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Introduction: Data on the perioperative bleeding risk associated with elevated plasma levels of direct factor Xa inhibitors (FXa inhibitors) are limited. This study examines perioperative red blood cell (RBC) loss in patients undergoing urgent surgery with a residual FXa inhibitor level exceeding 100 mcg/L and without preoperative FXa inhibitor reversal. Methods: This retrospective analysis includes data from 32 patients who underwent urgent noncardiac surgery between 2018 and 2022. This study aims to analyze perioperative RBC loss in patients undergoing urgent surgery with a residual FXa inhibitor level exceeding 100 mcg/L and without preoperative FXa inhibitor antidote‐based reversal or unspecific treatment with 4‐factor prothrombin complex concentrate (PCC). All patients were managed using a watch‐and‐wait strategy. Results: The last determination of FXa inhibitor plasma concentration prior to surgery showed a median of 245 mcg/L (IQR 144–345), with a median time interval of 3.8 h (IQR 2.4–7.2) before incision. Median RBC loss during surgery was 49 mL (IQR 0–253), 189 mL (IQR 104–217) until POD1 and 254 mL (IQR 58–265) until POD3. Only one patient required intraoperative treatment with 4‐factor‐PCC and none required reversal with andexanet alfa. Linear regression models found no significant influence of FXa inhibitor plasma levels on intraoperative RBC loss. Rivaroxaban was associated with higher RBC loss until postoperative Day 1 compared with apixaban. No thromboembolic events were observed. Conclusion: Despite markedly elevated plasma concentrations of residual direct FXa inhibitors, perioperative RBC loss was limited in patients undergoing urgent noncardiac surgery. The intraoperative watch‐and‐wait strategy with selective intraoperative FXa inhibitor reversal or treatment only when required appears to be an appropriate approach. [ABSTRACT FROM AUTHOR]

Background: There are limited data about left atrial appendage closure (LAAC) in patients with cancer. We therefore sought to compare the outcome after LAAC in patients with vs. without cancer in a multicentre registry. Methods: In this sub-analysis of the prospective Austrian LAAC Registry, we analysed consecutive patients undergoing LAAC to assess the relationship between baseline characteristics and outcome in patients with vs. without cancer. Inverse probability weighting was performed to adjust for differences in baseline characteristics. Results: A total of 486 consecutive patients from 9 centres with a median age of 75 years (IQR 70–79 years; 35.8% female) were included. Fifty-seven patients (11.7%) had a history of cancer. The median CHA2DS2-VASc and HAS-BLED scores were similar in both groups (median [IQR], 4 [4–6] vs. 5 [3–5], p = 0.415; 4 [3–4] vs. 3 [3–4], p = 0.428 in cancer vs. other patients). Cancer patients were significantly older, and anaemia and gastrointestinal bleeding were significantly more common. Major procedural complications occurred in 5.3% vs. 7.0% (p = 0.276) of patients. The cumulative five-year survival rates were 80.7% and 84.8% in cancer vs. other patients (adjusted hazard ratio for death 1.29 [95% CI 0.67–2.48], p = 0.443). There were also no differences in one-year survival (96.1% vs. 94.0%, p = 0.582) and five-year event-free survival (64.9% vs. 74.4%, p = 0.124). Conclusions: In daily clinical practice, LAAC has already been accepted as a treatment option in patients with cancer. This retrospective analysis shows that short-term and adjusted long-term complications are similar in patients with vs. without cancer undergoing LAAC. [ABSTRACT FROM AUTHOR]

Image-guided biopsy is an integral step in the diagnosis and management of suspicious image-detected breast or axillary lesions, allowing for accurate diagnosis and, if indicated, treatment planning. Tissue sampling can be performed under guidance of a full spectrum of breast imaging modalities, including stereotactic, tomosynthesis, sonographic, and MRI, each with its own set of advantages and limitations. Procedural planning, which includes consideration of technical, patient, and lesion factors, is vital for diagnostic accuracy and limitation of complications. The purpose of this paper is to review and provide guidance for breast imaging radiologists in selecting the best procedural approach for the individual patient to ensure accurate diagnosis and optimal patient outcomes. Common patient and lesion factors that may affect successful sampling and contribute to postbiopsy complications are reviewed and include obesity, limited patient mobility, patient motion, patients prone to vasovagal reactions, history of anticoagulation, and lesion location, such as proximity to vital structures or breast implant. [ABSTRACT FROM AUTHOR]

Objective We evaluated if venous thromboembolism (VTE) prophylaxis in the inpatient antepartum period was associated with wound hematomas, VTE occurrence, and other adverse outcomes. Study Design This study is a secondary analysis of a retrospective cohort of patients who delivered at University of Alabama at Birmingham (UAB). Patients receiving outpatient anticoagulation (AC) were excluded. We grouped patients into those who received inpatient antepartum prophylactic AC and those who did not. The primary outcome was wound hematomas from delivery to 6 weeks postpartum (PP). Secondary outcomes included VTE occurrence and select adverse outcomes, including other wound complications, unplanned procedures, mode of anesthesia, and intensive care unit (ICU) admission. Analyses were performed with no AC group as the reference. A sensitivity analysis excluding those who received inpatient PP AC was performed. Results Of 1,035 included patients, only 169 patients received inpatient prophylactic AC. They were older, had higher body mass indices, and more comorbidities. Patients receiving inpatient antepartum AC had higher wound hematomas (adjusted odds ratio [aOR] 23.81; 95% confidence interval [CI] 7.04–80.47). They had similar risk for developing VTE as the control group (aOR 2.68; 95% CI 0.19–37.49) but were more likely to have wound complications (aOR 2.36; 95% CI 1.24–4.47), maternal deaths (p < 0.05), and require PP ICU admission (aOR 13.38; 95% CI 4.79–37.35). When excluding those receiving any PP AC, there was no difference in bleeding complications between the two groups and VTE rates remained unchanged. Rates of maternal deaths and PP ICU admissions remained higher in those who received inpatient antepartum AC prophylaxis. Conclusion In this small cohort study, increased wound hematomas were found in those who received inpatient antepartum AC prophylaxis with no difference in VTE occurrence. While adverse events were increased in the inpatient AC group, this was mostly associated with PP AC prophylaxis. Larger studies should be conducted to describe the true benefits and risks of antepartum AC prophylaxis and determine efficacy of this widely used practice. Key Points Peripartum chemoprophylaxis is associated with increased wound hematomas. VTE is rare, despite its association with significant peripartum morbidity/mortality. Large studies are needed to guide practices that optimize the risk/benefit ratio of chemoprophylaxis. [ABSTRACT FROM AUTHOR]

Approximately 20% of patients sustaining a fragility femur fracture use an anticoagulant, and over 30% use an antiplatelet medication, both of which can result in surgical delay. Previously confined to fractures of the proximal femur, performance assessment, outcome and surgical delay is now assessed for all fractures of the femur in older patients, including those involving implants. This narrative review draws together all literature pertaining to anticoagulation and antiplatelet management in older patients with a fracture of the femur to address 5 key points: prevalence of anticoagulant and antiplatelet use; analysis of management protocols; collation of national guidelines; comparison of perioperative management; timing of surgery and perioperative outcomes. Our review found that the prevalence of fragility femur fracture patients taking anticoagulant and antiplatelet medication ranges from 20–40% and 25–35% respectively. More anticoagulated patients are taking direct oral anticoagulants compared to vitamin k antagonists with growing implications for variation in practice and delays to surgery. Several national guidelines exist although these are characterised by marked variation, there is little standardisation, and none are generalised across all fragility femur fractures. Expedited surgery within 36 hours of admission in patients taking an anticoagulant or antiplatelet medication is safe and has been demonstrated in fractures of the proximal femur across many small number studies although no such evidence exists in non-proximal femur fractures despite this population sharing similar characteristics. There is a need for all fractures of the femur in older people to be considered when researching and assessing performance in this population to prevent needless variation and delay. [ABSTRACT FROM AUTHOR]

Introduction: There are several types of surface treatments (coatings) aimed at improving the biocompatibility of cardiopulmonary bypass (CPB) circuit. Some coatings appear to require higher doses of heparin to maintain anticoagulation goals, and some of them might induce postoperative coagulopathy. In this study, we compared the amount of heparin required, postoperative bleeding, and inflammatory response according to three types of coatings. Method: We retrospectively included 300 consecutive adult patients who underwent cardiac surgery with CPB and received one of three coatings (Phisio®, Trillium®, and Xcoating™). Our primary objective was to compare, according to coating, the amount of heparin required to maintain an ACT > 400s during CPB. Our secondary objectives were to compare postoperative bleeding for 48 h and CRP rate. Results: Baseline characteristics were comparable between groups except for age and preoperative CRP. We did not find a significant difference between the 3 coatings regarding the amount of heparin reinjected. However, we found less postoperative bleeding with the Xcoating™ circuit compared to the Phisio® circuit (−149 mL [−289; −26.5]; p = 0.02) and a lower elevation of CRP with the Phisio® circuit (2.8 times higher than preoperative CRP) compared to Trillium® (4.9 times higher) and Xcoating™ (6.4 times higher); p < 10–3. Conclusion: The choice of coating did not influence the amount of heparin required during CPB; however, the post-CPB inflammatory syndrome may be impacted by this choice. [ABSTRACT FROM AUTHOR]

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation is a growing epidemic in Africa. Anticoagulation, considered the backbone for non-valvular atrial fibrillation (NVAF) management, is limited to warfarin as the mainstay of available anticoagulation therapy in most low- and middle-income countries (LMIC). The optimal time in the therapeutic range (TTR) while on warfarin is essential to avoid bleeding and thromboembolic complications. This study assessed anticoagulation control in patients with NVAF on warfarin in Johannesburg, South Africa. Methods: We conducted a cross-sectional retrospective study on patients with NVAF managed in the Division of Cardiology, at a tertiary-level academic centre in Johannesburg, South Africa, between 1 January 2015 and 31 December 2019. Anticoagulation control for patients with NVAF was assessed by calculating the TTR using the Rosendaal method. Results: The study population comprised 177 patients diagnosed with NVAF. The mean age was 65.0 ± 13.1 years. The median TTR among patients with NVAF was 46% [interquartile range (IQR): 8.7–86.0], and 63 (35.6%) patients with NVAF had a TTR ≥ 70% (optimal anticoagulation control). Patients with poor anticoagulation control (TTR < 70%) were on warfarin for a shorter duration compared with those with optimal anticoagulation control [56 days (IQR: 43–84) vs. 70 days (IQR: 56–140), p = 0.0013]. The mean CHA2DS2-VASc score was 4 ± 1.5, and it did not differ between patients with poor or optimal anticoagulation control. Among the 175 patients with available HAS-BLED scores, 21 (12.0%), 112 (64.0%) and 42 (24.0%) were at a low, moderate, and high risk for bleeding, respectively. Of the 21 patients in the HAS BLED low-risk category, only 4 (19.0%) had a TTR < 70% (p < 0.001). Warfarin toxicity was documented in 13 (7.3%) patients. Conclusion: In our study, a TTR ≥ 70%, suggesting optimal anticoagulation control, was found in only 35.6% of patients with NVAF on warfarin. [ABSTRACT FROM AUTHOR]

Background: Bleeding complications following intramuscular (IM) injections are generally considered rare with reported incidence of 0.06%. However, evidence on safety of IM injections among anticoagulated hospitalized patients is lacking. The objective of the current study was to examine the incidence of injection site bleeding complications following IM injection among anticoagulated hospitalized patients. Methods: A retrospective comparative study comprised of all hospitalized patients ≥ 18 years old that were treated with ≥ 1 IM injection between 2009 and 2019 in a large tertiary medical center. Bleeding complications were defined as focal hematoma, local bleeding, intramuscular bleeding or compartment syndrome. Each case with IM injection was searched for ICD9 codes (e.g., hematoma, hemorrhage or compartment syndrome) and for indirect evidence suggestive of potential bleeding: hemoglobin drop ≥ 2 g/dl, AST or CPK increase, packed red blood cell transfusion, or abrupt cessation of the anticoagulation. These case were then verified for true injection-site bleeding by natural language processing model and manual review of the electronic medical record. Results: A total of 71,710 patients were treated with 236,406 IM injections. Mean age 53 (± 22) and 63% were females. Concomitant anticoagulation (Heparins: 90.3%, warfarin: 6.8% and DOACs: 4.7%) occurred in 40,819 IM injections (8189 patients). Suspected bleeding complications at the IM injection site were identified among 7,111 patients following 23,089 IM injections, the majority were unrelated to the IM injection-site (e.g., gastrointestinal bleeding, retroperitoneal, etc.). Two cases were verified as true injection site bleeding complication, both in the anticoagulated group (2/8189, 0.02%). Conclusion: Bleeding complications at site of IM injections among anticoagulated hospitalized patients are rare, and their risk is probably not higher compared to patients without anticoagulation. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation. We investigated the impact of UFH dose during ECMO therapy at the coagulation–inflammation interface level, focusing on complement activation and changes in circulating large EV (lEV) subsets. In a post hoc analysis of a multicenter randomized controlled trial comparing two anticoagulation management algorithms, we examined lEV levels and complement activation in 23 veno-venous-ECMO patients stratified by UFH dose. Blood samples were collected at different time points and grouped into three phases of ECMO therapy: initiation (day 1), mid (days 3–4), and late (days 6–7). Immunoassays detected complement activation, and flow cytometry analyzed lEV populations with an emphasis on mitochondria-carrying subsets. Patients receiving <15 IU/kg/h UFH exhibited higher levels of the complement activation product C5a and soluble terminal complement complex (sC5b-9). Lower UFH doses were linked to increased endothelial-derived lEVs, while higher doses were associated with elevated RBC-derived and mitochondria-positive lEVs. Our findings suggest the potential theranostic relevance of EV detection at the coagulation–inflammation interface. Further research is needed to standardize EV detection methods and validate these findings in larger ECMO patient cohorts. [ABSTRACT FROM AUTHOR]

Background: Inconsistent study results and contradictory recommendations from health authorities regarding the use of apixaban in patients on hemodialysis have generated considerable uncertainty among clinicians, making investigations of appropriate dosing an unmet need. Methods: We analyzed pre-dialysis apixaban drug levels from a tertiary care dialysis unit, comparing 2.5 mg once versus twice daily dosing. We applied mixed-effects models including dialysis modality, adjusted standard Kt/V, ultrafiltration, and dialyzer characteristics. We included an exploratory analysis of bleeding events and compared the drug levels of our dialysis patients to those from non-CKD reference populations taking the standard dose of 5 mg twice daily. Results: We analyzed 143 drug levels from 24 patients. Mean (SD) age at first drug level measurement was 64.7 (15.9) years (50 % female), median (IQR) follow-up was 12.5 (5.5 – 21) months. For the apixaban 2.5 mg once and twice daily groups, median (IQR) drug levels were 54.4 (< 40 – 72.1) and 71.3 (48.8 – 104.1) ng/mL respectively (P < 0.001). Levels were below the detection limit in 30 % (with 2.5 mg once daily) and 14 % (with 2.5 mg twice daily) respectively. Only dosing group (twice versus once daily) was independently associated with higher drug levels (P = 0.002). Follow-up did not suggest accumulation. The 95th percentile of drug levels did not exceed those of non-CKD populations taking 5 mg twice daily. Median (IQR) drug levels before a bleeding (8 episodes) were higher than those without a subsequent bleeding: 111.6 (83.1 – 129.3) versus 54.8 (< 40 – 77.1) ng/mL (P < 0.001). Concomitant antiplatelet therapy was used in 86% of those with bleeding events versus 6% without bleeding events (P < 0.001). Conclusions: Drug monitoring may be a contributory tool to increase patient safety. Despite non-existing target ranges, drug levels on both edges of the spectrum (e.g. below detectability or beyond the 95th percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to estimate the effect of remote nursing guidance based on WeChat platform for female patients receiving subcutaneous anticoagulation during the COVID-19 epidemic. Methods: Retrospective analysis of clinical data, including demographic data and anticoagulation complications, of 126 female patients who received subcutaneous anticoagulation therapy and received remote nursing guidance using WeChat platform in our hospital from January 2022 to December 2022. The Anti-Clot Treatment Scale (ACTS) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale were used to evaluate patients' satisfaction with anticoagulation and quality of life at the beginning of anticoagulation, half a month after anticoagulation, and after three months of anticoagulation. Results: In total, 126 patients were involved in this study, all of them were female, 115 cases were natural pregnancy, 11 cases were assisted reproduction. This study included seven cases of lower extremity deep vein thrombosis, 100 cases of hypercoagulable state, 10 cases of antiphospholipid syndrome, and eight cases of protein S deficiency, one case of hyperhomocysteinemia. During the follow-up period, four patients (3.17%) had subcutaneous injection complications, including three cases of subcutaneous hemorrhage and one case of liquid leakage. A total of 123 patients had completed the planned anticoagulation therapy or were receiving anticoagulation therapy as planned, and three patients did not receive anticoagulation therapy as planned (zero cases lost contact, two cases changed treatment units, and one case refused treatment). ACTS score (55.03 ± 1.73) and WHOQOL-BREF score (62.18 ± 3.17) after three months of anticoagulation, ACTS score (54.18 ± 1.20) and WHOQOL-BREF score (60.37 ± 2.25) after half a month of anticoagulation was significantly higher than the ACTS score (47.81 ± 1.69) and WHOQOL-BREF score (55.25 ± 1.85) at the beginning of anticoagulation, and the difference was statistically significant (P value < 0.01). Conclusions: During the COVID-19 pandemic, remote nursing instruction via the WeChat platform for female patients receiving subcutaneous anticoagulation can increase anticoagulation compliance, satisfaction, and quality of life. [ABSTRACT FROM AUTHOR]

Unfractionated heparin is the most used anticoagulative agent for extracorporeal settings in children, including acute hemodialysis modalities. In certain situations, such as heparin‐induced thrombocytopenia, alternatives must be applied. The direct thrombin inhibitor bivalirudin has come forth as an attractive substitute. Bivalirudin is currently only approved for adult use in specific percutaneous coronary intervention settings. However, it has a growing off‐label popularity in different contexts for both adult and pediatric patients. Experience with bivalirudin in children is mainly limited to extracorporeal membrane oxygenation, ventricular assist devices and during cardiopulmonary bypass surgery. Literature about its use as anticoagulation strategy for pediatric hemodialysis is very scarce. Here, we present two pediatric cases where bivalirudin was used during acute hemodialysis, followed by a short summary of recent literature. [ABSTRACT FROM AUTHOR]

Hemorrhage remains a major complication of anticoagulants, with bleeding leading to serious and even life-threatening outcomes in rare settings. Currently available anticoagulants target either multiple coagulation factors or specifically coagulation factor (F) Xa or thrombin; however, inhibiting these pathways universally impairs hemostasis. Bleeding complications are especially salient in the medically complex population who benefit from medical devices. Extracorporeal devices—such as extracorporeal membrane oxygenation, hemodialysis, and cardiac bypass—require anticoagulation for optimal use. Nonetheless, bleeding complications are common, and with certain devices, highly morbid. Likewise, pharmacologic prophylaxis to prevent thrombosis is not commonly used with many medical devices like central venous catheters due to high rates of bleeding. The contact pathway members FXI, FXII, and prekallikrein serve as a nexus, connecting biomaterial surface-mediated thrombin generation and inflammation, and may represent safe, druggable targets to improve medical device hemocompatibility and thrombogenicity. Recent in vivo and clinical data suggest that selectively targeting the contact pathway of coagulation through the inhibition of FXI and FXII can reduce the incidence of medical device-associated thrombotic events, and potentially systemic inflammation, without impairing hemostasis. In the following review, we will outline the current in vivo and clinical data encompassing the mechanism of action of drugs targeting the contact pathway. This new class of inhibitors has the potential to herald a new era of effective and low-risk anticoagulation for the management of patients requiring the use of medical devices. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to discuss medical management of patients with left ventricular assist devices (LVADs) and to summarize recent advancements, specifically focusing on medications for anticoagulation, blood pressure, and heart failure. Recent Findings: Omission of aspirin in LVAD recipients is not associated with an increased risk of pump thrombosis, stroke, or peripheral arterial thromboembolism. Early data from small studies suggest that direct oral anticoagulants can be safely used in patients with the newer generation HeartMate 3 devices. Data supports a mean arterial blood pressure goal of 75-90 mmHg, with avoidance of hypotension. Finally, retrospective studies demonstrate that quadruple guideline-directed medical therapy can be used in patients on LVAD support without an increased risk of adverse events. Summary: Management of LVAD patients is complex, requiring ongoing active decision-making for titration of medications. Larger studies of medical management are needed to further reduce the incidence of gastrointestinal bleeding, right ventricular failure, and increase the potential for myocardial recovery. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the utility of the dilute prothrombin time (DPT) in diagnosing antiphospholipid syndrome (APS), alone and when paired with the dilute Russell viper venom time (DRVVT). Methods Dilute prothrombin time and DRVVT testing was performed on plasma samples spiked with apixaban or rivaroxaban, or depleted of vitamin K–dependent clotting factors. A retrospective analysis of all functional APS testing results over a 44-month period at the University of Chicago Medical Center was performed. Results In spiking studies, the screening clotting time in the DPT (DPTS) is more sensitive to deficiency of vitamin K–dependent factors than is the screening clotting time in the DRVVT (DRVVTS). The converse is true for factor Xa direct oral anticoagulant (DOAC)–spiked plasma. In a 44-month retrospective analysis, only 2.6% of clinical APS panels showed isolated positivity in the DPT-based system. Comparing the DPT-based system with the DRVVT-based system showed utility in identifying false-positive DRVVT results due to anticoagulation. A DRVVTS/DPTS ratio of 0.785 or lower predicted an international normalized ratio of 1.5 or higher (sensitivity, 86.3%; specificity, 60.4%; likelihood ratio, 2.18). Conversely, a DRVVTS/DPTS ratio of 1.165 or higher was the optimal cutoff for predicting the identification of factor Xa DOAC (sensitivity, 61.8%; specificity, 77.8%; likelihood ratio, 2.78). Within the data set that had full DRVVT and DPT results, parameters were identified that could further improve identification of samples with anticoagulation interference. Conclusions Dilute prothrombin time lupus anticoagulant assay is rarely the sole laboratory functional evidence for APS, but when combined with the DRVVT, the DPT can serve as an effective screen for common anticoagulant interference. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) have overtaken warfarin in the treatment of nonvalvular atrial fibrillation (AF) and venous thromboembolism (VTE). Limited data explore the safety of DOACs in obesity. Methods: This multicenter retrospective study between June 2015 and September 2019 uses the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to compare DOACs and warfarin across weight classes (not obese: body mass index (BMI) ⩾ 18.5 and < 30; obese: BMI ⩾ 30 and < 40; severely obese: BMI ⩾ 40). Primary outcomes include major, clinically relevant nonmajor (CRNM), and minor bleeding events per 100 patient-years. Secondary outcomes include stroke, recurrent VTE, and all-cause mortality. Results: DOACs were prescribed to 49% of the 4089 patients with AF and 46% of the 3162 patients with VTE. Compared to patients treated with warfarin, those treated with DOACs had a higher estimated glomerular filtration rate across BMI categories regardless of indication. In the AF population, severely obese patients treated with DOACs had more major (3.4 vs 1.8, p = 0.004), CRNM (8.6 vs 5.9, p = 0.019), and minor bleeding (11.4 vs 9.9, p = 0.001). There was no difference in stroke or all-cause mortality. In the VTE population, both CRNM (7.5 vs 6.7, p = 0.042) and minor bleeding (19.3 vs 10.5, p < 0.001) events occurred at higher rates in patients treated with DOACs. There was no difference in recurrent pulmonary embolism, stroke, or all-cause mortality. Conclusion: There is a higher rate of bleeding in severely obese patients with VTE and AF treated with DOACs compared to warfarin, without a difference in secondary outcomes. Further studies to compare the anticoagulant classes and understand bleeding drivers in this population are needed. [ABSTRACT FROM AUTHOR]

Background: A multidisciplinary Quality Assurance/Performance Improvement study to identify the incidence of "heparin rebound" in our adult cardiac surgical population instead detected a thromboelastometry pattern suggestive of initial protamine overdose in 34% despite Hepcon-guided anticoagulation management. Analysis of our practice led to an intervention that made an additional lower-range Hepcon cartridge available to the perfusionists. Methods: One year later, an IRB-approved retrospective study was conducted in >500 patients to analyze the effects of the intervention, specifically focusing on the impact of the initial protamine dose accuracy and 18-h mediastinal chest tube drainage (MCTd). Results: No differences were observed between group demographics, surgical procedures, duration of CPB or perioperative blood product transfusion. Both groups were managed using the same perfusion and anesthesia equipment, strategies, and protocols. The median initial protamine dose decreased by 19% (p <.001) in the intervention group (170 [IQR 140–220] mg; n = 295) versus the control group (210 [180–250] mg; n = 257). Mean 18-h MCTd decreased by 13% (p <.001) in the intervention group (405.15 ± 231.54 mL; n = 295) versus the control group (466.13 ± 286.73 mL; n = 257). Covariate-adjusted mixed effects model showed a significant reduction of MCTd in the intervention group, starting from hour 11 after surgery (group by time interaction p =.002). Conclusion: Though previous investigators have associated lower protamine doses with less MCTd, this study demonstrates that more accurately matching the initial protamine dose to the remaining circulating heparin concentration reduces postoperative bleeding. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective is to evaluate the impact of consultant pharmacist-directed anticoagulation management in the post-acute and long-term care (PALTC) setting. DESIGN: Retrospective study. PARTICIPANTS: Patients whose clinical details were included in the ASCP aggregate data and were older than 65 years of age, admitted to PALTC facility, and had active anticoagulant therapy were included in the study. INTERVENTIONS: Pharmacists enrolled in the ASCP (Quality Improvement Project) and performed monthly chart reviews per standard practice. The 30-day postchart review follow-up data were entered into the ASCP data collection. The research team assessed for consultant pharmacist interventions associated with anticoagulant therapy management. RESULTS: Data were collected from November 2022 through March 2023, during which 807 charts were assessed. Within the charts reviewed, 274 patients received anticoagulation therapy, of which 173 (63%) were identified as having a medication-related problem concerning anticoagulant use. Two hundred sixteen pharmacist recommendations were sent to providers to address the inappropriate anticoagulant therapy. Providers completed modifications to 190 (88%) of the recommendations. CONCLUSION: This study emphasized pharmacist involvement in managing anticoagulant therapy within the PALTC setting and identified the need for further investigation of patient specific outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Venous thromboembolism (VTE) remains a leading cause of preventable harm among hospitalized patients. Pharmacologic VTE prophylaxis reduces the rate of in-hospital VTE by 60%, but medication administration is often missed for various reasons. Electronic medical record (EMR) prompts may be a useful tool to decrease withholding of critical VTE chemoprophylaxis medications. Methods: In August 2021, an EMR prompt was implemented at a tertiary referral academic medical center mandating nursing staff to contact a provider for approval before withholding VTE chemoprophylaxis. A pre-intervention group from August 2020 to August 2021 was compared to a post-intervention group from August 2021 to August 2022. Rates of VTE chemoprophylaxis withholding were compared between the groups with a P <.01 considered significant. Results: A total of 16,395 patients prescribed VTE chemoprophylaxis were reviewed, with 13,395 (81.7%) receiving low molecular weight heparin. Of the 16,395 patients included, 10,701 (65.3%) were medical and 5694 (34.7%) were surgical. Patients in the pre-intervention cohort (n = 8803) and post-intervention cohort (n = 7592) were similar in hospital length of stay and duration of DVT prophylaxis. In the post-intervention group, the frequency of surgical patients with at least one missed dose had increased by 4.2% (P =.002), with the trauma and acute care surgery (TACS) show an increase of 6.6% (P <.001). However, the frequency of medical patients and non-TACS patients with missed doses decreased by 3.1% (P =.002) and 1.0% (<.001), respectively. Conclusions: EMR prompts appear to be a low-cost intervention that increases the rate of VTE prophylaxis administration among medical and elective surgery patients. [ABSTRACT FROM AUTHOR]

Venous thromboembolism prophylaxis with subcutaneous unfractionated heparin or low molecular weight heparin is a common practice in hospitalized patients. Typically, prophylactic doses of these medications have poor bioavailability and thus do not reach therapeutic serum concentrations. However, in certain circumstances, heparin binding proteins may become saturated. Here we report a case series of 5 patients who had elevated anti-Xa levels while receiving prophylactic dosing of subcutaneous unfractionated heparin. [ABSTRACT FROM AUTHOR]

Background: Four-factor prothrombin complex concentrate (4F-PCC) is indicated for vitamin K antagonist (VKA) reversal but is associated with thrombotic events (TE). In 2018, the institution revised 4F-PCC dosing for VKA reversal from INR and weight-based dosing to a fixed-dose of 1500 units. Objective: The purpose of this study was to compare hemostatic efficacy and TE rate of fixed-dose 4PCC to weight-based dosing. Methods: This was a retrospective, single-center, quasi-experimental study of adult patients who received 4F-PCC for VKA reversal from January 2014 through May 2016 (INR and weight-based dosing) or April through October 2018 (fixed-dosing). The primary endpoint was hemostatic efficacy, defined by achieving an INR of ≤1.4, or an INR of ≤1.7 with evidence of hemostasis. The key secondary endpoint was TE within 14 days of 4F-PCC administration. Data were analyzed using descriptive statistics, chi-squared for nominal data and Mann-Whitney U for ordinal and continuous data. Results: The study included 163 patients who received weight-based dosing and 45 who received fixed-dose 4F-PCC. Hemostatic efficacy was 76.9% of patients in the weight-based group and 77.4% of patients in the fixed-dose group (P =.229). TE occurred in 13.5% of the weight-based vs 6.7% of the fixed-dose group (P =.181). Conclusion: This study found no difference in hemostatic efficacy with fixed-dose 4F-PCC for VKA reversal compared to INR and weight-based dosing. The occurrence of TE was reduced by 50% with the 4F-PCC fixed-dose strategy; however, this difference was not statistically significant. Further randomized studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Purpose: To report an incident of a breakthrough deep vein thrombosis (DVT) and potential example of a drug-drug interaction in a patient treated with edoxaban and rifabutin who was being treated for respiratory tuberculosis. Case: A 76-year-old male presented with anemia requiring transfusion and subsequent shortness of breath that was later diagnosed to be respiratory tuberculosis. He experienced a prolonged hospital stay due to persistently positive Mycobacterium tuberculosis respiratory samples and a complicated social situation that required continuous hospitalization for approximately five months. During his treatment the patient was transitioned from apixaban to edoxaban due to a drug-drug interaction with rifabutin. He subsequently had a DVT while on edoxaban after two months of therapy that would require him to transition to warfarin. Conclusion: This case represents an example of a potentially significant drug-drug interaction between edoxaban and rifabutin. Other direct oral anticoagulants (DOACs) exhibit a potential drug-drug interaction that limit their effectiveness when used with rifamycins. This report describes the first known case of a patient experiencing a DVT after prolonged edoxaban use in combination with rifabutin. Treatment with DOACs for patients taking concomitant cytochrome P450 (CYP) inducers such as rifabutin may be more complicated than previously believed. [ABSTRACT FROM AUTHOR]

A comparative analysis of the specific pharmacological activity and wound-healing properties of zinc oxide nanoparticles (ZnO-NPs) was carried out. It has been shown that ZnO-NP forms reduce the severity of formalin paw edema in mice and the exudative reaction in "felt" granuloma in rats. Notably, the effectiveness of the ointment form exceeded the effectiveness of the gel form. The ability of ointment and gel based on ZnO-NPs has been shown to significantly reduce the recovery time of hemorrhagic soft tissue injuries in rats and, unlike medicinal forms of heparin, to increase the blood clotting time of rabbits by 1.25 times and 1.19 times, respectively. Thus, ointment and gel containing ZnO-NPs are potential medicines with anti-inflammatory, anticoagulant properties and the property of shortening the recovery time of hemorrhagic soft tissue injuries. It is concluded that the therapeutic effect of samples containing ZnO-NPs, due to the ability of these nanoparticles to penetrate the skin epithelium, providing regenerating and fibrinolytic activity, blocking the activity of inflammatory mediators and providing, including the systemic effect on blood clotting. [ABSTRACT FROM AUTHOR]

Purpose: Post-traumatic cerebral venous sinus thrombosis (ptCVT) is a rare but serious complication of traumatic brain injury (TBI). Managing ptCVT is challenging due to the concurrent risk of traumatic intracranial hematoma (ICH) expansion. Limited data exists on the safety and efficacy of anticoagulation therapy (ACT) in these cases. Methods: This single-center observational cohort study included adult TBI patients with concurrent ICH and ptCVT. Low-molecular-weight heparin (LMWH) or heparin infusion was used to treat all ptCVTs based on institutional protocols. The outcomes of interest were hemorrhagic and thrombotic complications. Results: Out of 1,039 TBI-patients admitted between 2006 and 2020, 32 met the inclusion criteria. The median time from injury to ptCVT diagnosis was 24 h. ACT was initiated at a median of 9 h after ptCVT diagnosis. Patients were administered either heparin infusion (n = 8) or LMWH at dosages ranging from 28 to 72% of the therapeutic level (n = 24). There were no hemorrhagic complications, even in patients receiving LMWH at ≥ 50% of the therapeutic dose. Thrombotic complications occurred in 3 patients (9.4%) – two cases of thrombus progression and one venous infarct. The patients who developed thrombotic complications differed from those who did not by having a 17-h delay in ACT initiation after diagnosis or by receiving an initial LMWH dose at 28% of the therapeutic level. Conclusion: LMWH at approximately 50% of the therapeutic level was effective for managing ptCVT associated with TBI in our retrospective dataset, with no risk of hematoma expansion. Prospective trials are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

The document titled "2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)" provides comprehensive guidelines for the management of atrial fibrillation (AF). It covers various aspects of AF, including definitions, diagnostic criteria, symptoms, patient pathways, comorbidity and risk factor management, stroke prevention, rate and rhythm control, evaluation, and dynamic reassessment. The guidelines also address specific clinical settings, such as acute coronary syndromes, stroke, pregnancy, and congenital heart disease. Additionally, it discusses screening and prevention strategies for AF. The document aims to provide evidence-based recommendations to improve the care and outcomes of patients with AF. [Extracted from the article]

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. The prevalence of both AF and dementia is steadily rising and is expected to rise further in the coming decades. There is increasing evidence to suggest an association between AF and various degrees of cognitive dysfunction, from mild cognitive impairment to severe dementia. In this review, we aimed to discuss the epidemiological aspects, pathophysiological mechanisms, role of neuroimaging, impact of treatment modalities, and clinical and socioeconomic impact of this association. Numerous observational studies and meta-analyses have revealed this association to exist in AF patients with and without a history of stroke, and the association also persists after adjusting for shared risk factors such as hypertension and diabetes mellitus. Various pathophysiological mechanisms have been proposed for this association, including silent cerebral infarcts, cerebral microbleeds, cerebral hypoperfusion, inflammation, and atherosclerosis. While neuroimaging findings have been utilized to suggest some of these pathophysiological mechanisms, more studies are needed to further elucidate this and to determine the potential role of neuroimaging in altering anticoagulation and other treatment decisions. Anticoagulants have shown effectiveness in reducing the rate of cognitive decline in AF patients; however, their role in low-risk AF patients remains under investigation. Even though AF patients receiving catheter ablation may have post-operative cognitive dysfunction in the short term, long-term follow-up studies have shown an improvement in cognitive function following ablation. Cognitive decline in AF patients often occurs with greater functional decline and other psychosocial impairments such as depression and anxiety and future research on this association must incorporate aspects of social determinants of health and associated outcomes. [ABSTRACT FROM AUTHOR]

Phyllophorus proteus is a low-value sea cucumber from Indonesia and other tropical peripheral waters. In this study, a fucosylated glycosaminoglycan (FG) was extracted from P. proteus. It consists of GlcA, GalNAc, and Fuc, with a molecular weight of 67.1 kDa. The degraded FG (dFG) was prepared by β-elimination. Structural analysis revealed that the main chain of dFG was composed of GalNAc and GlcA, linked alternately by β1,3 and β1,4 glycosidic bonds. The sulfate group was located at the 4 and 6 positions of GalNAc. Fuc was attached to the 3 position of GlcA by an α1,3 glycosidic bond, and the side chain of Fuc exhibited various sulfate substitutions. FG significantly prolonged the coagulation time of APTT, PT, TT, and FIB, surpassing the effect of LMWH, thereby demonstrating its ability to exert anticoagulant effects in both the endogenous and exogenous coagulation pathways. Conversely, dFG had no significant effect on the clotting time of PT, suggesting its lack of impact on the intrinsic coagulation pathway. This study elucidates the structural properties and potent anticoagulant activities of fucosylated glycosaminoglycan from P. proteus. [ABSTRACT FROM AUTHOR]

Background: Early neurological deterioration (END) occurs in many patients with acute ischemic stroke due to a variety of causes. Although pharmacologically induced hypertension (PIH) and anticoagulants have been investigated in several clinical trials for the treatment of END, the efficacy and safety of these treatments remain unclear. Here, we investigated whether PIH or anticoagulation is better as a rescue therapy for the progression of END in patients with lacunar stroke. Methods: This study included patients with lacunar stroke who received rescue therapy with END within 3 days of symptom onset between April 2014 and August 2021. In the PIH group, phenylephrine was administered intravenously for 24 h and slowly tapered when symptoms improved or after 5 days of PIH. In the anticoagulation group, argatroban was administered continuously intravenously for 2 days and twice daily for next 5 days. We compared END recovery, defined as improvement in NIHSS from baseline, excellent outcomes (0 or 1 mRS at 3 months), and safety profile. Results: Among the 4818 patients with the lacunar stroke, END occurred in 147 patients. Seventy-nine patients with END received PIH (46.9%) and 68 patients (46.3%) received anticoagulation therapy. There was no significant difference in age (P = 0.82) and sex (P = 0.87) between the two groups. Compared to the anticoagulation group, the PIH group had a higher incidence of END recovery (77.2% vs. 51.5%, P < 0.01) and excellent outcomes (34.2% vs. 16.2%, P = 0.04). PIH was associated with END (HR 2.49; 95% CI 1.06–5.81, P = 0.04). PIH remained associated with END recovery (adjusted HR 3.91; 95% CI 1.19–12.90, P = 0.02). Safety outcomes, like hemorrhagic conversion and mortality, were not significantly different between the two groups. Conclusions: As a rescue therapy for the progression of END in lacunar stroke patients, PIH with phenylephrine was more effective with similar safety compared to anticoagulation with argatroban. [ABSTRACT FROM AUTHOR]

Aims This study aimed to compare the effects of the combination of rivaroxaban and aspirin with aspirin alone on health-related quality of life in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. Methods and results Health-related quality of life assessed using the EQ-5D-3L. The treatment effects on health utility and EQ visual analogue scale (EQ VAS) scores were compared between rivaroxaban plus aspirin and aspirin alone in terms of adjusted mean difference in change from baseline and odds ratio of having deterioration events. Nine thousand forty-nine (98.9%) and 6916 (75.5%) completed the EQ-5D-3L at baseline and at final visit, respectively. Nine thousand twenty-eight (98.9%) and 6887 (76.3%) completed the EQ-5D-3L at baseline and final visit, respectively. Mean (standard deviation) health utility and EQ VAS scores at baseline were 0.871 (0.141) and 76.0 (15.3), respectively, for the rivaroxaban plus aspirin group, compared with 0.873 (0.139) and 75.8 (15.1) for the aspirin group. Adjusted mean difference in change from baseline utility was −0.002 [95% confidence interval (CI), −0.006, 0.002, P = 0.30] between the combination therapy group and the aspirin group. The odds ratio (95% CI) of experiencing deterioration in health utility was 1.01 (95% CI, 0.93, 1.10, P = 0.81) between the two groups. Adjusted mean difference in change from baseline EQ VAS was 0.02 (95% CI, −0.43, 0.47, P = 0.93) between the two groups. Conclusion This analysis of the COMPASS trial demonstrated that the quality of life of patients was similar between the rivaroxaban plus aspirin group and the aspirin alone group. Registration Trial registration number: ClinicalTrials.gov number (NCT01776424). Trial protocol and statistical analysis plan: https://www.nejm.org/doi/full/10.1056/NEJMoa1709118#APPNEJMoa1709118PRO. [ABSTRACT FROM AUTHOR]

Background/Objective: Whether left atrial appendage thrombus (LAAT) in patients with atrial fibrillation (AF) on chronic anticoagulation significantly increases cardiovascular risk is unknown. This study aimed to assess LAAT prevalence and its predictive role in cardiovascular events among consecutive anticoagulated patients with AF admitted for electrical cardioversion. Methods: This prospective study included 500 patients. The primary outcome was LAAT on transesophageal echocardiography. Patients were followed up for a median of 1927.5 (interquartile range 1004–2643) days to assess cardiovascular events. Results: LAAT was detected in 65 (13%) patients. No significant differences in stroke, transient ischemic attack, systemic thromboembolic events, or myocardial infarction prevalence were observed between patients with AF with and without LAAT. Hospitalization for heart failure (HF) was more frequent in patients with LAAT than in those without LAAT; however, the effect of LAAT on HF hospitalization was not statistically significant. Patients with LAAT had a significantly higher risk of cardiovascular death than those without LAAT. LAAT and greater left atrial (LA) diameter were associated with higher rates of cardiovascular death. The independent HF hospitalization predictors were greater LA diameter, lower left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR). Conclusions: Patients with AF who received anticoagulation therapy showed a high prevalence of LAAT. LAAT and greater LA diameter were associated with significantly higher rates of cardiovascular death. LAAT, greater LA diameter, lower LVEF, and lower eGFR were associated with poor prognosis in anticoagulated patients with AF and were predictors of disease severity. [ABSTRACT FROM AUTHOR]

With many available data sources, clinicians need to consider the benefit‐risk profile of individual anticoagulants when balancing the need for anticoagulation, including evaluating the risks in patients with comorbidities and potential drug‐drug interactions. This narrative review presents clinical data across multiple phases of drug development for the use of apixaban, a selective factor Xa inhibitor, when taken concomitantly with other agents, and evaluates the benefit‐risk profile of apixaban with these interacting medications. Key subgroup analyses from the phase 3 ARISTOTLE trial (NCT00412984) are presented using data from patients who received either concomitant inhibitors or inducers of cytochrome P450 3A4 and/or P‑glycoprotein. We also review the available evidence for the use of apixaban in patients with cancer‐associated thromboembolism, as well as the use of apixaban in patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Introduction: Patients who undergo percutaneous coronary intervention (PCI) with stenting usually require a period of dual antiplatelet therapy (DAPT) but, when an indication for long-term oral anticoagulation (OAC) such as atrial fibrillation (AF) coexists, triple antithrombotic therapy (TAT) with DAPT and OAC causes concern for excessive bleeding. Achieving the right balance between bleeding and adequate protection from ischemic events remains an issue of debate and subject to ongoing investigation of various antithrombotic regimens and durations. Areas covered: This review describes the landmark clinical trials comparing TAT to a period of dual antithrombotic therapy (DAT) and subsequent meta-analyses. It also describes the international recommendations that have been derived from this evidence and identifies outstanding issues that could be addressed in upcoming or future trials. Expert opinion: The current recommended default strategy of a short period of TAT with clopidogrel followed by the withdrawal of aspirin faces a challenge from the prospect of more consistent P2Y12 inhibition provided by ticagrelor and prasugrel. Ticagrelor monotherapy has already been trialed in patients after PCI without an indication for OAC. DAT with ticagrelor or prasugrel immediately post-procedure could emerge as a comparably safe and more efficacious regimen than one involving clopidogrel in the right setting. [ABSTRACT FROM AUTHOR]

Background Aortobronchial fistulas (ABFs) are rare but potentially life-threatening conditions, often presenting with haemoptysis. They can develop following various thoracic aortic conditions or procedures. Case Presentation A 70-year-old patient with a history of descending aorta replacement and ischaemic stroke presented with chest pain and upper gastrointestinal bleeding. Imaging revealed a fistula between the aortic prosthesis and the lung, along with other cardiovascular abnormalities. Despite the indication for anticoagulant therapy, tranexamic acid was initiated due to bleeding risk. The patient showed clinical improvement with tranexamic acid treatment but experienced recurrence of bleeding after discontinuation. Endovascular treatment for the contained rupture at the proximal stent anastomosis was indicated. Discussion Haemoptysis is the primary symptom of ABFs, often recurring until the fistula enlarges. Postoperative aortic fistulas into the airways are uncommon and can occur years after surgery. Thoracic endovascular aortic repair has become the primary treatment for high-risk patients with thoracic aortic disease. Various diagnostic modalities can visualize a fistula tract, but practical visualization is rare. Untreated ABFs invariably lead to death. Conclusion This case highlights the challenges in diagnosing and managing ABFs, emphasizing the need for a multidisciplinary approach and regular follow-up. Patient education and prompt reporting of symptoms are essential. Early intervention upon suspicion of recurrence is crucial for optimizing patient outcomes. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) in the postoperative phase is a manifestation of numerous factors, including surgical stress, anesthetic effects, and underlying cardiovascular conditions. The resultant cardiac hyperactivity can induce new onset or exacerbate existing AF. A common phenomenon, postoperative atrial fibrillation (POAF) affects nearly 40% of patients and is associated with longer hospitalization stays, and increased mortality, heart failure, stroke, and healthcare costs. Areas of controversy in POAF include whether to anticoagulate patients who have short-lived POAF, especially given their higher bleeding risk in the postoperative period, and the identification of patients who would benefit the most from preventive drug therapy for POAF. This review discusses the pathophysiology and management of POAF, and strategies to reduce its occurrence. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the application value and safety of Warfarin, Rivaroxaban, and Dabigatran in elderly patients with atrial fibrillation. Methods: A total of 180 elderly patients with atrial fibrillation admitted to our hospital were retrospectively analyzed. According to their anticoagulant treatment regimen, patients were divided into three groups: Warfarin (57 cases), Rivaroxaban (61 cases), and Dabigatran (62 cases). General demographic information was collected, and coagulation function indicators—including fibrinogen (FIB), thrombin time (PT), activated partial thrombin time (APTT), and D‐dimer (D‐D)—as well as liver function indexes—including total bilirubin (TbiL), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transferase (ALT)—were compared before and after 4 weeks of treatment. Results: There were no significant differences in demographic characteristics such as gender, age, body mass index, or disease course among the three groups. The total effective rate in the Warfarin group (84.21%) was significantly lower than in the Rivaroxaban (98.36%) and Dabigatran (96.77%) groups (p < 0.05). However, there was no significant difference in the total effective rate between the Rivaroxaban and Dabigatran groups (p > 0.05). Additionally, no significant differences were found in the effects of the three drugs on coagulation function, liver function, or the incidence of bleeding (p = 0.052). Conclusion: Warfarin, Rivaroxaban, and Dabigatran can effectively prevent thrombosis in elderly patients with atrial fibrillation, with Rivaroxaban and Dabigatran showing superior effectiveness. All three drugs demonstrated similar low rates of bleeding events and had no significant impact on coagulation and liver function. [ABSTRACT FROM AUTHOR]

Background: This review article discussed the use of bridging therapy with low‐molecular‐weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). Hypotheses: Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. Results: This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. Conclusion: The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision‐making and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: To determine if anti-Xa testing is associated with improved outcomes for patients <19-years-old on ECMO. Methods: We evaluated the clinical benefit of anti-Xa heparin monitoring utilizing the Bleeding and Thrombosis during ECMO (BATE) database of 514 patients <19-years-old. The BATE database includes incidences of bleeding, thrombosis, and mortality. The database also describes anti-coagulation test utilization. We grouped and analyzed patients based on ECMO indication (cardiac, respiratory, or extracorporeal cardiopulmonary resuscitation [E-CPR]) and age (neonatal vs pediatric). We constructed multivariable logistic regression models to analyze the impact of anti-Xa testing on mortality, bleeding, and thrombosis in each group. Results: Across the entire population, anti-Xa testing did not have a significant effect on the incidence of mortality (43% with anti-Xa testing vs 49% without), bleeding (68% vs 74%), or thrombosis (37% vs 39%). However, among cardiac indicated patients on ECMO (n = 207), anti-Xa testing was significantly associated with reduced odds ratio (OR) of mortality (adjusted OR 0.527, p =.040) and bleeding (adjusted OR 0.369, p =.021). In addition, among neonatal patients on ECMO (n = 264), anti-Xa testing was associated with a significant reduction in the odds ratio of bleeding (adjusted OR 0.534, p =.046). Conclusion: Anti-Xa testing is associated with improved outcomes among cardiac indicated and neonatal patients on ECMO. Additional research to find the optimal heparin monitoring regimen is needed to better support these critically ill patients. In the interim, we recommend clinicians consider utilizing anti-Xa assays as part of their heparin monitoring plan for neonatal and cardiac indicated patients on ECMO. [ABSTRACT FROM AUTHOR]

Background: The impact of anticoagulants (AC) and antiplatelets (AP) on the management of acute epistaxis remains unclear. This study investigated the association between AC/AP therapy and treatment outcomes in patients with acute epistaxis. Methodology: A retrospective analysis of patients presented to the otolaryngology emergency room with acute epistaxis (2014–2022). Patients were categorized based on their regular medications: AP, dual AP therapy (DAPT), new oral anticoagulants (NOAC), vitamin K antagonists (VKA), or no regular AC/AP use (control group). Outcome measures included rates of minor interventions (chemical or electrical cautery, nasal tamponade), major interventions (endoscopic ligation, embolization), recurrent emergency department visits, admission rates, and duration. Results: 786 patients were included with an average follow-up period of 52.56 ± 20.4 months. Compared to the control group, patients on AP, DAPT, or VKA had significantly higher rates of minor interventions (63.1% vs. 74.4%, 79.6%, and 77.3%, respectively, p < 0.05). DAPT users exhibited a higher rate of major interventions than the control (5.6% vs. 1.3%, p = 0.053). NOAC users showed no significant difference in minor interventions compared to control and required no major interventions. Both NOAC and VKA users had significantly higher rates of recurrent epistaxis events and prolonged hospitalization compared to the control (p < 0.01 and p < 0.05, respectively). Conclusions: NOAC demonstrated more favorable outcomes than VKA in patients with acute epistaxis, and DAPT use was associated with an increased need for major interventions. These findings suggest a more conservative approach in NOAC users than other AC/AP agents. [ABSTRACT FROM AUTHOR]

BACKGROUND: A transfeminine patient is a 79-year-old with past medical history significant for type 2 diabetes mellitus, hypertension, gender dysphoria, chronic kidney disease, dyslipidemia, total left hip replacement, and recent provoked deep venous thromboembolism (DVT). She was seen by a pharmacist in a primary care clinic after her discharge from a skilled nursing facility. The patient was experiencing symptoms of gender dysphoria after discontinuation of her estradiol in setting of her DVT. ASSESSMENT: Her renal function was calculated to ensure she was on appropriate dosing of her medications. Because her DVT was provoked, providers determined she would require only 3 months of anticoagulation. Her laboratory test results showed a subtherapeutic estradiol level and her estradiol was restarted. Additionally, aspirin was being prescribed for primary prevention of atherosclerotic cardiovascular disease and was discontinued. OUTCOME: She has significant improvement in her gender dysphoria symptoms with resuming her estradiol and now has a therapeutic estradiol level. She is tolerating her direct oral coagulant well and reports good quality of life. CONCLUSION: When reviewing medications for patients it is important to take several factors into account, including dose, appropriate indication, and patient preference. Pharmacists play a key role, through collaboration with providers, in assessing these medication-specific factors. Estradiol was stopped in this patient because of her DVT, but given her DVT was provoked after a recent surgery, it was unlikely that estradiol was the cause of her clot. Weighing the risks and benefits for any patient is important when determining what medications are appropriate to continue. Additionally, calculating renal function appropriately in a gender-non-conforming patients ensures appropriate and safe dosing. [ABSTRACT FROM AUTHOR]

Introduction: Heparin, a commonly used anticoagulant in cardiac surgery, binds to antithrombin III (ATIII) to prevent clot formation. However, heparin resistance (HR) can complicate surgical procedures, leading to increased thromboembolic risks and bleeding complications. Proper diagnosis and management of HR are essential for optimizing surgical outcomes. Methodology: Diagnosis of HR involves assessing activated clotting time (ACT) and HR assays. Management strategies were identified through a comprehensive review of the literature, including studies exploring heparin dosage adjustments, antithrombin supplementation, and alternative anticoagulants in cardiac surgery patients with HR. A thorough search of relevant studies on HR was conducted using multiple scholarly databases and relevant keywords, resulting in 59 studies that met the inclusion criteria. Discussion: HR occurs when patients do not respond adequately to heparin therapy, requiring higher doses or alternative anticoagulants. Mechanisms of HR include AT III deficiency, PF4 interference, and accelerated heparin clearance. Diagnosis involves assessing ACT and HR assays. HR in cardiac surgery can lead to thromboembolic events, increased bleeding, prolonged hospital stays, and elevated healthcare costs. Management strategies include adjusting heparin dosage, supplementing antithrombin levels, and considering alternative anticoagulants. Multidisciplinary management of HR involves collaboration among various specialities. Strategies include additional heparin doses, fresh frozen plasma (FFP) administration, and antithrombin concentrate supplementation. Emerging alternatives to heparin, such as direct thrombin inhibitors and nafamostat mesilate, are also being explored. Conclusion: Optimizing the management of HR is crucial for improving surgical outcomes and reducing complications in cardiac surgery patients. Multidisciplinary approaches and emerging anticoagulation strategies hold promise for addressing this challenge effectively. [ABSTRACT FROM AUTHOR]

Ambulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times. Patients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation. The cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021). VTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation. [ABSTRACT FROM AUTHOR]

The article outlines the British Society for Haematology's guidelines for investigating and managing antiphospholipid syndrome (APS), an autoimmune disease linked to thrombosis and pregnancy complications. Diagnosis requires clinical events and detection of antiphospholipid antibodies on multiple occasions. It covers the pathophysiology, clinical signs, and lab tests for APS, with specific recommendations for managing patients in different scenarios, like surgery or pregnancy. The guidance stresses accurate testing, tailored treatment plans, and a holistic approach considering individual risks and needs. [Extracted from the article]

Background: There has been growing interest in exploring combined interventions to achieve a more effective heparin-free treatment approach. Aim: to evaluate combination of interventions compared to standard practice (intermittent flushes) to prevent clotting and consequently reduce premature interruptions of hemodialysis. Methods: This open-label randomized controlled trial recruited chronic hemodialysis patients with contra-indication to systemic heparinization. Participants were randomized into one of five groups to receive different strategies of heparin-free hemodialysis treatment for up to three sessions. Primary endpoint: the successful completion of hemodialysis without clotting. Secondary outcomes: the clotting of the air traps assessed by a semi-quantitative scale, online KT/V, and safety of the interventions. Results: Forty participants were recruited and randomized between May and December 2020. Participants showed similar baseline biochemistry results and coagulation profiles. The highest success rates were observed in group 3 (heparin-coated dialyzers combined with intermittent flushes) (100%) and group 5 (hemodiafiltration with online predilution combined with heparin-coated dialyzers), with 91% vs. the control (intermittent flushes) (64%). Group 2 (heparin-coated dialyzers alone) had the poorest success rate, with 38% of the sessions being prematurely terminated due to clotting. KT/V and clotting scores were similar between groups. No adverse events related to the trial interventions were observed. Conclusions: The proposed combination of interventions may have had additive effects, leading to less frequent clotting and the premature termination of an HD/HDF session. Our study supports the feasibility of conducting a larger randomized controlled trial focusing on the efficacy of combined interventions for heparin-free HD in patients with a high risk of bleeding. [ABSTRACT FROM AUTHOR]

Superficial venous thrombosis (SVT) is a fairly common disorder, characterized by the formation of thrombi inside superficial veins, with or without an associated inflammatory reaction. Its evolution is frequently self-limited. However, serious complications may change this clinical course with extension to deep vein thrombosis (DVT) and pulmonary embolism (PE). SVT shares similar risk factors with DVT and is frequently associated with the presence of varicose veins. However, the occurrence of non-varicose veins could conceal risk factors such as malignancies, thrombophilia, or Buerger's disease. While the clinical diagnosis is generally straightforward, additional diagnostic evaluations are often necessary. Duplex ultrasound (DUS) is an invaluable tool that provides the location of SVT, the proximity to the sapheno–femoral junction, and the clot length, all of which influence the decision for optimal management. The treatment of SVT should be symptomatic, pathogenic (limiting the extension of thrombosis), and prognostic (to prevent complications). There are several guidelines that provide recommendations, and despite the need for more consensus and for further studies, the treatment of SVT should be mainly medical, including anticoagulation in specific clinical situations and symptom relief, with invasive treatment in a minority of cases. Initiation, intensity, and length of anticoagulant treatment should be based on the eventual risk of progression to DVT or PE, which can be high, intermediate, or low, based on the location of SVT and the clot length. Our review summarizes the evaluation and proper management of SVT and highlights the importance of a shared decision within the heart team regarding this condition in order to prevent further complications. [ABSTRACT FROM AUTHOR]

Introduction: Antithrombin (AT) deficiency is a rare but highly thrombogenic inherited thrombophilia. Its association with adverse pregnancy outcomes (APO) is undefined. There is limited guidance on managing AT deficiency in pregnancy. Some significant issues remain controversial, including risk assessment for prophylactic anticoagulation, anticoagulant therapy, and monitoring. Our goal was to examine if the antepartum management of patients with AT deficiency affected their pregnancy outcomes. Materials and Methods: This retrospective, single‐center observational study included pregnant women with inherited AT deficiency in Peking Union Medical College Hospital between 2013 and 2024. Results: Seventeen pregnancies in 6 women with AT deficiency were identified. A total of 7 pregnancies received adjusted‐dose low‐molecular‐weight heparin (LMWH) and were monitored by anti‐Xa level, AT activity, and D‐dimer. There were 5 live births (all received LMWH), 7 second‐trimester abortions (1 received LMWH), and 5 early pregnancy losses (1 received LMWH). There were 5 abruptio placentae events (3 received LMWH) and 7 thrombotic events (2 received LMWH). Conclusions: AT deficiency is at least an important partial factor contributing to APO. It is suggested to make a full assessment of AT patients both for venous thrombus embolism and APO risk. We observed a high prevalence of heparin resistance and a positive correlation between adequate anticoagulation and pregnancy outcome based on tight monitoring with anti‐Xa level and timely adjustment of the LMWH dosage. [ABSTRACT FROM AUTHOR]

Background: American Association for Thoracic Surgery and The International Society for Heart and Lung Transplantation (AATS/ISHLT) guidelines recommend warfarin in patients with continuous-flow left ventricular assist devices (LVADs) to reduce the risk of device thrombosis and systemic embolization. Left ventricular assist device patients often undergo elective and emergent procedures that require interrupted anticoagulation. Data and experience vary on the optimal strategy to rapidly reverse warfarin in LVAD patients when an emergent procedure is planned. Objective: The purpose of this study was to describe the use of 4-factor prothrombin complex concentrate (PCC4) for warfarin reversal in patients with LVADs undergoing elective and emergent procedures. Methods: This retrospective, single-center, cohort review describes the use of PCC4 in patients with LVADs who require warfarin reversal for elective or emergent procedures. The primary outcome was a composite incidence of pump thrombosis, venous thromboembolism, and ischemic stroke within 30 days of PCC4 administration. Results: In total, 14 patients received 17 administrations of PCC4. One patient received 3 administrations, and 1 other patient received 2 administrations during separate encounters. The median dose was 500 units or 6.6 units/kg (range = 4.2-14.1 units/kg). Of the PCC4 administrations, 82% (14/17) were for low bleed risk procedures and 76% (13/17) were for elective procedures. There were no cases of pump thrombosis, venous thromboembolism, or stroke within 30 days of the procedure. Conclusions and Relevance: Low-dose PCC4 appears to be a safe and effective temporary reversal strategy for patients with LVADs undergoing low-bleed risk elective procedures. [ABSTRACT FROM AUTHOR]

Background and purpose: The impact of bridging thrombolysis prior to endovascular thrombectomy (EVT) compared to EVT alone on intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH), and death in anticoagulated atrial fibrillation (AF) patients with acute ischaemic stroke (AIS) is not well defined. Methods: A retrospective study was conducted using data from a federated research network (TriNetX) including 114 health care organisations in the United States. Anticoagulated AF patients with AIS who received either bridging thrombolysis (BT) or EVT alone from September 2018 to November 2023 were included. Following propensity score matching, Cox regression analyses examined the risk of ICH, SAH, and death within 30 and 90 days, comparing anticoagulated AF patients receiving BT versus EVT only. Results: A total of 3156 patients with AIS were treated with BT or EVT alone. Following 1:1 propensity score matching, the cohort included 766 patients in each group. ICH occurred within 30 and 90 days in 6.9% and 8.0% in the BT group compared with 7.4% and 7.7% in the EVT‐only group (hazard ratios [HR] = 0.92, 95% confidence interval [CI] = 0.63–1.33 and HR = 1.01, 95% CI = 0.71–1.45, respectively). SAH occurred within 30 and 90 days in 4.2% and 4.4% of patients in the BT compared to 3.0% and 3.4% in the EVT‐only group (HR = 1.38, 95% CI = 0.81–2.38 and HR = 1.29, 95% CI = 0.77–2.14, respectively). Death occurred within 30 and 90 days in 17.8% and 19.8% of patients in the BT compared to 22.2% and 27.3% in the EVT‐only group (HR = 0.77, 95% CI = 0.62–0.97 and HR = 0.65, 95% CI = 0.56–0.86, respectively). Conclusions: In anticoagulated AF patients with AIS, BT was associated with a significantly lower risk of death, with no difference in ICH or SAH risk within 30 and 90 days compared to EVT only. [ABSTRACT FROM AUTHOR]

Background : Several studies have examined INR fluctuations using pharmacokinetic (PK) models or post-hoc INR values after completing nirmatrelvir/ritonavir, but further study of the effects of the drug interaction with warfarin during treatment is necessary. Case Summary : Nirmatrelvir/ritonavir is largely utilized in the outpatient setting so data regarding INR trends in hospitalized patients on warfarin is limited. However, many who receive nirmatrelvir/ritonavir outpatient experience difficulty with presenting to clinic for INR checks due to feeling acutely ill along with isolation precautions. We present the case of a patient receiving warfarin and utilizing home INR testing for monitoring. After diagnosis of coronavirus disease of 2019 (COVID-19), she was started on nirmatrelvir/ritonavir on day five after testing positive. Most recent INR prior to the start of therapy was 2.7 and had been stable on the same dose for months prior to infection. On day two of nirmatrelvir/ritonavir, her INR rose to 4.0 on home point of care INR testing. Despite reducing her dose of warfarin by 15%, her INR remained supratherapeutic the day after completing nirmatrelvir/ritonavir (4.0) and for several checks after. One month after completion of therapy, her INR returned to therapeutic levels. Practice Implications : While PK models and case series have hypothesized both potential increases or decreases in INR with the nirmatrelvir/ritonavir and warfarin interaction, COVID-19 infection itself can cause several pharmacodynamic changes which can increase INR, including decreased appetite and, in severe cases, organ dysfunction. This case provides real-world insight into the drug interaction between nirmatrelvir/ritonavir and the drug-disease state interaction between warfarin and COVID-19. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use. [ABSTRACT FROM AUTHOR]