Detection of a Hypercoagulable State in Nonvalvular Atrial Fibrillation and the Effect of Anticoagulant Therapy

Mitüsch, Rolf; Siemens, Hans-Joachim; Garbe, M. Connor; Wagner, Thomas; Sheikhzadeh, Abdolhamid; Diederich, K. W.

doi:10.1055/s-0038-1650247

Cited by 102 publications

(58 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Marin, et al 15) reported increased PAI-I, but normal tPA levels, in MS with SR and concluded there was defective fibrinolytic activity. Mitusch, et al 16) reported stimulation of fibrinolysis in patients with AF revealed by elevated plasma tPA levels, but they found no difference in PAI-I. In our study, left atrial tPA and plasmin levels were elevated in patients with AF, reflecting increased fibrinolytic activity, but only tPA was elevated in peripheral blood.…”

Section: Discussioncontrasting

confidence: 62%

Regional Left Atrial Coagulation and Fibrinolytic Activities in Patients With Mitral Stenosis

et al. 2004

View full text Add to dashboard Cite

SUMMARYSystemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved.Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty.Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05).The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation. (Jpn Heart J 2004; 45: 779-788)

show abstract

Section: Discussioncontrasting

confidence: 62%

Regional Left Atrial Coagulation and Fibrinolytic Activities in Patients With Mitral Stenosis

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Fibrinogen, PAI-1 concentration, and thrombin-antithrombin III complex levels are elevated in patients with AF compared with matched controls. 2,6,25,26 It is interesting to note that these abnormalities do not develop immediately after the onset of AF. Evidence of activation of fibrinocoagulation is first detectable 12 hours after onset of the arrhythmia and increases progressively with the duration of the episode.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation

et al. 2002

View full text Add to dashboard Cite

Background— In the arterial endothelium, laminar flow and cyclical stretch induce expression of NO synthase (NOS). We hypothesized that atrial fibrillation (AF) causes a downregulation of atrial endocardial NOS expression and NO · production. Because NO · has antithrombotic properties, this may contribute to thromboembolism in AF. Methods and Results— In pigs, AF was produced with rapid atrial pacing at 600 bpm for 1 week, whereas controls had atrial pacing at 100 bpm. All animals had catheter ablation of the AV junction and ventricular pacing at 100 bpm. NO · production from freshly isolated tissue was measured by a NO · -specific microelectrode. Left atrial basal and stimulated NO · production was decreased in AF by 73% and 71% ( P <0.01). Endocardial NOS expression, determined by Western analysis, was also significantly decreased by 46%. Expression of the prothombotic protein plasminogen activator inhibitor 1 (PAI-1) is known to be regulated by NO · and was increased in the left atrium by 1.8-fold in AF ( P <0.05). NO · concentration was decreased in the left atrial appendage, although NOS expression was not affected. Neither NOS concentration, NO · levels, nor PAI-1 expression were altered in the aortas or right atria of animals with AF. Conclusions— AF is associated with a marked decrease in endocardial NOS expression and NO · bioavailability and an increase in PAI-1 expression in the left atrium. These data suggest that organized atrial contraction is needed to maintain normal endocardial expression of NOS. It is likely that loss of this antithrombotic enzyme contributes to the thromboembolic phenomena commonly observed in AF.

show abstract

“…Similar observations of the marked reduction in hemostatic markers with conventional anticoagulation have been reported in previous studies. 29,30 The introduction of conventional adjusted-dose warfarin (achieving an INR 2.0-3.0) seems to normalize abnormal levels of thrombogenic markers. 21,29 Plasma levels of vWF antigen are somewhat reduced by OAC treatment.…”

Section: Discussionmentioning

confidence: 99%

Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

López-Castaneda

Valencia-Hernández

Arean

et al. 2017

Clin Appl Thromb Hemost

View full text Add to dashboard Cite

von Willebrand factor (vWF) is a multimeric glycoprotein present in blood plasma. It is synthesized in megakaryocytes and endothelial cells, secreted into circulation in the form of high-molecular-weight multimers (HMWMs), and cleaved into shorter, less active multimers by ADAMTS13. It is essential for platelet adhesion and aggregation. Previous studies have investigated the relationship between vWF levels and thromboembolic events with little regard to vWF multimeric structure. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 levels. One hundred seven patients with AF, 51 anticoagulated and 56 nonanticoagulated, were eligible for the study. Plasma samples were analyzed for vWF antigen, vWF activity, and ADAMTS13; vWF multimers were analyzed by Western blot in 1% to 1.3% sodium dodecyl sulfate agarose gel electrophoresis. Patients with AF without oral anticoagulation (OAC) had significantly higher vWF plasma levels (154.00 [75-201] UI/dL) and vWF activity (60.00% [20%-210%]) compared to patients with ] UI/dL, P ¼ <.001; 50.00% [20%-160%], P ¼ .02). Both were specially decreased in patients treated with acenocumarin. Patients without OAC also showed lower ADAMTS13 levels and presence of vWF HMWMs. Patients with AF show higher plasma levels and vWF activity. Moreover, treatment with traditional OAC (acenocumarin) significantly reduced vWF levels. Patients without OAC might have an increased risk of thrombotic events showing lower ADAMTS13 and higher vWF levels. Patients with stroke had higher plasma levels, vWF activity, and HMWMs. Our study suggests that increased vWF levels and presence of HMWMs could be related to cerebrovascular disease and may represent useful biomarkers for stroke in AF.

show abstract

Detection of a Hypercoagulable State in Nonvalvular Atrial Fibrillation and the Effect of Anticoagulant Therapy

Cited by 102 publications

References 21 publications

Regional Left Atrial Coagulation and Fibrinolytic Activities in Patients With Mitral Stenosis

Regional Left Atrial Coagulation and Fibrinolytic Activities in Patients With Mitral Stenosis

Downregulation of Endocardial Nitric Oxide Synthase Expression and Nitric Oxide Production in Atrial Fibrillation

Von Willebrand Factor: Multimeric Structure and Functional Activity in Patients With Atrial Fibrillation With and Without Oral Anticoagulation

Contact Info

Product

Resources

About