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Cancers Jun 2024Patients with cancer are at increased risk of arterial thromboembolic disease due to the presence of risk factors common to both the development of cancer and arterial... (Review)
Review
Patients with cancer are at increased risk of arterial thromboembolic disease due to the presence of risk factors common to both the development of cancer and arterial thrombosis, the cancer itself, and the treatments provided to treat cancer. We review here the epidemiology and pathophysiology of arterial thromboembolic disease in cancer, along with its prevention and treatment strategies. We also propose a generalized approach for the management of arterial thromboembolic disease in this patient population.
PubMed: 38927943
DOI: 10.3390/cancers16122238 -
Biomedicines Jun 2024Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk... (Review)
Review
Lipoprotein(a) is a low-density-lipoprotein-like particle that consists of apolipoprotein(a) bound to apolipoprotein(b). It has emerged as an established causal risk factor for atherosclerotic cardiovascular disease, stroke, and aortic valve stenosis through multifactorial pathogenic mechanisms that include inflammation, atherogenesis, and thrombosis. Despite an estimated 20% of the global population having elevated lipoprotein(a) levels, testing remains underutilized due to poor awareness and a historical lack of effective and safe therapies. Although lipoprotein(a) has a strong association with coronary artery disease and cerebrovascular disease, its relationship with peripheral artery disease is less well established. In this article, we review the epidemiology, biology, and pathogenesis of lipoprotein(a) as it relates to peripheral artery disease. We also discuss emerging treatment options to help mitigate major adverse cardiac and limb events in this population.
PubMed: 38927436
DOI: 10.3390/biomedicines12061229 -
BMJ (Clinical Research Ed.) Jun 2024To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.
OBJECTIVE
To investigate the incidence of cardiovascular disease (CVD) overall and by age, sex, and socioeconomic status, and its variation over time, in the UK during 2000-19.
DESIGN
Population based study.
SETTING
UK.
PARTICIPANTS
1 650 052 individuals registered with a general practice contributing to Clinical Practice Research Datalink and newly diagnosed with at least one CVD from 1 January 2000 to 30 June 2019.
MAIN OUTCOME MEASURES
The primary outcome was incident diagnosis of CVD, comprising acute coronary syndrome, aortic aneurysm, aortic stenosis, atrial fibrillation or flutter, chronic ischaemic heart disease, heart failure, peripheral artery disease, second or third degree heart block, stroke (ischaemic, haemorrhagic, and unspecified), and venous thromboembolism (deep vein thrombosis or pulmonary embolism). Disease incidence rates were calculated individually and as a composite outcome of all 10 CVDs combined and were standardised for age and sex using the 2013 European standard population. Negative binomial regression models investigated temporal trends and variation by age, sex, and socioeconomic status.
RESULTS
The mean age of the population was 70.5 years and 47.6% (n=784 904) were women. The age and sex standardised incidence of all 10 prespecified CVDs declined by 19% during 2000-19 (incidence rate ratio 2017-19 2000-02: 0.80, 95% confidence interval 0.73 to 0.88). The incidence of coronary heart disease and stroke decreased by about 30% (incidence rate ratios for acute coronary syndrome, chronic ischaemic heart disease, and stroke were 0.70 (0.69 to 0.70), 0.67 (0.66 to 0.67), and 0.75 (0.67 to 0.83), respectively). In parallel, an increasing number of diagnoses of cardiac arrhythmias, valve disease, and thromboembolic diseases were observed. As a result, the overall incidence of CVDs across the 10 conditions remained relatively stable from the mid-2000s. Age stratified analyses further showed that the observed decline in coronary heart disease incidence was largely restricted to age groups older than 60 years, with little or no improvement in younger age groups. Trends were generally similar between men and women. A socioeconomic gradient was observed for almost every CVD investigated. The gradient did not decrease over time and was most noticeable for peripheral artery disease (incidence rate ratio most deprived least deprived: 1.98 (1.87 to 2.09)), acute coronary syndrome (1.55 (1.54 to 1.57)), and heart failure (1.50 (1.41 to 1.59)).
CONCLUSIONS
Despite substantial improvements in the prevention of atherosclerotic diseases in the UK, the overall burden of CVDs remained high during 2000-19. For CVDs to decrease further, future prevention strategies might need to consider a broader spectrum of conditions, including arrhythmias, valve diseases, and thromboembolism, and examine the specific needs of younger age groups and socioeconomically deprived populations.
Topics: Humans; Female; Male; United Kingdom; Incidence; Aged; Middle Aged; Cardiovascular Diseases; Adult; Aged, 80 and over; Social Class; Age Distribution; Sex Distribution; Young Adult
PubMed: 38925788
DOI: 10.1136/bmj-2023-078523 -
Hamostaseologie Jun 2024May-Thurner syndrome (MTS) is a pelvic venous disorder involving compression of the left common iliac vein by the right common iliac artery, which results in...
Current Diagnostic and Therapeutic Approaches in May-Thurner Syndrome in Children, Adolescents, and Young Adults: A Survey among Thrombosis Experts of the German Society of Thrombosis and Haemostasis.
May-Thurner syndrome (MTS) is a pelvic venous disorder involving compression of the left common iliac vein by the right common iliac artery, which results in predisposition for deep vein thrombosis. Although MTS is increasingly recognized in young patients, specific guidelines on diagnosis and management for children, adolescents, and young adults do not exist so far. The aim of this study was to assess current diagnostic and therapeutic practice in Germany, Austria, and Switzerland in children and young adults with thrombosis and MTS.We designed an online survey with 11 questions, which we sent via a mailing list to all members of the German, Austrian, and Swiss Society of Thrombosis and Haemostasis Research. Between July and October 2022, 33 specialists answered the questionnaire. Most participating specialists worked at pediatric hospitals (61%). Numbers of annually treated thromboses ranged from <5 (26%) to >30 (13%). Most specialists used venous ultrasound to diagnose deep vein thrombosis, 53% magnetic resonance imaging. Only 25% of specialists systematically screened for MTS in deep vein thrombosis. MTS was managed with anticoagulation (65%), iliac vein stent placement (32%), or balloon angioplasty (13%). In total, 31% of specialists reported to use more than one therapeutic method. Diagnostic and therapeutic approaches for MTS differed between specialists. Lack of standardization resulted in individualized and highly diverse management. Prospective observational clinical studies investigating the outcome of different management strategies including long-term follow-up on outcome and incidence of postthrombotic syndrome will help in defining patient groups who benefit most from revascularizing interventional strategies and developing standardized guidelines.
PubMed: 38925155
DOI: 10.1055/a-2282-4565 -
Advanced Healthcare Materials Jun 2024Whilst blood-contacting materials are widely deployed in medicine in vascular stents, catheters and cannulas, devices fail in-situ because of thrombosis and restenosis....
Whilst blood-contacting materials are widely deployed in medicine in vascular stents, catheters and cannulas, devices fail in-situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials could provide significant benefits for patients in terms of safety and patency as well as substantial cost savings.Herein, we describe a novel but simple strategy for coating a range of medical materials, that can be applied to objects of complex geometry, involving plasma-grafting of an ultra-thin hyperbranched polyglycerol coating (HPG). Plasma activation creates highly reactive surface oxygen moieties that readily react with glycidol. Irrespective of the substrate, coatings are uniform and pinhole free, comprising O-C-O repeats, with HPG chains packing in a fashion that holds reversibly binding proteins at the coating surface.In vitro assays with planar test samples show that HPG prevents platelet adhesion and activation, as well as reducing (>3log) bacterial attachment and preventing biofilm formation. Ex vivo and preclinical studies show that HPG-coated nitinol stents do not elicit thrombosis or restenosis, nor complement or neutrophil activation. Subcutaneous implantation of HPG coated disks under the skin of mice showed no evidence of toxicity nor inflammation. This article is protected by copyright. All rights reserved.
PubMed: 38924692
DOI: 10.1002/adhm.202401545 -
Plastic and Reconstructive Surgery Jun 2024Reconstructive surgery has experienced a paradigm shift in favor of free flaps. Yet, local flaps may be of particular use in foot and ankle reconstruction among comorbid...
BACKGROUND
Reconstructive surgery has experienced a paradigm shift in favor of free flaps. Yet, local flaps may be of particular use in foot and ankle reconstruction among comorbid patient populations. Thus, we sought to better characterize long-term outcomes in this setting.
METHODS
A single-center, retrospective cohort study of patients undergoing local muscle and fasciocutaneous flaps of the foot and ankle from January 2010-November 2022 was performed. Flap were performed on wounds measuring 3x6cm or smaller, and flap selection depended on preoperative vascular assessment, Doppler findings, comorbidity profile, and wound location, depth, and geometry.
RESULTS
Two-hundred and six patients met inclusion criteria. Median age was 61.0 years (IQR 16.8), and comorbidities included diabetes mellitus (DM; n=149/206, 72.3%) and peripheral arterial disease (PAD; n=105/206, 51.0%). Presentations included chronic, non-healing wounds (n=77/206, 39.1%) or osteomyelitis (n=45/206, 22.8%), and most frequently extended to the bone (n=128/206, 62.1%). Eighty-seven patients (n=87/206, 42.2%) received muscle flaps, while 119 received fasciocutaneous flaps (n=119/206, 57.8%). Six patients (n=6/206, 2.9%) necessitated return to the operating room, with thrombosis occurring in two cases (n=2/206, 1.0%). Flap success rate was 98.1%. By a median follow-up duration of 21.7 months (IQR 39.0), 45 patients (n=45/206, 21.8%) necessitated ipsilateral amputation, 73% (n=145/199) were ambulatory, and two deaths were related to the operated wound (n=2/49, 4.1%). Multivariate analysis revealed positive predictors of complications included DM, end-stage renal disease, and prior histories of venous thromboembolism or smoking.
CONCLUSION
Local flaps remain a reliable option to reconstruct smaller defects of the foot and ankle in a highly comorbid population.
PubMed: 38923878
DOI: 10.1097/PRS.0000000000011601 -
Advanced Science (Weinheim,... Jun 2024Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate...
Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs-mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal-regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin-11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin-11 pathways, which are associated with NCK1. The anti-platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases.
PubMed: 38922767
DOI: 10.1002/advs.202401683 -
Journal of Cardiovascular Pharmacology Apr 2024Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors...
Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. Here, analyses of activated partial thromboplastin time (aPTT) in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identify synergistic anticoagulation effects. Both an FeCl3-induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery (tMCAO) mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
PubMed: 38922574
DOI: 10.1097/FJC.0000000000001573 -
Annals of the Academy of Medicine,... Nov 2023Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The... (Observational Study)
Observational Study
INTRODUCTION
Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures. The objective of the study is to describe the real-world experience of emicizumab in a cohort of adult and paediatric haemophilia A patients in Singapore, including its use in the periprocedural setting.
METHOD
This was an observational study conducted at the 2 main haemophilia treatment centres in Singapore. All haemophilia A patients who commenced treatment with emicizumab before 1 July 2022 were recruited.
RESULTS
A total of 18 patients with haemophilia A were included in this study. Ten (55.6%) patients had active inhibitors. The median annual bleeding rate for all patients before emicizumab use was 4.5 events (interquartile range [IQR] 2.8-8.3) compared with 0 events (IQR 0-0) after emicizumab was commenced (P=0). There were no adverse events of venous or arterial thrombosis, thrombotic microangiopathy, or death. A total of 6 procedures in 5 patients were performed during the study period with no major bleeding complications.
CONCLUSION
Emicizumab effectively protects against bleeding in haemophilia A patients with and without inhibitors, including in children less than 12 years old. More studies are required to address clinical nuances, such as periprocedural management and the role of immune tolerance in patients with inhibitors on emicizumab.
Topics: Humans; Hemophilia A; Antibodies, Bispecific; Singapore; Antibodies, Monoclonal, Humanized; Adult; Male; Child; Hemorrhage; Adolescent; Middle Aged; Young Adult; Child, Preschool; Female
PubMed: 38920147
DOI: 10.47102/annals-acadmedsg.2023100 -
Hospital Pharmacy Aug 2024Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who...
Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who receive both andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC). The aim of this case series is to evaluate the safety and efficacy outcomes in patients receiving the two agents in combination. Electronic medical records of patients who received both 4F-PCC and andexanet alfa for nontraumatic intracranial hemorrhage from January 2019 to March 2022 were retrospectively reviewed. Hemostatic efficacy and complications related to concurrent use of 4F-PCC with andexanet alfa were documented. Nine patients received 4F-PCC and andexanet alfa for reversal of factor Xa inhibitor-associated intracranial bleeding, eight of whom required reversal of apixaban. Of these nine patients, five patients died within 28 days for a 56% incidence of mortality. The average time from 4F-PCC administration to andexanet alfa administration was 3 hours and 9 minutes. Most doses of andexanet alfa were given for concern for bleed expansion after 4F-PCC administration. Hemostatic efficacy based on stability of repeat computed tomography scans post-administration of both agents was found in six patients (66.67%), with a 55.56% n incidence of thromboembolism, including two pulmonary embolisms, two deep vein thromboses, and one renal artery thrombosis. : Risks and benefits should be weighed to determine if there is benefit to adding andexanet alfa to 4F-PCC in patients with incomplete hemostasis and life-threatening hemorrhage. The combination of andexanet alfa and 4F-PCC may increase the risk of thrombotic complications without improving mortality.
PubMed: 38919755
DOI: 10.1177/00185787241229192