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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 -
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 -
European Review For Medical and... May 2018Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a...
OBJECTIVE
Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats.
MATERIALS AND METHODS
Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed.
RESULTS
Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group.
CONCLUSIONS
This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.
Topics: Adenosine Diphosphate; Animals; Arachidonic Acid; Bleeding Time; Hemostasis; Humans; Male; Partial Thromboplastin Time; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Progranulins; Prothrombin Time; Rats
PubMed: 29863272
DOI: 10.26355/eurrev_201805_15087 -
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 -
Renal Failure Nov 2020The risk of bleeding has led to screening of the primary hemostasis before renal biopsy. A bleeding time test (BT) is considered standard practice, but reliance on this... (Comparative Study)
Comparative Study
The risk of bleeding has led to screening of the primary hemostasis before renal biopsy. A bleeding time test (BT) is considered standard practice, but reliance on this test is controversial and its benefits remain questionable. A possible alternative is thromboelastography (TEG). However, data regarding TEG in patients with renal dysfunction is limited. To determine TEG abnormalities and their consequences in patients who underwent a native kidney biopsy. A retrospective study of 417 consecutive percutaneous native renal biopsies performed in our Center. If serum creatinine >1.5 mg/dL, the patient underwent either a BT test (period A, January 2015-31 December 2016) or TEG (period B, January 2017-August 2018). In patients with prolonged BT, or an abnormal low maximal amplitude (MA) parameter of TEG, or suspected clinical uremic thrombopathy, the use of desmopressin acetate (DDAVP) was considered. Most biopsies (90.6%) were done by the same dedicated radiologist. Fifty-one patients had a BT test, which was normal in all tested patients. Seventy-one patients underwent TEG, and it was abnormal in 34 of them, most patients had combined abnormalities. The only parameter related to abnormal TEG was older age (Odds Ratio 1.21 [95% CI 1.09-2.38] = 0.04 for abnormal Kinetics; OR 1.37 (1.05-1.96) = 0.037 for abnormal MA). Twenty-six patients (6.23%) had bleeding complications. Risk of bleeding was significantly related to age (1.4 [1.11-7.48] = 0.04), systolic blood pressure (1.85 [1.258-9.65] = 0.02), and serum creatinine (1.21 [1.06-3.134] = 0.048). TEG abnormalities in patients with renal dysfunction are variable and fail to predict bleeding during kidney biopsy. The decision to administer DDAVP as a preventive measure during these procedures should be based on clinical judgment only.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Bleeding Time; Clinical Decision-Making; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Kidney; Kidney Diseases; Male; Middle Aged; Point-of-Care Testing; Postoperative Hemorrhage; Retrospective Studies; Risk Assessment; Thrombelastography; Ultrasonography, Interventional; Young Adult
PubMed: 31842662
DOI: 10.1080/0886022X.2019.1700805 -
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