Thrombosis Update最新文献

Bleeding is the main complication of treatment with anticoagulants, the most common adverse drug event that leads to emergency department visits, hospital admission, and death. While direct oral anticoagulants (DOACs) reduce the risk of major, fatal and intracranial bleeding compared to vitamin K antagonists, DOAC-associated bleeding is associated with substantial short-term mortality rates. To optimize management and improve outcomes, a standardized approach to managing severe bleeding includes rapid recognition, provision of treatments to reverse anticoagulation or enhance hemostasis, resumption of anticoagulation safety after bleed cessation and attention to secondary prevention measures and long-term monitoring. This narrative review outlines a pragmatic multimodal framework for severe DOAC bleed management with case examples to illustrate key principles.

Introduction

Replacement therapy with intravenous (IV) protein C concentrate (Ceprotin®; Baxalta US Inc., a Takeda company, Lexington, MA, USA; Takeda Manufacturing Austria AG, Vienna, Austria) is an approved treatment approach for patients with severe congenital protein C deficiency (SCPCD). Data on the real-world use of protein C concentrate are limited.

Materials and methods

In this non-interventional real-world study, physicians in Europe and the United States (US) with experience using protein C concentrate to treat patients with SCPCD completed an internet-based survey. Information collected included physician clinical practice details, experience treating patients with SCPCD, and opinions on the subcutaneous (SC) administration of protein C concentrate. Physicians responded based on their best recall.

Results

The analysis included 19 physicians (Europe, n = 12; US, n = 7) who had used protein C concentrate to treat 32 patients with SCPCD. Sixteen patients received IV long-term prophylaxis (LTP; treatment duration ≥3 months) and 12 received SC LTP. Five patients received both IV and SC LTP. Eighteen physicians indicated an interest in adding SC administration to the approved administration routes.

Conclusion

This survey shows that LTP with IV protein C concentrate is used in clinical practice by physicians in both Europe and the US for the treatment of patients with SCPCD. Protein C concentrate is also prescribed for SC administration by some physicians in Europe. Although only approved for IV administration, physicians in both Europe and the US indicated an interest in SC administration being an approved administration route for protein C concentrate.

Introduction

For patients with mechanical aortic valves, guideline recommended INR targets range from 2.0 to 3.5, depending on thromboembolic risk factors. Supporting data is largely historical and of low quality. We aimed to characterize clinicians’ practices around INR targets for these patients and perceptions of evidence supporting these recommendations.

Methods

A 33-question web-based survey was sent to 75 cardiologists, cardiac surgeons, and thrombosis specialists globally. We inquired about anticoagulation practices for patients with mechanical aortic valves, perceptions of guideline recommendations, and interest in participating in a randomized controlled trial comparing lower and higher INR targets in these patients.

Results

Of 55 respondents (73% response rate), 78% worked in academic hospitals. In patients with mechanical aortic valve and no additional thromboembolic risk factors, 80% targeted an INR of 2.5. Among patients with additional thromboembolic risk factors, 48% targeted an INR of 2.5, while 44% targeted an INR of 3.0. Additionally, 57% of respondents believed that evidence for the guidelines was up to date, and 53% believed that it applied to bi-leaflet valves.

However, 57% of respondents said that the evidence was not high quality. Lastly, 66% of respondents would accept a higher thromboembolic risk to reduce risk of major bleeding; 86% were willing to randomize patients with mechanical aortic valve to a target INR of 2.0 if they had no thromboembolic risk factors.

Conclusion

Clinicians target different INRs for patients with mechanical aortic valves; their perception of the evidence and guidelines varies. Of respondents, 86% would randomize patients to lower INR targets.

The severe coronavirus disease 2019 (COVID-19) triggers various coagulation cascades, culminating in the manifestation of venous thromboembolism (VTE). The efficacy of anticoagulant prophylaxis in averting VTE occurrence in severe COVID-19 cases in Thailand remains uncertain. We aimed to determine the prevalence of symptomatic VTE in patients with severe COVID-19 who received a standard dose of anticoagulants and to evaluate the risk factors. Our prospective cohort study included patients with severe COVID-19 who received anticoagulant prophylaxis. VTE, bleeding events and mortality were monitored until 60 days after VTE prophylaxis initiation. Of the 250 study patients, pulmonary embolism was observed in 7.2% of patients. In a multivariate Cox regression model, endotracheal intubation [hazard ratio (HR) = 13.75; 95% confidence interval (CI) = 2.87–65.82; p = 0.001] and high D-dimer levels [HR = 1.052; 95% CI = 1.023–1.081; p < 0.001) were significantly associated with higher VTE risk within 60 days of VTE prophylaxis. Bleeding and major hemorrhage occurred in 35 (14%) and eight (3.2%) patients, respectively. These findings indicated that a standard dose of anticoagulant may not be sufficient for preventing thrombosis in patients who require intensive care. Further research on the appropriate dose is necessary.

Aim

The risk of venous thromboembolism (VTE) and arterial thrombosis events (ATE) and potential corresponding risk factors were assessed in patients with cancer diagnosed with COVID-19.

Methods

Adults with cancer treated in community health systems who were diagnosed with COVID-19 in 2020 were evaluated for absolute risk (risk) of ATE and VTE. Thrombotic events were ascertained in the 90-day window starting with COVID-19 diagnosis (index). ICD codes defined baseline comorbidities, COVID-19, and thrombotic events.

Results

7591 patients were included with median age of 67, 6% with cardiovascular disease (CVD), 4% with prior VTE, and 24% were hospitalized at index. Risk of ATE and VTE were 2.1% (95%CI: 1.8, 2.5) and 3.2% (95%CI: 2.8, 3.6), respectively. Patients with CVD had increased risk [ATE: 20.1% (95%CI: 16.7, 24.1); VTE: 4.9% (95%CI: 3.3, 7.3)] as did patients with prior VTE [ATE: 3.8% (95%CI: 2.2, 6.6; VTE: 20.5% (95%CI: 16.4, 25.3)] and patients hospitalized with ventilator support [(ATE: 5.7% (95%CI: 2.6, 11.8; VTE: 6.6% (95%CI: 3.2, 13.0)]. Incidence rates for ATE and VTE were 0.094 and 0.141 per person-year, respectively.

Conclusions

This study of cancer patients, conducted in a time period prior to vaccine availability, found patients with CVD, prior VTE, and with higher severity of COVID-19 were at increased risk for ATE and VTE. Identifying patients most at risk can help to target interventions.

Background

The use of anticoagulant medications is complex and prone to inappropriate prescribing that impacts patient safety. Anticoagulation stewardship is a growing field that requires more focus and attention.

Aim

This review aimed to retrieve and synthesise the available research studies on the clinical and economic value of Anticoagulation Stewardship Programmes (ASPs) in line with the Anticoagulation Forum Core Elements of Anticoagulation Stewardship.

Methods

A comprehensive electronic literature search was conducted using three databases (Cochrane Central Register of Controlled Trials (CENTRAL), Embase and PubMed) from inception up to and including January 2023. Inclusion criteria were primary research studies where the purpose of the study was any hospital ASP intervention applicable to optimising antithrombotic drug use, across all anticoagulation medications and in adult hospital inpatients.

Results

A total of 787 records were identified after duplicates were removed. Twenty-eight papers were included in this review. Twenty-four of these studies were single-centre studies; four of these studies were multi-centre studies. Eleven studies took a prospective approach, fifteen took a retrospective approach and two were quasi-experimental studies. Interventions implemented by either multidisciplinary ASP teams or pharmacist-led anticoagulation services included the provision of education to healthcare professionals and patients, undertaking medication reviews and implementing guidelines and protocols, and interventions to facilitate transitions of care. Clinical benefits to patients and cost savings were observed across many studies.

Conclusion

Implementing multidisciplinary ASP teams and pharmacist-led anticoagulation services is associated with an overall improvement in the safe use of anticoagulation among hospital patients. Studies identified incorporated some of the core elements of ASP, however further work and research are necessary to standardise the adoption and implementation of ASP and ensure that it is prioritised among healthcare professionals, in the healthcare setting, and among health systems and policy-makers.