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Background: In Venezuela, the predominant vaccines administered are BBIBP-CorV and Gam-COVID-Vac. Despite robust evidence from randomized clinical trials validating the effectiveness of COVID-19 vaccines in mitigating hospitalization and mortality, there is still a lack of post-authorization safety studies conducted within this demographic population. Methods: A prospective observational study from October 5, 2021 to March 31, 2022 encompassed COVID-19 vaccinated and unvaccinated patients from four sentinel hospitals in Venezuela. Patient lethality was predicted using Charlson Comorbidity index. Clinical outcomes were assessed through WHO's COVID-19 Clinical Progression Scale. Results: Out of the 175 patients assessed, 85 (48.6%) were vaccinated. The median Charlson Comorbidity index was 3 points, with no statistically significant differences observed between the groups (p = 0.2). A total of 50 (28.6%) patients died during the study period, with higher proportion of deaths in unvaccinated patients (35.6% vs. 21.2%, p = 0.035). Advanced age (OR = 1.043, 95% CI = 1.015–1.071, p = 0.002) was associated with increased death risk, whereas vaccination against COVID-19 (OR = 0.428, 95% CI = 0.185–0.99, p = 0.047), high oxygen saturation (OR = 0.964, 95% CI = 0.934–0.995, p = 0.024), and enoxaparin administration (OR = 0.292, 95% CI = 0.093–0.917, p = 0.035) were associated with decreased death risk. Conclusion: During the third and fourth waves of the pandemic, COVID-19 vaccination was associated with a 57% reduction in lethality among patients in four public hospitals in Venezuela. Key summary points: Less than half (48.6%) of the patients were vaccinated against SARS-CoV-2. At least one out of four patients died during the study period, mainly in the unvaccinated group. Advanced age was associated with a higher risk of death. Vaccination against COVID-19, high oxygen, and enoxaparin administration were factors associated with a lower risk of death. [ABSTRACT FROM AUTHOR]

Background: To evaluate the safety and efficacy of percutaneous biopsy and microwave ablation (B + MWA) in patients with pulmonary nodules (PNs) who are receiving antithrombotic therapy by rivaroxaban as bridging therapy. Methods: The study comprised 187 patients with PNs who underwent 187 B + MWA sessions from January 1, 2020, to December 31, 2021. The enrolled patients were divided into two groups: Group A, who received antithrombotic therapy five days before the procedure and received rivaroxaban as a bridging drug during hospitalization, and group B, who had no antithrombotic treatment. Information about the technical success rate, positive biopsy rate, complete ablative rate, and major complications were collected and analyzed. Results: Group A comprised 53 patients and group B comprised 134 patients. The technical success rate was 100% in both groups. The positive biopsy rates were 88.68% and 91.04%, respectively (p = 0.6211, X2 = 0.2443). In groups A and B, the complete ablative rates at 6, 12, and 24 months were 100.0% versus 99.25%, 96.23% versus 96.27%, and 88.68% versus 89.55%, respectively. There were no significant differences in bleeding and thrombotic complications between the two groups. No grade 5 complications occurred. Conclusions: It is generally considered safe and effective that patients who are on antithrombotic therapy by rivaroxaban as bridging to undergo B + MWA for treating PNs. [ABSTRACT FROM AUTHOR]

Introduction: Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration. Methods: This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days. Results: 43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780 mL vs. 850 mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively. Conclusion: There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT. [ABSTRACT FROM AUTHOR]

Limited data exists on the safety and efficacy with the concomitant use of 4 factor prothrombic complex concentrate (4F-PCC) and andexanet alfa (AA). This case series describes 7 patients at our institution who received both 4F-PCC and AA for the management of life-threatening bleeding associated with apixaban or rivaroxaban. Four patients received AA due to worsening bleeding after 4F-PCC. Of the 7 patients in this case series, 1 had a documented thrombotic event which was an acute ischemic stroke. The thrombotic event rate in our case series was similar to the incidence of thrombotic events reported with the use of AA alone. In-hospital mortality occurred in 2 of 7 patients with 1 additional patient discharged to hospice care. [ABSTRACT FROM AUTHOR]

Introduction: To determine if anti-Xa testing is associated with improved outcomes for patients <19-years-old on ECMO. Methods: We evaluated the clinical benefit of anti-Xa heparin monitoring utilizing the Bleeding and Thrombosis during ECMO (BATE) database of 514 patients <19-years-old. The BATE database includes incidences of bleeding, thrombosis, and mortality. The database also describes anti-coagulation test utilization. We grouped and analyzed patients based on ECMO indication (cardiac, respiratory, or extracorporeal cardiopulmonary resuscitation [E-CPR]) and age (neonatal vs pediatric). We constructed multivariable logistic regression models to analyze the impact of anti-Xa testing on mortality, bleeding, and thrombosis in each group. Results: Across the entire population, anti-Xa testing did not have a significant effect on the incidence of mortality (43% with anti-Xa testing vs 49% without), bleeding (68% vs 74%), or thrombosis (37% vs 39%). However, among cardiac indicated patients on ECMO (n = 207), anti-Xa testing was significantly associated with reduced odds ratio (OR) of mortality (adjusted OR 0.527, p =.040) and bleeding (adjusted OR 0.369, p =.021). In addition, among neonatal patients on ECMO (n = 264), anti-Xa testing was associated with a significant reduction in the odds ratio of bleeding (adjusted OR 0.534, p =.046). Conclusion: Anti-Xa testing is associated with improved outcomes among cardiac indicated and neonatal patients on ECMO. Additional research to find the optimal heparin monitoring regimen is needed to better support these critically ill patients. In the interim, we recommend clinicians consider utilizing anti-Xa assays as part of their heparin monitoring plan for neonatal and cardiac indicated patients on ECMO. [ABSTRACT FROM AUTHOR]

Thromboembolism (TE) complicates the course of pediatric cancer in a considerable number of cases. Cancer-related TE is attributed to an interaction of the underlying malignancy, the effects of therapy, and a possible thrombophilia predisposition. More specifically, recognized risk factors include a very young age and adolescence, non-O blood group, type and site of cancer, inherited thrombophilia, presence of central venous catheter, and type of chemotherapy. TE in children with cancer most commonly occurs in their extremities. In the absence of evidence-based guidelines for the management of thrombotic complications in pediatric oncology patients, TE management follows general recommendations for the management of pediatric TEs. Given the limitations of conventional anticoagulant therapy, direct oral anticoagulants could provide an alternative; however, their safety and efficacy in children with cancer remain to be seen. As for thromboprophylaxis, numerous studies have been conducted, albeit with conflicting results. Although the survival of pediatric oncology patients has significantly improved in recent years, morbidity due to cancer-related TE remains, underlying the need for large multicenter trials investigating both TE management with currently available agents and primary prevention. [ABSTRACT FROM AUTHOR]

In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body's antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies. Highlights: Geniposide is an active iridoid glycoside compound extracted from the Chinese medicine Gardenia jasminoides Ellis. Geniposide can combat atherosclerosis through various mechanisms. Geniposide modulates immune cells and the reverse cholesterol transport, thereby limiting the formation of macrophage foam cells and improving lipid metabolism. The effects of geniposide on autophagy and apoptosis in VSMCs may be the emphasis of additional research. Whether geniposide can regulate the interaction between apoptosis and autophagy in CVD needs further investigation. Whether geniposide can target intestinal flora to inhibit atherosclerosis development needs further investigation. By selecting an appropriate route of administration and dosage regimen for geniposide, potential safety concerns can be effectively addressed. [ABSTRACT FROM AUTHOR]

Objective: Traumatic axillary and subclavian artery injuries are uncommon. Limited data are available regarding patient and injury characteristics, as well as management strategies and outcomes. Methods: Retrospective chart review was performed on patients presenting to University of Louisville Hospital, an urban Level One Trauma Center, with traumatic axillary and subclavian artery injuries from 2015-2021. Patients were identified using University of Louisville trauma, radiology, and billing database searches based on ICD9/10 codes for axillary and subclavian artery injuries. Descriptive statistics are expressed as frequencies and percentages. Comparisons were performed using Fisher's Exact and Chi-squared tests. Results: Forty-four patients with traumatic axillary-subclavian arterial injuries were identified for analysis. Blunt and penetrating trauma were equally represented (n = 22 for both). A variety of injury types were seen, including minimal/intimal injury, laceration, pseudoaneurysm, transection, occlusion, and arteriovenous fistula. Management strategies were also variable, including non-operative, endovascular, planned hybrid, open, and endovascular converted to open. In operative patients, revascularization technical success was high (n = 31, 97%) with low likelihood of thrombosis (n = 2, 6%) and no infections. Among all patients, amputation rate was 5% (n = 2) and mortality rate was 9% (n = 3). Regarding arterial involvement, blunt injury was more likely to affect the subclavian (n = 18) than the axillary artery (n = 6) (P =.04). No significant difference was seen in brachial plexus injury based on artery involved (subclavian = 9 vs axillary = 11, P =.14) or mechanism (blunt = 6 vs penetrating = 11, P =.22). Non-operative management was more likely with subclavian artery injury (n = 11) vs axillary artery injury (n = 1) (P =.008). There was no significant difference between decision for non-operative (blunt = 9, penetrating = 3) vs operative (blunt = 13, penetrating = 19) management based on mechanism (P =.09). Transection injury was associated with an open repair strategy (endovascular/hybrid = 1, open/endovascular to open conversion = 11, P =.0003). Of the three patients requiring endovascular to open conversion, two required amputation, which were the only two patients in the study undergoing amputation. Conclusions: Both open and endovascular/hybrid strategies are useful when treating traumatic axillary and subclavian artery injuries and are associated with high likelihood of revascularization technical success, with low rates of thrombosis or infection, when treated promptly at a trauma center with vascular specialists available. Transection injuries were most often treated with open revascularization. Patients undergoing amputation had blunt transection injuries to the subclavian artery and underwent endovascular to open conversion after failed attempts at endovascular revascularization. [ABSTRACT FROM AUTHOR]

Purpose The need for monitoring and standardization of anticoagulation management has garnered the attention of national organizations, driving the implementation of antithrombotic stewardship programs (ASPs). Established ASPs have highlighted interdisciplinary collaboration between physicians, nurses, and pharmacists and demonstrated financial benefits and positive patient care outcomes. While pharmacy technicians are key members of the pharmacy profession, they are rarely utilized to expand clinical programs. The aim of this report is to describe the impact of adding a pharmacy technician to an ASP at an academic medical center. Summary The departments of pharmacy and quality at West Virginia University Hospitals (WVUH) developed a business plan and financially justified an ASP. The ASP was implemented in January 2022 and consisted of 2 full-time clinical pharmacist specialists, 1 full-time clinical pharmacy technician, 2 full-time clinical nurse specialists, and 1 part-time physician medical director. The clinical pharmacy technician's primary role was to review patients' sequential compression device (SCD) compliance and newly started oral anticoagulants prior to discharge. The clinical nurse specialists educated patients newly started on oral anticoagulants within 24 hours of discharge and triaged any postdischarge medication access issues. The medical director provided high-level program oversight and acted as a clinical consultant on complex patient cases. In the first 6 months after the program's implementation, the clinical pharmacy technician made 174 recommendations to the clinical pharmacist specialists regarding discharge transitions of care and assessed SCD compliance in 246 patients. Of the 246 patients assessed, 217 patients (88%) were deemed to be noncompliant. Conclusion The pharmacy department at WVUH successfully justified and implemented an interprofessional ASP at an academic medical center, which is the first ASP to date to incorporate a clinical pharmacy technician. [ABSTRACT FROM AUTHOR]

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this seventh section of the report offers a comprehensive analysis of disorders of heart rhythm in China. In 2021, China has achieved significant development and gratifying results in many aspects of the field of arrhythmia. Left bundle branch pacing (LBBP), as an emerging pacing technique originating from China, has received widespread attention. New research results have emerged on its indications, surgical procedures, clinical evaluation, and comparison with other pacing techniques. Its feasibility, effectiveness, and safety have been basically verified, but its long-term prognosis still needs further confirmation from larger samples and longer follow-up time research results. Leadless pacemakers have begun to be used in a wider range of clinical applications, and related large sample cohort studies have been reported. In addition, there are also noteworthy new achievements in the fields of pacemaker remote programming, anticoagulation and radiofrequency catheter ablation (RFCA) therapy for atrial fibrillation, and implantable cardioverter defibrillator prevention of sudden cardiac death. In terms of clinical practice, due to COVID-19 pandemic, the number of RFCA procedures and other device implantations in China has fluctuated, but it has gradually recovered since 2020. [ABSTRACT FROM AUTHOR]

Introduction: Balancing the prevention of thrombosis with bleeding risk when combining anticoagulants and platelet antagonists remains a concern among clinicians, particularly in patients with acute coronary syndrome (ACS) who are treated with potent antiplatelet therapy. This may be because the available antiplatelet and anticoagulants are unable to uncouple physiological hemostasis and pathological thrombosis. Therefore, their use is associated with an unavoidable elevated risk of bleeding. Areas covered: Evidence available from studies evaluating FXIa inhibitors and milvexian was collected from a selective literature search. In this review, the authors describe the potential role of FXI/XIa in experimental thrombosis, evidence for FXIa inhibition in the treatment of clinical thrombotic events, and highlight the current evidence supporting the role of milvexian, a novel FXIa inhibitor, in patients with ACS. Expert opinion: The ongoing LIBREXIA-ACS trial is a large-scale study currently investigating milvexian in patients with ACS. This study may support the proof of concept of differentiating physiological hemostasis and pathological thrombosis and achieving maximum antithrombotic efficacy with minimum bleeding risk when used on top of dual antiplatelet therapy with potent P2Y12 receptor blockers. [ABSTRACT FROM AUTHOR]

Background: JAK2‐mutated polycythaemia vera (PV) is associated with reduced survival because of thrombotic events and haematological disease transformation. Therapeutic venesection has traditionally been used to lower haematocrit, but the technique of erythrocytapheresis has emerged over the last decade. Aim: To compare erythrocytapheresis with venesection as treatment for PV by assessing medical efficacy and financial viability. Methods: One hundred sixteen patients with PV who received red cell depletion therapy at Barwon Health between 2014 and 2021 were identified. The haematocrit drop after each session, interval between treatment times and number of sessions required to achieve a haematocrit <0.45 were compared with an independent t test. Thrombosis rates were compared with Pearson's chi‐squared test. Cost‐funding analysis was done by assessing the Weighted Inlier Equivalent Separation and National Weighted Activity Unit funding models. Results: Patients treated with erythrocytapheresis achieved a greater haematocrit drop each treatment session (0.075 vs 0.03, P < 0.01), required fewer sessions to achieve a haematocrit <0.45 (1 vs 4, P < 0.01) and experienced fewer thrombotic complications (8.7% vs 32.1%, P = 0.02) than those treated with venesection. Cost‐funding analysis demonstrated that erythrocytapheresis was more financially viable with a surplus of AU$297 per session compared to a deficit of AU$176 with venesection. Even if funding for venesection is increased, the cost of erythrocytapheresis may be mitigated by a lower number of procedures required per year (3.8 vs 5.3, P < 0.01). Conclusions: Erythrocytapheresis is more efficacious than venesection for the treatment of PV and is accompanied by rapid reductions in haematocrit and reduced thrombotic complications. [ABSTRACT FROM AUTHOR]

Formyl peptide receptors (FPRs) are members of seven transmembrane G protein-coupled receptors superfamily that exhibit different responses based on the nature of stimulating ligand type. FPRs have been shown to be present in platelets and regulate their function. However, the effect of formyl peptide receptor 2 (FPR2/ALX) lipid ligands on platelets has not yet been addressed. Hence, we sought to study the role of FPR2/ALX ligand and lipoxin A4 lipid analogue, BML-111, in the modulation of platelet function and thrombus formation. Immunofluorescence microscopy showed subcellular distribution and peripheral mobilisation of FPR2/ALX in stimulated platelets. This variation in distribution was further confirmed using flow cytometry. BML-111 inhibited a range of platelet activities in a dose-dependent manner in response to several platelet agonists. This included aggregation, fibrinogen binding to integrin αIIbβ3, α-granule secretion, dense granule secretion, Ca2 + mobilisation and integrin αIIbβ3-mediated outside-in signaling. The selectivity of BML-111 for FPR2/ALX was confirmed using FPR2/ALX deficient mice in flow cytometry assays. In vitro thrombus formation was also inhibited by various concentrations of BML-111. Moreover, the levels of vasodilator stimulated phosphorylation (VASP-S157) increased significantly after BML-111 treatment in resting and stimulated platelets via protein kinase A (PKA) independently of cyclic adenosine monophosphate (cAMP) signaling. Together, our findings demonstrate the significance of BML-111 as a modulator of platelet function via FPR2/ALX and unravel the thrombo-protective potentials of BML-111 induced signaling against thrombo-inflammatory diseases. Key points: • Lipoxin A4 analogue, BML-111 reduces platelet function. • BML-111 augments platelet inhibitory signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Due to the risk of thrombosis, nearly all children supported by extracorporeal membrane oxygenation (ECMO) receive systemic anticoagulation. While heparin has traditionally been used, there are reports of increased use of direct thrombin inhibitors. We sought to describe the use of anticoagulation in children supported by ECMO in the United States using a large administrative database. Methods: We performed a retrospective cohort study of children supported by ECMO within the Pediatric Health Information System (PHIS) database. Pediatric encounters involving ECMO from 2012 to 2020 were identified. Data regarding demographics, diagnoses, anticoagulation, complications, and outcomes were extracted for eligible encounters. Results: Eleven thousand five hundred ninety-five encounters that involved ECMO were identified. Fifty-four percent were male with an age range of 0–17 years and a median (IQR) age of 0 (0–2) years. Unfractionated heparin (UFH) only was used in 94% (95% CI: 93.6–94.5%) of encounters and UFH followed by bivalirudin in 5% (95% CI: 4.3–5.1%) of cases. There was a significant difference in the use of bivalirudin from 2012 to 2020 (p < 0.001). Differences in anticoagulation regimens were observed between infants and children (p = 0.004) and between those with and without cardiac indications for ECMO (p < 0.001). Four percent (95% CI: 4.1–4.8%) of encounters were associated with diagnostic coding for thrombosis and differences in occurrence of thrombosis were observed between different anticoagulant regimens (p < 0.001). Conclusions: Though the majority of children on ECMO in the United States receive heparin anticoagulation, there is an increase in use of direct thrombin inhibitors. Prospective studies must evaluate the efficacy of different anticoagulants in this patient population. [ABSTRACT FROM AUTHOR]

Background: The study explores left atrial appendage closure (LAAC) as a safe and effective alternative to anticoagulation for atrial fibrillation (AF) patients at high bleeding risk. Complications, such as cardioembolic events due to left atrial appendage thrombus (LAAT), highlight the need for alternative stroke prevention strategies. Aims: This research assesses LAAC's safety and efficacy in patients with LAAT, aiming to offer valuable insights into its potential as a viable option for stroke prevention in such cases. Methods: The study included 205 patients who underwent LAAC using specific devices between September 2015 and February 2023. Among them, 32 patients had persistent LAAT. Baseline characteristics, antithrombotic medications, risk scores, and LAAC indications were documented. Patients were followed to monitor significant clinical events like stroke, cardiovascular mortality, and all‐cause mortality. Results: The mean age was 71.9 and mostly female. Indications for LAAC were ischemic cerebrovascular events (CVE) despite anticoagulation (25%), bleeding complications (major/minor, 37.5% each), or both. Successful LAA closure was achieved in all cases, with minimal pericardial effusion in one. One‐month follow‐up showed no major events or device‐related issues. Median follow‐up of 16.5 months saw 21.9% non‐cardiac deaths. The study underscores LAAC's efficacy for stroke prevention in patients with persistent LAAT. Conclusions: The LAAC in cases of LAAT, whether pursued initially or as a deferred approach, demonstrates feasibility and safety, exhibiting notable procedural success and minimal incidence of periprocedural complications. [ABSTRACT FROM AUTHOR]

Background and objective: Left ventricular thrombus (LVT) formation in patients with acute myocardial infarction (AMI) or cardiomyopathies is not uncommon. The optimal oral anticoagulation therapy for resolving LVT has been under intense debate. Vitamin K antagonists (VKAs) remain the anticoagulant of choice for this condition, according to practice guidelines. Evidence supporting the use of direct oral anticoagulants (DOACs) in the management of LVT continues to grow. We performed a systematic review and meta-analysis to compare the efficacy and safety of DOACs versus VKAs. Methods: A comprehensive literature search was carried out in PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases in July 2023. The efficacy outcomes of this study were thrombus resolution, ischemic stroke, systemic embolism, stroke/systemic embolism, all-cause mortality, and adverse cardiovascular events. The safety outcomes were any bleeding, major bleeding, and intracranial hemorrhage. A total of twenty-seven eligible studies were included in the meta-analysis. Data were analyzed utilizing Stata software version 15.1. Results: There was no significant difference between DOACs and VKAs with regard to LVT resolution (RR = 1.00, 95% CI 0.95–1.05, P = 0.99). In the overall analysis, DOACs significantly reduced the risk of stroke (RR = 0.74, 95% CI 0.57–0.96, P = 0.021), all-cause mortality (RR = 0.70, 95% CI 0.57–0.86, P = 0.001), any bleeding (RR = 0.75, 95% CI 0.61–0.92, P = 0.006) and major bleeding (RR = 0.67, 95% CI 0.52–0.85, P = 0.001) when compared to VKAs. Meanwhile, in the sub-analysis examining randomized controlled trials (RCTs), the aforementioned outcomes no longer differed significantly between the DOACs and VKAs groups. The incidences of systemic embolism (RR = 0.81, 95% CI 0.54–1.22, P = 0.32), stroke/systemic embolism (RR = 0.85, 95% CI 0.72–1.00, P = 0.056), intracranial hemorrhage (RR = 0.59, 95% CI 0.23–1.54, P = 0.28), and adverse cardiovascular events (RR = 0.99, 95% CI 0.63–1.56, P = 0.92) were comparable between the DOACs and VKAs groups. A subgroup analysis showed that patients treated with rivaroxaban had a significantly lower risk of stroke (RR = 0.24, 95% CI 0.08–0.72, P = 0.011) than those in the VKAs group. Conclusion: With non-inferior efficacy and superior safety, DOACs are promising therapeutic alternatives to VKAs in the treatment of LVT. Further robust investigations are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: The use of direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparin (LMWH) for extended thromboprophylaxis of abdominal/pelvic cancer-related postoperative thromboembolism (VTE) is unclear. We aim to investigate the efficacy and safety of DOACs vs. LMWH in these patients. Methods: A systematic review was conducted using EMBASE, MEDLINE, CENTRAL, and Web of science through May 19th, 2023 for all randomized controlled trials (RCTs) and observational studies that compared the outcomes with DOACs vs. LMWH for extended thromboprophylaxis among patients undergoing abdominal/pelvic cancer surgery. Primary efficacy outcome was clinical VTE, and safety outcome was clinically relevant bleeding complications reported within the 30-day postoperative period. This study was registered in PROSPERO (CRD42023413175). Results: We identified 5078 articles and selected 29 full-text articles for eligibility. A total of 9 studies (2 RCTs and 7 observational studies) encompassing 2651 patients were included for systematic review and 7 for meta-analysis. When compared with LMWH extended thromboprophylaxis, DOACs had a similar incidence of VTE (RR: 0.65 [95% CI: 0.32–1.33], I2 = 0%), major bleeding (RR: 1.68 [95% CI: 0.36–7.9], I2 = 26%), and clinically relevant non-major bleeding (RR: 0.68 [95% CI: 0.39–1.19], I2 = 0%). Subgroup analysis suggested no difference according to the study type (RCTs versus observational studies) regarding clinical VTE or major bleeding (Pinteraction = 0.43 and Pinteraction = 0.71, respectively). Conclusion: Our results suggest that DOACs for extended thromboprophylaxis were an effective and safe alternative to LMWH after major abdominal/pelvic cancer-related surgery. [ABSTRACT FROM AUTHOR]

Introduction: Patients of acute coronary syndrome (ACS) at a high-bleeding risk (HBR) often require dual antiplatelet therapy (DAPT) to reduce the risk of recurrent cardiovascular events. Clopidogrel and ticagrelor are the most commonly used antiplatelet agents in DAPT regimens. However, the safety profiles of these drugs in ACS patients at HBR remain a subject of ongoing debate. Aim: To investigate any difference between the safety of clopidogrel and ticagrelor used as a part of DAPT regimen in ACS patients at HBR. Methods: A systematic search on PubMed, Cochrane Library, and Google Scholar was conducted to identify experimental and observational studies published up to the knowledge cutoff date in September 2023. Studies comparing the safety of clopidogrel and ticagrelor in ACS patients at HBR were included for analysis. The primary outcomes assessed were major bleeding events, stroke, and myocardial infarction (MI), while secondary outcomes included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and net adverse clinical and cerebral events (NACCE). Results: We included a total of 8 observational studies in our meta-analysis. The pooled analysis revealed a statistically significant increase in the risk of MI (pooled RR = 1.43; 95% CI 1.12–1.83; P = 0.005) in the patients using clopidogrel. There were no statistically significant differences in major bleeding events (pooled RR = 0.94; 95% CI 0.82–1.09; P = 0.44), stroke (pooled RR = 1.36; 95% CI 0.86–2.14; P = 0.18), all-cause mortality (pooled RR = 1.17; 95% CI 0.97-1.41; P = 0.10), MACCE (pooled RR = 1.07; 95% CI 0.76–1.50; P = 0.69) and NACCE (pooled RR = 0.95; 95% CI 0.66–1.37; P = 0.78) between the two groups. Subgroup analyses based on region were performed. Conclusion: Both drugs are generally safe for treating ACS patients with HBR at baseline, although a higher risk of MI was observed with the use of clopidogrel. Nevertheless, drug choice should factor in regional variations, patient-specific characteristics, cost, accessibility, and potential drug interactions. [ABSTRACT FROM AUTHOR]

Menopausal hormone therapy (MHT) which is initiated in women less than 60 years old or within 10 years after the onset of menopause for the relief of menopausal symptoms, treatment of urogenital syndrome or osteoporosis, is currently the only way to reduce the risk of developing cardiovascular diseases, thrombotic and metabolic disorders in healthy middle-aged women. This article presents the results of evaluating the use of hormone therapy in women during the menopausal transition to the state of somatic health in postmenopause by determining its effect on the state of the cardiovascular and bone systems, changes in the lipid profile, as well as on the risk of thrombosis in the postmenopause period. The objective: to determine the effect of MHT on somatic morbidity in postmenopausal women. Materials and methods. An analysis of the anamnesis, anthropometric indicators, results of general clinical and biochemical data of 120 women of menopausal age, who were divided depending on the use of menopausal hormone therapy into a study group (patients used MHT, n=60) and a control group (patients did not use MHT, n=60), is presented. All women were observed on the basis of the communal non-profit enterprise “Kyiv Perinatal Center” in the period from 2013 to 2023. Results. There was no significant difference in the indicators of the metabolic profile (levels of lipid fractions and glucose), as well as in anthropometric parameters (systolic and diastolic blood pressure, body mass index) between women of both groups (p>0.05). The risk of cardiovascular events (especially angina pectoris, hypertension) was higher in women of the control group who did not use hormonal drugs (related risk (RR) 0.5 with a 95% confidence interval (CI) from 0.28 to 0.91; p<0.007). However, it was found that there were significant differences between the groups in bone mineral density (the frequency of women with osteopenia was 43.3% in the control group versus 35% in the study group, and osteoporosis was diagnosed in 15% of women in the group without MHT versus 5% of women from the study group; RR is 0.69 with 95% CI≥0.5 at the confidence level p=0.05) and parameters affecting the risk of thrombotic complications (platelet level was 239.4±28.4×109 /l in the control group versus 295.6±28.2×109 /l in the study group, p<0.001; the level of fibrinogen was 7.7±1.2 mmol/l in women without MHT versus 8.7±2.0 mmol/l in women with MHT, p=0.001; prothrombin time was 13.2±1.3 sec in the control group versus 15.0±1.1 sec in the study group, p<0.001). Conclusions. Menopausal hormone therapy (MHT) is an effective method of preventing the development of osteopenic and osteoporotic conditions in women during the perimenopause period, but it also reliably significantly affects certain indicators of blood coagulation properties – the level of platelets, fibrinogen and prothrombin time – in the direction of their increase. It was established that the use of hormone replacement therapy the risks of developing adverse cardiovascular events (especially arterial hypertension and angina pectoris) are reduced, but, given the lack of difference between the compared groups of women in indicators of lipid metabolism, glucose, as well as in anthropometric data (which are the main risk factors for the development of cardiovascular diseases), further research is needed to establish the relationships of these parameters in more detail. During the appointment of MHT, one should be guided by the results of an individual risk/benefit assessment for the patient, paying special attention to the study of her anamnestic data. [ABSTRACT FROM AUTHOR]

Various lead‐in dosing strategies have been used in clinical practice for venous thromboembolism (VTE), and guidelines do not currently address if the full lead‐in dosing duration is necessary after receiving parenteral anticoagulation. This study aims to identify whether full lead‐in dosing duration surrounding parenteral anticoagulation affects thrombotic and bleeding outcomes. A single‐center, retrospective cohort study was conducted of hospitalized patients diagnosed with VTE and treated with apixaban or rivaroxaban. Patients were grouped depending on duration of lead‐in dosing, with the full lead‐in dosing group considered as the appropriate duration of the direct oral anticoagulant. The primary outcome was the recurrence of VTE within the index admission to 6 months. Secondary outcomes included major bleeding, clinically relevant minor bleeding, and mortality. Ninety‐three patients were prescribed full lead‐in dosing, while 99 patients received reduced lead‐in dosing. The primary outcome of recurrent VTE was similar between the reduced lead‐in group compared to the full lead‐in group (3% vs 2%; P = 1.0). Major bleeding within the index admission was significantly higher in the reduced lead‐in group: 11 versus 2 (P =.02). There were no significant differences in other secondary outcomes. Full lead‐in dosing compared to reduced lead‐in dosing duration for VTE had similar rates of thrombotic and mortality events. The higher rate of major bleeding in the reduced lead‐in dosing group likely reflects the prescribing practices in less stable patients. This study provides evidence to support reduced lead‐in dosing duration in high‐risk patients without compromising efficacy outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal surgery (CORS) patients are at the highest risk of any general surgery population for the development of post-operative venous thromboembolism (VTE) and are also at an increased risk for post-operative bleeding, especially with procedures related to early cancer stages. Low molecular weight heparin (LMWH) is recommended for VTE prophylaxis in this surgical population. Current guidelines and primary literature along with institutional protocols support dosage adjustments for obesity and impaired renal function, but literature providing optimal VTE prophylactic LMWH dosing is extremely limited for underweight, surgical patients. Objectives: The aim of this study was to evaluate both bleeding and VTE rates for hospitalized underweight colorectal surgery patients receiving post-operative VTE prophylaxis with standard enoxaparin 40 mg subcutaneously (SQ) every 24 hours versus reduced dose enoxaparin 30 mg SQ every 24 hours. Methods: This trial was a multicenter, retrospective chart review with data collected on post-operative CORS patients over a 10-year period. Patients were included if aged 18 years and older, weighed less than 50 kg, and received at least 1 dose of enoxaparin 40 mg or 30 mg post-operatively. The primary endpoint was a descriptive comparison of post-operative bleeding with use of standard enoxaparin 40 mg SQ every 24 hours compared to reduced dose enoxaparin 30 mg SQ every 24 hours for post-operative VTE prophylaxis. The secondary endpoint was the descriptive comparison of post-operative thrombotic event rates in the same population. Results: The total population investigated included 146 patients. One hundred twenty-nine (88.4%) received standard enoxaparin and 17 (11.6%) received reduced enoxaparin. Overall, 9 bleeding events (7.0%) and 2 major VTE events (1.6%) occurred, all within the standard enoxaparin group. Conclusion: Standard dose enoxaparin for post-operative VTE prophylaxis demonstrated increased bleeding and thrombotic events requiring medical and surgical intervention in comparison to reduced dose enoxaparin for low body weight CORS patients. The results of this study are hypothesis generating and continued research involving more robust systematic reviews are needed to evaluate both safety and efficacy of reduced VTE prophylaxis with LMWH in the underweight, surgical patient population. [ABSTRACT FROM AUTHOR]

This study sought to evaluate the impact of the subcutaneous tunneling technique on peripherally inserted central catheter (PICC) placement. We randomized 694 patients who needed PICC placement to either the tunneled PICCs (experimental group) or the non-tunneled PICCs (control group) from August to December 2021. The cumulative frequency of complications was assessed as the primary outcome. Secondary outcomes comprised of the amount of bleeding, catheter insertion time, self-reported pain score, and one-puncture success rate. After 6 months of follow-up, the tunneled PICCs group showed a significant decrease in the frequency of total complications, especially in infection (3.0% vs. 7.1%, p =.021) and catheter-related thrombosis (3.3% vs. 8.3%, p =.008), although approximately 0.5 ml bleeding and 3.5 min time were increased. This randomized multicenter study supports the efficacy of subcutaneous tunneling technology in reducing PICC-related complications, enhancing patient comfort, and encouraging using subcutaneous tunneling technology for PICC placement. [ABSTRACT FROM AUTHOR]

This systematic review addresses the crucial role of anticoagulation in microsurgical procedures, focusing on free flap reconstruction and replantation surgeries. The objective was to balance the prevention of thrombotic complications commonly leading to flap failure, with the risk of increased bleeding complications associated with anticoagulant use. A meticulous PubMed literature search following Evidence-Based-Practice principles yielded 79 relevant articles, including both clinical and animal studies. The full-texts were carefully reviewed and evaluated by the modified Coleman methodology score. Clinical studies revealed diverse perioperative regimens, primarily based on aspirin, heparin, and dextran. Meta-analyses demonstrated similar flap loss rates with heparin or aspirin. High doses of dalteparin or heparin, however, correlated with higher flap loss rates than low dose administration. Use of dextran is not recommended due to severe systemic complications. In animal studies, systemic heparin administration showed predominantly favorable results, while topical application and intraluminal irrigation consistently exhibited significant benefits in flap survival. The insights from this conducted systematic review serve as a foundational pillar towards the establishment of evidence-based guidelines for anticoagulation in microsurgery. An average Coleman score of 55 (maximum 103), indicating low overall study quality, however, emphasizes the need for large multi-institutional, randomized-clinical trials as the next vital step. [ABSTRACT FROM AUTHOR]

Embolic cerebral protection devices are not routinely used in clinical practice during electrophysiological interventions. We report a case series of patients with intracardiac thrombosis undergoing a percutaneous left atrial appendage (LAA) closure and a ventricular tachycardia (VT) catheter ablation supported by TriGuard 3 Cerebral Embolic Protection Device. [ABSTRACT FROM AUTHOR]

Key questions in bleeding management are "Why does my patient bleed?" and "How to fix it?" To answer the first question, the high negative predictive value of viscoelastic testing can be used to identify coagulopathic bleeding. Accordingly, goal-directed bleeding management (GDBM) guided by viscoelastic testing has been shown to be an effective and essential part of the second pillar of patient blood management (PBM) with the aim to improve patients' outcomes and safety. Patient's medical and drug history - with a focus on medication with oral anticoagulants and antiplatelet drugs - are important in emergency, urgent, and elective surgery. Furthermore, risk scores have been developed and validated for traumatic and obstetric hemorrhage and can be helpful tools to predict severe hemorrhage and the need for massive transfusion. Acidosis, hypocalcemia, anemia, and hypothermia ("diamond of death in trauma") are important basic conditions for hemostasis and good predictors of coagulopathy and should be closely monitored by blood gas analysis and corrected in bleeding patients. Earlier time to hemostasis was associated with decreased mortality in trauma studies. Therefore, GDBM aims to stop the bleeding as soon as possible and avoid the main killers in blood transfusion: Transfusion-associated circulatory overload, transfusion-related acute lung injury, transfusion-related immune modulation, and thrombosis. Thromboelastometry-guided bleeding management follows the concepts of Good Medical Practice and Precision Medicine. Here, rotational thromboelastometry (ROTEM)-guided bleeding management algorithms are using a stepwise approach based on the sequence "Treat first what kills first:" (1) Fibrinolysis management, (2) clot firmness management, (3) thrombin generation management, and (4) avoidance of hypercoagulability and thrombosis. Here, thromboelastometry can not only identify patients with hypercoagulability and increased risk of thrombosis but also ROTEM-guided bleeding management can avoid thromboembolic complications, too. This may support the idea of personalized antithrombotic therapy guided by viscoelastic testing in the postoperative period. Finally, PBM is not about blood transfusion: It is about patients' outcomes. Accordingly, several meta-analyses based on more than 20 randomized controlled trials on the effect of viscoelastic testingguided perioperative bleeding management did not only demonstrate a significant reduction in transfusion requirements but also a significant reduction in mortality and postoperative acute kidney injury. The reduction in postoperative acute kidney injury again has a significant impact on long-term survival. Accordingly, recent PBM guidelines recommend the implementation of viscoelastic testing-guided bleeding management algorithms with a 1B or 1A recommendation. This is also addressed in the World Health Organization policy brief about the urgent need to implement PBM in all member states in a timely manner. However, even if the number of national activities is increasing, there is still a long way to go. [ABSTRACT FROM AUTHOR]

Background & Objective: In this placebo-controlled randomized clinical trial, we aimed to investigate the effect of low molecular weight heparin (LMWH) on the assisted reproductive technology (ART) success rate in women without thrombophilic disorder undergoing assisted reproductive technology. Materials & Methods: The study population consisted of 276 patients referred to the infertility center at Shiraz University of Medical Sciences and who underwent in vitro fertilization (IVF) for the first time. Patients were randomly assigned into two groups (control group = 137 women who underwent IVF and received placebo; case group = 139 women who underwent IVF and received LMWH). The case group was treated with LMWH and the control group received placebo. Specifications for egg harvesting, processing sperm, the number of fertilized eggs and embryos, the number of frozen and transferred embryos, and the IVF outcome were assessed. Results: The mean age of subjects was 32.59 ± 4.41 years old in the case group and 32.62 ± 5.18 in the control group (p = 0.955). The final outcome of IVF treatment in the control group was treatment failure (62%), clinical pregnancy (21.2%), chemical pregnancy (5.9%), and live birth (7.3%), while in the case group, it was treatment failure (48.2 %), clinical pregnancy (21.6%), chemical pregnancy (2.2%), and live births (28.1%). There was a significant difference in IVF outcome in the two groups (P < 0.001). Conclusion: Given the significant difference in the number of live births and reduction of pregnancy complications in the LMWH group, it can be concluded that LMWH prophylaxis may be effective in ART success. [ABSTRACT FROM AUTHOR]

Cancer-associated thrombosis (CAT) is a substantial burden and an emerging topic of great interest in Vietnam. The management of CAT is complex, with several challenges, including a high risk of bleeding and thrombosis, treatment burden, and low treatment motivation due to the short life expectancy of patients. Another challenge in CAT management is the low awareness among local physicians regarding CAT. The introduction of direct oral anticoagulants, which offer a better risk-benefit profile compared to conventional anticoagulation, has brought about a revolution in CAT management. To address these challenges, a group of 14 experts, including cardiologists and oncologists, convened in January 2023 to discuss and provide comprehensive information on CAT management in Vietnam, along with recommendations to optimize clinical outcomes. This review will encompass the available evidence in the medical literature and the expert opinions derived from the meeting. [ABSTRACT FROM AUTHOR]

Angelica keiskei Koidzumi (Ashitaba) is a traditional folk medicine and health supplement in Japan. Ashitaba yellow stem exudate (AYE) contains abundant chalcones and thus has the potential to treat and prevent many pathological states such as cancer, inflammation, obesity, diabetics, thrombosis, and hypertension. Levels of plasminogen activator inhibitor 1 (PAI-1), a key regulator of the fibrinolytic system, increase with age in mouse plasma. Therefore, we aimed to determine the effects of AYE on plasma thrombotic parameters in aging mice. Long-term (52 weeks) AYE supplementation significantly decreased age-induced increases of PAI-1 in mouse plasma. Supplementation with AYE decreased levels of the acute-phase and fibrinolytic protein plasma plasminogen, and significantly decreased those of tumor necrosis factor α. These results suggested that continuous intake of AYE throughout life decreases age-induced systemic inflammation and prevents thrombotic tendencies without affecting body weight gain in aged mice. Our findings showed that supplementing diets with AYE might help to prevent thrombotic diseases in elderly individuals. [ABSTRACT FROM AUTHOR]

Background The extracorporeal circuit, which is all the apparatus for carrying a patient's blood outside the body -- for example, intravenous cannulas, dialysis tubing, membranes and lines -- will clot due to inadequate anticoagulation or blood flow, as well as due to air in the circuit. Clotting of circuits result in blood loss, interrupted dialysis treatments and poor solute clearances. Therefore, anticoagulation agents such as regional citrate anticoagulants (RCA), low molecular weight heparins (LMWH) and 0.9% sodium chloride (0.9% NaCl) are often used to prevent circuit clotting. Aim The aim of this study is to investigate whether RCA are more effective in preventing or reducing clots in the extracorporeal circuit compared to LMWH and 0.9% NaCl in adult renal replacement therapy (RRT) patients. Methods Peer reviewed papers published in English between January 2010 to December 2021 were considered for this review. The patient population included haemodialysis (HD) patients 18 years and older. Paediatric HD patients were excluded. Results A total of 16 studies were selected for this review, with evidence levels ranging from primary evidence Levels II & III to secondary evidence Levels I & II. The findings of this study show that citrates do not affect systemic coagulation and have a reduced bleeding risk than systemic anticoagulants. However, citrates can cause citrate toxicity in critically ill patients. Patients dialysing with 0.9% NaCl flushes and without anticoagulation of any kind, that is systemic or regional, clotted their extracorporeal circuits. The consensus of the findings from most of the studies included in this review is that LMWH, for example enaxoparin, can be administered quickly and has a low risk of dosing mistakes due to the prefilled single dose syringes used in Australia. Conclusion The findings of this study underscore the importance of continuing using LMWH for anticoagulation in unsupported centres without adequate protocols, for example satellite clinics. Overall, having reviewed the literature, it can be said that citrate is safe and efficacious, reducing bleeding and clotting of circuits. [ABSTRACT FROM AUTHOR]

Long COVID is a broad range of symptoms that develop in a subset of people after acute SARS-CoV-2 infection. Current treatment options are investigational, not yet standardized, and aimed at symptomatic management of individual organ systems. This report presents the case of a 73-year-old male patient who achieved sustained improvements in symptoms associated with long COVID after two prolonged water-only fasting and refeeding interventions. [ABSTRACT FROM AUTHOR]

United States Food and Drug Administration (FDA)‐approved viscoelastic testing (VET) methodologies have significantly changed in the last 10 years, with the availability of cartridge‐based VET. Some of these cartridge‐based methodologies use harmonic resonance‐based clot detection. While VET has always allowed for the evaluation of real‐time clot formation, cartridge‐based VET provides increased ease of use as well as greater portability and robustness of results in out‐of‐laboratory environments. Here we review the use of VET in a variety of clinical contexts, including cardiac surgery, trauma, liver transplant, obstetrics, and hypercoagulable states such as COVID‐19. As of now, high quality randomized trial evidence for new generation VET (TEG 6s, HemoSonics Quantra, ROTEM sigma) is limited. Nevertheless, the use of VET‐guided transfusion algorithms appears to result in reduced blood usage without worsening of patient outcomes. Future work comparing the new generation VET instruments and continuing to validate clinically important cut‐offs will help move the field of point‐of‐care coagulation monitoring forward and increase the quality of transfusion management in bleeding patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The coronavirus disease 2019 (COVID-19) continues to have an enormous and extensive effect on global health, causing widespread devastation. Patients who have recovered from COVID-19 have an increased risk of thromboembolic disease. We suggest that soluble P-selectin and anti-platelet factor 4 (anti-PF4) plays a significant role in platelet activation, ultimately resulting in thrombosis. The purpose of this study is to compare the role of soluble P-selectin, anti-PF4, and platelet maximal aggregation levels in COVID-19 patients. MATERIALS AND METHODS: A cross-sectional study was conducted among COVID-19 patients who were admitted to the hospital between October 2021 and January 2022. RESULTS: From 160 individuals, we found that a number of individuals with older age (P = 0.014) and lower hemoglobin levels (P = 0.042) were significantly higher in the severe COVID-19 group compared to the nonsevere COVID-19 group. Remarkably, soluble P-selectin levels in mild-to-moderate COVID-19 were found to be significantly higher than the severe group, with statistical significance (P = 0.02). However, there was no significant difference in anti-PF4 levels between severe and nonsevere COVID-19 groups. Furthermore, platelet maximum aggregation was also significantly higher in the severe COVID-19 group than in the mild-to-moderate COVID-19 group by using 2.5 μM (P = 0.024), 5 μM (P = 0.026), and 10 μM adenosine-diphosphate (P = 0.02). CONCLUSION: Soluble P-selectin, an indicator of platelet activation, was shown to be significantly higher in mild-to-moderate COVID-19 group than the severe COVID-19 group. The maximum aggregation of platelets was also observed to be significantly greater in the severe COVID-19 group. [ABSTRACT FROM AUTHOR]

Simple Summary: People with cancer are at an increased risk of developing blood clots. Both cancer and anti-cancer treatment are responsible for this risk. In some types of cancer, such risk is higher than in others. There are different types of blood thinners also known as anticoagulants. Blood thinners prevent the recurrence of deep venous thrombosis (a blood clot in the limbs) or pulmonary embolism (a blood clot in the lungs) in people with cancer. In some clinical situations and, specifically, in patients with active cancer, injectable blood thinners are safer than tablets to be taken orally and work just as well. Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer. [ABSTRACT FROM AUTHOR]

Tranexamic acid (TXA) is a widely used antifibrinolytic agent that has been used since the 1960's to reduce blood loss in various conditions. TXA is a lysine analogue that competes for the lysine binding sites in plasminogen and tissue-type plasminogen activator impairing its interaction with the exposed lysine residues on the fibrin surface. The presence of TXA therefore, impairs the plasminogen and tPA engagement and subsequent plasmin generation on the fibrin surface, protecting fibrin clot from proteolytic degradation. However, critical lysine binding sites for plasmin(ogen) also exist on other proteins and on various cell-surface receptors allowing plasmin to exert potent effects on other targets that are unrelated to classical fibrinolysis, notably in relation to immunity and inflammation. Indeed, TXA was reported to significantly reduce post-surgical infection rates in patients after cardiac surgery unrelated to its haemostatic effects. This has provided an impetus to consider TXA in other indications beyond inhibition of fibrinolysis. While there is extensive literature on the optimal dosage of TXA to reduce bleeding rates and transfusion needs, it remains to be determined if these dosages also apply to blocking the non-canonical effects of plasmin. [ABSTRACT FROM AUTHOR]

Simple Summary: Outcomes for patients with acute promyelocytic leukemia (APL) have improved over the past 40 years due to the development of targeted treatment regimens and an expanded understanding of the unique complications arising from both the disease and its treatments. Despite these advances, clinically significant bleeding and/or thrombosis in the first 30 days of treatment remain the most common causes of morbidity and mortality. Moreover, there is a lack of large clinical trials investigating approaches for the prevention and treatment of these complications. This review aims to provide a comprehensive overview and update on the coagulopathy associated with APL, compile current best practices for optimal management, and establish areas of potential future investigation to further improve outcomes for patients with APL. Acute promyelocytic leukemia (APL) has a well-established mechanism and a long-term prognosis that exceeds that of any other acute leukemia. These improving outcomes are due, in part, to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two targeted and highly active agents in this disease. However, there remains a considerable morbidity and mortality risk in APL secondary to clinically significant hemorrhagic and/or thrombotic events. Prevention and treatment of these coagulopathic complications remain significant impediments to further progress in optimizing outcomes for patients with APL. Moreover, the relative rarity of APL hinders adequately powered randomized controlled trials for evaluating APL coagulopathy management strategies. This review draws from peer-reviewed works falling between initial descriptions of APL in 1957 and work published prior to January 2023 and provides an updated overview of the pathophysiology of hemorrhagic and thrombotic complications in APL, outlines risk stratification parameters, and compiles current clinical best practices. An improved understanding of the pathophysiologic mechanisms driving hemorrhage and thrombosis along with the completion of well-designed trials of management strategies will assist clinicians in developing interventions that mitigate these devastating complications in an otherwise largely curable disease. [ABSTRACT FROM AUTHOR]

The article discusses various aspects of anticoagulation management, including the pathophysiology of heparin-induced thrombocytopenia (HIT), the use of antiplatelet agents, plasmapheresis, and alternative anticoagulants such as bivalirudin and argatroban. It also touches upon specific prothrombotic disorders and inherited coagulopathies, emphasizing the need for tailored anticoagulation strategies in these conditions.

Antiphospholipid syndrome (APS) is an acquired hypercoagulable state necessitating long-term anticoagulation for secondary thrombosis prevention. Anticoagulation guidelines are predominantly based on data in high risk, triple positive patients, and favor Vitamin K antagonists over other forms of anticoagulation. The efficacy of alternative anticoagulants for secondary thrombosis prevention in low risk, single and double positive APS remains uncertain. This study aimed to assess the incidence of recurrent thrombosis and major bleeding for patient with low risk APS on long-term anticoagulation. We performed a retrospective cohort study of patients who met revised criteria for thrombotic APS between January, 2001 and April, 2021 and received care through the Lifespan Health System. Primary outcomes included recurrent thrombosis and WHO Grades 3 and 4 major bleeding. A total of 190 patients were followed over a median duration of 3.1 years. At time of APS diagnosis, 89 patients were treated with warfarin and 59 patients with a direct oral anticoagulant (DOAC). There were similar rates of recurrent thrombosis in low risk patients on warfarin versus DOACs (adjusted IRR 6.91; 95% CI 0.90–53.40, p = 0.064). Major bleeding events only occurred in low risk patients on warfarin (n = 8, log-rank p = 0.13). In conclusion, despite the choice of anticoagulation, patients with low risk APS had similar rates of recurrent thrombosis suggesting DOACs may be a potential treatment option for this cohort. There was a non-significant increase in major bleeding rates in low risk patients on warfarin versus DOACs. Study limitations include a retrospective study design and small event numbers. [ABSTRACT FROM AUTHOR]

Purpose: Achieving effective anticoagulation during neonatal extracorporeal membrane oxygenation (ECMO) without increasing the risk of hemorrhage remains challenging. The use of antithrombin III (AT-III) for this purpose has been examined, but studies have been limited to intermittent bolus dosing. We aimed to evaluate the efficacy and safety of an institutionally developed AT-III continuous infusion protocol in neonates receiving ECMO for the treatment of congenital diaphragmatic hernia (CDH). Methods: In this single center, retrospective study, all neonates with a CDH who received ECMO support during the study period were included. Data on anticoagulation labs and therapy, life-threatening bleeding, and circuit changes were analyzed. Results: Eleven patients were divided into two groups: patients with AT-III continuous infusion (n = 5) and without (n = 6). There were no differences in the gestational age (p = 0.29), sex (p = 1.00), ECMO duration (p = 0.59), or initial AT-III levels (p = 0.76) between groups. Patients in the AT-III infusion group had on average 18.5% higher AT-III levels (p < 0.0001). Patients receiving continuous AT-III infusions spent a significantly higher percentage of ECMO time within the therapeutic range, measured using anti-Factor Xa levels (64.9±4.2% vs. 29.1±8.57%, p = 0.008), and required fewer changes to the heparin infusion rate (6.48±0.88 vs 2.38±0.36 changes/day changes/day, p = 0.005). Multivariate analysis revealed continuous infusion of AT-III did not increase the rate of intracranial or surgical bleeding (p = 0.27). Conclusion: AT-III as a continuous infusion in CDH neonates on ECMO provides a decreased need to modify heparin infusion and more consistent therapeutic anticoagulation without increasing the risk of life-threatening bleeding. [ABSTRACT FROM AUTHOR]

Purpose: In this article, we aimed to elaborate on perioperative and complication management in treatment of pheochromocytoma crisis with extracorporeal membrane oxygenation (ECMO). Material and methods: We report a case of relatively rare grant paraganglioma-induced pheochromocytoma crisis leading to severe circulatory failure, treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO) as a bridge to curative adrenalectomy. Weaning of ECMO was followed by successful surgical removal of the tumor, and patient survival. However, distal ischemia of the cannulated leg occurred during ECMO operation, which eventually led to amputation. In addition, the patient developed new cerebral infarction and left hemiplegia, half a month after paraganglioma resection. Conclusions: We believe that patients with pheochromocytoma crisis, who cannot maintain blood circulation, are eligible for V-A ECMO treatment. Moreover, care should be taken to prevent thrombosis and individualized and precise blood pressure management targets. Early detection and treatment of thrombosis is imperative to long-term prognosis of patients with ECMO. [ABSTRACT FROM AUTHOR]

The article focuses on anticoagulation strategies during cardiopulmonary bypass (CPB), including the use of heparin, which is necessary to prevent thrombus formation and acute disseminated intravascular coagulation while on bypass. Topics include Heparin is a sulfated glycosaminoglycan polymer that binds to antithrombin III and disrupts both the intrinsic and common pathways of plasma coagulation; and discusses strategies for achieving hemostasis after the bypass period.

The article discusses the Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis Extended Antiplatelet Monotherapy (HOST-EXAM) trial. It compares clopidogrel to low-dose aspirin monotherapy after percutaneous coronary intervention (PCI) for 24 months, where Kang J, Park KW and others performed a post-trial extended follow-up and it was observed in the trial that clopidogrel was superior for preventing thrombotic events and bleeding compared to aspirin.

Integrins are heterodimeric receptors comprising α and β subunits. They are expressed on the cell surface and play key roles in cell adhesion, migration, and growth. Several types of integrins are expressed on the platelets, including αvβ3, αIIbβ3, α2β1, α5β1, and α6β1. Among these, physically αIIbβ3 is exclusively expressed on the platelet surface and their precursor cells, megakaryocytes. αIIbβ3 adopts at least three conformations: i) bent-closed, ii) extended-closed, and iii) extended–open. The transition from conformation i) to iii) occurs when αIIbβ3 is activated by stimulants. Conformation iii) possesses a high ligand affinity, which triggers integrin clustering and platelet aggregation. Platelets are indispensable for maintaining vascular system integrity and preventing bleeding. However, excessive platelet activation can result in myocardial infarction (MI) and stroke. Therefore, finding a novel strategy to stop bleeding without accelerating the risk of thrombosis is important. Regulation of αIIbβ3 activation is vital for this strategy. There are a large number of molecules that facilitate or inhibit αIIbβ3 activation. The interference of these molecules can accurately control the balance between hemostasis and thrombosis. This review describes the structure and signal transduction of αIIbβ3, summarizes the molecules that directly or indirectly affect integrin αIIbβ3 activation, and discusses some novel antiαIIbβ3 drugs. This will advance our understanding of the activation of αIIbβ3 and its essential role in platelet function and tumor development. [ABSTRACT FROM AUTHOR]

Objectives Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β2glycoprotein-I (anti-β2GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1 * alleles and thrombosis in SLE. Conventional aPL were included for comparison. Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2GPI and aCL of IgA/G/M isotypes and LA were quantified. Results aPS/PT antibodies associated positively with HLA-DRB1 *13 [odds ratio (OR) 2.7, P  = 0.002], whereas anti-β2GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P  = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1 * alleles. HLA-DRB1*13 , but not DRB1*04 , remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03 , on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides. Conclusions HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation monitoring practices vary during extracorporeal membrane oxygenation (ECMO). The Extracorporeal Life Support Organization describes that a multimodal approach is needed to overcome assay limitations and minimize complications. Objective: Compare activated clotting time (ACT) versus multimodal approach (activated partial thromboplastin time (aPTT)/anti-factor Xa) for unfractionated heparin (UFH) monitoring in adult ECMO patients. Methods: We conducted a single-center retrospective pre- (ACT) versus post-implementation (multimodal approach) study. The incidence of major bleeding and thrombosis, blood product and antithrombin III (ATIII) administration, and UFH infusion rates were compared. Results: Incidence of major bleeding (69.2% versus 62.2%, p = 0.345) and thrombosis (23% versus 14.9%, p = 0.369) was similar between groups. Median number of ATIII doses was reduced in the multimodal group (1.0 [IQR 0.0-2.0] versus 0.0 [0.0 -1.0], p = 0.007). The median UFH infusion rate was higher in the ACT group, but not significant (16.9 [IQR 9.6-22.4] versus 13 [IQR 9.6-15.4] units/kg/hr, p = 0.063). Fewer UFH infusion rate changes occurred prior to steady state in the multimodal group (0.9 [IQR 0.3 -1.7] versus 0.1 [IQR 0.0-0.2], p < 0.001). Conclusion: The incidence of major bleeding and thrombosis was similar between groups. Our multimodal monitoring protocol standardized UFH infusion administration and reduced ATIII administration. [ABSTRACT FROM AUTHOR]

Introduction: Apixaban is currently the only oral direct factor Xa inhibitor approved for treatment and prevention of venous thromboembolism (VTE) in patients on hemodialysis. Exclusion of dialysis patients from major clinical trials results in prescriber uncertainty regarding the optimal dose of apixaban for VTE treatment in this population. This study sought to characterize the variance in apixaban prescribing patterns for thrombotic indications other than atrial fibrillation. Methods: This retrospective, multi-center, descriptive study analyzed apixaban dosing patterns for hospitalized chronic dialysis patients with history of thrombosis. The primary outcome was incidence of deviation from manufacturer recommendations for dosing, assessed for either a new start or receipt prior to hospitalization. Secondary outcomes included observation of recurrent thrombotic and bleeding event rates during subsequent hospitalizations. Patients were analyzed into subgroups according to type of thrombotic indication for treatment. Data are reported with descriptive statistics. Results: A total of 101 patients were included. Deviations in recommended dosing were observed in 53 of 80 (66.2%) patients receiving apixaban for treatment of acute or chronic thrombosis. Of 44 patients started on apixaban during hospitalization for the indication of acute VTE, a dose deviation was observed in 79.5% of patients. Rates of rehospitalization for recurrent thrombotic events and bleeding were 11.8% and 9.9%, respectively. Conclusion: Variation in apixaban prescribing practices for the treatment of VTE in dialysis patients is common, suggesting an urgent need for prospective studies and updated dosing guidance to optimize safety with apixaban use in this population. [ABSTRACT FROM AUTHOR]

The volume of the bone in a site past an extraction degrades significantly and thus it is imperative to evaluate the situation for implant placement. Besides the need for sufficient bone, the amount and quality of the soft tissue covering the bone in the missing tooth area and nature of the adjacent teeth must be carefully assessed. In anterior sites, reconstructive surgery is usually performed to restore these hard and soft tissues, mainly for esthetic reasons, but it is equally essential in posterior sites to ensure adequate functional support. In guided bone regeneration procedures, barrier membranes block the augmented areas, provide and maintain space for regenerative material, and protect the blood clot, allowing a normal wound stability process. Clinicians prefer using resorbable membranes in most cases, whereas a nonresorbable membrane is selected to correct large defects. This report proposes the use of a collagen scaffold as a core material for guided bone regeneration in the case of a missing tooth between two existing teeth, when there is sufficient bone to place an implant but a horizontal defect is present in the crestal ridge. The tested question is whether a thick, reinforced, resorbable collagen scaffold (Ossix Volumax) can provide a stable basis for restoring the lost volume of a deficient ridge. The regeneration procedure presented with the collagen scaffold resulted in restoration of the lost tissue volume and a favorable lifelike emergence profile for the implant-supported crown. This augmentation procedure is simpler to perform in certain cases than existing procedures with bone substitute material and/or an interpositional connective tissue graft harvested from a remote donor site, the harvest of which is not required. [ABSTRACT FROM AUTHOR]

The article focuses on the periprocedural management of a hemodialysis patient with a mechanical heart valve using therapeutic tinzaparin as a bridge therapy to avoid hospitalization during hernia surgery. It reports on the challenges of using low-molecular-weight heparin (LMWH) for patients undergoing hemodialysis, and it highlights emphasizes the beneficial effects of tinzaparin because of its minimum level of dependence on kidney function.