Fibrin Clot Permeability as a Predictor of Stroke and Bleeding in Anticoagulated Patients With Atrial Fibrillation.
BACKGROUND AND PURPOSE
Formation of denser fiber networks has been reported in atrial fibrillation and ischemic stroke. In this longitudinal cohort study, we evaluated whether fibrin clot density may predict thromboembolic and bleeding risk in patients with atrial fibrillation on vitamin K antagonists.


METHODS
In 236 patients with atrial fibrillation receiving vitamin K antagonists treatment, we measured ex vivo plasma clot permeability (Ks), a measure of the pore size in fibrin networks.


RESULTS
During a median follow-up of 4.3 (interquartile range, 3.7-4.8) years, annual rates of ischemic stroke or transient ischemic attack and major bleeds were 2.96% and 3.45%, respectively. In multivariate Cox regression analysis, patients with lower Ks (<6.8 cm2×10-9, median) had increased risk of ischemic stroke or transient ischemic attack (hazard ratio [HR], 6.55; 95% confidence interval [CI], 2.17-19.82) and major bleeds (HR, 10.65; 95% CI, 3.52-32.22). Patients with elevated Ks (≥6.8 cm2×10-9) had an increased rate of minor bleeding compared with the remainder (11.63% per year versus 3.55% per year; P<0.0001). The independent predictors of stroke or transient ischemic attack were low Ks (<6.8 cm2×10-9; HR, 7.24; 95% CI, 2.53-20.76), age (HR, 1.05; 95% CI, 1.01-1.10), and treatment with angiotensin-converting enzyme inhibitors (HR, 2.27; 95% CI, 1.08-4.77). Major bleeds were predicted by low Ks (<6.8 cm2×10-9; HR, 8.48; 95% CI, 2.99-24.1) and HAS-BLED score ≥3 (HR, 2.22; 95% CI, 1.12-4.38).


CONCLUSIONS
This study is the first to show that unfavorable fibrin properties reflected by formation of denser fibrin networks determine, in part, the efficacy and safety of anticoagulation with vitamin K antagonists in patients with atrial fibrillation.
['Drabik|Leszek|L|', 'Wołkow|Paweł|P|', 'Undas|Anetta|A|']
D000368:Aged D000925:Anticoagulants D001281:Atrial Fibrillation D001777:Blood Coagulation D002199:Capillary Permeability D015331:Cohort Studies D005260:Female D005337:Fibrin D005500:Follow-Up Studies D006470:Hemorrhage D006801:Humans D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D011237:Predictive Value of Tests D020521:Stroke D013927:Thrombosis
fibrin stroke anticoagulants atrial fibrillation hemorrhage humans