Thromboembolic prevention and anticoagulant therapy during the COVID-19 pandemic: updated clinical guidance from the anticoagulation forum.

Thromboembolism is a common and deadly consequence of COVID-19 infection for hospitalized patients. Based on clinical evidence pre-dating the COVID-19 pandemic and early observational reports, expert consensus and guidance documents have strongly encouraged the use of prophylactic anticoagulation for patients hospitalized for COVID-19 infection. More recently, multiple clinical trials and larger observational studies have provided evidence for tailoring the approach to thromboprophylaxis for patients with COVID-19. This document provides updated guidance for the use of anticoagulant therapies in patients with COVID-19 from the Anticoagulation Forum, the leading North American organization of anticoagulation providers. We discuss ambulatory, in-hospital, and post-hospital thromboprophylaxis strategies as well as provide guidance for patients with thrombotic conditions who are considering COVID-19 vaccination.

Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes. While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic. It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients. Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients. Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience. The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19. We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

BACKGROUND: Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle. OBJECTIVE: We compared cystatin C-based eGFR (eGFRcys) with multiple creatinine-based estimates of kidney function in hospitalized patients receiving anticoagulants, to assess for discordant results that could impact medication dosing. DESIGN: Retrospective chart review of hospitalized patients over 1 year who received non-vitamin K antagonist anticoagulation, and who had same-day measurements of cystatin C and creatinine. PARTICIPANTS: Seventy-five inpatient veterans (median age 68) at the San Francisco VA Medical Center (SFVAMC). MAIN MEASURES: We compared the median difference between eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation using cystatin C (eGFRcys) and eGFRs using three creatinine-based equations: CKD-EPI (eGFREPI), Modified Diet in Renal Disease (eGFRMDRD), and Cockcroft-Gault (eGFRCG). We categorized patients into standard KDIGO kidney stages and into drug-dosing categories based on each creatinine equation and calculated proportions of patients reclassified across these categories based on cystatin C. KEY RESULTS: Cystatin C predicted overall lower eGFR compared to creatinine-based equations, with a median difference of - 7.1 (IQR - 17.2, 2.6) mL/min/1.73 m2 versus eGFREPI, - 21.2 (IQR - 43.7, - 8.1) mL/min/1.73 m2 versus eGFRMDRD, and - 25.9 (IQR - 46.8, - 8.7) mL/min/1.73 m2 versus eGFRCG. Thirty-one to 52% of patients were reclassified into lower drug-dosing categories using cystatin C compared to creatinine-based estimates. CONCLUSIONS: We found substantial discordance in eGFR comparing cystatin C with creatinine in this group of anticoagulated inpatients. Our sample size was limited and included few women. Further investigation is needed to confirm these findings and evaluate implications for bleeding and other clinical outcomes. NIH TRIAL REGISTRY NUMBER: Not applicable.

Anticoagulation for the treatment of venous thromboembolism in patients with brain metastases: a meta-analysis and systematic review.

The risk benefit decision in providing anticoagulation for patients with brain metastases is amongst the most difficult decisions faced by clinicians. The purpose of our study was to evaluate both the risk of intracerebral hemorrhage (ICH) associated with anticoagulation therapy and the effect of anticoagulation on survival in patients with brain metastases and venous thromboembolism (VTE). A systematic review of the literature was performed via the PubMed, EMBASE, and the Cochrane databases. Our initial search resulted in 1304 unique citations, and 5 studies satisfied all eligibility criteria and were included for analysis. The odds ratio for development of ICH in the setting of anticoagulation was 1.37 (CI 0.86-2.17, p = 0.18). The hazard ratio for survival was 0.96 (CI 0.51-1.81, p = 0.90). While limited, the best available evidence suggests that there is no increased risk of ICH and no survival benefit associated with providing anticoagulation to patients with brain metastases who develop VTE. These patients merit individualized discussion of the risk and benefit of anticoagulation therapy. Current guidelines should be updated to include more recent studies and highlight the uncertainty of the net clinical benefit associated with anticoagulation.

2023 ISTH update of the 2022 ISTH guidelines for antithrombotic treatment in COVID-19.

Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR). Five recommendations had the LOE upgraded to A and 2 new recommendations on antithrombotic treatment for patients with COVID-19 were added. Furthermore, a section was added to answer questions about COVID-19 vaccination and vaccine-induced immune thrombotic thrombocytopenia (VITT), for which studies have provided some evidence. We only included recommendations with LOE A or B. Panelists agreed on 19 recommendations, 4 for nonhospitalized, 5 for noncritically ill hospitalized, 3 for critically ill hospitalized, and 2 for postdischarge patients, as well as 5 for vaccination and VITT. A strong recommendation (COR 1) was given for (a) use of prophylactic dose of low-molecular-weight heparin or unfractionated heparin in noncritically ill patients hospitalized for COVID-19, (b) for select patients in this group, use of therapeutic-dose low-molecular-weight heparin/unfractionated heparin in preference to prophylactic dose, and (c) for use of antiplatelet factor 4 enzyme immunoassays for diagnosing VITT. A strong recommendation was given against (COR 3) the addition of an antiplatelet agent in hospitalized, noncritically ill patients. These international guidelines provide recommendations for countries with diverse healthcare resources and COVID-19 vaccine availability.

Direct Oral Anticoagulants in Obese Patients with Venous Thromboembolism: Results of an Expert Consensus Panel.

In clinical practice, direct oral anticoagulants (DOACs) are increasingly used for venous thromboembolism treatment and prevention. A substantial proportion of patients with venous thromboembolism are also obese. International guidance published in 2016 stated that DOACs could be used in standard doses in patients with obesity up to a body mass index (BMI) of 40 kg/m2, but should not be used in those with severe obesity (BMI >40 kg/m2) owing to limited supporting data at the time. Although updated guidance in 2021 removed this limitation, some health care providers still avoid DOACs even in patients with lower levels of obesity. Furthermore, there are still evidence gaps regarding treatment of severe obesity, the role of peak and trough DOAC levels in these patients, use of DOACs after bariatric surgery, and appropriateness of DOAC dose reduction in the setting of secondary venous thromboembolism prevention. This document describes proceedings and outcomes of a multidisciplinary panel convened to review these and other key issues regarding DOAC use for treatment or prevention of venous thromboembolism in individuals with obesity.

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.

Diagnosis and management of venous thromboembolism.

Venous thromboembolic disease is a common disease associated with significant morbidity and mortality. Accurate and timely diagnosis should be guided by the use of validated clinical prediction rules. The mainstay of therapy is anticoagulation, although alternative approaches, such as use of concurrent thrombolysis or placement of vena caval filters, may be appropriate in selected patients. Determination of duration of anticoagulation requires a detailed assessment of the risk factors associated with the event allowing estimation of recurrence risk, and careful assessment of bleeding risk. Although extremely effective, anticoagulants have a narrow therapeutic window; systems should be in place to reduce risk of adverse events associated with these agents.

Cost considerations surrounding current and future anticoagulant therapies.

Because the costs of anticoagulation therapy are substantial and the difference between the risks and benefits of this therapy are often narrow, economic analyses are particularly valuable when weighing anticoagulation options. Economic analyses to date suggest that anticoagulation is most effective and results in the greatest cost savings when applied to populations at highest risk for thrombotic events. They also suggest that in situations where a more costly anticoagulant agent is available, that agent is cost-effective only if it is clearly more efficacious or if it substantially reduces costs in other areas, such as hospitalization. These principles should guide clinicians' choices of anticoagulation strategies.

Developing educators, investigators, and leaders during internal medicine residency: the area of distinction program.

BACKGROUND: Professional organizations have called for individualized training approaches, as well as for opportunities for resident scholarship, to ensure that internal medicine residents have sufficient knowledge and experience to make informed career choices. CONTEXT AND PURPOSE: To address these training issues within the University of California, San Francisco, internal medicine program, we created the Areas of Distinction (AoD) program to supplement regular clinical duties with specialized curricula designed to engage residents in clinical research, global health, health equities, medical education, molecular medicine, or physician leadership. We describe our AoD program and present this initiative's evaluation data. METHODS AND PROGRAM EVALUATION: We evaluated features of our AoD program, including program enrollment, resident satisfaction, recruitment surveys, quantity of scholarly products, and the results of our resident's certifying examination scores. Finally, we described the costs of implementing and maintaining the AoDs. RESULTS: AoD enrollment increased from 81% to 98% during the past 5 years. Both quantitative and qualitative data demonstrated a positive effect on recruitment and improved resident satisfaction with the program, and the number and breadth of scholarly presentations have increased without an adverse effect on our board certification pass rate. CONCLUSIONS: The AoD system led to favorable outcomes in the domains of resident recruitment, satisfaction, scholarship, and board performance. Our intervention showed that residents can successfully obtain clinical training while engaging in specialized education beyond the bounds of core medicine training. Nurturing these interests 5 empower residents to better shape their careers by providing earlier insight into internist roles that transcend classic internal medicine training.

Hospitalized ulcerative colitis patients have an elevated risk of thromboembolic events.

AIM: To compare thromboembolism rates between hospitalized patients with a diagnosis of ulcerative colitis and other hospitalized patients at high risk for thromboembolism. To compare thromboembolism rates between patients with ulcerative colitis undergoing a colorectal operation and other patients undergoing colorectal operations. METHODS: Data from the National Hospital Discharge Survey was used to compare thromboembolism rates between (1) hospitalized patients with a discharge diagnosis of ulcerative colitis and those with diverticulitis or acute respiratory failure, and (2) hospitalized patients with a discharge diagnosis of ulcerative colitis who underwent colectomy and those with diverticulitis or colorectal cancer who underwent colorectal operations. RESULTS: Patients diagnosed with ulcerative colitis had similar or higher rates of combined venous thromboembolism (2.03%) than their counterparts with diverticulitis (0.76%) or respiratory failure (1.99%), despite the overall greater prevalence of thromboembolic risk factors in the latter groups. Discharged patients with colitis that were treated surgically did not have significantly different rates of venous or arterial thromboembolism than those with surgery for diverticulitis or colorectal cancer. CONCLUSION: Patients with ulcerative colitis who do not undergo an operation during their hospitalization have similar or higher rates of thromboembolism than other medical patients who are considered to be high risk for thromboembolism.

Breaking bad news: a practical approach for the hospitalist.

Communicating bad news to patients and their families is a difficult but routine responsibility for hospitalists. Most practitioners have little or no formal training for this task. Preparation for, delivery of, and follow-up to these conversations should be deliberately planned in order to meet patients' needs. In this article, we review the literature that guides this process and, with a case example, describe steps practitioners can take to effectively deliver bad news and pitfalls that should be avoided. As competency in this skill set is necessary for effective patient care, hands-on training should be part of the core curriculum for all health care practitioners. Hospitalists should be proficient in this area and may serve as role models and instructors for colleagues and trainees.