Paroxysmal atrial fibrillation is associated with early coagulation activity regardless of risk factors for embolism.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is associated with an increased incidence of embolic events, even in patients with no embologenic risk factors. This fact raises the question for the hypercoagulability in PAF as a state closely related to the arrhythmia itself, independent of other well established embologenic risk factors. The scarce data on that topic predisposed our aim that was to study coagulation activity in the early hours (up to the twenty-fourth hour) of the disease. METHODS: Fifty-one non-anticoagulated patients (26 men, 25 women; mean age 59.84±1.60 years) and 52 controls (26 men, 26 women; mean age 59.50±1.46 years) were consequently selected for the study. Plasma coagulation activity of factor II (FII), factor V (FV) and factor X (FX) was examined. RESULTS: In the PAF group, there was a higher activity of FII (167.81±9.12% vs. 100.43±5.77%, P<0.001), FV (198.47±10.88% vs. 121.53±4.79%, P<0.001) and FX (193.20±11.85 vs. 116.20±5.86, P<0.001). The deviations were independent of age, sex, body mass index, presence of hypertension and CHA2DS2-VASc risk score (P>0.05). PAF duration was a significant predictor of FII activity (r=0.83, P<0.001) but no correlation was established between FV and FX activity and the arrhythmia duration (r=0.10, P>0.05; r=0.11, P>0.05, respectively). CONCLUSIONS: We established high coagulation activity during the first twenty-four hours of PAF. The observed deviations in the studied parameters give us reason to consider PAF a procoagulant state independent of the well-established prothrombotic risk factors, even in its early clinical manifestation.

Paroxysmal atrial fibrillation: changes in factor VIII and von Willebrand factor impose early hypercoagulability.

INTRODUCTION: Paroxysmal atrial fibrillation (PAF) is a well-documented prothrombotic state that carries significant embolic risk. However, precise hemostatic changes in the very early stage of the disease are not completely studied. The aim of the study was to study von Willebrand factor (vWF) and coagulation factor VIII (FVIII) plasma levels and activity in the first hours (up to 24 h) of PAF clinical manifestation. MATERIAL AND METHODS: We selected consecutively 51 non-anticoagulated patients (26 men, 25 women, mean age: 59.84 ±1.60) with PAF and 52 controls (26 men, 26 women, mean age: 59.50 ±1.46 years) corresponding in gender, accompanying diseases and conducted treatment. The indicators were examined using enzyme-linked immunoassays and photometric tests. RESULTS: All patients were hospitalized between the 2nd and 24th h after the onset of arrhythmia (mean: 8.14 ±0.74 h). Higher FVIII levels (107.52 ±3.48% vs. 93.85 ±2.93%, p < 0.05) and activity (200.03 ±11.11% vs. 109.73 ±4.90%, p < 0.001) were found in the PAF group. vWF levels (178.40 ±12.95% vs. 119.53 ±6.12%, p < 0.001) and activity (200.92 ±12.45% vs. 110.80 ±5.14%, p < 0.001) were also higher. These changes did not depend on age, sex, body mass index or CHA2DS2-VASc score in the PAF group (p > 0.05). PAF duration was a significant predictor of increased FVIII levels and activity. Increased PAF duration was followed by increased values of the factors (r = 0.85, p < 0.001; r = 0.83, p < 0.001). CONCLUSIONS: The results presented an activated coagulation cascade and endothelial injury, suggesting hypercoagulability still in the early hours of PAF. These changes in PAF did not correlate with CHA2DS2-VASc score risk factors, outlining PAF as a possible independent embolic risk factor.

Paroxysmal Atrial Fibrillation: Insight Into the Intimate Mechanisms of Coagulation.

BACKGROUND: Atrial fibrillation (AF) is a hypercoagulable state. However, the intimate mechanisms leading to impaired coagulation and the timing of their activation are unclear. The aim of the study was to investigate the factors that initiate the coagulation cascade in the early hours (up to 48 h) of clinical manifestation of paroxysmal atrial fibrillation (PAF). METHODS: Tissue factor (TF) level, coagulation activity of factor VII (FVIIa), factor XII (FXIIa) and factor XI (FXIa) were measured in plasma of 51 non-anticoagulated patients (26 men and 25 women, aged 59.84 ± 11.42 years) and 52 controls (26 men and 26 women, aged 59.50 ± 10.53 years) by enzyme-linked immunoassays and kinetic assays. RESULTS: TF was higher in the PAF group (268.63 ± 90.62 pg/mL vs. 170.21 ± 66.19 pg/mL, P < 0.001) as well as FVIIa (170.82±59.39% vs. 95.17±37.90%, P < 0.001), FXIIa (218.31±84.04% vs. 148.41±53.94%, P < 0.001) and FXIa (178.41±55.94% vs. 111.75±37.33%, P < 0.001). Regression analysis showed that in the first 6 h of the disease, increase in time led to increase in FXIIa (r = 0.25, P < 0.05), FXIa (r = 0.75, P < 0.05), TF level (r = 0.25, P < 0.05) and FVIIa (r = 0.25, P < 0.05). CONCLUSION: Hemocoagulation changes were observed even < 6 h after the onset of the disease. They suggest that PAF has an early tendency for hypercoagulability, with the involvement of the intrinsic and extrinsic pathways of coagulation.

Paroxysmal Atrial Fibrillation: An Independent Risk Factor for Prothrombotic Conditions.

OBJECTIVE: It remains unclear whether atrial fibrillation (AF) alone determines systemic changes in hemocoagulation. Our aim was to examine the prothrombin fragment F1+2 and fibrinopeptide A (FPA) as early markers of coagulation activity still in the first twenty-four hours of paroxysmal AF (PAF) and to correlate them with the arrhythmia onset. METHODS: 51 non-anticoagulated patients (26 men, 25 women, aged 59.84±1.6 years) and 52 controls (26 men, 26 women, aged 59.50±1.46 years) were sequentially selected. F1+2 and FPA plasma levels were measured by enzyme-linked immunoassays. RESULTS: F1+2 was significantly higher in patients (292.61pmol/L±14.03pmol/L vs 183.40pmol/L±8.38pmol/L; p<0.001). FPA was also substantially higher (4.47ng/mL±0.25 ng/mL vs 3.09ng/mL±0.15ng/mL, p<0.001). Among the potential predictors for these deviations: age, gender, BMI, PAF duration and CHA2DS2-VASc score, it was established that higher F1+2 and FPA plasma levels were independently associated only with PAF duration (p<0.05). Moreover, longer episodes were associated with higher values of F1+2 (Adjusted R2 = 0.68) and FPA (Adjusted R2 = 0.70). CONCLUSIONS: Increased coagulation activity was present still in the first twenty-four hours of PAF clinical presentation. The disease itself was associated with increasing hypercoagulability over time, suggesting its importance as an independent risk factor for thromboembolic events.

Decreased Activity of the Protein C Anticoagulant Pathway in the Early Hours of Paroxysmal Atrial Fibrillation.

BACKGROUND: Increased coagulation activity has been established in paroxysmal atrial fibrillation (PAF), but data on the anticoagulant system are scarce. PURPOSE: To examine the protein C anticoagulant pathway in the early hours of the disease. MATERIALS AND METHODS: Fifty-one patients (26 men and 25 women; mean age 59.84 ± 1.60 years) and 52 controls (26 men and 26 women; mean age 59.50 ± 1.46 years) were selected for the study. Protein C antigen and its activity, total protein S, free protein S and its activity, soluble forms of endothelial protein C receptor (sEPCR), and thrombomodulin (sTM) were examined in the plasma. RESULTS: The indicators were studied in patients between the 2nd and the 24th hour after the onset of arrhythmia. Levels of protein C were significantly elevated in patients compared to controls (111.40% ± 6.66% vs 94.83% ± 4.47%; P = .039). Protein C activity showed significant reduction in PAF (73.13% ± 5.80% vs 103.3% ± 3.80%; P < .001). Total protein S levels did not differ significantly (108.20% ± 4.07% vs 102.40% ± 3.65%; P = .30). Free protein S (76.81% ± 6.01% vs 122.10% ± 3.97%; P < .001) and its activity (71.39% ± 6.27% vs 119.50% ± 6.54%; P < .001) were reduced in patients. Higher levels of sEPCR (203.10 ± 10.33 vs 133.10 ± 7.37 ng/mL; P < .001) and sTM (6.50±0.40 vs 4.48±0.28 ng/mL; P < .001) were measured in PAF. CONCLUSION: Protein C activity is reduced still in the first hours (until the 24th hour) of PAF clinical manifestation, determining reduced activity of the anticoagulant pathway as a whole. The established low levels of free protein S and its activity as well as low sEPCR and sTM levels are a possible explanation of the changes in protein C activity.

Early effects of paroxysmal atrial fibrillation on plasma markers of fibrinolysis.

There are no studies to date on the early changes in the hemostasis profile of patients with paroxysmal atrial fibrillation (PAF).Given the key role of the fibrinolytic system in maintaining blood fluidity, our aim was to examine its activity in patients with clinical manifestation of the disease <24 hours.We studied 51 nonanticoagulated patients with a first episode of the disease (26 men, 25 women; mean age 59.84 ±â€Š1.60 years) and 52 controls (26 men, 26 women; mean age 59.50 ±â€Š1.46 years) who matched the patients in terms of gender, age, comorbidities, and conducted treatment. Using enzyme-linked immunoassays and colorimetric assays we assessed the plasminogen activity, tissue plasminogen activator level (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), α2-antiplasmin activity (α2-AP), D-dimer level, and vitronectin level. Blood samples were collected immediately after hospitalization.Patients were hospitalized between the second and twenty fourth hours (mean 8.14 ±â€Š0.76 hours) after the onset of PAF. Compared to controls, plasminogen (159.40 ±â€Š4.81 vs 100.2 ±â€Š2.88%, P < 0.001) and t-PA levels (11.25 ±â€Š0.35 vs 6.05 ±â€Š0.31 ng/mL, P < 0.001) were significantly higher in the patient group. PAI-1 activity (7.33 ±â€Š0.37 vs 15.15 ±â€Š0.52 AU/mL, P < 0.001) and α2-AP (112.9 ±â€Š2.80 vs 125.60 ±â€Š3.74%, P < 0.05) as well as vitronectin plasma levels (134.7 ±â€Š5.83 vs 287.3 ±â€Š10.44 mcg/mL, P < 0.001) were lower in the PAF group. Conversely, the levels of D-dimer in patients were significantly higher (0.53 ±â€Š0.07 vs 0.33 ±â€Š0.02 ng/mL, P < 0.05).Early changes in the fibrinolytic system occur in PAF, suggesting their close relationship with the manifestation of the disease. There is high plasma fibrinolytic activity, during the very first 24 hours of the disease, which is most likely a pathophysiological response to the intensified procoagulation process.

Significant Increase in C-Reactive Protein and Serum Amyloid A in the Early Hours of Paroxysmal Atrial Fibrillation.

BACKGROUND: A number of data have been accumulated on inflammation in persistent and permanent atrial fibrillation (AF). Our aim was to study the process in paroxysmal AF (PAF) by measuring plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and fibrinogen in dynamics. METHODS: The markers were investigated in 51 patients (26 males and 25 females; 59.84 ± 1.60 years) at hospital admission (baseline), 24 hours and 28 days after sinus rhythm restoration. Fifty-two controls (26 males and 26 females; 59.50 ± 1.46 years) were selected. RESULTS: At baseline, hs-CRP and SAA concentrations were higher in patients (8.12 ± 0.82 vs. 5.57 ± 0.21 mg/L, P = 0.003; 16.04 ± 0.93 vs. 5.12 ± 0.23 ng/mL, P < 0.001, respectively) and these changes persisted 24 hours after sinus rhythm restoration (8.16 ± 0.71 vs. 5.57 ± 0.21 mg/L, P < 0.001; 12.99 ± 0.75 vs. 5.12 ± 0.23 ng/mL, P < 0.001, respectively). On the 28th day, no significant difference was measured (5.42 ± 0.29 vs. 5.57 ± 0.21 mg/L, P = 0.68; 5.89 ± 0.38 vs. 5.12 ± 0.23 ng/mL, P = 0.08, respectively). At any measurement, fibrinogen levels did not differ between patients and controls (3.30 ± 0.17 vs. 3.22 ± 0.11 g/L, P = 0.70; 3.32 ± 0.11 vs. 3.22 ± 0.11 g/L, P = 0.52; 3.24 ± 0.13 vs. 3.22 ± 0.11 g/L, P = 0.90, respectively). CONCLUSION: PAF is associated with dynamics in hs-CRP and SAA plasma levels. The results suggest that inflammation is closely related to the arrhythmia initiation.

Early Changes in the Antithrombin and Thrombin-Antithrombin Complex in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Data on coagulation changes in paroxysmal atrial fibrillation (PAF) are scarce. The aim of this study was to examine plasma antithrombin (AT) levels and activity as well as thrombin-antithrombin (TAT) complex levels in the early hours of the clinical manifestation of PAF. METHODS: Fifty-one patients (26 men and 25 women; mean age 59.84 ± 1.60 years) were consecutively selected with PAF duration < 24 hours, and 52 controls (26 men and 26 women; mean age 59.50 ± 1.46 years) matched the patients in terms of gender, age and comorbidities. Plasma levels and activity of AT and levels of the covalent TAT complex were studied once in each study participant. RESULTS: AT plasma levels in PAF patients were statistically significantly lower compared to controls (164.69 ± 10.51 vs. 276.21 ± 8.29 µg/mL, P < 0.001). Plasma activity of the anticoagulant was also significantly lower in PAF (71.33±4.87 vs. 110.72±3.09%, P < 0.001). TAT complex concentration in plasma was higher in the patient group (5.32 ± 0.23 vs. 3.20 ± 0.14 µg/L, P < 0.001). CONCLUSION: We can say that PAF is associated with significantly reduced AT levels and activity and increased levels of TAT complex during the first 24 hours after its manifestation. These changes indicate a reduced activity of AT anticoagulant system, which is a probable prerequisite for the established enhanced coagulation (high TAT complex levels).

Paroxysmal atrial fibrillation: dynamics of the main antioxidant enzymes--superoxide dismutase and catalase.

INTRODUCTION: Researchers have a particularly strong interest in the mechanisms implicated in the clinical manifestation of atrial fibrillation. OBJECTIVE: To examine dynamically the activity of the antioxidant enzymes, superoxide dismutase and catalase in patients with paroxysmal atrial fibrillation (duration < 48 hours). MATERIALS AND METHODS: The studied parameters were examined in the erythrocytes of 51 patients (59.84 +/- 1.60, 26 men) immediately after their hospitalization, at 24 hours and 28 days after restoration of sinus rhythm. 52 controls (59.50 +/- 1.46, 26 men) were also included, none of which had a history of arrhythmia. Propafenone was used to manage the rhythm abnormality. The enzyme activity was determined by a spectrophotometric method. RESULTS: The average duration of atrial fibrillation episodes until the time of hospitalization was 8.14 hours (from 2 to 24 hours). During patient hospitalization the activity of superoxide dismutase and catalase was considerably higher compared to that of the controls (8.46 +/- 0.26 vs 5.81 +/- 0.14 U/mg Hb; 7.36 +/- 0.25 vs 4.76 +/- 0.12 E240/min/mg Hb; P < 0.001). This difference was maintained 24 hours after the rhythm regularization (7.19 +/- 0.25 vs 5.81 +/- 0.14 U/mg Hb, p < 0.001; 5.30 +/- 0.21 vs 4.76 +/- 0.12 E240/min/mg Hb, p < 0.05). Twenty-eight days after the restoration of sinus rhythm, the activity of catalase remained increased (5.11 +/- 0.08 vs 4.76 +/- 0.12 E240/min/mg Hb, p < 0.05). CONCLUSION: The paroxysmal atrial fibrillation in our study was characterized with significantly increased activity of superoxide dismutase and catalase even in the early hours of clinical manifestation of the disorder, which then slowly decreased with the restoration of sinus rhythm. Therefore, we can conclude that changes in oxidative status are closely related to the disease and are probably a part of the intimate mechanisms related to its initiation and clinical course.