Objectives We sought to evaluate the rate of bleeding in relation to age (<80 and ≥80 years), the quality of anticoagulation (expressed as time spent in international normalized ratio therapeutic ...range), and factors associated with bleeding events. Background Stroke prevention in patients with atrial fibrillation (AF) is an increasingly crucial public health target, particularly in patients ages ≥80 years. Methods We conducted a prospective observational study on 783 patients with AF on oral anticoagulant treatment (OAT). Results Patients spent a median 14%, 71%, and 15% of time below, within, and above the intended therapeutic range, respectively. No difference in OAT quality was found between patients age <80 and ≥80 years. During follow-up, 94 patients experienced bleeding complications (rate 3.7 × 100 patient/years), 37 major (rate 1.4 × 100 patient/years), and 57 minor (rate 2.2 × 100 patient/years). Different rates of major hemorrhage were observed between patients age <80 and ≥80 years (0.9 vs. 1.9 × 100 patient/years; p = 0.004). Bleeding risk also was greater in patients with a history of previous cerebral ischemic event (odds ratio OR: 2.5; 95% confidence interval: 1.3 to 4.8; p = 0.007). A Cox regression analysis confirmed age ≥80 years associated with bleeding risk (OR: 2.0). Conclusions These results indicate that the rate of major bleeding complications may be kept acceptably low also in very elderly AF patients on OAT, provided a careful management of anticoagulation is obtained.
Background: Little information is available on the long‐term clinical outcome of cerebral vein thrombosis (CVT).
Objectives and methods: In an international, retrospective cohort study, we assessed ...the long‐term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode.
Results: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient‐years. Median follow‐up was 40 months (range 6, 297 months). At the end of follow‐up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score mRS 0–1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty‐four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient‐years (95% confidence Interval CI 17.8, 28.7) and of 35.1 events/1000 patient‐years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio HR 2.70; 95% CI 1.25, 5.83).
Conclusions: The long‐term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.
Background All stroke risk stratification schemes categorize a history of stroke as a “truly high” risk factor. Therefore, stratifying stroke risk in atrial fibrillation (AF) should perhaps ...concentrate on primary prevention. However, the risk factors for stroke also lead to an increase in the risk of bleeding. Our objective was to evaluate the agreement among the currently used stroke risk stratification schemes in “real-world” patients with AF in the primary prevention setting, their correlation with adverse events recorded during warfarin treatment, and the relationship between stroke and bleeding risk. Methods We prospectively followed up 3,302 patients with AF taking warfarin for primary prevention. Stroke risk was assessed using the CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes, previous stroke or transient ischemic attack), Atrial Fibrillation Investigators, American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy, American College of Cardiology/American Heart Association/European Society of Cardiology, and National Institute for Health and Clinical Excellence schemas, and for bleeding risk, the outpatient bleeding risk index was calculated. Bleeding and thrombotic events occurring during follow-up were recorded. Results Patients classified into various stroke risk categories differed widely for different schemes, especially for the moderate- and high-risk categories. The rates of bleeding and thrombotic events during follow-up were 1.24 and 0.76 per 100 patient-years, respectively. All stroke stratification schemes correlated closely to bleeding risk. Stroke rate increased progressively from low- to moderate- to high-risk patients. Conclusions Stroke risk stratification models differed widely when categorizing subjects into the moderate- and high-stroke-risk categories. Bleeding and stroke risk were closely correlated and both were low among low-risk patients and were similarly high among moderate/high-risk groups.
Abstract We report a case of non-traumatic splenic rupture in a 57-year-old man on dual antiplatelet therapy (DAPT) with aspirin and ticagrelor, seven months after percutaneous coronary intervention ...and drug-eluting stent implantation for non-ST elevation myocardial infarction. No splenic abnormalities were found at histopathological analysis after splenectomy, and no history of recent trauma was reported. Once restarted, DAPT after splenectomy, assessment of platelet function was performed by light transmittance aggregometry, showing a profound inhibition of platelet function by adenosine diphosphate, arachidonic acid, and collagen. Taking into account the bleeding risk associated with low on-treatment platelet reactivity, and to switch the patient from ticagrelor to a less potent P2Y12 inhibitor such as clopidogrel, cytochrome P450, genetic polymorphisms accounting for clopidogrel response variability were analyzed. The polymorphisms associated with lower response (CYP2C19*2, CYP2C19*3) were absent. Therefore, ticagrelor was withdrawn, and DAPT was continued with aspirin and clopidogrel. Rupture of the spleen may occur in the absence of major trauma or previous splenic diseases, and could be a complication of antithrombotic treatments. Moreover, low on-treatment platelet reactivity during DAPT is emerging as a possible risk factor for bleeding complications, so underlining the usefulness of assessing platelet function in special conditions to ensure that the patient receives the best tailored antiplatelet therapy. < Learning objective: Non-traumatic splenic rupture is a rare event, and is more often associated with pre-existing splenic abnormalities. However, it may be also a complication of medical treatments, especially with antithrombotic drugs. Low on-treatment platelet reactivity is emerging as a possible risk factor for bleeding complications; therefore, assessing platelet function in special conditions could be useful to ensure the patient receives the best-tailored antiplatelet therapy.>
Reply Poli, Daniela, MD; Antonucci, Emilia, MS; Grifoni, Elisa, MD
Journal of the American College of Cardiology,
2010, Letnik:
55, Številka:
9
Journal Article
The stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of research, especially in patients with pulmonary embolism (PE). Elevated D-dimer ...levels and residual vein obstruction (RVO) at compression ultrasonography have been studied as predictors of recurrence after withdrawing oral anticoagulant treatment (OAT). It is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. In the present study, we evaluated the association of PD with PE recurrence. The relationship between PD, elevated D-dimer levels, and RVO was also investigated. We prospectively followed 236 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep-vein thrombosis. After at least three months of OAT, treatment was withdrawn in 139 patients. D-dimer levels were evaluated at one month of OAT withdrawal, RVO was measured, and perfusion lung scan (P-scan) was performed to evaluate PD. During follow-up, 20 patients experienced a recurrent episode of VTE. Elevated D-dimer levels were significantly associated with VTE recurrence, (p=0.003). RVO was present in 22% of the patients with recurrence and in 7.5% of those without (p=0.07). No significant association was found between PD >10% and VTE recurrence, D-dimer, or RVO. In conclusion, we confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are neither predictive of recurrence nor related to D-dimer levels or RVO.
Reportedly, fibrin isolated from patients with chronic thromboembolic pulmonary hypertension (CTEPH) is resistant to lysis. Persistence of regions within the fibrin beta chain, which mediate cell ...signaling and migration, could trigger the organization of pulmonary thromboemboli into chronic intravascular scars.
Ascertain whether fibrin resistance to lysis occurs in patients with pulmonary hypertension (PAH) other than CTEPH, and in those with prior pulmonary embolism (PE) and no pulmonary hypertension.
Fibrinogen was purified from 96 subjects (17 with CTEPH, 14 with PAH, 39 with prior PE, and 26 healthy control subjects) and exposed to thrombin to obtain fibrin clots. Plasmin-mediated cleavage of fibrin beta chain was assessed hourly over a 6-hour period by polyacrylamide gel electrophoresis. Fibrin band intensity was measured by densitometry of stained gels. Data were normalized to the band intensity of the undigested protein.
By 1 hour of digestion, fibrin band intensity had decreased by a median of 25% (interquartile range IQR, 20 to 27%) in control subjects, and by 15% (IQR, 11 to 18%) in patients with prior PE (P < 0.0001). The 1-hour median reduction in band intensity was 2% (IQR, 1 to 3%) in CTEPH, and 4% (IQR, 2 to 7%) in PAH (P < 0.0001 vs. control subjects and PE). The decline in fibrin band intensity remained significantly different among the four groups up to 6 hours (P < 0.0001).
Fibrin resistance to lysis occurs in pulmonary hypertension other than CTEPH and, to a smaller extent, in patients with prior PE and no pulmonary hypertension.
Vitamin K antagonists (VKA) therapy is increasingly used in elderly for prevention of venous thromboembolism (VTE) and of stroke in atrial fibrillation (AF). Glomerular filtration rate (GFR), usually ...estimated from different equations, decreases progressively with age and it is a risk factor for bleeding. In the frame of the EPICA study, a multicentre prospective observational study including 4,093 patients ≥80 years naïve to VKA treated for AF or after VTE, we performed this ancillary study to evaluate the prevalence of chronic kidney diseases (CKD) by estimated GFR (eGFR). Incidence of bleedings was recorded and bleeding risk was evaluated in relation to eGFR calculated by Cockroft-Gault (C-G); Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. In addition, the agreement among the three eGFR formulas was evaluated. We recorded 179 major bleedings (rate 1.87 x100 patient-years py), 26 fatal (rate 0.27 x100 py). Moderate CKD was detected in 69.3%, 59.3% and 47.0% and severe CKD in 5.8%, 7.4% and 10.0% of cases by C-G, MDRD and CKD-EPI, respectively. Bleeding risk was higher in patients with severe CKD irrespective of the applied equation. This study confirms that CKD represents an independent risk factor for bleeding and that a wide proportion of elderly on VKA had severe or moderate CKD, suggesting the need for frequent monitoring. Although the different available equations yield different eGFR, all appear to similarly predict the risk of major bleeding.
Introduction
The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding ...and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing.
Materials and Methods
Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke.
Results
A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80).
Discussion
our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events.
Conclusions
Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
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