Prevention Of Thromboembolism Research Articles

Clinical outcomes of edoxaban treatment without parenteral anticoagulation therapy for acute venous thromboembolism: Insight from the COMMAND VTE Registry-2

Abstract Background Direct oral anticoagulants (DOACs) including edoxaban are currently widely used all over the world. Each DOAC has a specific usage for the treatment and second prevention of venous thromboembolism (VTE) in the acute phase as well as in the chronic phase. Edoxaban is recommended to be administered after an appropriate initial treatment including parenteral anticoagulation therapy such as heparin. However, because of the rapid anticoagulant effect of edoxaban after oral intake, some physicians could administer edoxaban initially without parenteral anticoagulation therapy in the daily clinical practice, which has not been investigated so far. Purpose The purpose of this study is to explore the effectiveness and safety of edoxaban treatment for VTE without initial parenteral anticoagulation therapy. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Of those, 1842 patients received edoxaban including 848 patients with pulmonary embolism (PE) and 994 patients with deep vein thrombosis (DVT) alone, who were divided into 2 groups based on the presence or absence of initial parenteral anticoagulation therapy with heparin. Propensity score matching (PSM) was performed to adjust for potential baseline differences in the 2 groups. Results PE and DVT patients with initial parenteral anticoagulation therapy with heparin accounted for 623 (73.5%) and 244 (24.5%), respectively. After the PSM, 195 pairs of PE patients and 226 pairs of DVT patients were matched. In PE patients, those matched by the PSM were relatively mild cases compared to the unmatched cases (simplified PESI score=0: 25.9% vs. 12.4%, P<0.001). Whereas, in DVT patients, those matched were relatively severe cases compared to unmatched cases (isolated distal DVT: 24.1% vs. 71.0%, P<0.001). In the matched cohort, there was no significant difference in baseline characteristics between the 2 groups, including simplified PESI score in PE patients and thrombus location profile in DVT patients. In both PE patients and DVT patients, the 30-day cumulative incidences of all-cause death were not significantly different between the 2 groups (PE patients: 3.7% vs. 2.6%, P=0.56; DVT patients: 2.7% vs. 4.5%, P=0.31). Similarly, the 30-day cumulative incidences of recurrent VTE and major bleeding were not significantly different between the 2 groups (recurrent VTE: PE patients: 0% vs. 0.5%, P=0.32; DVT patients: 0.6% vs. 0.9%, P=0.99; major bleeding: PE patients: 1.5% vs. 3.2%, P=0.32; DVT patients: 2.2% vs. 3.2%, P=0.54) Conclusion In this current real-world VTE registry, a certain number of patients received edoxaban without parenteral anticoagulation therapy, who did not show a signal of worse clinical outcomes.

The influence of concomitant antiplatelet therapy in venous thromboembolism patients treated with anticoagulants in the DOAC era: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction The mainstay of treatment and second prevention of venous thromboembolism (VTE) is anticoagulation therapy, and recently direct oral anticoagulant (DOAC) for VTE have prevailed all over the world as oral anticoagulation therapy. Although concomitant antiplatelet therapy in addition to oral anticoagulation therapy could have an influence on both recurrent VTE and bleeding events, there have been still limited real-world data on the issue in the DOAC era. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with concomitant antiplatelet therapy in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulation therapy, the current study population was consisted of 4790 VTE patients with oral anticoagulation therapy, who were divided into 374 patients (7.8%) treated with concomitant antiplatelet therapy and 4416 patients (92.2%) treated with only oral anticoagulation therapy. Results Patients with concomitant antiplatelet therapy were older (Concomitant antiplatelet therapy: 74.1 vs. Only oral anticoagulation therapy: 67.3 years, P<0.001), were less often women (52% vs 59%, P=0.005) and more frequently had history of major bleeding (9.8% vs 6.0%, P=0.003), myocardial infarction (16% vs 0.9%, P<0.001) and stroke (33% vs 6.8%, P<0.001). The cumulative incidences of recurrent VTE were not significantly different between the 2 groups (5.9% vs 9.6% at 5-year, Log rank P=0.06). Similarly, the cumulative incidences of major bleeding (14.6% vs 13.3% at 5-year, Log rank P=0.11) and stroke (8.3% vs 6.0% at 5-year, Log rank P=0.12) were not significantly different between 2 groups. However, the cumulative incidences of clinically relevant all bleeding (29.0% and 23.0% at 5-year, Log rank P=0.007) were significantly higher in concomitant antiplatelet therapy group, which was statistically significant even after adjusting confounders. Conclusion In the current large VTE registry in the DOAC era, concomitant antiplatelet therapy in addition to oral anticoagulation therapy for patients with VTE was not significantly associated with the risks recurrent VTE, major bleeding or stroke, but was associated with an increased risk of clinically relevant all bleeding.Study Flow ChartMain results

Procoagulant platelet activation promotes venous thrombosis.

Platelets are key players in cardiovascular disease and platelet aggregation represents a central pharmacological target, particularly in secondary prevention. However, inhibition of adenosine diphosphate and thromboxane signaling has low efficacy in preventing venous thromboembolism, necessitating the inhibition of the plasmatic coagulation cascade in this disease entity. Anticoagulation carries a significantly higher risk of bleeding complications, highlighting the need of alternative therapeutic approaches. We hypothesized that procoagulant activation (PA) of platelets promotes venous thrombus formation and that targeting PA could alleviate venous thrombosis. Here, we found elevated levels of procoagulant platelets in the circulation and in thrombi of patients with deep vein thrombosis (DVT) and pulmonary embolism, and in mice developing DVT following inferior vena cava stenosis. Further, we detected procoagulant activation of recruited platelets within murine venous thrombi and human pulmonary emboli. Mice with platelet-specific deficiency in central pathways of procoagulant activation – cyclophilin D and transmembrane protein 16F – were more resistant towards low flow-induced venous thrombosis. Finally, we found that a clinically approved carbonic anhydrase inhibitor, methazolamide, reduced platelet procoagulant activity and alleviated murine thrombus formation without affecting trauma-associated hemostasis. These findings identify an essential role of platelet procoagulant function in venous thrombosis and delineate novel pharmacological strategies targeting platelets in the prevention of venous thromboembolism.

Frequency, characteristics, antithrombotic therapies, and outcomes of thromboembolism in paediatric patients with CHD undergoing cardiac surgery: a single centre retrospective study.

Thromboembolism is a complication in paediatric patients with CHD requiring cardiac surgery. Previous research has focused on post-operative thromboembolism. This study aimed to describe thromboembolism frequency before or after cardiac surgery in children with CHD. We performed a single-centre retrospective study from October 2020 to June 2023 (inclusive). Patients were eligible for inclusion if they were <21 years of age and underwent cardiac surgery. Outcomes of interest included the occurrence and characteristics of thromboembolism in the 12 months before and after surgery, antithrombotic therapies, recurrent thromboembolism, and clinically significant bleeding. Among 260 patients included, 35 (13.5%) developed an index thromboembolism. Twelve (34.3%) patients had an index thromboembolism <12 months before surgery and 23 (65.7%) had an index thromboembolism <12 months after surgery, including 8 (22.9%) patients who had thromboembolism during both exposure periods. The median interquartile range (IQR) time of thromboembolism relative to cardiac surgery was -26 (-4 to -140) days and 15 (4 to 41) days, respectively. Seven (20%) patients had arterial, 18 (51.4%) venous, and 3 (8.6%) had both arterial and venous thromboembolism. Median (IQR) antithrombotic therapy duration was 49 (24-84) days. Nine (25.7%) patients developed recurrent thromboembolism and five (14.3%) patients experienced clinically significant bleeding. The risk of thromboembolism and recurrence is high both before and after cardiac surgery among paediatric patients with CHD. Prospective multi-centre studies should seek to identify risk factors for preoperative and postoperative thromboembolism to inform the design of future risk-stratified thromboembolism prevention trials in children with CHD.

Low-molecular-weight heparin in the prevention of venous thromboembolism among patients with acute intracerebral hemorrhage: A meta-analysis.

It remains unclear whether low-molecular-weight heparin (LMWH) is effective and safe for intracerebral hemorrhage (ICH) patients. This study presents a meta-analysis for elucidating effect of LMWH on preventing venous thromboembolism (VTE) among ICH patients. Articles were located by systematically searching PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG DATA, VIP, and SinoMed databases. The literature was independently screened by two authors, who also extracted data and conducted a qualitative evaluation. With regard to outcomes, their risk ratios (RRs) and 95% confidence intervals (CIs) were computed, and the findings were combined using the random effects model by using Mantel-Haenszel approach. 30 studies involving 2904 patients were analyzed and compared to control group. According to our findings, early low-dose LMWH, prophylaxis for VTE, was related to the markedly reduced deep vein thrombosis (DVT) (3.6% vs. 17.5%; RR, 0.25; 95% CI, 0.18-0.35; p-value<0.00001) and pulmonary embolism (PE) (0.4% vs. 3.2%; RR, 0.29; 95% CI, 0.14-0.57; p-value = 0.003), while the non-significantly increased hematoma progression (3.8% vs. 3.4%; RR, 1.06; 95% CI, 0.68-1.68; p-value = 0.79) and gastrointestinal bleeding (3.6% vs. 6.1%; RR, 0.63; 95% CI, 0.31-1.28; p-value = 0.20). Also, mortality (14.1% vs. 15.8%; RR, 0.90; 95% CI, 0.63-1.28; p-value = 0.55) did not show any significant difference in LMWH compared with control groups. Our meta-analysis suggested that early low-dose of LMWH are safe and effective in ICH patients. More extensive, multicenter, high-quality randomized clinical trials (RCTs) should be conducted to validate the findings and inform clinical practice.

Effect of Nurse-Assisted Early Warning Intervention for Prevention of Venous Thromboembolism Following Cesarean Delivery

Abstract Objective The aim of the study is to assess the role of a nurse-assisted early warning intervention in improving prophylaxis against obstetric venous thromboembolism (VTE) and preventing VTE following cesarean delivery (CD). Methods A prospective cohort study conducted between January 1, 2020, and December 30, 2022, enrolled pregnant women who underwent CD in the obstetric unit of Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital. The patients were assigned to a control group (routine nursing care) or the intervention group (nurse-assisted early warning intervention) depending on whether or not the nurse-assisted early warning intervention had been implemented. The χ 2 test and Student’s t test were used for statistical analysis. The primary outcome was the incidence of systemic VTE following CD, and secondary outcomes were the rates of mechanical or pharmacologic prophylaxis receipts for VTE and the frequency and severity of adverse events related to pharmacologic prophylaxis. Results A total of 27,074 cases were enrolled. The incidence of symptomatic VTE following CD was significantly lower in the intervention group (0.29 per 1000 deliveries) than in the control group (2.4 per 1000 deliveries) (P &lt; 0.001). Significantly more cases received mechanical and pharmacological VTE prophylaxis in the intervention group than in the control group (respectively, 19.8% vs. 12.6% receiving mechanical prophylaxis and 0.9% vs. 0.2% receiving pharmacological prophylaxis). No cases of life-threatening bleeding occurred in either group. Conclusion The application of nurse-assisted early warning intervention may be an effective method for preventing VTE following CD.

Thromboprophylaxis in varicose veins surgery: The everyday concern.

Venous thromboembolic disease (VTE) occupies an important place as a cause of morbidity and mortality in surgical patients in all specialties. Despite the existence of guidelines for thrombo prophylaxis in surgery, it is not clear due to the lack of current evidence, how to develop antithrombotic prophylaxis in varicose vein surgery and many questions arise when the surgeon is faced with a patient to be operated on. A comprehensive review of the literature was conducted to examine the evidence about the prevention of the venous thromboembolism in varicose veins surgery patients, and aims to guide the reader through questions that arise in daily practice, discussing the different scenarios presented in the literature for the choice of the most appropriate prophylaxis for each case. The lack of conclusive literature determines that risk should be individualized using available scales and other procedure-related factors, so that the type and duration of prophylaxis can be determined on a case-by-case basis.

Knee

The October 2024 Knee Roundup360 looks at: Managing the unexpected: treatment of intraoperative medial collateral ligament injuries; Identifying subgroups of patients that may benefit from robotic arm-assisted total knee arthroplasty: secondary analysis of data from a randomized controlled trial; Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial; Cartilage regeneration and long-term survival in medial knee osteoarthritis patients treated with high tibial osteotomy and osteochondral autologous transfer system; Treatment of chronic and complex meniscal tears with arthroscopic meniscus repair augmented with collagen matrix wrapping: failure rate and functional outcomes; Long-term outcomes of multiligament knee injuries in American football players.

Association between bariatric surgery preoperative chemoprophylaxis and postoperative bleeding.

Use of chemoprophylaxis for prevention of venous thromboembolism (VTE) after bariatric surgery is a generally accepted principle; however, the optimal strategy in terms of medication type and pre- and postoperative dosing is uncertain. In our healthcare system, four hospitals performed bariatric surgery and utilized differing protocols for VTE prophylaxis. The analysis sought to evaluate the association of differing prophylaxis strategies on bleeding and VTE occurrence. Adult patients who underwent laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) from 2018 to 2021 at four hospitals were studied. Patients were grouped by whether or not they received preoperative chemoprophylaxis. The primary outcome was postoperative bleeding, defined as requiring a blood transfusion or reoperation for bleeding within 30days. Bivariate analyses were performed with Chi-square and Wilcoxon Rank tests where applicable. Multivariate logistic regression was performed for the outcome of postoperative bleeding. A total of 2145 bariatric surgeries were evaluated (33.6% RYGB, 66.4% SG). Among 1712 patients who underwent surgery at Hospitals A, B, and C, 93.1% received preoperative VTE prophylaxis, compared with 1 patient (0.1%) among 433 patients operated on at Hospital D. Postoperative bleeding occurred more frequently in patients who received preoperative VTE prophylaxis versus those who did not (3.7% vs 1.1%; p < 0.01). After multivariable regression analysis, only RYGB (OR 3.59; p < 0.01) and preoperative VTE prophylaxis (OR 3.54; p = 0.02) were significantly associated with postoperative bleeding. Rates of VTE for patients receiving preoperative VTE prophylaxis or no prophylaxis were not significantly different (0.6% vs. 0.2%; p = 0.26). Preoperative VTE prophylaxis prior to bariatric surgery was associated with postoperative bleeding without differences in VTE occurrence. These results call into question the routine use of VTE chemoprophylaxis for all patients undergoing bariatric surgery and favor selective usage.

Cost-effectiveness analysis of direct oral anticoagulants versus low-molecular-weight heparin and no thromboprophylaxis in primary prevention of cancer-associated venous thromboembolism in China.

Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China. A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses. Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase. Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.

Anticoagulation for the Prevention of Arterial Thromboembolism in Cancer Patients by Primary Tumor Site: A Systematic Review and Meta-Analysis of Randomized Trials.

Incidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site. We conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites. Based on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.

Efficacy and safety of aspirin in venous thromboembolism prevention after total hip arthroplasty, total knee arthroplasty or fracture.

Background: This study aims to analyse the efficacy and safety of aspirin in the prevention of venous thromboembolism (VTE) for patients undergoing total hip arthroplasty (THA), total knee arthroplasty (TKA) or fracture. Patients and methods: Two independent investigators searched PubMed, Embase, Cochrane and ClinicalTrials.gov from January 2000 to June 2023 to retrieve randomized control trials (RCTs) about aspirin in VTE prevention after arthroplasty or fracture. Then, the relative risk (RR) was utilized to evaluate its efficiency and safety. Results: A total of 16 RCTs with 27,864 patients were included. There was no statistical difference in the incidence of deep-vein thrombosis (RR: 1.31, p = 0.100), pulmonary embolism (RR:1.05, p = 0.850), VTE (RR:1.28, p = 0.290), major bleeding (RR:0.96, p = 0.900), and death (RR:1.01, p = 0.960) between the aspirin group and the anticoagulants group. Subgroup analysis showed that a relatively higher incidence of deep-vein thrombosis in patients undergoing TKA (RR:1.49, p = 0.030), fracture (RR:1.48, p = 0.001), patients receiving 81 mg aspirin twice daily (RR:1.48, p = 0.001) and patients from North America (RR:1.57, p<0.001) when comparing aspirin with anticoagulants. Meanwhile, the incidence of VTE was higher in patients receiving 100 mg aspirin once daily (RR:1.82, p<0.001) compared with anticoagulants. Additionally, the incidence of all bleeding (RR:2.00, p = 0.030) was higher in patients receiving aspirin in Asia compared with anticoagulants. Conclusions: In terms of clinical effectiveness and safety, aspirin (antiplatelet agent) was generally not inferior to anticoagulants in the prevention of VTE after THA, TKA, or fracture. Notably, the clinical effectiveness of aspirin was affected by different surgical types, the doses of aspirin and races.

Venous thromboembolism prevention program implementation in a community oncology practice: a cohort study

While national guidelines recommend Venous Thromboembolism (VTE) risk assessment in cancer outpatients and consideration of pharmacologic prophylaxis in high-risk patients, prophylaxis rates are low in community oncology practices. A successful model for guideline implementation (the Vermont Model, VM) is validated in an academic tertiary oncology setting. We undertook an implementation study to determine the success of this model in a multi-site community oncology practice. The study objectives were to: 1) adapt the VM to the community practice setting; 2) implement the adapted VM into practice; and 3) evaluate clinical and implementation outcomes. The study was carried out in three phases: (1) Pre-implementation, a multidisciplinary team addressed the need to adapt the VM to the local context including electronic medical record (EMR) optimisation and clinician education; (2) implementation of the strategies adapted to the local context, informed by VM and adapted based on stakeholder feedback; (3) prospective evaluation of clinical and implementation outcomes at six months after implementation. Following creation of a comprehensive initiation roadmap for the adaptation of VM program to the community practice, 302 cancer outpatients initiating new treatment met inclusion criteria over a 6 month implementation period. VTE risk education was provided to 100% of patients, and 98% (296) of patients received a VTE risk assessment. Of 52 patients (18%) who scored as high risk based on a modified Khorana (Protecht) score, 14 (27%) initiated prophylaxis. Barriers to program adaptation included EMR optimization challenges and practice-level responsibility assignment, time constraints, concern about potential drug interactions, and financial & insurance issues. Implementation of a multidisciplinary VTE prevention model in the community-based oncology setting successfully increased VTE education and risk assessment rates. AC prophylaxis rates were modestly increased, highlighting the need to understand and address barriers to anticoagulant prophylaxis prescribing in this setting. Northern New England Clinical Oncology Society Research Funding Program.

The Association of Abdominoplasty with Breast Reduction (Mommy Makeover): Experience in An African University Hospital

Background: The popularity of breast reduction and abdominoplasty has significantly increased over the years, according to statistics from the American Society of Plastic Surgeons 2022. As a result, the Mommy Makeover, a procedure combining breast surgery and abdominoplasty, is not uncommon. Patients and Methods: A retrospective descriptive study was conducted over a four-year period within the Plastic and Aesthetic Surgery Department of the IBN SINA University Hospital, Rabat, Morocco. Results: Five cases of Mommy Makeover were operated on within the Plastic and Aesthetic Surgery Department of the IBN SINA University Hospital, Rabat, Morocco. One case was addressed two years after bariatric surgery. The procedure combined breast reduction with the superior-internal pedicle technique with Wise’s pattern and abdominoplasty. No major complications were observed. Discussion: Since the introduction of abdominoplasties combined with breast surgery, several concerns have been associated with this combination. Venous thromboembolism is the most commonly discussed consequence in combined plastic surgery procedures. The risk of venous thromboembolism is not elevated when abdominoplasty and breast reduction are combined. The study emphasizes the importance of careful patient selection and attentive venous thromboembolism prevention. It assesses the validity of the Davison-Caprini framework for venous thromboembolism risk stratification and prophylaxis in plastic surgery. Other measures to prevent complications were cited in the literature and followed by our operating team. Conclusion: With the help of a simple risk stratification tool that takes into account diabetes, age, BMI, and ASA status, we can guarantee favorable results for women who may want combined surgery.

The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects

ABSTRACT Background Inhibiting the coagulation factor XI (FXI) is a novel strategy for prevention and treatment of thromboembolism without affecting extrinsic coagulation pathways. SHR-2004 is a humanized monoclonal antibody that selectively binds to FXI and factor XIa (FXIa). Research design & methods This randomized, double-blind, dose-escalation, placebo-controlled study evaluated SHR-2004 administered either intravenously (i.v.; Part A) or subcutaneously (s.c.; Part B). In Part A, 24 subjects received a single i.v. dose of SHR-2004 (0.1, 0.3, or 1.0 mg/kg) or placebo. In Part B, 40 subjects received a single s.c. dose of SHR-2004 (0.5, 1.0, 3.0, or 4.5 mg/kg) or placebo. Results SHR-2004 was well tolerated. Plasma exposure to SHR-2004 increased in a dose-dependent manner. The geometric mean half-time ranged from 11.6 to 13.0 days. FXI activity decreased, and the activated partial thromboplastin time (APTT) was prolonged after i.v. and s.c. administration in a dose- and time-dependent manner. FXI activity was nearly completely abolished immediately after administering the highest i.v. dose, with the average APTT prolonged to nearly three times of baseline. Conclusion SHR-2004 is a promising candidate for further development as an anticoagulant drug that exerts effective anticoagulation with minimal risk of bleeding. Clinical trial registration www.clinicaltrials.gov identifier is NCT05369767.

Hot topics in thromboembolic risk prevention, heart failure monitoring, and cardiomyopathy risk stratification.

Hot topics in thromboembolic risk prevention, heart failure monitoring, and cardiomyopathy risk stratification.

Venous thrombosis and thromboembolism in cancer patients

Deep vein thrombosis and pulmonary embolism are the most frequent cardiovascular complications of cancer, they can occur at any stage of its development. Treatment and prevention of these complications are undergoing great changes. The aim of the review is to analyze the special scientific literature, to evaluate the principles of prevention and treatment of cancer-associated thrombosis and thromboembolism.

Milvexian: An Oral, Bioavailable Factor XIa Inhibitor.

Direct oral anticoagulants have a dose-dependent increased bleeding risk which limits use in certain populations. Studies in both animals and humans with inherited variations in factor XI levels provide a theoretical basis for a drug target capable of addressing current unmet needs. Milvexian is an oral factor XIa inhibitor that has the potential to provide robust anticoagulant effect without increased bleeding compared with current standard of care. Several key studies in the preclinical, phase I, and phase II stages have reported promising safety data in venous thromboembolism and stroke prevention without compromising hemostasis. The planned phase III trials will examine the efficacy of milvexian for prevention of thrombotic events in patients with acute stroke, acute coronary syndrome, and atrial fibrillation.

Lower Limb Doppler Ultrasound Prior to Pneumatic Compression for the Prevention of Pulmonary Embolism in Gynecological Cancer Patients: A Retrospective Cohort Study.

Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cardiovascular disease after myocardial infarction and stroke. This study aimed to determine the effect of Doppler ultrasound on the prophylaxis and prevention of postoperative venous thromboembolism in gynecological oncology. This is a retrospective cohort study of procedures performed at King Abdulaziz Medical City in Jeddah, Saudi Arabia, between 2016 and 2021. The study included all patients diagnosed with gynecological cancers who underwent major cancer resection. A total of 295 eligible patients were enrolled and divided into two groups: the first group consisted of 104 patients who were screened for deep vein thrombosis using lower limb Doppler ultrasound prior to their gynecologic oncology surgery, while the second group included 190 patients who were not screened. The prevalence of pulmonary embolism and/or deep vein thrombosis was found to be eight out of 104 patients (7.7%) in the group screened for deep-vein thrombosis using lower limb Doppler ultrasound prior to their gynecologic oncology surgery. In the group that was not screened, one out of 190 patients (0.5%) developed deep vein thrombosis. The prevalence of postoperative pulmonary embolism and/or deep-vein thrombosis was reported in four out of 104 screened patients (3.8%) and in three out of 190 patients (1.6%) in the unscreened group. This study concluded that Doppler screening did not change the incidence of pulmonary embolism and/or deep-vein thrombosis postoperatively, but it may be helpful in detecting these conditions preoperatively. Therefore, Doppler screening for deep-vein thrombosis before surgical procedures in gynecological oncology could be considered after clinical assessment of the patient. To improve the study and address its limitations, a larger sample size would help to further investigate and identify relevant factors and determine their significance.

From Other Journals: A Review of Recent Articles by Our Editorial Team.

In this review we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address: 1- The use of AI in fetal echocardiography, 2- The role of Apixaban in thromboembolism prevention in pediatric congenital heart disease, 3- Cardiovascular events in childhood cancer survivors, and lastly 4- the new consensus statement on cardiac catheterization for pediatrics and adults with congenital heart disease.