Search Results (46)

Background: ABO blood type was reported to have a profound influence on hemostasis. This study aimed to determine the association between ABO blood type and the hemoglobin drop after total hip arthroplasty (THA). Methods: We retrospectively reviewed the changes in hemoglobin after elective primary THA. Demographic characteristics were analyzed for 794 eligible THAs. Changes in hemoglobin at postoperative days 1, 7, and 14 relative to the preoperative level were analyzed for 777 THAs that did not require allogenic blood transfusion (ABT). The effects of blood type were examined using a multivariate regression model and a propensity score matching model. Results: The hemoglobin drop was largest at 7 days, and the values differed significantly between type O cases and non-type O cases (2.68 ± 1.08 g/dL vs. 2.41 ± 1.02 g/dL; p = 0.0013). In the multivariate model, blood type O was identified as an independent factor for larger hemoglobin drop at 7 days (p = 0.015). Lower body mass index, non-hybrid THA, higher preoperative hemoglobin level, direct lateral approach, and prophylactic use of factor Xa inhibitor were also identified as independent risk factors for larger hemoglobin drop. After successful matching of 232 THAs in type O patients with 232 THAs in non-type O patients, hemoglobin drop at 7 days was significantly larger in type O patients (−2.44 ± 1.05 g/dL vs. −2.70 ± 1.05 g/dL, p = 0.0092). Conclusions: Blood type O was independently associated with a slightly greater postoperative hemoglobin decline after primary THA; however, the absolute between-group difference was small and was not accompanied by a higher allogenic transfusion rate. Therefore, ABO blood type may represent a minor risk marker and should be interpreted in the context of clinically more relevant bleeding- and hemodilution-related factors (e.g., perioperative anticoagulant/antiplatelet therapy and underlying coagulopathies). Full article

Background: atrial fibrillation (AF) patients with obesity and high thromboembolic risk need oral anticoagulant therapy. Limited data are available on direct oral anticoagulants (DOACs) in this population, and a point-of-care method has been validated to support rapid clinical decisions and to identify on-off plasma concentration thresholds. Methods: This is a monocentric, cross-sectional diagnostic accuracy study on obese AF outpatients referred to Policlinico Umberto I of Rome. Urinary Dipsticks were assessed with separate pads for factor Xa (FXA-i) and thrombin inhibitor (THR-i) and compared to the reference standard of trough and peak plasma concentrations with chromogenic assays/dTT and prespecified plasma thresholds for each DOAC. Study endpoints were the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of DOACs Dipstick compared to plasma concentrations. Sub-analyses according to obesity severity and type of DOAC were performed. Results: 320 paired plasma and urine samples were available from 160 enrolled patients (mean age 73.2 ± 9.1 years). Compared to trough plasma concentrations, DOACs Dipstick showed a sensitivity of 99.24% (mean, 95% confidence interval, CI 95.82–99.98), specificity of 6.89% (0.85–22.76), PPV 82.80% (81.32–84.18), NPV 66.67% (15.79–95.52). On the other hand, compared to peak plasma concentrations, DOACs Dipstick showed a sensitivity of 97.8% (93.7–99.5), specificity of 0% (0.0–15.4), and PPV of 85.9% (85.6–86.2). Urinary Dipstick showed a sensitivity of 99.10% (95.4–100.0), specificity of 4.70% (0.60–16.20) and a PPV and NPV of 74.50% (73.2–75.8) and 66.70 (15.7–95.6), compared to plasma thresholds > 30 ng/mL of FXA-I and THR-I. Sub-analyses showed similar results between FXA-i and THR-i. Conclusions: The urine point-of-care has high sensitivity, acceptable PPV, but low specificity and NPV in AF obese patients and may be useful only in selected clinical scenarios. Full article

Background: Unfractionated heparin (UFH) is the standard anticoagulant during cardiopulmonary bypass (CPB). A clinically relevant subset develops heparin resistance (HR)—failure to reach adequate anticoagulation with usual UFH—raising thrombotic risk and complicating perioperative care. Objectives: To synthesize contemporary evidence on the mechanisms, clinical implications, and perioperative management of HR in adult cardiac surgery with CPB. Methods: This narrative review synthesizes contemporary evidence on the epidemiology, mechanisms, recognition, and management of HR in adult cardiac surgery with CPB, emphasizing clinically actionable points. Results: Incidence varies across centers and definitions. Mechanisms include antithrombin (AT) deficiency or consumption and AT-independent drivers such as systemic inflammation or sepsis, protein-loss states, thrombocytosis, hyperfibrinogenemia, obesity, prior heparin exposure, and drug interactions. Sole reliance on activated clotting time (ACT) may misestimate anticoagulant effect; anti–factor Xa (anti-Xa) assays or heparin titration systems improve assessment when available. Management is stepwise: UFH dose escalation; targeted AT supplementation (or fresh frozen plasma where concentrates are unavailable); and transition to direct thrombin inhibitors when HR persists or UFH is contraindicated. Protocolized pathways and multidisciplinary coordination reduce delays and adverse events. Conclusions: HR is a multifactorial, common challenge in CPB. Pre-bypass risk assessment, multimodal monitoring, and an algorithm prioritizing UFH optimization, AT repletion, and timely use of direct thrombin inhibitors provide a pragmatic framework to limit thrombosis and bleeding. Harmonized definitions and comparative trials remain priorities. Full article

Background/Objectives: Different anti-Xa assays are routinely used to evaluate the plasma concentrations of direct factor X inhibitors (DXIs) rivaroxaban and apixaban, despite a lack of data on assay equivalence. Information on assay performance is particularly important at clinical decision cut-offs, such as 50 ng/mL or 30 ng/mL. The aim of this study was to evaluate the equivalence of different anti-Xa assays with the reference LC-MS/MS method for measuring rivaroxaban and apixaban concentrations in a multicenter study. In addition, the usefulness of the dRVVT as a simple coagulation test for emergency situations was evaluated. Methods: We included 122 patients with atrial fibrillation. Trough and peak blood samples were collected from 60 patients treated with rivaroxaban and 62 patients treated with apixaban. Rivaroxaban and apixaban plasma levels were measured by LC–MS/MS. Different anti-Xa assays were used in three laboratories to evaluate equivalence. Results: The concentrations in the analyzed samples ranged from 2 to 781 ng/mL for rivaroxaban and 9 to 568 ng/mL for apixaban. Only one of the anti-Xa assays gave equivalent results to LC-MS/MS for rivaroxaban, and none for apixaban. All anti-Xa assays significantly underestimated apixaban concentration, with a proportional bias between 10% and 20%. A high correlation was found between DXI concentration and dRVVT clotting time, but dRVVT was not consistently prolonged at clinically relevant DXI concentrations in plasma. Conclusions: Only one of the anti-Xa assays showed equivalence with LC-MS/MS for rivaroxaban, and none for apixaban. Several anti-Xa assays provided reliable results for rivaroxaban in the range of clinically relevant cut-off values, but none for apixaban, which could expose patients to a higher risk of bleeding and urgently needs further clinical research. The dRVVT test was not sensitive enough for reliable detection of clinically relevant DXI plasma concentrations and therefore cannot replace the anti-Xa assay in emergency situations. Full article

The utilisation of cardiopulmonary bypass (CPB) during cardiac surgery is often associated with complex haemostatic perturbations, frequently manifesting as a paradoxical risk of both bleeding and thrombosis. This is postulated to be driven by systemic inflammation, endothelial activation and contact activation of the coagulation cascade due to extracorporeal circulation. However, the coronavirus disease 2019 (COVID-19) pandemic revealed a unique hypercoagulable state, termed COVID-19-associated coagulopathy (CAC), also observed in those vaccinated against COVID-19. CAC displays similar physiological manifestations to those of disseminated intravascular coagulation (DIC), characterised by elevated fibrinogen and D-dimer values. The precise pathogenesis of CAC requires further elucidation though proposed mechanisms include: an exaggerated inflammatory response to COVID-19 infection or antibody proliferation due to vaccination, direct epithelial cell damage mediated by angiotensin converting enzyme 2, and ‘hypoxithrombosis’. CAC has since provided a unique framework to understand and potentially mitigate coagulation complications encountered during CPB in the post-pandemic era, as it is no longer sufficient to view COVID-19 as a transient influence on surgical risk. Rather, it must be recognized as a persistent modifier of the haemostatic environment across the population, with direct implications upon patient selection, intraoperative management and postoperative care in cardiac surgery. This review examines the pathological drivers behind CAC alongside the insights obtained from CAC management during ECMO deployment, to investigate the potential translation of such knowledge into improved anticoagulation strategies and monitoring during cardiac surgery. The use of alternative anticoagulants including factor XI inhibitors and the modulation of heparinase activity offers promising avenues to attenuate coagulopathies more commonly observed during CPB in the post-pandemic climate, whilst anti-Xa assays and viscoelastic testing have offered applicability to modern perfusion practices. By bridging the knowledge gained during the pandemic with that of conventional CPB, this review aims to inform future strategies for haemostasis management in cardiac surgery in a novel cohort of surgical patients. Full article

Extracorporeal membrane oxygenation (ECMO) is a continuously evolving and increasingly utilized life-support therapy. ECMO requires systemic anticoagulation, which exposes patients to an increased risk of heparin-induced thrombocytopenia (HIT). Clinical experience with alternative anticoagulants in this setting remains limited. The 2022 Extracorporeal Life Support Organization (ELSO)—Anticoagulation Guidelines provide no specific recommendations regarding anticoagulant selection for ECMO patients with HIT. This article aims to review current practices, available evidence, and most recent advances concerning the use of alternative anticoagulants in ECMO patients with HIT. In patients with a high suspicion or confirmed diagnosis of HIT, management includes discontinuing all forms of heparin exposure and initiating an alternative anticoagulant, such as a direct thrombin inhibitor and/or factor Xa inhibitor. Direct thrombin inhibitors act independently of antithrombin and have a short half-life, providing a more consistent and predictable anticoagulation effect. Most available data, primarily from retrospective studies, describe the use of argatroban in ECMO patients with HIT. Bivalirudin has also been used as an alternative anticoagulant in this population, with no significant increase in bleeding or thrombotic complications. However, the current evidence remains limited to small, retrospective, single-center or case–control studies. Fondaparinux has shown effectiveness in the HIT setting and appears to have a low risk of complications. Factor XIIa inhibitors represent a novel class of anticoagulants currently under investigation, evaluated only in animal models. Growing clinical experience with alternative anticoagulants, particularly direct thrombin inhibitors, suggests that their use will likely become a primary focus in ECMO anticoagulation management in the coming years. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) have transformed the prevention of thromboembolic events, but their efficacy and safety remain highly variable across individuals. DD217, a novel oral direct factor Xa inhibitor, has demonstrated potent anticoagulant activity in preclinical and clinical studies. No pharmacogenetic data are currently available for this compound. Based on in silico predictions of metabolic pathways and transporter involvement, and evidence from other DOACs, we hypothesized that variants in CYP2C and P-glycoprotein genes may contribute to variability in pharmacokinetics (PK) and clinical outcomes. Methods: Fifty-two patients undergoing total knee arthroplasty were enrolled, of whom 34 received the investigational drug (40 mg/day, n = 16; 60 mg/day, n = 18). DNA was extracted from peripheral blood cells, and genotyping of CYP2C9, CYP2C19, CYP2C8, CYP3A4, CYP3A5, and ABCB1 was performed by real-time PCR. Pharmacokinetics (PK) parameters (T_max, AUC_last, C_max) were assessed. In silico docking and pathway modeling predicted CYP2C and P-glycoprotein (ABCB1) involvement in drug disposition. Associations of genetic variants with PK parameters and adverse events (thrombosis, bleeding) were analyzed. Results: Carriers of reduced-function CYP2C9 alleles (intermediate [IM] or poor metabolizers [PM]) in the 60 mg group had a significantly shorter T_max compared with normal metabolizers (p = 0.005227), with trends toward higher AUC_last (p = 0.06926) and C_max (p = 0.1259). No significant associations were observed for CYP2C19, CYP3A4/5, or CYP2C8. In contrast, ABCB1 polymorphisms were associated with systemic exposure: carriers of the C allele at rs1045642 had higher AUC_last and C_max compared to TT (wild-type) homozygotes, while rs2032582 T allele carriers showed lower exposure (p < 0.05). At the haplotype level, the C–G–C–T combination of ABCB1 was more frequent in patients with thrombotic events at the 40 mg dose (p = 0.038). Overall, 5 thrombosis events and 1 bleedings were recorded on DD217, with no consistent associations to single SNPs. Conclusions: This first pharmacogenetic evaluation of DD217 shows that CYP2C9 variants are associated with differences in early-phase pharmacokinetics (T_max), while ABCB1 polymorphisms appear to modulate systemic exposure (AUC_last, C_max) and may influence thrombotic risk. These observations are consistent with in silico predictions of metabolic and transporter pathways. Despite limitations in sample size and event frequency, the study highlights the feasibility and importance of early pharmacogenetic evaluation during the drug development cycle of novel DOACs. Full article

Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro^® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article

Background: Direct oral anticoagulants (DOACs) are generally preferred over warfarin for preventing arterial and venous thromboembolism. However, the efficacy and safety of DOACs in patients with extremely low body weight (BW) are uncertain. This study investigates anti-factor Xa (anti-FXa) activity of apixaban and compares it between patients with normal BW (>50 kg) and underweight (≤50 kg). Methods: We enrolled 150 patients on branded generic apixaban (Apixan^TM) for atrial fibrillation (AF), venous thromboembolism, and intracardiac thrombus. Anti-FXa activity of apixaban was measured at peak concentration (C_peak) and trough concentration (C_trough) after at least one week of therapy. Results: Mean age was 64.0 ± 12.7 years, with 53.3% being male. Mean BW was 61.3 ± 15.3 kg. Of the 150 patients, 132 (88%) had AF, and 43 (28.7%) had low BW. Overall, 87.3% and 84.7% of patients had C_trough and C_peak within the expected range. Underweight patients had significantly higher mean C_trough and C_peak than normal BW patients. A higher proportion of low-BW patients exceeded the expected C_peak range compared to normal-BW patients (25.6% vs. 3.7%, p < 0.001). Low BW was the only independent predictor of exceeding C_peak specified range (adjusted OR 4.87, 95% CI 1.31–18.15, p = 0.018). Conclusions: Most patients maintained apixaban levels within expected ranges, but those with low BW were more likely to exceed the specified range of C_peak. Full article

Background: Administering intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) on direct oral anticoagulants (DOACs) remains a clinical challenge. Current guidelines restrict IVT within 48 h of DOAC intake unless anticoagulant activity can be confidently excluded. However, reliable medication histories are often unavailable, and conventional coagulation tests inadequately detect DOAC activity. This study evaluated whether viscoelastic point-of-care testing (ClotPro^®) could identify the absence of anticoagulant effect in AIS patients on DOACs, thus enabling IVT administration and potentially improving clinical outcomes. Methods: We conducted a prospective observational cohort study of 40 AIS patients with documented DOAC use, admitted between February 2023 and May 2025. ClotPro^® was performed at admission using the Russell’s viper venom (RVV) assay for factor Xa inhibitors and the ecarin clotting time (ECT) assay for dabigatran. Subtherapeutic anticoagulation was defined as a clotting time (CT) of <100 s for RVV and <180 s for ECT, respectively. Patients identified as being subtherapeutic were assessed for IVT eligibility. To evaluate IVT effects, we performed propensity score-matched bootstrap resampling (1000 iterations), matching patients by age, admission National Institutes of Health Stroke Scale (NIHSS), and pre-stroke modified Rankin Scale (mRS). Primary endpoints were NIHSS-shift (change from admission to 72 h) and mRS-shift (change from pre-stroke mRS to 90-day mRS). Predictors of outcomes were analyzed using multivariate regression models. Results: ClotPro^® identified 15/40 patients (37.5%) as subtherapeutic, all on factor Xa inhibitors. Of these, seven received IVT. In matched analyses, IVT-treated patients showed a numerically greater neurological improvement than untreated patients (mean NIHSS-shift: −2.83 vs. 3.94; mean difference: −6.76, 95% confidence interval [CI]: −24.00 to 7.55; p = 0.495). Functional outcome by mRS-shift showed only minor differences between groups (2.74 vs. 2.10 mean difference: 0.64; 95% CI: −2.00 to 2.50; p = 0.510). IVT showed a favorable trend for early neurological recovery (p = 0.081) but was not independently associated with functional outcome (p = 0.380). Conclusions: ClotPro^® identified a substantial subset of AIS patients on DOAC therapy without measurable anticoagulant activity, enabling IVT in cases that would otherwise have been excluded based on medication history. These findings support the feasibility of ClotPro^®-guided decision-making in acute stroke care and highlight its potential to improve IVT selection by enabling real-time assessment of coagulation status at the bedside. Full article

An isocratic reverse-phase high-performance liquid chromatography (RP-HPLC) method, coupled with photodiode array detection (PDA), was developed for the identification and characterization of stress degradation products and an unknown process-related impurity of rivaroxaban in bulk drug form. Rivaroxaban, a selective and direct Factor Xa inhibitor, underwent forced degradation under hydrolytic (acidic, alkaline, and neutral), photolytic, thermal, and oxidative stress conditions, following the ICH’s guidelines. The drug displayed significant susceptibility to acid, base, and oxidative environments leading to the formation of eleven degradation products. All degradation products, along with process impurities and Rivaroxaban, were effectively separated using a (4.6 × 250 mm, 5 µm) C18 Thermo ODS Hypersil column at ambient temperature. The mobile phase composed of acetonitrile and monobasic potassium phosphate (pH 2.9) in a 30:70 (v/v) ratio, with a flow rate of 1.0 mL/min, and detection was carried out at 249 nm. The LC-PDA method was validated in accordance with the ICH’s guidelines and USP38-NF33, demonstrating specificity, linearity, accuracy, precision, and robustness. Recovery studies showed results within the range of 98.6–103.4%, with a % RSD LT 2%. The limits of detection (LOD) and quantitation (LOQ) for rivaroxaban were determined to be 0.30 ppm and 1.0 ppm, respectively. Stress studies confirmed that the degradation products did not interfere with rivaroxaban detection, establishing the method as stability-indicating. Specific impurities were identified, including impurity G at 2.79 min, impurity D at 3.50 min, impurity H at 5.32 min, impurity C at 6.14 min, impurity E at 8.36 min, impurity A at 9.03 min, and impurity F at 9.49 min. Additionally, several unknown impurities were observed at 3.20, 4.00, 4.59, and 4.77 min. Statistical evaluation confirmed the method’s reliability, making it suitable for routine analysis, quality control of raw materials, formulations of varying strengths, dissolution studies, and bioequivalence assessments of rivaroxaban formulations. Full article

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease. Full article

Direct oral anticoagulants (DOACs) are increasingly used for the treatment of thrombosis. While inhibitors of factor IIa and factor Xa have shown effectiveness, the risk of bleeding remains a significant concern. Recently, direct factor XIa inhibitors—including asundexian and milvexian—have emerged as potential anticoagulation therapies, based on clinical observations that patients with factor XIa deficiencies seldom present with spontaneous bleeding tendencies. The interferences associated with DOACs in routine and specialised coagulation assays are well-described; however, the interferences associated with emerging FXIa inhibitors are largely uncharacterised. Here, we briefly report the impact of asundexian and milvexian in routine coagulation assays using in vitro plasma-based systems. Asundexian and milvexian induce concentration-dependent prolongations in APTT-based assays with curvilinear regressions, which may be suitable for the measurement of pharmacodynamic effects at peak levels ex vivo. We also report differential sensitivities of APTT-based assays—particularly at higher FXIa inhibitor concentrations—highlighting the clinical need for an extensive evaluation of interferences associated with FXIa inhibitors in coagulation assays. Full article

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is linked to deep vein thrombosis (DVT) or pulmonary embolism (PE) in up to one fourth of cases. Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban, however, these require further evidence. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps. Full article

Aims: Our aims were to describe the clinical characteristics, adverse clinical events, healthcare resource utilization (HCRU) and costs of patients with major bleeding during direct Factor Xa inhibitor (FXai) use. Methods: This is a retrospective cohort study that included secondary data from computerized health records of seven Spanish Autonomous Communities. Patients with a first major bleeding during treatment with a direct FXai were analyzed during a 3-year period. Results: Of 8972 patients taking a direct FXai, 470 (5.24%) had major bleeding (mean age (SD) 77.93 (9.71) years, 61.06% women). The most frequent indications for using FXais were atrial fibrillation (78.09%) and venous thromboembolism (17.66%). Among those with major bleeding, 88.94% presented with gastrointestinal bleeding, 6.81% intracranial bleeding, 2.13% trauma-related bleeding and 4.26% other major bleeding. Prothrombin complex concentrates were used in 63.19%, followed by transfusion of blood products (20.21%) and Factor VIIa (7.66%). In total, 4.26% of patients died in the hospital due to the first major bleeding. At the study end (after 3-year follow-up), 28.94% of the patients had died, 12.34% had a myocardial infarction and 9.15% an ischemic stroke. At year 3, overall bleeding cost was EUR 5,816,930.5, of which 79.74% accounted for in-hospital costs to treat the bleeding episode. Conclusions: Despite the use of replacement agents being high, major events were common, with a 29% mortality at the end of the follow up, and HCRU and costs were high, evidencing the need for new reversal treatment strategies. Full article