Abstract
Aim
When assessing bleeding risk in patients with atrial fibrillation (AF), risk stratification is often based on the baseline risks. We aimed to investigate changes in bleeding risk ...factors and alterations in the HAS-BLED score in AF patients. We hypothesized that a follow-up HAS-BLED score and the ‘delta HAS-BLED score’ (reflecting the change in score between baseline and follow-up) would be more predictive of major bleeding, when compared with baseline HAS-BLED score.
Methods and Results
A total of 19,566 AF patients receiving warfarin and baseline HAS-BLED score ≤2 were studied. After a follow-up of 93,783 person-years, 3,032 major bleeds were observed. The accuracies of baseline, follow-up, and delta HAS-BLED scores as well as cumulative numbers of baseline modifiable bleeding risk factors, in predicting subsequent major bleeding, were analysed and compared. The mean baseline HAS-BLED score was 1.43 which increased to 2.45 with a mean ‘delta HAS-BLED score’ of 1.03. The HAS-BLED score remained unchanged in 38.2% of patients. Of those patients experiencing major bleeding, 76.6% had a ‘delta HAS-BLED’ score ≥1, compared with only 59.0% in patients without major bleeding (
p
< 0.001). For prediction of major bleeding, AUC was significantly higher for the follow-up HAS-BLED (0.63) or delta HAS-BLED (0.62) scores, compared with baseline HAS-BLED score (0.54). The number of baseline modifiable risk factors was non-significantly predictive of major bleeding (AUC = 0.49).
Conclusion
In this ‘real-world’ nationwide AF cohort, follow-up HAS-BLED or ‘delta HAS-BLED score’ was more predictive of major bleeding compared with baseline HAS-BLED or the simple determination of ‘modifiable bleeding risk factors’. Bleeding risk in AF is a dynamic process and use of the HAS-BLED score should be to ‘flag up’ patients potentially at risk for more regular review and follow-up, and to address the modifiable bleeding risk factors during follow-up visits.
Background
The Hypertension, Abnormal renal/liver function, Stroke, Bleeding, Labile International Normalized Ratio (INR), Elderly, Drugs or alcohol use (HAS‐BLED) score has strong predictive ...validity for major bleeding complications, but limited validation has been conducted in venous thromboembolism (VTE). This study evaluates the HAS‐BLED score in a large cohort of VTE patients.
Methods and Results
A retrospective cohort of adults ≥18 years with primary diagnosis of VTE between January 1, 2010 and November 31, 2013 were identified in an insurance claims database. Patients were tracked until death, any bleed event, or end of study period. HAS‐BLED score and components were evaluated via proportional hazard models. Cumulative incidence functions were reported at 30, 60, 90, and 180 days. N=132 280 patients with a VTE were identified, with 73.8% having HAS‐BLED scores of 0 to 2, 3.6% score ≥4, and 4789 bleeding events (3.6% all patients). A 1‐point HAS‐BLED score increase was associated with 20% to 30% bleeding rate increase overall, but in a cancer cohort only the increase from 3‐ to 4‐points was significant for all bleeds (csHR=1.41, 95% CI: 1.17–1.69; sdHR=1.40, 95% CI: 1.17–1.69) and major bleeds (csHR=1.66, 95% CI: 1.26–2.20; sdHR=1.66, 95% CI: 1.25–2.19). Adding cancer to the model as an independent covariate provided the strongest association among all covariates, with csHR=2.25 (95% CI: 1.98–2.56) and sdHR=2.11 (95% CI: 1.85–2.41) in the model for major bleeds.
Conclusions
The HAS‐BLED score has good predictive validity for bleeding risks in patients with VTE. The addition of cancer as an independent bleeding risk factor merits consideration, possibly as part of the “B” criterion (“bleeding tendency or predisposition”).
Dalam upaya tata laksana fibriasi atrium (FA) untuk mencegah risiko stroke, antikoagulan seperti warfarin dapat digunakan. Indeks terapi yang sempit mendukung bahwa pengawasan selama penggunaan ...warfarin diperlukan untuk mencegah risiko perdarahan. Penelitian ini bertujuan untuk menggambarkan status risiko perdarahan pada sekelompok pasien FA yang menggunakan warfarin berdasarkan nilai HAS-BLED di RS ABC Gianyar, Bali. Penelitian observasional deskriptif dilakukan dengan pendekatan retrospective case study terhadap data pasien rawat jalan di RS ABC Gianyar. Penelitian ini mengikutsertakan seluruh pasien FA penerima warfarin berdasarkan riwayat selama periode Januari 2022-Mei 2023. Pencatatan dan asesmen risiko perdarahan mencakup komponen penilaian HAS-BLED yang diilustrasikan dalam bentuk tabel dan gambar sesuai profil pasien keseluruhan. Dari sejumlah delapan pasien FA, lima pasien (62,5%) memiliki risiko perdarahan sedang (nilai 1-2), dan sisanya berada dalam kategori risiko rendah (nilai 0). Mayoritas proporsi pada stratifikasi risiko perdarahan sedang dipengaruhi oleh parameter usia lanjut >65 tahun (50,00%), penggunaan antiplatelet atau antiinflamasi nonsteroid (NSAID) (25,00%), dan nilai INR yang tinggi (12,50%). Meskipun tidak ditemukan risiko perdarahan tinggi, pemantauan selama penggunaan warfarin diperlukan dengan berfokus pada faktor risiko yang dapat dimodifikasi. Keterbatasan jumlah sampel dan beberapa parameter laboratorium pada penelitian ini dapat menjadi masukan untuk kemajuan praktik klinis maupun pengembangan penelitian selanjutnya
The mobile atrial fibrillation application (mAFA-II) randomized trial reported that a holistic management strategy supported by mobile health reduced atrial fibrillation-related adverse outcomes. The ...present study aimed to assess whether regular reassessment of bleeding risk using the Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol (HAS-BLED) score would improve bleeding outcomes and oral anticoagulant (OAC) uptake.
Bleeding risk (HAS-BLED score) was monitored prospectively using mAFA, and calculated as 30 days, days 31-60, days 61-180, and days 181-365. Clinical events and OAC changes in relation to the dynamic monitoring were analyzed.
We studied 1793 patients with atrial fibrillation (mean, standard deviation, age 64 years, 24 years, 32.5% female).
Comparing baseline and 12 months, the proportion of atrial fibrillation patients with HAS-BLED ≥3 decreased (11.8% vs 8.5%, P = .008), with changes in use of concomitant nonsteroidal antiinflammatory drugs/antiplatelets, renal dysfunction, and labile international normalized ratio contributing to the decreased proportions of patients with HAS-BLED ≥3 (P < .05). Among 1077 (60%) patients who had 4 bleeding risk assessments, incident bleeding events decreased significantly from days 1-30 to days 181-365 (1.2% to 0.2%, respectively, P < .001). Total OAC usage increased from 63.4% to 70.2% (Ptrend < .001). Compared with atrial fibrillation patients receiving usual care (n = 1136), bleeding events were significantly lower in atrial fibrillation patients with dynamic monitoring of their bleeding risk (mAFA vs usual care, 2.1%, 4.3%, P = .004). OAC use decreased significantly by 25% among AF patients receiving usual care, when comparing baseline to 12 months (P < .001).
Dynamic risk monitoring using the HAS-BLED score, together with holistic App-based management using mAFA-II reduced bleeding events, addressed modifiable bleeding risks, and increased uptake of OACs.
Rare earth element (REE) enrichment in Algerian phosphorites has been evoked recently by a number of authors and are considered among the richest Paleocene-Eocene phosphorites worldwide. The Bled El ...Hadba deposit belongs to the giant Djebel Onk phosphorite complex in northeast Algeria. The deposit was subject to many geological studies that were focused on P2O5 contents for commercial purposes. The upper Thanetian phosphorite layer is about 30 m thick, and subdivided into three sub-layers (lower, main and upper sub-layer), based on P2O5 contents, where the main sub-layer is considered to be the richest. Despite this, few detailed geochemical investigations were carried out on this deposit thus far. In this work, major, trace and REE analyses were conducted on phosphate particles (pellets, coprolites and glauconites) using ‘in situ’ LA-ICP MS, and on whole-rock samples using XRF technique. The results show that the main sub-layer displays the highest whole-rock P2O5 contents, varying between 19.65 and 21.32 wt% compared to the lower (10.47–16.87 wt%) and upper (9.43–13.87 wt%) sub-layers. Among the phosphate particles, glauconites display the lowest P2O5 contents in the three sub-layers (17.45–19.35 wt%) compared to pellets (21.14–24.33 wt%) and coprolites (21.75–24.12 wt%), and largely the highest Al2O3, SiO2, MgO and Fe2O3(t). Glauconites also show higher ΣREE contents (764–2050 ppm) compared to pellets (221–910 ppm) and coprolites (214–909 ppm). Within the glauconite particles, the ΣREE, along with Al2O3, SiO2, MgO, and Fe2O3(t) contents, increase from core to the rim, whereas P2O5 contents decrease, which suggests that glauconitization postdates phosphatization processes. Also, the glauconitization process increase from the lower to the upper sub-layer; this is shown by the positive correlations between Al2O3 contents and those of MgO and SiO2 in one hand, and negative correlations between Al2O3 and P2O5 on the other hand. Ce, Eu, Y anomalies, along with La/Nd ratios and Nd contents, all point towards phosphatization under oxic conditions as a result of warm water upwelling, whereas glauconitization started under more reduced (sub-oxic) conditions; i.e., during early diagenesis, the peak of REE uptake from porewater, and under slow sedimentation rates.
Despite their relatively low P2O5 concentrations, the ΣREE contents of the Bled El Hadba phosphate particles record the highest concentrations in all Algerian and north African phosphorites. The main sub-layer is considered to be the most glauconite-rich phosphorite in Algeria. Therefore, more extensive REE analyses are recommended to better evaluate its economic potential in terms of critical raw materials.
Display omitted
•The REE-enriched Bled El Hadba deposit belongs to the Dj. Onk phosphorite complex.•Phosphate particles were in situ LA-ICP-MS analyzed for their chemistry.•Glauconite particles are very enriched in REE compared to pellets and coprolites.•Phosphatization predates glauconitization processes.
•The post-collisional Bled M’Dena ring complex is located in Yetti–Eglab junction-zone.•The western part of the Bled M’Dena ring complex is dominated by volcanic rocks.•The Palaeoproterozoic Bled ...M’Dena volcanic complex dated at 2.01Ga.•The volcanic rocks show a transitional-tholeiitic and high-K calc-alkaline series.•The Bled M’Dena ring complex was emplaced during a post-collisional period.
The Palaeoproterozoic Bled M’Dena ring complex (BRC) dated at 2.01Ga (Rb–Sr isochron) situated in the eastern part of the Yetti–Eglab junction-zone, belongs to the Aftout orogenic province, intruding the Aftout granite (2.07Ga). It exhibits a centripetal evolution from gabbro to granodiorite. The western part of the Bled M’Dena ring complex is dominated by volcanic rocks varying in composition from basalt, trachyandesite, andesite, dacite to rhyolite. Andesite constitutes the major volcanic type in the Bled M’Dena ring complex. Chemistry of these rocks suggest two distinct magmatic trends: A transitional-tholeiitic suite localised at the outer part of the ring complex, and a high-K calc-alkaline suite situated within the inner ring structure. Basic volcanics exhibit flat primitive REE patterns with insignificant Eu anomalies, suggesting that they probably represent a parental basaltic melt from which the Bled M’Dena complex evolved, (Eu/Eu∗=2.06–4.07). The europium anomaly did not vary significantly, as it evolved progressively through the volcanic series by differentiation and feldspar accumulation.
It is proposed that a primitive basic magma from the mantle was contaminated by Eburnian crust (2.2–2.0Ga). Thus the transitional-tholeiitic volcanic rocks, dominant in the region have developed a high-K calc-alkaline suite. Their source is melted shortly after its generation when the lithosphere was still hot, which restricts high-K calc-alkaline magmatism mainly to post-collisional settings. This has been linked to large movement along mega-shear zones (Yetti–Eglab junction) due to subduction of oceanic basins in a post collisional setting.
While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to ‘flag up’ those at risk of bleeding for more ...regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a ‘MBR factors’ score) against established bleeding risk stratification scores (HEMORR2HAGES, HAS-BLED, ATRIA, ORBIT).
A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves AUCs, or c-index) and the net reclassification index (NRI).
During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR2HAGES (p=0.003), HAS-BLED (p<0.001) and MBR factors score (p=0.013) but not ATRIA and ORBIT scores. When HAS-BLED was compared to other bleeding scores, c-indexes were significantly higher compared to MBR factors (p<0.001) and ORBIT (p=0.05) scores for major bleeding. C-indexes for the MBR factors score was significantly lower compared to all other scores (De long test, all p<0.001). When NRI was performed, HAS-BLED outperformed all other bleeding risk scores for major bleeding (all p<0.001). C-indexes for ATRIA and ORBIT scores suggested no significant prediction for ICH.
All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score.
V obdobju od julija do decembra 2019 so na Pristavi na Bledu, na območju nekdanje obrtne cone in srednjeveške pristave, potekale arheološke raziskave v okviru gradnje muzeja sodobne umetnosti Lah ...Contemporary. Izkopavanja so razkrila zapleteno stratigrafsko sliko. Na podlagi natančnejše časovne opredelitve odkritih najdb in rezultatov radiokarbonskega datiranja je bilo ugotovljenih šest naselbinskih faz. Strmo pobočje hriba Pristava je bilo v pozni bronasti in starejši železni dobi terasirano. Na izravnavah je bilo postavljenih več lesenih objektov, kurišča in številne jame. V članku so predstavljene novoodkrite ostaline ter najdbe železnodobne naselbine.
Background The association between cancer types and specific bleeding events in patients with atrial fibrillation has been scarcely investigated. Also, the performance of bleeding risk scores in this ...high-risk subgroup of patients is unclear. We investigated the rate of any bleeding, intracranial hemorrhage, major bleeding, and gastrointestinal bleeding according to cancer types in patients with atrial fibrillation. We also tested the predictive value of HAS-BLED, ATRIA, and ORBIT bleeding risk scores. Methods and Results Observational retrospective cohort study including hospitalized patients with atrial fibrillation and cancer from the French National Hospital Discharge Database (Programme de Medicalisation des Systemes d'Information) from January 2010 to December 2019. Major bleeding was defined according to Bleeding Academic Research Consortium definitions. Patients with HAS-BLED ≥3, ATRIA ≥5, or ORBIT ≥4 were classified as at high bleeding risk. Receiver operating characteristic analysis for each score against any bleeding, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage was performed. Areas under the curve (AUCs) were then compared. We included 399 344 patients. Mean age was 77.9±10.2 years, and 63.2% were men. The highest intracranial hemorrhage rates were found in leukemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year), and pancreas cancer (1.41%/year). Receiver operating characteristic analysis showed that ORBIT score predicted best for any bleeding. In addition, ORBIT score ≥4 had the highest predictivity for major bleeding (AUC, 0.805), followed by HAS-BLED ≥3 and ATRIA ≥5 (AUCs, 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for intracranial hemorrhage (AUCs, 0.744 and 0.742 for continuous scores, respectively), better than ATRIA (AUC, 0.635). For gastrointestinal bleeding, ORBIT ≥4 had the highest predictivity (AUC, 0.756), followed by the HAS-BLED ≥3 (AUC, 0.702) and ATRIA ≥5 (AUC, 0.662). Conclusions Some cancer types carry a greater bleeding risk in patients with atrial fibrillation. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up.
PDF
