Elevated thrombin generation levels in the left atrial appendage in patients with atrial fibrillation.

Background: Atrial Fibrillation (AF) is the most common sustained tachi-arrhythmia. Thrombus formation in the left atrial appendage (LAA) increases the risk of stroke and systemic embolism in patients with AF. Objectives: The aim of this study was to compare thrombin generation in the LAA to the LA among patients with AF. Methods: A cross-sectional study of consecutive patients with AF undergoing pulmonary veins catheter ablation. Blood samples from the femoral vein (FV), right atrium (RA), left atrium (LA), and LAA were collected during the catheter ablation procedures. Thrombin generation was assessed by a Calibrated Automated Thrombogram. The LAA-calibrated automated thrombogram parameters were compared with the RA, LA, and FV. Results: A total of 47 consecutive patients were enrolled in the study. The endogenous thrombin potential and peak height were significantly higher in the LAA compared with the LA, the mean differences and 95% CI between the LA and LAA were -378.9 (-680.5, -77.2) (nM∗min) and -66.7 (-119.6, -13.8) (nM) in the endogenous thrombin potential and peak height respectively. Conclusion: In patients with AF undergoing catheter ablation, the LAA demonstrated increased thrombin generation compared with the LA. This finding might contribute to the understanding of why the LAA is more predisposed to thrombus formation than the LA. Clinical Trials Registration: NCT03795883.

Calibrated Automated Thrombogram During Pregnancy in Unexplained Recurrent Miscarriages: A Pilot Study.

BACKGROUND: Recurrent miscarriages are associated with a high prevalence of thrombophilia. Use of a calibrated automated thrombogram (CAT) can serve as a universal test for thrombophilia. OBJECTIVES: To examine whether thrombin generation measured by CAT is elevated during the first trimester in women with unexplained recurrent miscarriages. METHODS: This study comprised 25 pregnant women with recurrent pregnancy loss referred for thrombophilia screening and treated with low-molecular-weight heparin (LMWH). Thrombin generation parameters were measured in women who had miscarriages or live births and who were diagnosed as positive or negative for thrombophilia. RESULTS: Of the pregnancies, 76% resulted in live birth and 24% ended in miscarriages. Among the women, 76% were positive for thrombophilia. Thrombin generation parameters between pregnancies that ended in miscarriage compared to live births were not significantly different, and CAT parameters failed to predict pregnancy outcome. Although the CAT parameters demonstrated a trend toward a hypercoagulable state in women with thrombophilia, there was no statistical significance (P > 0.05). CONCLUSIONS: Women with unexplained pregnancy loss demonstrated similar thrombin generation in the first trimester, regardless of the pregnancy outcome. CAT parameters failed to predict pregnancy outcome in women with recurrent unexplained pregnancy loss. Our results should be interpreted with caution due to the small number of participants.

Enhanced thrombin generation in patients with arterial hypertension.

BACKGROUND: Arterial hypertension is associated with greater risk of cardiovascular diseases and thrombotic complications, suggesting that hypertension is a prothrombotic state. OBJECTIVES: To investigate the relationship between arterial hypertension and thrombin generation, and between blood pressure level and thrombin generation in hypertensive patients. METHODS: A total of 165 hypertensive patients and 47 healthy adults controls were include in the study. Thrombin generation was assessed in both groups by the Calibrated Automated Thrombogram (CAT) method. Ambulatory blood pressure monitoring (ABPM) was also performed for all patients in the hypertensive group. RESULTS: Hypertensive patients had significantly higher levels of ETP and peak heights compared to healthy controls; means of ETP 1720.6 ±â€¯267 and 1544.7 ±â€¯302, respectively (P < 0.001) and means of peak height were 297.26 ±â€¯48 and, 273 ±â€¯53, respectively (P < 0.001). On multivariate linear regression analysis, hypertension remained independently associated with increased ETP (ß = 0.185, P = 0.047). Analysis restricted to the hypertensive group with ABPM measurement showed statistically significant correlations between all measures of diastolic blood pressure (DBP) and ETP, and multivariate analysis showed that awake DBP was significantly associated with ETP (ß = 0.194 for each 1-mm Hg increase in awake DBP, P = 0.012). Furthermore, hypertensive patients with cardiovascular complications had statistically elevated levels of peak height compared to hypertensive patients without cardiovascular complications. CONCLUSIONS: Hypertensive patients possess enhanced thrombin generation compared healthy controls. Diastolic blood pressure level is independently correlated with increased thrombin generation in hypertensive patients. These findings suggest that arterial hypertension is a prothrombotic state.

The Effect of Vitamin D Supplementation on Thrombin Generation Assessed by the Calibrated Automated Thrombogram.

Observational and in vitro studies suggest that vitamin D may have antithrombotic activity. This study aimed to examine the relationship between vitamin D supplementation and thrombin generation. Serum 25-hydroxyvitamin D (25(OH)D) and thrombin generation parameters were measured in 73 healthy volunteers. Participants with serum 25(OH)D <50 nmol/L (n = 53) were treated with vitamin D3and tested for 25(OH)D and thrombin generation at the end of treatment. Lag time and time to peak decreased after treatment by a mean of -0.49 ± 0.51 minute (P< .001) and -0.76 ± 0.70 minute (P< .001), respectively, whereas endogenous thrombin potential and peak height increased after treatment by a mean of 170.1 ± 339.8 nmol/L minute (P= .001) and 34.2 ± 47.8 nmol/L (P< .001), respectively. Treatment with vitamin D supplementation seems to have prothrombotic effect in patients with vitamin D insufficiency. These findings should be interpreted with caution and need to be replicated in future studies.

Padua prediction score and thrombin generation in hospitalized medical patients.

INTRODUCTION: The Padua prediction score is a risk assessment model used to identify medical patients at high risk for venous thromboembolim (VTE).We aimed to assess the relationship between the severity of Padua score and thrombin generation as a measure of overall thrombotic activity. MATERIALS AND METHODS: A total of 253 patients hospitalized in the medical wards, at the Haemek Medical Center, Israel, were enrolled in the study. Patients treated with anticoagulation, and those admitted for VTE were excluded. Padua score was classified into two categories; low-risk for VTE (<4 points), and high-risk for VTE (≥4 points). Thrombin generation was assessed by the Calibrated Automated Thrombogram (CAT) method. RESULTS: Overall 187 (73.9%) patients had Padua score<4, and 66 (26.1%) patients had Padua score ≥4. Comparison of the thrombogram parameters between the two Padua score categories showed no significant difference; lag time (P=0.066), ETP (P=0.266), peak height (P=0.418), and time to peak (P=0.415). Among the individual Padua score risk factors, only active cancer was significantly associated with peak height, myocardial infarction or stroke with lag time, and none of the risk factors was significantly associated with ETP. Because of their low frequency, the association with previous VTE, known thrombophilia, hormonal treatment, and recent trauma or/and surgery was not assessed. CONCLUSIONS: Single thrombin generation measurement obtained at the same time in acutely hospitalized patients didn't bear any correlation with the Padua prediction score. This finding should be interpreted with caution considering the underrepresentation of risk factors that may influence thrombin generation.

Non-therapeutic anti-FXa levels are common among medical ward patients treated with enoxaparin.

Thromboembolism is treated with a weight-adjusted enoxaparin dose without the need for laboratory monitoring. This study aims to determine the prevalence of sub and supra-therapeutic anti-factor Xa (aFXa) levels among medical ward patients treated with enoxaparin, and to identify potential factors associated with non-therapeutic aFXa levels. aFXa levels were measured in a cohort of medical ward patients treated with curative enoxaparin regimen (1 mg/kg bid) in the Ha'emek Medical Center in the northeastern area of Israel. The relative risk (RR) ratio for sub and supra-therapeutic aFXa levels was estimated in demographic and clinical subgroups. Of the 294 included patients, only 78.6% had therapeutic aFXa levels, while 13.3% and 8.1% had sub and supra-therapeutic levels, respectively. On univariate analysis, females, smoking, BMI ≥ 30, and cancer were significantly associated with supra-therapeutic aFXa levels; fibrates and warfarin use were significantly associated with sub-therapeutic aFXa levels (P < 0.05). On multivariate analysis, females and patients with cancer were independently at increased risk for supra-therapeutic levels RR 3.35(95% CI 1.50, 7.48), RR 3.61(95% CI 1.50, 8.70), respectively. Fibrates and warfarin were associated with sub-therapeutic levels RR 2.99(95% CI 1.44, 6.20), RR 3.42(95% CI 1.73, 6.76), respectively. Standard curative enoxaparin regimen is associated with increased risk for supra-therapeutic aFXa levels in females and patients with cancer and sub-therapeutic levels in patients treated with fibrates and warfarin. This may suggest the need for anticoagulation monitoring in high-risk patients with these conditions.