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Consequences of warfarin suspension after major bleeding in very elderly patients with non valvular atrial fibrillation

Background Intracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH. Purpose Search for individual risk factors and bleeding risk scores (HAS-BLED, ATRIA and ORBIT) associated with ICHs in patients with atrial fibrillation treated with VKAs. Methods This is a retrospective case-control study in a single Thrombosis Center. During a 7-year period, patients with nonvalvular atrial fibrillation (NVAF) who developed ICH during VKAs were identified as cases. Four control patients matched for gender, age and length of VKAs were assigned to each case. The association between considered risk factors and ICHs was evaluated using a linear logistic regression method and expressed as odds ratio. Receiver operator characteristic (ROC) curves to assess the predictive ability of bleeding risk scores HAS-BLED, ATRIA and ORBIT were also evaluated. Results Fifty-one cases of ICH, most of whom were 80 years of age or older (72.5%), were retrieved from the Thrombosis Center's database. Compared to 204 controls, no individual risk factors were associated with ICH. Poor ability to predict ICH was also found using ROC curves (C-statistic for HAS-BLED, ATRIA, and ORBIT were 0.55, 0.53 and 0.54, respectively). Conclusions ICHs during VKA therapy preferentially occur in very elderly patients. The risk of ICH is not predicted by the commonly used risk scores.

Essentials Anticoagulation in the elderly is still a challenge and suspension of warfarin is common. This is an observational study reporting reasons and consequences of warfarin suspension. Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension. After suspension for bleeding or frailty, patients remain at high-risk of death or complications. SummaryBackground Anticoagulation in elderly patients with non-valvular atrial fibrillation (NVAF) is still a challenge, and discontinuation of warfarin is common. The aim of this study was to analyze the aspects related to warfarin discontinuation in a real-world population. Methods This was an observational cohort study on very elderly NVAF patients naive to warfarin therapy (VENPAF). The included subjects were aged at least 80 years, and started using warfarin after a diagnosis of NVAF. Warfarin discontinuation was assessed, and the reason reported for discontinuation, the person who decided to stop treatment, subsequent antithrombotic therapy and mortality, ischemic and bleeding events were collected. Results Over a period of 5 years, warfarin was discontinued in 148 of 798 patients. Despite similar CHA2DS2-VASc scores, the frequencies of thromboembolic and major bleeding events were significantly higher (P = 0.01 and P = 0.001, respectively) and the time in therapeutic range (TTR) was significantly lower (P < 0.001) in patients who discontinued warfarin. Independent risk factors for warfarin discontinuation were vascular disease (hazard ratio [HR] 2.5, P < 0.001), age ≥ 85 years (HR 1.4, P = 0.04), TTR < 60% (HR 1.8, P = 0.001), and bleeding events (HR 2.3, P < 0.001). The main reasons for warfarin discontinuation were physician-perceived frailty or low life-expectancy (45.9%), bleeding complications (19.6%), and sinus rhythm restoration (16.9%). Event and death rates were very high, especially in frail patients and in those with bleeding complications. Conclusions Warfarin discontinuation is frequent in very elderly patients, and is associated with increased risks of death and adverse events. Identification of elderly patients who are at high risk of bleeding and the poor quality of anticoagulation during warfarin are still unsolved clinical problems.

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ± 6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 μg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 μg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.