Role of Risk Factors in the Modulation of Tissue Factor Activity and Blood Thrombogenicity

Sambola, Antonia; Osende, Julio I.; Hathcock, James; Degen, Michael; Nemerson, Yale; Fuster, Valentı́n; Crandall, Jill P.; Badimón, Juan J.

doi:10.1161/01.cir.0000050621.67499.7d

Cited by 273 publications

(208 citation statements)

References 40 publications

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“…After “validating” our model, we first sought to investigate the impact of e‐cigarettes on thrombogenesis, as it is the major cause of tobacco‐induced CVD,38 including thrombosis‐based diseases 17, 77, 78, 79, 80, 81, 82, 83. Our findings revealed, for the first time, a drastic reduction in the time for carotid artery occlusion, indicating a prothrombotic phenotype, even after only a week of whole‐body exposure to e‐cigarettes.…”

Section: Discussionmentioning

confidence: 99%

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

Qasim

Karim

Silva‐Espinoza

et al. 2018

JAHA

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BackgroundCardiovascular disease is the main cause of death in the United States, with smoking being the primary preventable cause of premature death, and thrombosis being the main mechanism of cardiovascular mortality in smokers. Due to the perception that electronic/e‐cigarettes are “safer/less harmful” than conventional cigarettes, their usage—among a variety of ages—has increased tremendously during the past decade. Notably, there are limited studies regarding the negative effects of e‐cigarettes on the cardiovascular system, which is also the subject of significant debate.Methods and ResultsWe employed a passive e‐VapeTM vapor inhalation system and developed an in vivo whole‐body e‐cigarette mouse exposure protocol that mimics real‐life human exposure scenarios/conditions and investigated the effects of e‐cigarettes and clean air on platelet function and thrombogenesis. Our results show that platelets from e‐cigarette–exposed mice are hyperactive, with enhanced aggregation, dense and α granule secretion, activation of the αIIbβ3 integrin, phosphatidylserine expression, and Akt and ERK activation, when compared with clean air–exposed platelets. E‐cigarette–exposed platelets were also found to be resistant to inhibition by prostacyclin, relative to clean air. Furthermore, the e‐cigarette–exposed mice exhibited a shortened thrombosis occlusion and bleeding times.ConclusionsTaken together, our data demonstrate for the first time that e‐cigarettes alter physiological hemostasis and increase the risk of thrombogenic events. This is attributable, at least in part, to the hyperactive state of platelets. Thus, the negative health consequences of e‐cigarette exposure should not be underestimated and warrant further investigation.

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Section: Discussionmentioning

confidence: 99%

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

Qasim

Karim

Silva‐Espinoza

et al. 2018

JAHA

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“…The hypothesized mechanism for superior response of smokers to thrombolytic therapy is that smoking does not affect atherosclerotic plaque vulnerability as much as it increases hypercoagulability. Smoking has been directly associated with a procoagulant state with effects on endothelial dysfunction, increased platelet activation and aggregation, increased circulating levels of fibrinogen, and increased thrombin generation 36, 37. Components of cigarette smoke have also been shown to impair fibrin crosslinking 38.…”

Section: Discussionmentioning

confidence: 99%

Smoker's Paradox in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Gupta

Kolte

Khera

et al. 2016

JAHA

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BackgroundPrior studies have found that smokers undergoing thrombolytic therapy for ST‐segment elevation myocardial infarction have lower in‐hospital mortality than nonsmokers, a phenomenon called the “smoker's paradox.” Evidence, however, has been conflicting regarding whether this paradoxical association persists in the era of primary percutaneous coronary intervention.Methods and ResultsWe used the 2003–2012 National Inpatient Sample databases to identify all patients aged ≥18 years who underwent primary percutaneous coronary intervention for ST‐segment elevation myocardial infarction. Multivariable logistic regression was used to compare in‐hospital mortality between smokers (current and former) and nonsmokers. Of the 985 174 patients with ST‐segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, 438 954 (44.6%) were smokers. Smokers were younger, were more often men, and were less likely to have traditional vascular risk factors than nonsmokers. Smokers had lower observed in‐hospital mortality compared with nonsmokers (2.0% versus 5.9%; unadjusted odds ratio 0.32, 95% CI 0.31–0.33, P<0.001). Although the association between smoking and lower in‐hospital mortality was partly attenuated after baseline risk adjustment, a significant residual association remained (adjusted odds ratio 0.60, 95% CI 0.58–0.62, P<0.001). This association largely persisted in age‐stratified analyses. Smoking status was also associated with shorter average length of stay (3.5 versus 4.5 days, P<0.001) and lower incidence of postprocedure hemorrhage (4.2% versus 6.1%; adjusted odds ratio 0.81, 95% CI 0.80–0.83, P<0.001) and in‐hospital cardiac arrest (1.3% versus 2.1%; adjusted OR 0.78, 95% CI 0.76–0.81, P<0.001).ConclusionsIn this nationwide cohort of patients undergoing primary percutaneous coronary intervention for ST‐segment elevation myocardial infarction, we observed significantly lower risk‐adjusted in‐hospital mortality in smokers, suggesting that the smoker's paradox also applies to ST‐segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

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“…The earlier concept that blood coagulation is initiated after vascular damage when blood is exposed to "extrinsic" tissue factor has been broadened by the observations that tissue factor is also present in circulating blood (13,14,16,17) and that hematopoietic cell-associated tissue factor is important in thrombogenesis (18). For instance, circulating tissue factor has been associated with increased blood thrombogenicity in patients with cardiovascular disease (30), sickle cell disease (17), antiphospholipid antibody syndrome (31), hyperlipidemia (20), and disseminated intravascular coagulation (32). In addition, we (19) and others (20) have reported that patients with type 2 diabetes have increased blood levels of tissue factor PCA.…”

Section: Discussionmentioning

confidence: 99%

“…Tissue factor, which is present in the adventitia of normal blood vessels and is highly expressed in atherosclerotic plaques, has been recognized to initiate coagulation and thrombus formation when the vessel wall is injured or plaques are fissured (15). More recently, it has been shown that there is, in addition, a circulating pool of tissue factor in blood that is associated with cells and microparticles, is thrombogenic (13,14,16 -18), and is elevated in type 2 diabetes (19,20). Because premature ASVD risk depends partially on glycemic control (21,22), we hypothesized that hyperglycemia and/or hyperinsulinemia contribute to the rise in circulating tissue factor and to the prothrombotic state in these patients.…”

mentioning

confidence: 99%

Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand

et al. 2006

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Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor. Diabetes 55: [202][203][204][205][206][207][208] 2006

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Role of Risk Factors in the Modulation of Tissue Factor Activity and Blood Thrombogenicity

Cited by 273 publications

References 40 publications

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

Smoker's Paradox in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Effects of Hyperglycemia and Hyperinsulinemia on Circulating Tissue Factor Procoagulant Activity and Platelet CD40 Ligand

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