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Arteriosclerosis, Thrombosis, and... Mar 2019Activation of the intrinsic pathway of coagulation contributes to the pathogenesis of arterial and venous thrombosis. Critical insights into the involvement of intrinsic... (Review)
Review
Activation of the intrinsic pathway of coagulation contributes to the pathogenesis of arterial and venous thrombosis. Critical insights into the involvement of intrinsic pathway factors have been derived from the study of gene-specific knockout animals and targeted inhibitors. Importantly, preclinical studies have indicated that targeting components of this pathway, including FXI (factor XI), FXII, and PKK (prekallikrein), reduces thrombosis with no significant effect on protective hemostatic pathways. This review highlights the advances made from studying the intrinsic pathway using gene-specific knockout animals and inhibitors in models of arterial and venous thrombosis. Development of inhibitors of activated FXI and FXII may reduce thrombosis with minimal increases in bleeding compared with current anticoagulant drugs.
Topics: Animals; Anticoagulants; Bleeding Time; Blood Coagulation; Blood Coagulation Factors; Disease Models, Animal; Drug Design; Enzyme Activation; Hemorrhage; Humans; Mice, Knockout; Primates; Rabbits; Rats; Thrombosis
PubMed: 30700128
DOI: 10.1161/ATVBAHA.118.312130 -
BMB Reports Apr 2012Curcumin, a polyphenol responsible for the yellow color of the curry spice turmeric, possesses antiinflammatory, antiproliferative and antiangiogenic activities....
Curcumin, a polyphenol responsible for the yellow color of the curry spice turmeric, possesses antiinflammatory, antiproliferative and antiangiogenic activities. However, anticoagulant activities of curcumin have not been studied. Here, the anticoagulant properties of curcumin and its derivative (bisdemethoxycurcumin, BDMC) were determined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT) as well as cell-based thrombin and activated factor X (FXa) generation activities. Data showed that curcumin and BDMC prolonged aPTT and PT significantly and inhibited thrombin and FXa activities. They inhibited the generation of thrombin or FXa. In accordance with these anticoagulant activities, curcumin and BDMC showed anticoagulant effect in vivo. Surprisingly, these anticoagulant effects of curcumin were better than those of BDMC indicating that methoxy group in curcumin positively regulated anticoagulant function of curcumin. Therefore, these results suggest that curcumin and BDMC possess antithrombotic activities and daily consumption of the curry spice turmeric might help maintain anticoagulant status.
Topics: Animals; Anticoagulants; Bleeding Time; Blood Coagulation; Cells, Cultured; Curcumin; Diarylheptanoids; Factor Xa; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Inbred C57BL; Partial Thromboplastin Time; Prothrombin Time; Thrombin
PubMed: 22531131
DOI: 10.5483/bmbrep.2012.45.4.221 -
Annals of the Royal College of Surgeons... Jan 2020An increasing number of patients are taking oral antiplatelet agents. As a result, there is an important patient safety concern in relation to the potential risk of... (Review)
Review
INTRODUCTION
An increasing number of patients are taking oral antiplatelet agents. As a result, there is an important patient safety concern in relation to the potential risk of bleeding complications following major oral and maxillofacial surgery. Surgeons are increasingly likely to be faced with a dilemma of either continuing antiplatelet therapy and risking serious haemorrhage or withholding therapy and risking fatal thromboembolic complications. While there are national recommendations for patients taking oral antiplatelet drugs undergoing invasive minor oral surgery, there are still no evidence-based guidelines for the management of these patients undergoing major oral and maxillofacial surgery.
METHODS
MEDLINE and EMBASE databases were searched to retrieve all relevant articles published to 31 December 2017.
FINDINGS
A brief outline of the commonly used antiplatelet agents including their pharmacology and therapeutic indications is discussed, together with the haemorrhagic and thromboembolic risks of continuing or altering the antiplatelet regimen in the perioperative period. Finally, a protocol for the management of oral and maxillofacial patients on antiplatelet agents is presented.
CONCLUSIONS
Most current evidence to guide decision making is based upon non-randomised observational studies, which attempts to provide the safest possible management of patients on antiplatelet therapy. Large randomised clinical trials are lacking.
Topics: Administration, Oral; Anticoagulants; Bleeding Time; Blood Loss, Surgical; Drug Substitution; Drug Therapy, Combination; Humans; Oral Surgical Procedures; Orthognathic Surgical Procedures; Patient Safety; Platelet Aggregation Inhibitors; Risk Factors; Thromboembolism
PubMed: 31755732
DOI: 10.1308/rcsann.2019.0154 -
Platelets May 2020Hemostasis is the normal process that produces a blood clot at a site of vascular injury. Mice are widely used to study hemostasis and abnormalities of blood coagulation... (Review)
Review
Hemostasis is the normal process that produces a blood clot at a site of vascular injury. Mice are widely used to study hemostasis and abnormalities of blood coagulation because their hemostatic system is similar in most respects to that of humans, and their genomes can be easily manipulated to create models of inherited human coagulation disorders. Two of the most widely used techniques for assessing hemostasis in mice are the tail bleeding time (TBT) and saphenous vein bleeding (SVB) models. Here we discuss the use of these methods in the evaluation of hemostasis, and the advantages and limits of using mice as surrogates for studying hemostasis in humans.
Topics: Animals; Bleeding Time; Blood Coagulation; Disease Models, Animal; Hemorrhage; Hemostasis; Humans; Lacerations; Liver; Mice; Saphenous Vein; Tail
PubMed: 31992118
DOI: 10.1080/09537104.2020.1719056 -
Journal of the American Heart... Feb 2023Background Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT...
Background Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi. However, all currently used anticoagulants affect bleeding time at various degrees, and there is therefore a need for improved therapeutic regimens in DVT. It has recently been shown that mast cells play a crucial role in a DVT murine model. The underlying mechanism involved in the prothrombotic properties of mast cells, however, has yet to be identified. Methods and Results C57BL/6 mice and mouse mast cell protease-4 (mMCP-4) genetically depleted mice (mMCP-4 knockout) were used in 2 mouse models of DVT, partial ligation (stenosis) and ferric chloride-endothelial injury model of the inferior vena cava. Thrombus formation and impact of genetically repressed or pharmacologically (specific inhibitor TY-51469) inhibited mMCP-4 were evaluated by morphometric measurements of thrombi immunochemistry (mouse and human DVT), color Doppler ultrasound, bleeding times, and enzymatic activity assays ex vivo Recombinant chymases, mMCP-4 (mouse) and CMA-1 (human), were used to characterize the interaction with murine and human plasmin, respectively, by mass spectrometry and enzymatic activity assays. Inhibiting mast cell-generated mMCP-4, genetically or pharmacologically, resolves and prevents venous thrombus formation in both DVT models. Inferior vena cava blood flow obstruction was observed in the stenosis model after 6 hours of ligation, in control- but not in TY-51469-treated mice. In addition, chymase inhibition had no impact on bleeding times of healthy or DVT mice. Furthermore, endogenous chymase limits plasmin activity in thrombi ex vivo. Recombinant mouse or human chymase degrades/inactivates purified plasmin in vitro. Finally, mast cell-containing immunoreactive chymase was identified in human DVT. Conclusions This study identified a major role for mMCP-4, a granule-localized protease of chymase type, in DVT formation. These findings support a novel pharmacological strategy to resolve or prevent DVT without affecting the coagulation cascade through the inhibition of chymase activity.
Topics: Mice; Humans; Animals; Chymases; Bleeding Time; Fibrinolysin; Disease Models, Animal; Constriction, Pathologic; Mice, Inbred C57BL; Venous Thrombosis; Anticoagulants
PubMed: 36752268
DOI: 10.1161/JAHA.122.028056 -
Advances in Wound Care Apr 2021One of the leading causes of death following traumatic injury is exsanguination. Biological material-based hemostatic agents such as fibrin, thrombin, and albumin have...
One of the leading causes of death following traumatic injury is exsanguination. Biological material-based hemostatic agents such as fibrin, thrombin, and albumin have a high risk for causing infection. Synthetic peptide-based hemostatic agents offer an attractive alternative. The objective of this study is to explore the potential of h9e peptide as an effective hemostatic agent in both and models. blood coagulation kinetics in the presence of h9e peptide was determined as a function of gelation time using a dynamic rheometer. hemostatic effects were studied using the Wistar rat model. Results were compared to those of the commercial hemostatic product Celox™, a chitosan-based product. Adhesion of h9e peptide was evaluated using the platelet adhesion test. Biocompatibility of h9e peptide was studied using a mouse model. After h9e peptide solution was mixed with blood, gelation started immediately, increased rapidly with time, and reached more than 100 Pa within 3 s. Blood coagulation strength increased as h9e peptide wt% concentration increased. In the rat model, h9e peptide solution at 5% weight concentration significantly reduced both bleeding time and blood loss, outperforming Celox. Preliminary pathological studies indicate that h9e peptide solution is biocompatible and did not have negative effects when injected subcutaneously in a mouse model. For the first time, h9e peptide was found to have highly efficient hemostatic effects by forming nanoweb-like structures, which act as a preliminary thrombus and a surface to arrest bleeding 82% faster compared to the commercial hemostatic agent Celox. This study demonstrates that h9e peptide is a promising hemostatic biomaterial, not only because of its greater hemostatic effect than commercial product Celox but also because of its excellent biocompatibility based on the mouse model study.
Topics: Animals; Biocompatible Materials; Bleeding Time; Blood Coagulation; Chitosan; Female; Fibrin; Hemorrhage; Hemostasis; Male; Mice; Oligopeptides; Rats; Rats, Wistar; Thrombin
PubMed: 32716728
DOI: 10.1089/wound.2019.1109 -
British Journal of Anaesthesia Sep 1992
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Bleeding Time; Contraindications; Female; Humans; Pregnancy; Research Design
PubMed: 1389859
DOI: 10.1093/bja/69.3.330 -
Clinical and Applied... 2021The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range...
The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal's method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.
Topics: Aged; Anticoagulants; Atrial Fibrillation; Bleeding Time; Blood Coagulation; COVID-19; Dose-Response Relationship, Drug; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Pandemics; Patient Acceptance of Health Care; Pulmonary Embolism; Retrospective Studies; SARS-CoV-2; Self Medication; Thrombophilia; Warfarin
PubMed: 34142564
DOI: 10.1177/10760296211021495 -
Blood May 1992
Meta-Analysis
Topics: Bleeding Time; Humans; Meta-Analysis as Topic
PubMed: 1533324
DOI: No ID Found -
American Family Physician Jul 2005Garlic has long been used medicinally, most recently for its cardiovascular, antineoplastic, and antimicrobial properties. Sulfur compounds, including allicin, appear to... (Review)
Review
Garlic has long been used medicinally, most recently for its cardiovascular, antineoplastic, and antimicrobial properties. Sulfur compounds, including allicin, appear to be the active components in the root bulb of the garlic plant. Studies show significant but modest lipid-lowering effects and antiplatelet activity. Significant blood pressure reduction is not consistently noted. There is some evidence for antineoplastic activity and insufficient evidence for clinical antimicrobial activity. Side effects generally are mild and uncommon. Garlic appears to have no effect on drug metabolism, but patients taking anticoagulants should be cautious. It seems prudent to stop taking high dosages of garlic seven to 10 days before surgery because garlic can prolong bleeding time.
Topics: Animals; Bleeding Time; Clinical Trials as Topic; Drug Evaluation, Preclinical; Evidence-Based Medicine; Food-Drug Interactions; Garlic; Humans; Hyperlipidemias; Hypertension; Infection Control; Neoplasms; Phytotherapy; Research Design
PubMed: 16035690
DOI: No ID Found