Seminars in thrombosis and hemostasis最新文献

Fibrinolysis is initiated by the activation of plasminogen to plasmin via tissue-plasminogen activator (tPA) and urokinase-plasminogen activator (uPA); plasmin then converts fibrin to fibrin degradation products (FDPs). The antifibrinolytics counterbalancing this system include plasminogen activator inhibitor-1 (PAI-1), which inhibits tPA and uPA, α-2 antiplasmin (α₂AP), which inhibits plasmin, and thrombin activatable fibrinolysis inhibitor, which inhibits the conversion of fibrin to FDP. Inherited disorders of the fibrinolytic pathway are rare and primarily have hemorrhagic phenotypes in humans: PAI-1 deficiency, α₂AP deficiency, and Quebec platelet disorder. Patients with these disorders are usually treated for bleeds or receive prophylaxis to prevent bleeds in the surgical setting, with pharmacological antifibrinolytics such as aminocaproic acid and tranexamic acid. Disorders of the fibrinolytic pathway with fibrin deposition are extremely rare, mostly noted in patients with plasminogen deficiency, who have more recently benefited from advances in human plasma-derived plasminogen concentrates administered intravenously or locally. These disorders can be very difficult to diagnose using conventional or even specialized coagulation testing, as testing can be nonspecific or have low sensitivity. Testing of the corresponding protein's activity and antigen (where applicable) can be obtained in specialized centres, and routine laboratory measures are not diagnostic. Genetic testing of the pathogenic mutations is recommended in patients with a high suspicion of an inherited disorder of the fibrinolytic pathway.

Portal vein thrombosis (PVT) is commonly encountered in patients with cirrhosis, challenging our understanding of its development, particularly the ambiguous contribution of inflammation. This study utilized Mendelian randomization (MR) to explore the causal impact of circulating inflammatory markers on PVT.

Employing a two-sample MR framework, we merged genome-wide association study (GWAS) meta-analysis findings of 91 inflammation-associated proteins with independent PVT data from the FinnGen consortium's R10 release. A replication analysis was performed using a distinct GWAS dataset from the UK Biobank. Inverse variance weighting, MR-Egger regression, weighted median estimator, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were used for analysis, supplemented by multivariable MR (MVMR) to adjust for cirrhosis effects.

Findings indicate a significant inverse association between the genetically inferred concentration of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and PVT risk, evidenced by an odds ratio (OR) of 0.37 (95% confidence interval [CI]: 0.21–0.67; p = 9.2 × 10⁻⁴; adjusted for multiple testing p = 0.084). This association was corroborated in the replication phase (OR = 0.39, 95% CI: 0.17–0.93; p = 0.03) and through MVMR analysis (OR = 0.34, 95% CI: 0.15–0.79; p = 0.012). Sensitivity analyses disclosed no evidence of heterogeneity or pleiotropy.

Our investigation emphasizes the 4E-BP1 as a protective factor against PVT, underscoring its potential relevance in understanding PVT pathogenesis and its implications for diagnosis and therapy.

Interactions between food and oral anticoagulants (OACs), particularly vitamin K antagonists such as warfarin, are widely recognized and may also be clinically relevant for direct OACs. Pharmacokinetic and pharmacodynamic interactions with food or herbs can lead to anticoagulation potentiation, increased risk of bleeding, or reduced drug efficacy, all compromising patient safety. We conducted a systematic search for randomized controlled trials (RCTs) on PubMed for assessments of interactions between OACs and various ingestants. Since the RCT evidence was slim, we also reviewed prospective longitudinal studies, case series, and case reports to identify possible associations between foods and anticoagulation therapy. We referred to basic or translational studies that shared putative explanations for such interactions, but we failed to identify high-quality evidence in most cases. The limited evidence, small sample size of the studies, conflicting results, and possible heterogeneity in the contents of herbal products prevent a conclusive assessment of these interactions. Existing evidence suggests that (1) cranberry juice consumption (up to 240 mL/d and probably even more) with warfarin is safe; (2) use of green leafy vegetables with a high daily content (more than 250 µg) of vitamin K should be cautioned for patients receiving warfarin, because it may decrease warfarin efficacy. It is also advisable for patients to maintain highly constant intake of green leafy vegetables to ensure stable warfarin effectiveness; (3) ginger, even in small quantities (excluding commercial ginger-flavored beverages, which contain only negligible amounts of ginger), and mango (more than one fruit) can both potentiate warfarin effects; (4) patients taking OACs should avoid St. John's wort due to diminished anticoagulant effect; and (5) consumption of less than 240 mL of grapefruit juice daily is unlikely to interact with OACs. Future longitudinal observational cohort studies and RCTs with larger sample sizes are needed to study specific interactions between food or herbal products and OACs.

One of the hallmarks of coronavirus disease 2019 (COVID-19), particularly in complicated cases (i.e., requiring hospitalization or intensive care support), is persistent hemostasis activation, which may be associated with a vast array of thrombotic episodes involving both the arterial and venous systems. The renewed emphasis on the relationship between viral infections and venous thrombosis paves the way for determining whether a more common and often underestimated infection disease, such as influenza, may also be associated with a significant burden of venous thrombotic episodes, and how this eventual thrombotic risk compares to that seen in COVID-19, both in the past and with newer variants. Our review of studies comparing the burden of venous thromboembolism (VTE) in patients with COVID-19 or influenza revealed that the thrombotic risk appears to be significantly higher in patients with COVID-19 but remains certainly not meaningless in those with influenza, particularly in subjects infected by highly virulent strains (i.e., H1N1), in those who develop pneumonia and require intensive care support. In these specific clinical settings, the adoption of tailored thromboprophylaxis may be indicated though more studies are compellingly needed on this matter. As COVID-19 variants emerge, there is a possibility that the VTE burden of COVID-19 will decrease, and progress to that of other respiratory viruses.

The inferior vena cava (IVC) and superior vena cava are the main conduits of the systemic venous circulation into the right atrium. Developmental or procedural interruptions of vena cava might predispose to stasis and deep vein thrombosis (DVT) distal to the anomaly and may impact the subsequent rate of pulmonary embolism (PE). This study aimed to review the various etiologies of developmental or procedural vena cava interruption and their impact on venous thromboembolism. A systematic search was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines per each clinical question. For management questions with no high-quality evidence and no mutual agreements between authors, Delphi methods were used. IVC agenesis is the most common form of congenital vena cava interruption, is associated with an increased risk of DVT, and should be suspected in young patients with unexpected extensive bilateral DVT. Surgical techniques for vena cava interruption (ligation, clipping, and plication) to prevent PE have been largely abandoned due to short-term procedural risks and long-term complications, although survivors of prior procedures are occasionally encountered. Vena cava filters are now the most commonly used method of procedural interruption, frequently placed in the infrarenal IVC. The most agreed-upon indication for vena cava filters is for patients with acute venous thromboembolism and coexisting contraindications to anticoagulation. Familiarity with different forms of vena cava interruption and their local and systemic adverse effects is important to minimize complications and thrombotic events.

The coronavirus disease 2019 (COVID-19) pandemic seems to be at its end. During the first outbreak, alfa was the dominant variant, and in the two following years, delta was the dominant variant. Questions remain about the prevalence and severity of post-COVID syndrome (PCS). We compared the medium-term outcomes of a selected group of patients considered at high risk for PCS: hospitalized patients with severe COVID-19 infection who presented clinical evidence of the acute onset of venous thromboembolism. Weighted Cox regression was used to estimate the adjusted hazard ratios for the risk of early and medium-term complications and quality of life (QoL) in COVID-19 patients developing acute venous thrombo-embolism according to the period of admission to the hospital. The primary outcome was the modification of QoL at a median follow-up of 24 months in patients hospitalized for COVID-19. The secondary outcome was the modification of QoL related to COVID-19 severity. The absolute risk of mortality for hospitalized COVID-19 patients was higher during the first outbreak (risk difference, 19% [95% confidence interval [CI], 16-22%]). Patients with acute onset of thromboembolism during the first outbreak had increased mortality, hospital stay, and need for intensive care unit treatment (p < 0.01). In patients who suffered from severe COVID-19 infection and thromboembolism in the following 2 years, symptoms during follow-up were less common and milder (risk difference 45% [95% CI, 40-52%]. In total, 19 patients were alive at 24 months follow-up: 12 patients (63%) reported important physical symptoms and 10 patients (52%) relevant emotional/mental symptoms. All patients reported reduced QoL in comparison with the preinfection time; in 15 patients (79%), the reduced QoL limited significantly their social and work activities. All patients reported permanent worsening of QoL after discharge from the hospital. Comparing the three different February to April interval years (2020, 2021, and 2022), patients reported a somewhat worse perception of health condition in comparison with the preinfection time, respectively, in 100, 79, and 56% respectively. The findings of our study show reduced prevalence and severity of PCS in the last 2 years. Less virulent variants, herd immunity, and vaccination may played a significant role.

Introduction:  Deep vein thrombosis (DVT) poses a complex challenge and often leads to postthrombotic syndrome (PTS), a debilitating complication. The emergence of venous stents offers a potential preventive avenue against this complication. This study aimed to provide consensus recommendations on the use of venous stent for DVT.

Materials and methods:  From June to July 2023, 20 internal medicine, angiology and vascular surgery, and vascular and interventional radiology experts were involved in the Delphi process. Thirty-one recommendations, categorized into three thematic areas, were rigorously evaluated: indications for stent use, stent selection and placement, and monitoring and prevention of complications. Agreement was evaluated using a Likert scale, with consensus defined as agreement by two-thirds of the participants.

Results:  Consensus was reached for 23 (74.2%) of 31 recommendations. The agreement was centered on considerations, such as stent placement in specific acute DVT scenarios, emphasizing pivotal stent characteristics. However, there were divergences in the recommended stent length to prevent migration and stent characteristics based on iliocaval bifurcation morphology. Notably, there was no consensus on whether patients with DVT caused by a major transient risk factor need more than 3 months of anticoagulation therapy or whether aspirin should be added to anticoagulant treatment after venous stenting.

Conclusions:  These consensus recommendations offer practical insights into optimizing venous stent use to prevent PTS in DVT patients. Addressing the critical aspects of stent selection, placement, and postprocedural care, these recommendations contribute to clinical decision-making. The identified divergences underscore the importance of consensus and thus indicate the need for further investigation.

The diagnosis of pulmonary embolism (PE) relies essentially on a probabilistic approach that requires careful clinical assessments, targeted laboratory tests, and the use of appropriate imaging tools. Nowadays, the diagnostic gold standard is computed tomographic pulmonary angiography. Lung ultrasound (LUS) can play a role in the diagnosis of PE mainly by allowing the visualization of peripheral lung infarctions. Hypoechoic, pleural-based parenchymal consolidation is the most typical and common finding of pulmonary infarction. More than 85% of infarct lesions are wedge-shaped, extending to the pleural surface and are localized to where the patient complains of pleuritic chest pain. Contrast-enhanced ultrasound can be performed in addition to basic ultrasound examination to ascertain nonvascularization of the consolidation, thus confirming that the lesion is an infarct. The aim of this narrative review is to summarize the latest evidence on the application of LUS to the diagnosis of PE, focusing purely on thoracic/lung signs.