UNASSIGNED: Hospitalized patients with COVID-19 have shown a significant occurrence of thromboembolism and a heightened risk of death. It remains unclear whether factor Xa inhibitors are superior to enoxaparin in this context. Hence, there is a need for a direct comparison to assess the preventive effects and safety of factor Xa inhibitors versus enoxaparin in hospitalized COVID-19 patients.
UNASSIGNED: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) or retrospective studies that compared the effectiveness or safety of factor Xa inhibitors and enoxaparin in preventing thromboembolism in hospitalized patients with COVID-19. Embolic incidence, incidence of bleeding, and all-cause mortality were among the outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 percent CIs.
UNASSIGNED: The analysis included six RCTs and two retrospective studies containing 4048 patients. Meta-analysis showed a statistically significant reduction among patients on factor Xa inhibitors compared with low-molecular-weight heparin (LMWH) in the embolic incidence [risk ratio (RR) 0.64 (95%, CI 0.42, 0.98); P=0.04, I2=12%]. Upon subgroup analysis by type of study design, no significant reductions were noted in patients on factor Xa inhibitors in RCTs (RR: 0.62; 95% CI: 0.33-1.17; P=0.14) or observational studies (RR: 0.53; 95% CI: 0.23-1.26; P=0.15) when compared with enoxaparin Factor Xa inhibitors were not significantly associated with incidence of bleeding [RR 0.76 (95% CI 0.36, 1.61); P=0.47, I2=0%] or all-cause mortality (RR: 0.81; 95% CI: 0.48-1.36; P=0.43). Consistent results were obtained upon subgroup analysis by the type of study design.
UNASSIGNED: Factor Xa inhibitors are more effective than enoxaparin in preventing thromboembolism among patients with COVID-19 who are not acutely ill and are hospitalized. Additional rigorous RCTs comparing factor Xa inhibitors with enoxaparin are warranted.

UNASSIGNED: Protamine, first isolated from salmon fish sperm and now produced through recombinant biotechnology, is an antidote that neutralizes the anticoagulant properties of heparin. Protamine function is based on the capacity to dissociate the heparin-antithrombin III (AT III) complex (an important link that promotes blood fluidification by inhibiting coagulation), forming the inactive heparin-protamine complex. Protamine has itself dose-dependent anticoagulant properties: It interferes with coagulation factors and platelet function; it stimulates fibrinolysis; it can lead to thrombocytopenia and reduction in thrombin-related platelet aggregation; it decreases platelet response to thrombin receptor agonist in a dose-dependent manner. In this review, we will focus on protamine and its interaction with heparin. Notably, protamine is able to antagonize not only unfractionated heparin (UFH) but also low molecular weight heparins to various degrees. Protamine-allergic and anaphylactoid systemic reactions may affect up to 1 in 10 people and should be prevented and treated early.

BACKGROUND: Post-thrombotic syndrome (PTS) is common in patients with deep vein thrombosis (DVT). It is unclear if different types of anticoagulant therapies (e.g. vitamin K antagonists (VKA), direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH)) are associated with different risks of PTS. We sought to assess the incidence rates of PTS development following a proximal DVT of the lower extremity managed with different types of anticoagulation regimens.
METHODS: A systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2023 was performed. The primary outcome was development of PTS. The secondary outcomes included severe PTS, venous ulcers, and major bleeding. Incidence rates were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software.
RESULTS: A total of 21 (4342 patients) articles were included in the analysis. The adjusted pooled incidence of PTS was 15.1 (95 % CI: 8.7 to 26.1), 18.2 (95 % CI: 9.4 to 35.1) and 24.6 (95 % CI: 9.2 to 65.5) per 100 patient-years patients managed with VKA, DOAC and LMWH, respectively. The adjusted pooled incidence of severe PTS was 5.1 (95 % CI: 2.6 to 10.0) and 0.2 (95 % CI: 0.01 to 2.7) per 100 patient-years for VKAs and DOACs, respectively.
CONCLUSIONS: The development of PTS is common in patients with proximal lower extremity DVT. The incidence rates of PTS seem to be similar across the different anticoagulation regimens, but severe PTS may be lower among patients receiving a DOAC.

OBJECTIVE: The initiation of extracorporeal membrane oxygenation (ECMO) triggers complex coagulation processes necessitating systemic anticoagulation. Therefore, anticoagulation monitoring is crucial to avoid adverse events such as thrombosis and hemorrhage. The main aim of this work was to analyze the association between anti-Xa levels and thrombosis occurrence during ECMO support.
METHODS: Systematic literature review and meta-analysis (Scopus and PubMed, up to July 29, 2023).
METHODS: All retrospective and prospective studies.
METHODS: Patients receiving ECMO support.
METHODS: Anticoagulation monitoring during ECMO support.
RESULTS: A total of 16 articles with 1,968 patients were included in the review and 7 studies in the meta-analysis (n = 374). Patients with thrombosis had significantly lower mean anti-Xa values (standardized mean difference -0.36, 95% confidence interval [CI] -0.62 to -0.11, p < 0.01). Furthermore, a positive correlation was observed between unfractionated heparin infusion and anti-Xa levels (pooled estimate of correlation coefficients 0.31, 95% CI 0.19 to 0.43, p < 0.001). The most common adverse events were major bleeding (42%) and any kind of hemorrhage (36%), followed by thromboembolic events (30%) and circuit or oxygenator membrane thrombosis (19%). More than half of the patients did not survive to discharge (52%).
CONCLUSIONS: This work revealed significantly lower levels of anti-Xa in patients experiencing thromboembolic events and a positive correlation between anti-Xa and unfractionated heparin infusion. Considering the contemplative limitations of conventional monitoring tools, further research on the role of anti-Xa is warranted. New trials should be encouraged to confirm these findings and determine the most suitable monitoring strategy for patients receiving ECMO support.

OBJECTIVE: The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI.
METHODS: Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs).
RESULTS: When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72-0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57-0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66-0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72-0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13-2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24-0.65; P = 0.0003).
CONCLUSIONS: Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.

Extracorporeal Membrane Oxygenation (ECMO) is a technology that offers organ support for critically ill patients with respiratory and/or cardiac failure. Despite improvements in recent years in technology and the biocompatibility of circuits, patients on ECMO remain at high risk of hematologic complications, such as bleeding or thrombosis. Anticoagulation is required in most cases to limit the risk of clotting, but questions persist regarding the optimal anticoagulation strategy. More precisely, there is still debate around the best anticoagulation agent and monitoring tools as well as on the transfusion thresholds and appropriate corrective measures when faced with complications. This narrative review provides an overview of hemostasis on ECMO and the impact of circuit size and coating. The benefits and downsides of unfractionated heparin (UHF) and Direct Thrombin Inhibitors (DTIs) as anticoagulation agents are reviewed. Finally, commonly available coagulation tests (activated clotting time, activated partial thrombin time, anti-Xa, and viscoelastic tests) and their limitations are addressed. In conclusion, future research is needed to determine the best anticoagulation strategy for patients on ECMO.

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BACKGROUND: Heparin-bonded expanded polytetrafluoroethylene (hb-ePTFE) synthetic grafts are an alternative to autologous vein grafts (AVG) for surgical bypass interventions in lower limb peripheral arterial disease (LLPAD). However, the clinical benefits of hb-ePTFE grafts have not been reviewed systematically for patients undergoing below-the-knee (BK) surgical bypass. This study aimed to meta-analyze available data on the utility of hb-ePTFE in patients undergoing BK surgical bypass.
METHODS: Medline, Embase, and Cochrane databases were searched, restricted to material in English with no date restriction. In addition, proceedings from relevant congresses were screened going back 2 years. The search was performed in December 2021. Eligible studies included prospective or retrospective comparative studies or prospective single-arm cohorts with an hb-ePTFE arm. Methodological quality was assessed with the ROBINS-I criteria. Outcomes included primary patency, amputation/limb salvage, and overall survival. Clinical outcomes were expressed as event rates. Studies were compared using meta-analysis to generate a standardized mean event rate for each outcome, with its 95% confidence interval (95% CI), using a random-effects model.
RESULTS: Following deduplication, 10,263 records were identified and 261 were assessed as full texts. No prospective comparative studies were identified. The level of evidence was uniformly low. Seventeen publications describing data from 9 individual patient cohorts met the inclusion criteria. These cohorts included a total of 1,452 patients undergoing BK surgical bypass with hb-ePTFE. The primary patency rate was 78.9% [95% CI: 72.2-85.7%] at 1 year, 68.2% [95% CI: 62.8-73.6%] at 2 years, decreasing to 48.0% [95% CI: 27.3-68.7%] at 5 years. The secondary patency rate was 84.8% [95% CI: 77.0-92.5%] at 1 year and 68.9% [95% CI: 43.0-94.9%] at 3 years; the 1-year limb salvage rate was 88.3% [95% CI: 79.6-97.1%] at 1 year and 79.0% [95% CI: 56.7-100%] at 3 years.
CONCLUSIONS: In patients undergoing BK bypass surgery, hb-ePTFE synthetic grafts, compared to uncoated grafts, perform well for patency and limb salvage. However, the quality of the evidence is low, and well-performed randomized clinical trials are needed to inform clinical decision-making on the choice of synthetic graft.

Heparin, a member of the glycosaminoglycan family, is renowned as the most negatively charged biomolecule discovered within the realm of human biology. This polysaccharide serves a vital role as a regulator for various proteins, cells, and tissues within the human body, positioning itself as a pivotal macromolecule of significance. The domain of biology has witnessed substantial interest in the intricate design of heparin and its derivatives, particularly focusing on heparin-based polymers and hydrogels. This intrigue spans a wide spectrum of applications, encompassing diverse areas such as protein adsorption, anticoagulant properties, controlled drug release, development of implants, stent innovation, enhancement of blood compatibility, acceleration of wound healing, and pioneering strides in tissue engineering. This comprehensive overview delves into a multitude of developed heparin conjugates, employing various methods, and explores their functions in both the biomedicine and electronics fields. The efficacy of materials derived from heparin is also thoroughly investigated, encompassing considerations such as thrombogenicity, drug release kinetics, affinity for growth factors (GFs), biocompatibility, and electrochemical analyses. We firmly believe that by redirecting focus towards research and advancements in heparin-related polymers/hydrogels, this study will ignite further research and accelerate potential breakthroughs in this promising and evolving field of discovery.

BACKGROUND: Blunt cerebrovascular injury (BCVI) occurs in 1-3% of blunt traumas and is associated with stroke, disability, and mortality if unrecognized and untreated. Early detection and treatment are imperative to reduce the risk of stroke, however, there is significant variation amongst centers and trauma care providers in the specific medical management strategy used. This study compares antiplatelets vs. anticoagulants to determine BCVI-related stroke risk and bleeding complications to better understand the efficacy and safety of various treatment strategies.
METHODS: A systematic review of MEDLINE, Embase, and Cochrane CENTRAL databases was conducted with the assistance of a medical librarian. The search was supplemented with manual review of the literature. Included studies reported treatment-stratified risk of stroke following BCVI. All studies were screened independently by two reviewers, and data was extracted in duplicate. Meta-analysis was conducted using pooled estimates of odds ratios (OR) with a random-effects model using Mantel-Haenszel methods.
RESULTS: A total of 3315 studies screened yielded 39 studies for inclusion, evaluating 6552 patients (range 8 - 920 per study) with a total of 7643 BCVI. Stroke rates ranged from 0% to 32.8%. Amongst studies included in the meta-analysis, there were a total of 405 strokes, with 144 (35.5%) occurring on therapy, for a total stroke rate of 4.5 %. Meta-analysis showed that stroke rate after BCVI was lower for patients treated with antiplatelets vs. anticoagulants (OR 0.57; 95% CI 0.33-0.96, p = 0.04); when evaluating only the 9 studies specifically comparing ASA to heparin, the stroke rate was similar between groups (OR 0.43; 95% CI 0.15-1.20, p = 0.11). Eleven studies evaluated bleeding complications and demonstrated lower risk of bleeding with antiplatelets vs. anticoagulants (OR 0.29; 95% CI 0.13-0.63, p = 0.002); 5 studies evaluating risk of bleeding complications with ASA vs. heparin showed lower rates of bleeding complications with ASA (OR 0.16; 95% CI 0.04-0.58, p = 0.005).
CONCLUSIONS: Treatment of patients with BCVI with antiplatelets is associated with lower risks of stroke and bleeding complications compared to treatment with anticoagulants. Use of ASA vs. heparin specifically was not associated with differences in stroke risk, however, patients treated with ASA had fewer bleeding complications. Based on this evidence, antiplatelets should be the preferred treatment strategy for patients with BCVI.