (ORs). Results and Conclusions There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all‐cause death (OR, 0.76; 95% CI, 0.57‐1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45‐0.77). Organ support‐free days alive (OR, 1.29; 95% CI, 1.07‐1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment‐by‐subgroup interactions with illness severity for all‐cause death ( P = .034). In conclusion, therapeutic heparin is beneficial in moderately ill patients but not in severely ill patients hospitalized with COVID‐19.

Summary Background Left ventricular assist devices (LVADs) have dramatically increased the survival of adults with end‐stage systolic heart failure. However, rates of bleeding and thromboembolism remain high. Objectives We completed a systematic review to evaluate outcomes of adults with LVADs treated with various anticoagulant and antiplatelet strategies. Methods Databases were searched using the terms ‘assist device’, ‘thrombosis’, and ‘anticoagulant’ or ‘platelet aggregation inhibitor’ with appropriate synonyms, device names and manufacturers. Results and Conclusions Of 977 manuscripts, 24 articles met the inclusion criteria of adults with implanted LVADs where clinical outcomes were defined based on anticoagulant and/or antiplatelet regimen. Most studies reported treatment with unfractionated heparin post‐operatively which was transitioned to a vitamin K antagonist (VKA). Goal INR varied between 1.5–3.5. Antiplatelet regimens ranged from no treatment to dual therapy. Definition of major bleeding differed between trials and incidence varied between 0% and 58%. The available evidence could not demonstrate a clear benefit of aspirin compared with VKA therapy alone [stroke RR 1.02 (95% CI 0.49–2.1)]. There was a suggestion that treatment with aspirin and dipyridamole decreased the risk of thromboembolism compared to aspirin [RR 0.50 (0.36–0.68)], but the comparison is limited by differences in demographics, devices, and INR goals among studies. Additionally, most studies did not blind investigators to outcomes thus contributing to an increased risk for bias. Clinical equipoise exists as to the most appropriate antithrombotic therapy in LVAD patients. Randomization between regimens within a prospective trial is needed to define the treatment regimen that minimizes both bleeding and thrombotic complications.

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Objectives To review outcomes of massive transfusion protocol (MTP) activation and determine the impact of MTP implementation on blood bank use. Background MTP has been established to rapidly provide plasma and packed red blood cells in ratios approaching 1:1. Due to availability, MTP has been utilized in non-traumatic hemorrhage despite evidence of benefit in this population. Our hospital wide implementation of MTP was reviewed for propriety, outcomes, and effect on blood bank resources. Methods Retrospective cohort study of patients receiving transfusion after MTP activation from October 2009- 2011. Underlying medical conditions and baseline medication use were determined. In-hospital and 24-hour mortality were compared with evaluation for confounding by APACHE score and duration of MTP activation. Blood product use before and after MTP implementation was reviewed. Results MTP activation occurred in 62 trauma and 63 non-trauma patients. Non-trauma patients were older, had more underlying medical conditions, and higher APACHE scores compared to trauma patients. 24-hour mortality was higher in trauma compared to non-trauma patients (27.4% vs. 11.1%, p =0.02). There was no significant difference of in-hospital mortality. Transfusion ratio did not differ between trauma and non-trauma patients and was not associated with mortality even when MTP activation duration and APACHE score were considered. Hospital-wide blood product use did not change with MTP implementation. Conclusions MTP may be successfully used in trauma and non-trauma settings without significantly impacting overall blood product utilization. Inclusion of non-trauma patients into prospective studies of resuscitation with blood products is warranted to ensure benefit in these patients.

Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis.

Background COVID‐19 vaccinations in the United States are effective in preventing illness and hospitalization yet concern over post‐vaccination venous thromboembolism (VTE) risk has led to vaccine hesitancy. Methods The aim of this study was to compare VTE rates before and after COVID‐19 vaccination. COVID‐19 vaccinated patients ≥18 years between November 1, 2020 through November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE (upper or lower deep vein thrombosis or pulmonary embolism) occurring 90 days before and after the date of first vaccine dose. Results A total of 792 010 patients with at least one COVID‐19 vaccination were identified (Pfizer, n = 452 950, Moderna, n = 290 607, and Janssen [Johnson & Johnson], n = 48 453). A total of 1565 VTE events occurred in the 90 days before ( n = 772) and after ( n = 793) COVID‐19 vaccination. VTE post‐vaccination occurred in 326 patients receiving Moderna (0.11%, incidence rate [IR] 4.58 per 1000p‐years), 425 patients receiving Pfizer (0.09%, IR 3.84 per 1000p‐years), and 42 receiving Janssen (0.09%, IR 3.56 per 1000p‐years). Compared to the pre‐vaccination timeframe, the adjusted hazard ratio (aHR) for VTE after the Janssen vaccination was 0.97 (95% confidence interval [CI] 0.63–1.50), aHR 1.02 (95% CI 0.87–1.19) for Moderna, and aHR 1.00 (95% CI 0.87–1.15) for Pfizer. Conclusion In this large cohort of COVID‐19 vaccinated patients, no increased risk for acute VTE post‐vaccination was identified for the authorized vaccines in the United States.

Comparative statements in recommendation letters for internal medicine residency applicants were associated with professionalism scores during internship. Other variables traditionally examined when selecting residents were not associated with professionalism. These findings suggest that faculty physicians' direct observations, as reflected in letters of recommendation, are useful indicators of what constitutes a best student. Residency selection committees should scrutinize applicants' letters for strongly favorable comparative statements.