scholarly journals Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation

Heart ◽  
2018 ◽  
Vol 105 (3) ◽  
pp. 235-242 ◽  
Author(s):  
Christina Christersson ◽  
Lars Wallentin ◽  
Ulrika Andersson ◽  
John H Alexander ◽  
Marco Alings ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Bleeding Risk ◽  
Cd40 Ligand ◽  
Clinical Results ◽  
Soluble Cd40 Ligand ◽  
Registration Number ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

ObjectivesCompare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).MethodsThe biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.ResultsIn patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.ConclusionsTreatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.Trial registration numberNCT00412984.

scholarly journals Intracardiac Hemostasis and Fibrinolysis Parameters in Patients with Atrial Fibrillation

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Noémi Klára Tóth ◽  
Zoltán Csanádi ◽  
Orsolya Hajas ◽  
Alexandra Kiss ◽  
Edina Nagy-Baló ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Femoral Vein ◽  
Endothelial Damage ◽  
Control Group ◽  
Thrombotic Risk ◽  
Von Willebrand ◽  
And Control ◽  
Willebrand Factor ◽  
Pai 1 ◽  
D Dimer

Aims. To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism.Patients and Methods. Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen,α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples.Results. Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure.Conclusions. None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level.

scholarly journals Plasma von Willebrand factor, soluble thrombomodulin, and fibrin D-dimer levels in acute-onset nonrheumatic atrial fibrillation

2003 ◽  
Vol 41 (6) ◽  
pp. 130
Author(s):  
Francisco Marin ◽  
Vanessa Roldán ◽  
Vicente Climent ◽  
Alicia Ibáñez ◽  
Amaya García ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Von Willebrand Factor ◽  
Acute Onset ◽  
Soluble Thrombomodulin ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

scholarly journals Uninterrupted Dabigatran Administration Provides Greater Inhibition against Intracardiac Activation of Hemostasis as Compared to Vitamin K Antagonists during Cryoballoon Catheter Ablation of Atrial Fibrillation

2020 ◽  
Vol 9 (9) ◽  
pp. 3050
Author(s):  
Zsuzsa Bagoly ◽  
Orsolya Hajas ◽  
Réka Urbancsek ◽  
Alexandra Kiss ◽  
Edit Fiak ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Endothelial Damage ◽  
Cryoballoon Ablation ◽  
Fviii Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
D Dimer

Background. Cerebral thromboembolism is a rare but feared complication of transcatheter ablation in patients with atrial fibrillation (AF). Here, we aimed to test which pre-procedural anticoagulation strategy results in less intracardiac activation of hemostasis during ablation. Patients and methods. In this observational study, 54 paroxysmal/persistent AF patients undergoing cryoballoon ablation were grouped according to their periprocedural anticoagulation strategy: no anticoagulation (oral anticoagulation (OAC) free; n = 24), uninterrupted vitamin K antagonists (VKA) (n = 11), uninterrupted dabigatran (n = 17). Blood was drawn from the left atrium before and immediately after the ablation procedure. Cryoablations were performed according to standard protocols, during which heparin was administered. Heparin-insensitive markers of hemostasis and endothelial damage were tested from intracardiac samples: D-dimer, quantitative fibrin monomer (FM), plasmin-antiplasmin complex (PAP), von Willebrand factor (VWF) antigen, chromogenic factor VIII (FVIII) activity. Results. D-dimer increased significantly in all groups post-ablation, with lowest levels in the dabigatran group (median [interquartile range]: 0.27 [0.36] vs. 1.09 [1.30] and 0.74 [0.26] mg/L in OAC free and uninterrupted VKA groups, respectively, p < 0.001). PAP levels were parallel to this observation. Post-ablation FM levels were elevated in OAC free (26.34 [30.04] mg/L) and VKA groups (10.12 [16.01] mg/L), but remained below cut-off in all patients on dabigatran (3.98 [2.0] mg/L; p < 0.001). VWF antigen and FVIII activity increased similarly post-ablation in all groups, suggesting comparable procedure-related endothelial damage. Conclusion. Dabigatran provides greater inhibition against intracardiac activation of hemostasis as compared to VKAs during cryoballoon catheter ablation.

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

Levels of von Willebrand factor and ADAMTS13 determine clinical outcome after cardioversion for atrial fibrillation

2011 ◽  
Vol 105 (03) ◽  
pp. 435-443 ◽  
Author(s):  
Veronika Bruno ◽  
Rudolf Jarai ◽  
Susanne Gruber ◽  
Thomas Höchtl ◽  
Ivan Brozovic ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Independent Predictor ◽  
Thrombus Formation ◽  
Critical Role ◽  
Inverse Correlation ◽  
Von Willebrand ◽  
Rhythm Stability ◽  
Willebrand Factor

SummaryVon Willebrand factor (vWF) plays an essential role in platelet adhesion and thrombus formation. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 antigen levels compared to controls. Little is known about vWF and ADAMTS13 in AF patients treated with cardioversion (CV). Thus we investigated the alterations of plasma vWF and ADAMTS13 after CV and evaluated the predictive value of these parameters for recurrence of AF. In this observational study we determined plasma levels of vWF and ADAMTS13 in 77 patients before and immediately after CV, as well as 24 hours (h) and six weeks thereafter, by means of commercially available assays. The vWF/ ADAMTS13-ratio was significantly elevated immediately after CV (p=0.02) and 24 h after CV (p=0.002) as compared to baseline levels. ADAMTS13, 24 h after CV, exhibited a significant association with recurrence of AF (HR: 0.97; p=0.037). Accordingly, tertiles of ADAMTS13 showed a stepwise inverse correlation with the risk of recurrent AF (HR: 0.50; p=0.009). After adjustment for confounders, ADAMTS13 remained significant as an independent predictor of recurrent AF (HR: 0.61; p=0.047). Similarly, the vWF/ADAMTS13-ratio, 24 h after CV, was associated with rhythm stability and remained an independent predictor of recurrent AF (HR: 1.88; p=0.028). The regulation of vWF and its cleaving protease ADAMTS13 after CV might play a critical role in producing a pro-thrombotic milieu immediately after CV for AF. Since ADAMTS13 plasma concentration and the vWF/ADAMTS13-ratio are independently associated with rhythm stability, these indexes might be used for prediction of recurrence of AF.

Soluble CD40 Ligand, Platelet Surface CD40 Ligand, and Total Platelet CD40 Ligand in Atrial Fibrillation

CHEST Journal ◽  
2008 ◽  
Vol 134 (3) ◽  
pp. 574-581 ◽  
Author(s):  
Anirban Choudhury ◽  
Irene Chung ◽  
Nimai Panja ◽  
Jeetesh Patel ◽  
Gregory Y.H. Lip
Keyword(s):  
Atrial Fibrillation ◽  
Cd40 Ligand ◽  
Soluble Cd40 Ligand ◽  
Platelet Surface

scholarly journals Stroke Prevention in Atrial Fibrillation: Where are We Now?

2012 ◽  
Vol 6 ◽  
pp. CMC.S8976 ◽  
Author(s):  
Yousif Ahmad ◽  
Gregory Y.H. Lip
Keyword(s):  
Atrial Fibrillation ◽  
Stroke Prevention ◽  
Management Strategies ◽  
Bleeding Risk ◽  
Long Term Study ◽  
Risk Patients ◽  
First Time ◽  
Major Progress ◽  
Made In

Atrial fibrillation is the commonest arrhythmia worldwide and is a growing problem. AF is responsible for 25% of all strokes, and these patients suffer greater mortality and disability. Warfarin has traditionally been the only successful therapy for stroke prevention, but its limitations have resulted in underutilisation. Major progress has been made in AF research, leading to improved management strategies. Better risk stratification permits identification of truly low-risk patients who do not require anticoagulation and we are able to simplify ourevaluation of a patient's bleeding risk. The advent of novel anticoagulants means warfarin is no longer the only choice for stroke prophylaxis. These drugs circumvent many of warfarin's inconveniences, but only long-term study and use will conclusively demonstrate how they compare to warfarin. The landscape of stroke prevention in AF has changed with effective alternatives to warfarin available for the first time in 60 years—but each new option brings new considerations.

scholarly journals The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katarina D. Kovacevic ◽  
Stefan Greisenegger ◽  
Agnes Langer ◽  
Georg Gelbenegger ◽  
Nina Buchtele ◽  
...  
Keyword(s):  
Platelet Function ◽  
Von Willebrand Factor ◽  
Stroke Prevention ◽  
Adenosine Diphosphate ◽  
Target Range ◽  
Large Artery ◽  
Dependent Manner ◽  
Secondary Stroke Prevention ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.

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