Anticoagulation strategies and risk of bleeding events in critically ill COVID-19 patients.

OBJECTIVE: To evaluate the rate of thrombosis, bleeding and mortality comparing anticoagulant doses in critically ill COVID-19 patients. DESIGN: Retrospective observational and analytical cohort study. SETTING: COVID-19 patients admitted to the intensive care unit of a tertiary hospital between March and April 2020. PATIENTS: 201 critically ill COVID-19 patients were included. Patients were categorized into three groups according to the highest anticoagulant dose received during hospitalization: prophylactic, intermediate and therapeutic. INTERVENTIONS: The incidence of venous thromboembolism (VTE), bleeding and mortality was compared between groups. We performed two logistic multivariable regressions to test the association between VTE and bleeding and the anticoagulant regimen. MAIN VARIABLES OF INTEREST: VTE, bleeding and mortality. RESULTS: 78 patients received prophylactic, 94 intermediate and 29 therapeutic doses. No differences in VTE and mortality were found, while bleeding events were more frequent in the therapeutic (31%) and intermediate (15%) dose group than in the prophylactic group (5%) (p<0.001 and p<0.05 respectively). The anticoagulant dose was the strongest determinant for bleeding (odds ratio 2.4, 95% confidence interval 1.26-4.58, p=0.008) but had no impact on VTE. CONCLUSIONS: Intermediate and therapeutic doses appear to have a higher risk of bleeding without a decrease of VTE events and mortality in critically ill COVID-19 patients.

ISTH guidelines for antithrombotic treatment in COVID-19.

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.

Arterial Thrombotic Events in Hospitalized COVID-19 Patients: A Short Review and Meta-Analysis.

It is well established that the risk of venous thromboembolism is high in coronavirus disease 19 (COVID-19). The frequency of arterial thromboembolic events (ATEs) in hospitalized patients with COVID-19 is unclear, as is the magnitude of these events in comparison with other infections. We searched MEDLINE from February 2020 to February 2022 for prospective or retrospective cohort studies and randomized clinical trials that reported the number of acute myocardial infarction (AMI), acute ischemic stroke (AIS), acute limb ischemia (ALI), or other ATE as defined by the original authors in hospitalized patients with COVID-19. The pooled frequencies were calculated through meta-analysis using random effects model with logit transformation and presented with relative 95% prediction intervals (95% PI). We retrieved a total of 4,547 studies, 36 of which (28 retrospective cohorts, five prospective cohorts and three randomized trials) were finally included in our analysis. The resulting cohort counted 100,949 patients, 2,641 (2.6%) of whom experienced ATE. The pooled ATE frequency was 2.0% (95% PI, 0.4-9.6%). The pooled ATE frequency for AMI, AIS, ALI, and other ATE was 0.8% (95% PI, 0.1-8.1%), 0.9% (95% PI, 0.3-2.9%), 0.2% (95% PI, 0.0-4.2%), and 0.5% (95% PI, 0.1-3.0%), respectively. In comparison with the ATE incidence reported in three studies on non-COVID viral pneumonia, we did not detect a significant difference from the results in our analysis. In conclusion, we found a non-negligible proportion of ATE in patients hospitalized for COVID-19. Our results are similar to those found in hospitalized patients with influenza or with non-COVID viral pneumonia.

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.

Arterial Thrombotic Events in Hospitalized COVID-19 Patients: A Short Review and Meta-Analysis.

It is well established that the risk of venous thromboembolism is high in coronavirus disease 19 (COVID-19). The frequency of arterial thromboembolic events (ATEs) in hospitalized patients with COVID-19 is unclear, as is the magnitude of these events in comparison with other infections. We searched MEDLINE from February 2020 to February 2022 for prospective or retrospective cohort studies and randomized clinical trials that reported the number of acute myocardial infarction (AMI), acute ischemic stroke (AIS), acute limb ischemia (ALI), or other ATE as defined by the original authors in hospitalized patients with COVID-19. The pooled frequencies were calculated through meta-analysis using random effects model with logit transformation and presented with relative 95% prediction intervals (95% PI). We retrieved a total of 4,547 studies, 36 of which (28 retrospective cohorts, five prospective cohorts and three randomized trials) were finally included in our analysis. The resulting cohort counted 100,949 patients, 2,641 (2.6%) of whom experienced ATE. The pooled ATE frequency was 2.0% (95% PI, 0.4-9.6%). The pooled ATE frequency for AMI, AIS, ALI, and other ATE was 0.8% (95% PI, 0.1-8.1%), 0.9% (95% PI, 0.3-2.9%), 0.2% (95% PI, 0.0-4.2%), and 0.5% (95% PI, 0.1-3.0%), respectively. In comparison with the ATE incidence reported in three studies on non-COVID viral pneumonia, we did not detect a significant difference from the results in our analysis. In conclusion, we found a non-negligible proportion of ATE in patients hospitalized for COVID-19. Our results are similar to those found in hospitalized patients with influenza or with non-COVID viral pneumonia.

Venous Thromboembolism in COVID-19.

The coronavirus disease 2019 (COVID-19) is our latest pandemic, preceded by the H1N1 swine flu in 2009, which lasted approximately 19 months. One of the special characteristics of COVID-19 is the propensity to cause venous thromboembolism (VTE). Thromboinflammation seems to play a prominent role in the pathogenesis. We will here review some mechanisms in the pathogenesis and discuss some hematological biomarkers, and also whether they serve as useful risk factors for VTE. The role of general risk assessment models for medically ill patients specifically in COVID-19 is appraised. The type of prophylaxis and particularly whether standard or augmented doses of chemoprophylaxis should be used is reviewed based on available evidence. We are also comparing recommendations from 10 different guidance or position/consensus statements. Treatment recommendations for patients with COVID-19 and pulmonary embolism are discussed with current general treatment guidelines as reference. Specifics for patients with COVID-19 are pointed out and the potential role of thrombolytic treatment is explored.

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.