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Current Opinion in Hematology Jan 2024Models of arterial thrombus formation represent a vital experimental tool to investigate platelet function and test novel antithrombotic drugs. This review highlights... (Review)
Review
PURPOSE OF REVIEW
Models of arterial thrombus formation represent a vital experimental tool to investigate platelet function and test novel antithrombotic drugs. This review highlights some of the recent advances in modelling thrombus formation in vitro and suggests potential future directions.
RECENT FINDINGS
Microfluidic devices and the availability of commercial chips in addition to enhanced accessibility of 3D printing has facilitated a rapid surge in the development of novel in-vitro thrombosis models. These include progression towards more sophisticated, 'vessel on a chip' models which incorporate vascular endothelial cells and smooth muscle cells. Other approaches include the addition of branches to the traditional single channel to yield an occlusive model; and developments in the adhesive coating of microfluidic chambers to better mimic the thrombogenic surface exposed following plaque rupture. Future developments in the drive to create more biologically relevant chambers could see a move towards the use of human placental vessels, perfused ex-vivo. However, further work is required to determine the feasibility and validity of this approach.
SUMMARY
Recent advances in thrombus formation models have significantly improved the pathophysiological relevance of in-vitro flow chambers to better reflect the in-vivo environment and provide a more translational platform to test novel antithrombotics.
Topics: Female; Pregnancy; Humans; Endothelial Cells; Placenta; Thrombosis; Arteries; Hemostasis
PubMed: 37823547
DOI: 10.1097/MOH.0000000000000789 -
Platelets May 2020A confluence of technological advances in genetic manipulation and molecular-based fluorescence imaging has led to the widespread adoption of laser injury models to... (Review)
Review
A confluence of technological advances in genetic manipulation and molecular-based fluorescence imaging has led to the widespread adoption of laser injury models to study hemostasis and thrombosis in mice. In all animal models of hemostasis and thrombosis, detailing the nature of experimentally induced vascular injury is paramount in enabling appropriate interpretation of experimental results. A careful appraisal of the literature shows that direct laser-induced injury can result in variable degrees of vascular damage. This review will compare and contrast models of laser injury utilized in the field, with an emphasis on the mechanism and extent of injury, the use of laser injury in different vascular beds and the molecular mechanisms regulating the response to injury. All of these topics will be discussed in the context of how distinct applications of laser injury models may be viewed as representing thrombosis and/or hemostasis.
Topics: Animals; Disease Models, Animal; Endothelial Cells; Femoral Artery; Hemostasis; Humans; Intravital Microscopy; Laser Therapy; Mice; Platelet Activation; Saphenous Vein; Thrombosis; Thromboxane A2; Vascular System Injuries
PubMed: 32297542
DOI: 10.1080/09537104.2020.1748589 -
Journal of Vascular Surgery. Venous and... Jul 2021In the present study, we sought to better characterize the patients with coronavirus disease 2019 (COVID-19) most at risk of severe, outpatient thrombosis by defining... (Observational Study)
Observational Study
OBJECTIVE
In the present study, we sought to better characterize the patients with coronavirus disease 2019 (COVID-19) most at risk of severe, outpatient thrombosis by defining the patients hospitalized with COVID-19 with arterial or venous thrombosis diagnosed at admission.
METHODS
We conducted a single-center, retrospective analysis of COVID-19 patients. We found a shift in the proportions of thrombosis subtypes from 2019 to 2020, with declines in ST-segment myocardial infarction (from 22.0% to 10.1% of thrombotic events) and stroke (from 48.6% to 37.2%) and an increase in venous thromboembolism (from 29.4% to 52.7%). The patients with COVID-19-associated thrombosis were younger (age, 58 years vs 64 years; P = .043) and were less frequently women (31.3% vs 43.9%; P = .16). However, no differences were found in the body mass index or major comorbidities between those with and without COVID-19. COVID-19-associated thrombosis correlated with greater mortality (15.2% vs 4.3%; P = .016). The biometric profile of patients admitted with COVID-19-associated thrombosis compared with regular thrombosis showed significant changes in the complete blood count, liver function test results, D-dimer levels, C-reactive protein, ferritin, and coagulation panels.
CONCLUSIONS
Outpatients with COVID-19 who developed thrombosis requiring hospitalization had increased mortality compared with outpatients without COVID-19 who developed thrombosis requiring hospitalization. Given the significantly higher inflammatory marker levels, it is possible this is related to different mechanisms of thrombotic disease in these patients. The inflammation could be a therapeutic target to reduce the risk, or aid in the treatment, of thrombosis. We call for more studies elucidating the role that immunothrombosis might be playing in patients with COVID-19.
Topics: Aged; Arteries; Biomarkers; COVID-19; Case-Control Studies; Female; Hospitalization; Humans; Male; Middle Aged; Prognosis; Retrospective Studies; SARS-CoV-2; ST Elevation Myocardial Infarction; Stroke; Thrombosis; Venous Thromboembolism
PubMed: 33186750
DOI: 10.1016/j.jvsv.2020.11.004 -
International Journal of Cardiology Jan 2021COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous...
INTRODUCTION
COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated.
OBJECTIVES
To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event.
MATERIAL AND METHODS
We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis.
RESULTS
From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy.
CONCLUSION
Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.
Topics: Aged; Anticoagulants; Aorta; COVID-19; Coronary Occlusion; Extremities; Female; France; Humans; Ischemia; Italy; Male; Mesenteric Ischemia; Middle Aged; Platelet Aggregation Inhibitors; Retrospective Studies; SARS-CoV-2; Splenic Infarction; Stroke; Thrombosis
PubMed: 32918938
DOI: 10.1016/j.ijcard.2020.08.103 -
PloS One 2021The present meta-analysis aimed to investigate the differences in the incidence of thrombosis and vascular compromise in arterial anastomosis between microvascular... (Meta-Analysis)
Meta-Analysis
The present meta-analysis aimed to investigate the differences in the incidence of thrombosis and vascular compromise in arterial anastomosis between microvascular anastomotic devices and hand-sewn techniques during free tissue transfer in the head and neck. We searched for articles in PubMed/Medline, CNKI, WANFANG DATA, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science, from January 1, 1962 till April 1, 2020 that reported data of microvascular anastomosis during free tissue transfer in the head and neck. The incidence of arterial thrombosis or vascular compromise, or both was the primary outcome. The secondary outcome was anastomotic time. We also assessed the sensitivity and the risk of bias. This meta-analysis included 583 arterial anastomoses from six studies. The group using microvascular anastomotic devices tended to have an increased incidence of arterial thrombosis and vascular compromise (risk ratio (RR), 3.42; P = 0.38; 95% confidence interval (CI), 0.91-12.77). The hand-sewn technique took significantly longer to perform the anastomosis compared with that of the microvascular anastomotic devices (weighted mean difference, 15.26 min; P<0.01; 95% CI, 14.65-15.87). Microvascular anastomotic devices might increase the risk of arterial thrombosis and vascular compromise compared with the hand-sewn technique; however, further randomized controlled trials are needed to provide a more accurate estimate. The application of microvascular anastomotic devices will help to reduce anastomotic surgery time and achieve acceptable vessel opening, benefiting from the developments of arterial couplers and microsurgical techniques.
Topics: Anastomosis, Surgical; Arteries; Databases, Factual; Free Tissue Flaps; Head; Humans; Neck; Risk; Thrombosis; Vascular Diseases
PubMed: 33793654
DOI: 10.1371/journal.pone.0249418 -
Journal of the American Heart... Nov 2022Advances in stent technology and the design of endovascular devices with thinner struts, anti-inflammatory and antithrombotic polymers, and better drug kinetics have... (Review)
Review
Advances in stent technology and the design of endovascular devices with thinner struts, anti-inflammatory and antithrombotic polymers, and better drug kinetics have enhanced the safety and efficacy of the second-generation drug-eluting stents and broadened their use in the therapy of high-risk patients and complex anatomies. However, despite these developments, in-stent restenosis and stent thrombosis remain the Achilles' heel of percutaneous coronary intervention, with their cumulative incidence reaching up to 10% at 5 years following percutaneous coronary intervention. The treatment of stent failure poses challenges and is associated with a worse prognosis than conventional percutaneous coronary intervention. Several studies have recently highlighted the value of intravascular imaging in identifying causes of stent failure, underscored its role in treatment planning, and registries have shown that its use may be associated with better clinical outcomes. The present review aims to summarize the evidence in the field; it discusses the value of intravascular imaging in identifying the mechanisms of in-stent restenosis and stent thrombosis in assessing the morphological characteristics of neointima tissue that appears to determine long-term outcomes in evaluating procedural results, and presents the findings of studies supporting its value in guiding therapy in stent failure.
Topics: Humans; Coronary Restenosis; Coronary Vessels; Prosthesis Design; Percutaneous Coronary Intervention; Stents; Thrombosis; Tomography, Optical Coherence; Treatment Outcome
PubMed: 36326067
DOI: 10.1161/JAHA.122.026492 -
Antiphospholipid syndrome and the risk of myocardial infarction: current evidence and uncertainties.Kardiologia Polska Jan 2020Antiphospholipid syndrome (APS) encompasses a wide spectrum of disease manifestations that may prevail in the form of venous or arterial thrombosis or lead to pregnancy... (Review)
Review
Antiphospholipid syndrome (APS) encompasses a wide spectrum of disease manifestations that may prevail in the form of venous or arterial thrombosis or lead to pregnancy complications in the presence of persisting antiphospholipid antibodies (aPL). Unlike in the case of congenital thrombophilias, in which venous thromboses are more likely to occur as compared with arterial events, aPL may cause thrombosis in both types of vascular systems. Arterial thrombosis in APS is fairly common and often involve coronary or cerebral arteries leading to myocardial infarction (MI) or stroke. In this review, we summarize the complex pathomechanisms leading to aPL‑associated thrombosis and list challenges during the laboratory detection of these antibodies. Specific features of MI in patients with APS are summarized based on a comprehensive literature search of available case reports. Preventive and treatment strategies are discussed based on the current recommendations and most recent evidence. We conclude that the risk of MI in patients with APS is considerable and MI may be the first manifestation of the disease. MI in APS shows specific clinical features including relatively young age at presentation, no sex dominance, often normal coronaries without the sign of atherosclerosis, high risk of recurrent thrombotic events. Treatment of acute MI in patients with APS is often challenging and adverse events, including stent thrombosis, are more frequent as compared with patients without APS. Preventive strategies in APS should be personalized and include strict management of additional cardiovascular risk factors and long‑term anticoagulation with vitamin K antagonists. Current evidence does not support the use of direct oral anticoagulants in the management of patients with APS with arterial thrombosis due to the high risk of recurrent events.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Female; Humans; Myocardial Infarction; Pregnancy; Thrombosis
PubMed: 31808421
DOI: 10.33963/KP.15090 -
Clinical Medicine (London, England) Mar 2022Vaccine-induced thrombosis with thrombocytopenia (VITT) is a recently-described condition associated with arterial and venous thrombosis following vaccination with the...
Vaccine-induced thrombosis with thrombocytopenia (VITT) is a recently-described condition associated with arterial and venous thrombosis following vaccination with the ChAdOx1 nCoV-19 (AstraZeneca) vaccine. This report describes two cases of stroke caused by arterial and venous thromboses presenting within 28 days of receiving the AstraZeneca vaccine. The patients were otherwise young and healthy with minimal risk factors for thrombosis yet developed a rapid, ultimately fatal neurological deterioration.The patients were significantly thrombocytopenic with disproportionately raised D-dimers, both of which are widely reported in this condition. Both cases had measurable immunoglobulin G platelet factor-4 antibodies detected via enzyme-linked immunosorbent assay, similar to those described in heparin-induced thrombocytopenia.These cases illustrate that physicians should be especially mindful of VITT in the context of evolving evidence on treatment and in view of the potentially rapid and catastrophic neurological deterioration, leading to fatality despite best supportive care.
Topics: ChAdOx1 nCoV-19; Heparin; Humans; Stroke; Thrombosis; Thrombotic Stroke
PubMed: 35304381
DOI: 10.7861/clinmed.2021-0321 -
Scientific Reports Mar 2020Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the...
Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets. The composition of pulmonary emboli mirrored the most distal part of venous thrombi from which they originated, which differed from the structure of the body and head of the same thrombi. All thrombi and emboli contained few biconcave red blood cells but many polyhedrocytes or related forms of compressed red blood cells, demonstrating that these structures are a signature of clot contraction in vivo. Polyhedrocytes and intermediate forms comprised the major constituents of venous thrombi and pulmonary emboli. The structures within all of the thrombi and emboli were very tightly packed, in contrast to clots formed in vitro. There are distinctive, reproducible differences among arterial and venous thrombi and emboli related to their origin, destination and duration, which may have clinical implications for the understanding and treatment of thrombotic disorders.
Topics: Arteries; Blood Coagulation; Blood Platelets; Erythrocytes; Fibrin; Humans; Microscopy, Electron, Scanning; Pulmonary Embolism; Thromboembolism; Veins; Venous Thrombosis
PubMed: 32198356
DOI: 10.1038/s41598-020-59526-x -
Experimental and Clinical... Jun 2023Vascular complications after liver transplant can be lethal. High levels of suspicion and aggressive use of diagnostic tools may help with early diagnosis and treatment....
OBJECTIVES
Vascular complications after liver transplant can be lethal. High levels of suspicion and aggressive use of diagnostic tools may help with early diagnosis and treatment. Here, we share our experiences regarding this topic.
MATERIALS AND METHODS
Adult and pediatric patients who had liver transplant between February 1997 and June 2018 in our clinic were included in the study. Patients were grouped according to age (pediatric patients were those under 18 years old), male versus female, indication for transplant, type of liver transplant, type of vascular complication, treatment, and survival aftertreatment.We analyzed the statistical incidence of vascular complications according to age, male versus female, and type of liver transplant.
RESULTS
Our analyses included 607 liver transplant procedures, including 7 retransplants, with 349 (57.4%) from living donors and 258 (42.6%) from deceased donors. Of total patients, 539 were adults (89.8%) and 61 were children (10.2%). Vascular complications occurred in 25 patients (4.1%), with hepatic artery complications seen in 13 patients (2.1%) (10 adults [1.8%] and 3 children [4.9%]), portal vein complications seen in 9 patients (1.5%) (6 adults [1.1%] and 3 children [4.9%]), and hepatic vein complications seen in 3 patients (0.5%) (2 adults [0.36%] and 1 child [1.6%]). Rate of vascular complications was statistically higher in pediatric patients (11.4% vs 3.3%; P = .007) and higher but not statistically in recipients of livers from living donors (5.2% vs 2.7%; P = .19). Twelve patients (48.8%) were treated with endovascular approach, and 11 (0.44%)required surgicaltreatment. Two patients underwent immediate retransplant due to hepatic artery thrombosis.
CONCLUSIONS
Because vascular complications are the most severe complications afterlivertransplant,there must be close follow-up of vascular anastomoses, particularly early postoperatively, with radiologic methods. In cases of vascular complications, emergent treatment, including endovascular interventions, surgery, and retransplant, must be performed.
Topics: Adult; Child; Humans; Male; Female; Adolescent; Liver Transplantation; Thrombosis; Living Donors; Hepatic Artery; Portal Vein; Treatment Outcome; Retrospective Studies; Postoperative Complications
PubMed: 30880648
DOI: 10.6002/ect.2018.0240