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Journal of Clinical Medicine Dec 2020Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden... (Review)
Review
Venous leg ulcers (VLUs) are one of the most common ulcers of the lower extremity. VLU affects many individuals worldwide, could pose a significant socioeconomic burden to the healthcare system, and has major psychological and physical impacts on the affected individual. VLU often occurs in association with post-thrombotic syndrome, advanced chronic venous disease, varicose veins, and venous hypertension. Several demographic, genetic, and environmental factors could trigger chronic venous disease with venous dilation, incompetent valves, venous reflux, and venous hypertension. Endothelial cell injury and changes in the glycocalyx, venous shear-stress, and adhesion molecules could be initiating events in VLU. Increased endothelial cell permeability and leukocyte infiltration, and increases in inflammatory cytokines, matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species, iron deposition, and tissue metabolites also contribute to the pathogenesis of VLU. Treatment of VLU includes compression therapy and endovenous ablation to occlude the axial reflux. Other interventional approaches such as subfascial endoscopic perforator surgery and iliac venous stent have shown mixed results. With good wound care and compression therapy, VLU usually heals within 6 months. VLU healing involves orchestrated processes including hemostasis, inflammation, proliferation, and remodeling and the contribution of different cells including leukocytes, platelets, fibroblasts, vascular smooth muscle cells, endothelial cells, and keratinocytes as well as the release of various biomolecules including transforming growth factor-β, cytokines, chemokines, MMPs, tissue inhibitors of MMPs (TIMPs), elastase, urokinase plasminogen activator, fibrin, collagen, and albumin. Alterations in any of these physiological wound closure processes could delay VLU healing. Also, these histological and soluble biomarkers can be used for VLU diagnosis and assessment of its progression, responsiveness to healing, and prognosis. If not treated adequately, VLU could progress to non-healed or granulating VLU, causing physical immobility, reduced quality of life, cellulitis, severe infections, osteomyelitis, and neoplastic transformation. Recalcitrant VLU shows prolonged healing time with advanced age, obesity, nutritional deficiencies, colder temperature, preexisting venous disease, deep venous thrombosis, and larger wound area. VLU also has a high, 50-70% recurrence rate, likely due to noncompliance with compression therapy, failure of surgical procedures, incorrect ulcer diagnosis, progression of venous disease, and poorly understood pathophysiology. Understanding the molecular pathways underlying VLU has led to new lines of therapy with significant promise including biologics such as bilayer living skin construct, fibroblast derivatives, and extracellular matrices and non-biologic products such as poly-N-acetyl glucosamine, human placental membranes amnion/chorion allografts, ACT1 peptide inhibitor of connexin 43, sulodexide, growth factors, silver dressings, MMP inhibitors, and modulators of reactive oxygen and nitrogen species, the immune response and tissue metabolites. Preventive measures including compression therapy and venotonics could also reduce the risk of progression to chronic venous insufficiency and VLU in susceptible individuals.
PubMed: 33374372
DOI: 10.3390/jcm10010029 -
Journal of Thrombosis and Haemostasis :... Nov 2018Despite the development of catheter-based interventions for ischemic and valvular heart disease, hundreds of thousands of people undergo open heart surgery annually for... (Review)
Review
Despite the development of catheter-based interventions for ischemic and valvular heart disease, hundreds of thousands of people undergo open heart surgery annually for coronary artery bypass graft (CABG), valve replacement or cardiac assist device implantation. Cardiac surgery patients are unique because therapeutic anticoagulation is required during cardiopulmonary bypass. Developmental hemostasis and altered drug metabolism affect management in children. This narrative review summarizes the current evidence-based and consensus guidelines regarding perioperative, intraoperative and postoperative antithrombotic therapy in patients undergoing cardiac surgery. Anticoagulation preoperatively is required in the setting of cardiac arrhythmias, prior valve replacement or history of venous thromboembolism. In patients with ischemic heart disease, aspirin is continued in the perioperative period, whereas oral P2Y antagonists are withheld for 5-7 days to reduce the risk of perioperative bleeding. Intraoperative management of cardiopulmonary bypass in adults and children includes anticoagulation with unfractionated heparin. Variability in dose-response to heparin and influence of other medical conditions on dosing and reversal of heparin make intraoperative anticoagulation challenging. Vitamin K antagonist therapy is the standard anticoagulant after mechanical heart valve or left ventricular assist device (LVAD) implantation. Longer duration of dual antiplatelet therapy is recommended after CABG if patients undergo surgery because of acute coronary syndrome. Antiplatelet therapy after LVAD implantation includes aspirin, dipyridamole and/or clopidogrel in children and aspirin in adults. A coordinated approach between hematology, cardiology, anesthesiology, critical care and cardiothoracic surgery can assist to balance the risk of thrombosis and bleeding in patients undergoing cardiac surgery.
Topics: Adolescent; Adult; Anticoagulants; Aspirin; Blood Coagulation; Cardiac Surgical Procedures; Cardiology; Child; Coronary Artery Bypass; Drug Administration Schedule; Evidence-Based Medicine; Fibrinolytic Agents; Heart Valve Diseases; Heart-Assist Devices; Hemorrhage; Hemostasis; Heparin; Humans; Inflammation; Intraoperative Period; Perioperative Period; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Protamines; Risk; Thrombolytic Therapy; Thrombosis; Vitamin K
PubMed: 30153372
DOI: 10.1111/jth.14276 -
Journal of Thrombosis and Haemostasis :... Jun 2015Postoperative atrial fibrillation (POAF) is the most common perioperative cardiac arrhythmia. A major risk factor for POAF is advanced age, both in non-cardiac and... (Review)
Review
Postoperative atrial fibrillation (POAF) is the most common perioperative cardiac arrhythmia. A major risk factor for POAF is advanced age, both in non-cardiac and cardiac surgery. Following non-cardiac surgery, it is important to correct reversible conditions such as electrolytes imbalances to prevent the occurrence of POAF. Management of POAF consists of rate control and therapeutic anticoagulation if POAF persists for > 48 h and CHADS2 score > 2. After cardiac surgery, POAF affects a larger amount of patients. In addition to age, valve surgery carries the greatest risk for new AF. Rate control is the mainstay therapy in these patients. Prediction, prevention, and management of POAF should be further studied.
Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Cardiac Surgical Procedures; Heart Rate; Humans; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26149040
DOI: 10.1111/jth.12974 -
Endoscopy Mar 2017ESGE recommends cold snare polypectomy (CSP) as the preferred technique for removal of diminutive polyps (size ≤ 5 mm). This technique has high rates of...
ESGE recommends cold snare polypectomy (CSP) as the preferred technique for removal of diminutive polyps (size ≤ 5 mm). This technique has high rates of complete resection, adequate tissue sampling for histology, and low complication rates. (High quality evidence, strong recommendation.) ESGE suggests CSP for sessile polyps 6 - 9 mm in size because of its superior safety profile, although evidence comparing efficacy with hot snare polypectomy (HSP) is lacking. (Moderate quality evidence, weak recommendation.) ESGE suggests HSP (with or without submucosal injection) for removal of sessile polyps 10 - 19 mm in size. In most cases deep thermal injury is a potential risk and thus submucosal injection prior to HSP should be considered. (Low quality evidence, strong recommendation.) ESGE recommends HSP for pedunculated polyps. To prevent bleeding in pedunculated colorectal polyps with head ≥ 20 mm or a stalk ≥ 10 mm in diameter, ESGE recommends pretreatment of the stalk with injection of dilute adrenaline and/or mechanical hemostasis. (Moderate quality evidence, strong recommendation.) ESGE recommends that the goals of endoscopic mucosal resection (EMR) are to achieve a completely snare-resected lesion in the safest minimum number of pieces, with adequate margins and without need for adjunctive ablative techniques. (Low quality evidence; strong recommendation.) ESGE recommends careful lesion assessment prior to EMR to identify features suggestive of poor outcome. Features associated with incomplete resection or recurrence include lesion size > 40 mm, ileocecal valve location, prior failed attempts at resection, and size, morphology, site, and access (SMSA) level 4. (Moderate quality evidence; strong recommendation.) For intraprocedural bleeding, ESGE recommends endoscopic coagulation (snare-tip soft coagulation or coagulating forceps) or mechanical therapy, with or without the combined use of dilute adrenaline injection. (Low quality evidence, strong recommendation.)An algorithm of polypectomy recommendations according to shape and size of polyps is given (Fig. 1).
Topics: Adenomatous Polyps; Algorithms; Colon; Colonoscopy; Colorectal Neoplasms; Endoscopic Mucosal Resection; Humans; Intestinal Polyps; Postoperative Complications; Rectum
PubMed: 28212588
DOI: 10.1055/s-0043-102569 -
BMJ (Clinical Research Ed.) Jun 2021To determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the efficacy and safety of dalteparin postoperative bridging treatment versus placebo for patients with atrial fibrillation or mechanical heart valves when warfarin is temporarily interrupted for a planned procedure.
DESIGN
Prospective, double blind, randomised controlled trial.
SETTING
10 thrombosis research sites in Canada and India between February 2007 and March 2016.
PARTICIPANTS
1471 patients aged 18 years or older with atrial fibrillation or mechanical heart valves who required temporary interruption of warfarin for a procedure.
INTERVENTION
Random assignment to dalteparin (n=821; one patient withdrew consent immediately after randomisation) or placebo (n=650) after the procedure.
MAIN OUTCOME MEASURES
Major thromboembolism (stroke, transient ischaemic attack, proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, peripheral embolism, or vascular death) and major bleeding according to the International Society on Thrombosis and Haemostasis criteria within 90 days of the procedure.
RESULTS
The rate of major thromboembolism within 90 days was 1.2% (eight events in 650 patients) for placebo and 1.0% (eight events in 820 patients) for dalteparin (P=0.64, risk difference -0.3%, 95% confidence interval -1.3 to 0.8). The rate of major bleeding was 2.0% (13 events in 650 patients) for placebo and 1.3% (11 events in 820 patients) for dalteparin (P=0.32, risk difference -0.7, 95% confidence interval -2.0 to 0.7). The results were consistent for the atrial fibrillation and mechanical heart valves groups.
CONCLUSIONS
In patients with atrial fibrillation or mechanical heart valves who had warfarin interrupted for a procedure, no significant benefit was found for postoperative dalteparin bridging to prevent major thromboembolism.
TRIAL REGISTRATION
Clinicaltrials.gov NCT00432796.
Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Dalteparin; Double-Blind Method; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Surgical Procedures, Operative; Thromboembolism; Warfarin
PubMed: 34108229
DOI: 10.1136/bmj.n1205 -
Clinical Case Reports Jan 2022A new-onset neurological deficit after calcified aortic valve replacement and an hyperdense image on the computed tomography raised suspicion of an stroke of unusual...
A new-onset neurological deficit after calcified aortic valve replacement and an hyperdense image on the computed tomography raised suspicion of an stroke of unusual etiology.
PubMed: 35028138
DOI: 10.1002/ccr3.4962 -
Open Biology Dec 2020The a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS) family comprises 19 proteases that regulate the structure and function of extracellular... (Review)
Review
The a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS) family comprises 19 proteases that regulate the structure and function of extracellular proteins in the extracellular matrix and blood. The best characterized cardiovascular role is that of ADAMTS-13 in blood. Moderately low ADAMTS-13 levels increase the risk of ischeamic stroke and very low levels (less than 10%) can cause thrombotic thrombocytopenic purpura (TTP). Recombinant ADAMTS-13 is currently in clinical trials for treatment of TTP. Recently, new cardiovascular roles for ADAMTS proteases have been discovered. Several ADAMTS family members are important in the development of blood vessels and the heart, especially the valves. A number of studies have also investigated the potential role of ADAMTS-1, -4 and -5 in cardiovascular disease. They cleave proteoglycans such as versican, which represent major structural components of the arteries. ADAMTS-7 and -8 are attracting considerable interest owing to their implication in atherosclerosis and pulmonary arterial hypertension, respectively. Mutations in the gene cause progressive heart valve disease and missense variants in are associated with cardiac conduction. In this review, we discuss in detail the evidence for these and other cardiovascular roles of ADAMTS family members, their proteolytic substrates and the potential molecular mechanisms involved.
Topics: ADAMTS Proteins; Animals; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; Disease Management; Disease Susceptibility; Gene Expression Regulation; Humans; Molecular Targeted Therapy; Multigene Family; Proteoglycans; Proteolysis
PubMed: 33352066
DOI: 10.1098/rsob.200333 -
Annual Review of Pharmacology and... Jan 2024Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and... (Review)
Review
Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide.
Topics: Humans; Aged; Warfarin; Anticoagulants; Hemorrhage; Atrial Fibrillation; Renal Insufficiency, Chronic; Administration, Oral
PubMed: 37758192
DOI: 10.1146/annurev-pharmtox-032823-122811 -
Journal of the American Heart... Jul 2017The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The... (Meta-Analysis)
Meta-Analysis Review
Effects of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: A Systematic Review and Meta-Analysis.
BACKGROUND
The original non-vitamin K antagonist oral anticoagulant (NOAC) trials in nonvalvular atrial fibrillation (AF) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit-risk profiles of NOACs versus warfarin in AF patients with native valvular heart disease (VHD).
METHODS AND RESULTS
Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta-analytic summary hazard ratio (HR) and 95% confidence interval (CI) of efficacy and safety of NOACs versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with VHD. Pooling results from included trials showed that NOACs versus warfarin reduced stroke or systemic embolism (HR: 0.70; 95% CI, 0.60-0.82) and intracranial hemorrhage (HR: 0.47; 95% CI, 0.24-0.92) in AF patients with VHD. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95% CI, 0.69-0.91]; HR for intracranial hemorrhage: 0.33 [95% CI, 0.25-0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95% CI, 1.20-2.04]; HR for intracranial hemorrhage: 1.27 [95% CI, 0.77-2.10]).
CONCLUSIONS
Among patients with AF and native VHD, NOACs reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in VHD patients treated with rivaroxaban. NOACs are a reasonable alternative to warfarin in AF patients with VHD.
Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Chi-Square Distribution; Female; Heart Valve Diseases; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Odds Ratio; Risk Factors; Stroke; Treatment Outcome; Vitamin K; Warfarin
PubMed: 28720644
DOI: 10.1161/JAHA.117.005835 -
Cellular and Molecular Life Sciences :... May 2019Hippocratic Corpus, a collection of Greek medical literature, described the functional anatomy of the lymphatic system in the fifth century B.C. Subsequent studies in... (Review)
Review
Hippocratic Corpus, a collection of Greek medical literature, described the functional anatomy of the lymphatic system in the fifth century B.C. Subsequent studies in cadavers and surgical patients firmly established that lymphatic vessels drain extravasated interstitial fluid, also known as lymph, into the venous system at the bilateral lymphovenous junctions. Recent advances revealed that lymphovenous valves and platelet-mediated hemostasis at the lymphovenous junctions maintain life-long separation of the blood and lymphatic vascular systems. Here, we review murine models that exhibit failure of blood-lymph separation to highlight the novel mechanisms and molecular targets for the modulation of lymphatic disorders. Specifically, we focus on the transcription factors, cofactors, and signaling pathways that regulate lymphovenous valve development and platelet-mediated lymphovenous hemostasis, which cooperate to maintain blood-lymph separation.
Topics: Animals; Blood Platelets; Gene Expression Regulation, Developmental; Hemostasis; Humans; Lymph; Lymphangiogenesis; Lymphatic Vessels; Mice; Signal Transduction
PubMed: 30758642
DOI: 10.1007/s00018-019-03042-3