Minimize Bleeding Risk Research Articles

Bleeding risk of small intracranial aneurysms in a population treated in a reference center.

Large multicenter studies have shown that small intracranial aneurysms are associated with a minimal risk of bleeding. Nevertheless, other large series have shown that most ruptured aneurysms are, in fact, the smaller ones. In the present study, we questioned whether small aneurysms are indeed not dangerous. We enrolled 290 patients with newly-diagnosed aneurysms at our institution over a six-year period (43.7% ruptured). We performed multivariate analyses addressing epidemiological issues, cardiovascular diseases, and three angiographic parameters (largest aneurysm diameter, neck diameter and diameter of the nutrition vessel). Risk estimates were calculated using a logistic regression model. Aneurysm size parameters were stratified according to receiver operating characteristic (ROC) curves. Finally, we calculated odds ratios for rupture based on the ROC analysis. The mean largest diameter for the ruptured versus unruptured groups was 13.3 ± 1.7 mm versus 22.2 ± 2.2 mm (p < 0.001). Multivariate analysis revealed a positive correlation between rupture and arterial hypertension (p < 0.001) and an inverse correlation with all three angiographic measurements (all p < 0.01). Aneurysms from the anterior cerebral artery bled more often (p < 0.05). According to the ROC curves, at the largest diameter of 15 mm, the sensitivity and specificity to predict rupture were 83% and 36%, respectively. Based on this stratification, we calculated the chance of rupture for aneurysms smaller than 15 mm as 46%, which dropped to 25% for larger aneurysms. In the population studied at our institution, small aneurysms were more prone to bleeding. Therefore, the need for intervention for small aneurysms should not be overlooked.

MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans

AbstractA large unmet medical need exists for safer antithrombotic drugs because all currently approved anticoagulant agents interfere with hemostasis, leading to an increased risk of bleeding. Genetic and pharmacologic evidence in humans and animals suggests that reducing factor XI (FXI) levels has the potential to effectively prevent and treat thrombosis with a minimal risk of bleeding. We generated a fully human antibody (MAA868) that binds the catalytic domain of both FXI (zymogen) and activated FXI. Our structural studies show that MAA868 traps FXI and activated FXI in an inactive, zymogen-like conformation, explaining its equally high binding affinity for both forms of the enzyme. This binding mode allows the enzyme to be neutralized before entering the coagulation process, revealing a particularly attractive anticoagulant profile of the antibody. MAA868 exhibited favorable anticoagulant activity in mice with a dose-dependent protection from carotid occlusion in a ferric chloride–induced thrombosis model. MAA868 also caused robust and sustained anticoagulant activity in cynomolgus monkeys as assessed by activated partial thromboplastin time without any evidence of bleeding. Based on these preclinical findings, we conducted a first-in-human study in healthy subjects and showed that single subcutaneous doses of MAA868 were safe and well tolerated. MAA868 resulted in dose- and time-dependent robust and sustained prolongation of activated partial thromboplastin time and FXI suppression for up to 4 weeks or longer, supporting further clinical investigation as a potential once-monthly subcutaneous anticoagulant therapy.

Perioperative Blood Pressure Monitoring in Patients With Obesity.

Blood pressure monitoring plays a key part in the preoperative, intraoperative, and postoperative care of all patients. In patients with obesity, hypertension indicates increased metabolic and surgical risk and may signal the presence of significant medical comorbidities, including obstructive sleep apnea. Avoidance of hypertension postoperatively is necessary to minimize bleeding risk after surgery. Hypotension in the postoperative period may be the first sign of significant complications that require urgent management. With the problem of being overweight or obese now affecting two-thirds of adults in Western countries, the proportion of patients with obesity in perioperative environments is similarly increasing. Detection of aberrations in blood pressure is contingent on the accuracy of blood pressure measurement methods. Patients with obesity tend to have a large arm circumference and "cone-shaped arms." Standard blood pressure cuffs fit such patients poorly, and this compromises the accuracy of measurements. Alternatives to arm blood pressure cuffs, some made specifically for individuals with obesity, have been evaluated but are not widely available to clinicians. This focused narrative review will discuss the relevance of hypertension management in the care of patients with obesity, highlight the currently available methods for perioperative monitoring of blood pressure, and explore the opportunities that exist to improve the perioperative blood pressure care in patients with obesity undergoing surgical procedures.

Evaluation of safety and diagnostic yield of pleural cryobiopsies during thoracoscopy

BackgroundBiopsies using cryoprobe are now widely used in interventional pulmonology. There are only few data available on the use of cryotechnique through rigid thoracoscopy.AimThe aim of this work was to evaluate the diagnostic yield and safety of pleural cryobiopsies using rigid thoracoscopy.Patients and methodsA total of 30 patients with undiagnosed exudative pleural effusion who underwent rigid thoracoscopy were included in our study. Biopsies were obtained from suspicious areas by rigid forceps and cryoprobe.ResultsA total of 30 patients with undiagnosed exudative pleural effusion have been analyzed. Histopathological results of thoracoscopic pleural biopsies revealed that the most common diagnosis was malignancy (50%), followed by tuberculosis (26.7%). Cryobiopsy specimens were larger than forceps biopsy specimens, with no difference in diagnostic yield (76.7%). Cryotechnique proved to be beneficial in cases of thin highly vascular pleura, allowing easier biopsies with lesser risk of bleeding. In cases of thickened fibrous pleura, there was no difference between both the techniques.ConclusionPleural cryobiopsies through rigid thoracoscopy is a simple and safe procedure. It has a high diagnostic yield similar to rigid forceps biopsy, and it showed better performance in thin highly vascular pleura where biopsies can be performed with minimal risk of bleeding.

To Maintain or Cease Non-Vitamin K Antagonist Oral Anticoagulants Prior to Minimal Bleeding Risk Procedures: A Review of Evidence and Recommendations.

For procedures associated with minimal bleeding risk, there are data and experience to support the practice of continuing vitamin K antagonists rather than interrupting therapy, to prevent exposing patients to the undue risk of developing thromboembolism during anticoagulation cessation. Despite the increasing use of non-vitamin K oral anticoagulants (NOACs), there is little evidence to guide the management of these drugs around minimal bleeding risk procedures. This review examines and discusses the major society guidelines and recommendations addressing the management of NOACs around minimal bleeding risk procedures. Additionally, it summarizes the existing evidence, and highlights the gaps in knowledge where evidence is not yet available. Finally, recommendations are made to assist the proceduralist deal with this area of limited evidence.

Clinical Characteristics and Response Rates to Eltrombopag for Primary and Secondary Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplant (HCT)

Introduction Thrombocytopenia after HCT is multifactorial in etiology and frequently requires prolonged transfusions to minimize bleeding risks. Eltrombopag (TPO) is a thrombopoietin agonist that is FDA-approved for use in the setting of ITP. Given encouraging studies in aplastic anemia, TPO is increasingly used after HCT in the setting of poor engraftment and thrombocytopenia; however, published data is limited to small retrospective cases/series. We present our single institution experience. Methods We retrospectively reviewed HCT patients and identified the clinical characteristics and outcomes of those who received TPO post HCT from 1/1/13 to 10/1/18. We excluded patients with documented relapses at the time of TPO initiation. Results 17 patients were identified; 9 had primary failure of platelet recovery ( 30K without transfusion preceding 7 days). Of 7 responders, 5 were started as outpatients. Median time to response was 39 days (range 10 – 118). In 5 patients with unidentified relapse at TPO start, TPO preceded diagnosis of relapse by median 62 days (range 22-281). Of the 9 patients who started TPO as inpatient, 7 subsequently died with median time from TPO to death 195 days (range 18-398). No significant toxicities to TPO were identified. The median time from TPO outpatient prescription to start was 22 days due to insurance delays (range 8-40). Conclusion While causality is difficult to establish, TPO was associated with improvement of platelet counts in a subset of patients, with responses most likely to occur in outpatients with viral reactivation, GvHD, or primary poor engraftment. In 5 patients with unidentified relapse, start of TPO preceded a diagnosis of relapse by median 62 days. This should alert clinicians to assess for relapse when considering TPO. The start of TPO in inpatients generally reflects grave clinical outlook given low response rates and high number of subsequent deaths.

Canadian Urological Association guideline on perioperative thromboprophylaxis and management of anticoagulation

Surgery exposes patients to a risk of venous thromboembolism (VTE) and bleeding. VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE), which represent serious and sometimes fatal consequences of surgery. Therefore, optimizing treatment plans to reduce VTE risk while also minimizing bleeding risk is important to patients and the healthcare system. The goal of this Canadian Urological Association (CUA) guideline is to provide a structured approach to the prevention of perioperative thromboembolic events that may be applied in Canada. In this guideline, two forms of perioperative VTE prophylaxis are considered. The first is prophylaxis used for primary prevention VTE for patients undergoing surgery. The second is management of an anticoagulant or antiplatelet agent used for treatment or as a form of secondary prevention during the perioperative period. The CUA thromboprophylaxis guideline panel feels that it is important for urologists to be engaged in the discussion and management in each of these situations. The panel recognizes that in many clinical contexts, other specialists, including internists, cardiologists, neurologists, and hematologists, may also be involved in this aspect of patient care. The guidance provided in this document is intended to help urologists engage with their patients and colleagues in a collaborative context. The guidance provided in this document is intended to reflect best practice for the usual case for a specific surgery and patient population. This guideline is not intended for unusual conditions or circumstances, which are typically rare, and should be addressed involving appropriate specialists on a case-by-case basis. Decisions regarding thromboprophylaxis involve a tradeoff, in which the intended purpose is to decrease the risk of VTE while recognizing that thromboprophylaxis also increases the risk of bleeding. A systematic review and meta-analysis of randomized placebo-controlled trials performed for the American College of Chest Physicians VTE guideline reported that VTE prophylaxis decreases the relative risk of VTE by 50% and increases the relative risk of bleeding by 50%.1 In cases where the risk of VTE is high and the bleeding risk is low, VTE prophylaxis is usually warranted because the net benefit is favourable. When the risk of VTE is low and the bleeding risk is high, VTE prophylaxis may be harmful and is usually not warranted. In many cases, the tradeoff between VTE prevention and bleeding risk may be close and the “most favourable” approach to VTE prophylaxis is less clear. In these situations, individual patient values and preferences must be considered to determine the best management plan (Fig. 1). Open in a separate window Fig. 1 Graphical depiction of evaluating the tradeoffs of venous thromboembolism (VTE) and bleeding.

Preventing Thromboembolic Events in Atrial Fibrillation

Preventing thromboembolic events related to atrial fibrillation (AF) must be balanced with minimizing bleeding risk. In this systematic review of 6

Partial tubal devascularisation: a novel procedure for tubal conservation in ectopic pregnancy

Ectopic pregnancy is a serious condition that complicates 1–2% of pregnancies. Using surgical management is efficient, but may have an impact on future fertility. Although conservative tubal surgery has not been shown to have a significant advantage over a salpingectomy in terms of the future fertility potential, the conservative surgical techniques remain widely-utilised, particularly in the context of a contralateral diseased or absent tube. We hereby report a case series of a novel procedure to conserve the fallopian tube with the minimal risk of an incisional site bleeding through a partial segmental devascularisation. This technique seems to be an efficient method to minimise the intraoperative bleeding, limit the need for a blood transfusion, and yields a higher success rate of the procedure without jeopardising the blood supply and vitality of the tubes.Impact StatementWhat is already known on this subject? Conservative surgery has a significant value in women with a contralateral absent or diseased tube. However, a conservative management could be challenging due to the significant bleeding which can be encountered during the surgery.What the results of this study add? The partial devascularisation technique could achieve an adequate haemostasis by blocking the ascending blood supply only to the affected segment of the fallopian tube.What the implications are of these findings for clinical practice and/or further research? A partial devascularisation is a successful conservative surgical treatment option in most patients when the procedure is indicated.

A Review of Thrombolysis in Venous Thromboembolism With an Analysis of Alteplase Admixture Stability

Our objective is to review important and recent clinical trials of systemic and local thrombolysis for acute venous thromboembolism (VTE). While anticoagulation is the cornerstone of VTE treatment, systemic thrombolysis is recommended for the highest risk pulmonary embolism (PE) patients who present with hypotension and also have a low bleeding risk. Utilization of low-dose, catheter-directed thrombolytic administration with or without ultrasound energy may minimize bleeding risk beyond systemic thrombolysis. Venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a common cardiovascular disease. Current guidelines recommend anticoagulation over catheter-directed thrombolysis in acute DVT primarily due to the limitations of available data. Clinical trial information is conflicting on whether catheter-directed thrombolysis reduces rates of post-thrombotic syndrome and improves rates of vessel patency. Stability data on alteplase in the catheter-directed setting are limited. Our mass spectrometry analysis indicates that a wide range of alteplase concentrations are stable for at least 24 h. These data can reassure pharmacists, nurses, and physicians that alteplase remains stable during infusion durations utilized in catheter-directed thrombolysis. Individual facilities can tailor their alteplase preparation to meet their own institutional needs.

4:03 PM Abstract No. 228 Ultrasound-assisted catheter-directed thrombolysis for submassive pulmonary embolism: efficacy in relief of right heart strain

To determine the outcomes, safety profile, and efficacy of ultrasound-assisted catheter-directed thrombolysis for pulmonary embolism with right heart strain. The charts of 30 consecutive patients who underwent CDT as treatment for pulmonary embolism were reviewed. Risk factors for bleeding were noted. Indicators of right heart strain on computed tomography and echocardiogram, as well as degree of pulmonary vascular obstruction, were recorded before and after CDT. Thirty-day mortality and occurrence of bleeding events were recorded. Right ventricular systolic pressure decreased from an average of 53.1 mm Hg to 38.5 mm Hg (p = <0.001) and average Qanadli index of pulmonary vascular obstruction decreased from 49 to 34 (p = <0.001) after CDT. The average ratio of RV/LV diameter decreased from 1.48 to 1.17 (p = <0.001) The number of patients with RV hypokinesis decreased significantly (p = 0.016) from 19 (95% of those with available data) to 12 (60%). The number of patients with RV dilation decreased significantly (p = 0.031) from 19 (95% of those with available data) to 13 (65%). Nine (30%) patients had three or more minor contraindications to thrombolysis and fourteen (47%) had had major surgery in the month prior to CDT. No patients experienced major or moderate bleeding attributed to CDT. In our experience CDT proved effective in the rapid alleviation of right heart strain with minimal bleeding risk. Right heart strain is associated with increased mortality and long-term morbidity in pulmonary embolism and CDT may allow for a safe means of improving outcomes in submassive pulmonary embolism. We found CDT to be a safe alternative to systemic thrombolysis in patients with risk factors for bleeding such as prior surgery.Tabled 1Measures of Right Heart Strain Before and After CDTPre-CDT MeanSDPost-CDT MeanSDDifference MeanSDP ValueRVSP53.115.138.510.214.512.6<0.001RV/LV1.480.321.170.260.322.16<0.001Qanadli Index4918341315.410.1<0.001 Open table in a new tab

Ultrasound-Assisted Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism

Catheter-directed thrombolysis (CDT) is a relatively new therapy for pulmonary embolism that achieves the superior clot resolution compared to systemic thrombolysis while avoiding the high bleeding risk intrinsically associated with that therapy. In order to examine the efficacy and safety of CDT, we conducted a retrospective cohort study of patients undergoing ultrasound-assisted CDT at our institution. The charts of 30 consecutive patients who underwent CDT as a treatment of pulmonary embolism at our institution were reviewed. Risk factors for bleeding during thrombolysis were noted. Indicators of the right heart strain on computed tomography and echocardiogram, as well as the degree of pulmonary vascular obstruction, were recorded before and after CDT. Thirty-day mortality and occurrence of bleeding events were recorded. Nine (30%) patients had 3 or more minor contraindications to thrombolysis and 14 (47%) had major surgery in the month prior to CDT. Right ventricular systolic pressure and vascular obstruction decreased significantly after CDT. There was a significant decrease in the proportion of patients with right ventricular dilation or hypokinesis. Decrease in pulmonary vascular obstruction was associated with nadir of fibrinogen level. No patients experienced major or moderate bleeding attributed to CDT. Catheter-directed thrombolysis is an effective therapy in rapidly alleviating the right heart strain that is associated with increased mortality and long-term morbidity in patients with pulmonary embolism with minimal bleeding risk. Catheter-directed thrombolysis is a safe alternative to systemic thrombolysis in patients with risk factors for bleeding such as prior surgery. Future studies should examine the safety of CDT in patients with contraindications to systemic thrombolysis.

178 - A Single Institution Experience of Performing Bloodless Transplant in a Jehovah's Witness Patient Based on Data Gathered from Review of Transfusion Support Requirements in Autologous Stem Cell Transplantation for the Treatment of 60 Myeloma Patients

Background: High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has been shown to prolong survival in patients with multiple myeloma. A common and expected complication of pre-transplant conditioning chemotherapy is severe multi-lineage cytopenias, which results in significant transfusion requirements. Jehovah's Witnesses (JWs) are members of a large and growing religious group that do not accept transfusion of blood products, regardless of circumstance. Many large transplant centers refuse to transplant JWs due to the complexity of treating cytopenic patients without blood product transfusions. However, some transplant centers that specialize in bloodless medicine and surgery have successfully transplanted a large number of JWs without transfusion support. In order to increase the likelihood of successful outcomes in this population, potential ASCT candidates are treated with a variety of agents to maximize baseline hemoglobin and platelet counts. Methods: This is a retrospective case series of patients with multiple myeloma who underwent an ASCT at our institution in 2016. Sixty patients were included. All patients were greater than 18 years of age, and significant inclusion criteria included a high-dose melphalan conditioning regimen (200 mg/m2), a disease status of partial response or better at time of transplantation, and peripheral blood counts of hemoglobin ≥ 10 g/dL and platelet > 100 × 109/L prior to the initiation of melphalan. Results: A total of 60 cases were reviewed. Only 6 patients (10%) required at least 1 red blood cell (pRBC) transfusion while 39 patients (65%) required at least 1 platelet transfusion. The median time to first platelet transfusion was 10 days (range, 9-13 days) and the median time to first pRBC transfusion was 11 days (range, 10-13 days). We observed that majority of patients in our study required platelet transfusion whereas only 10% required pRBC transfusion. These findings assisted in designing a novel protocol for bloodless autologous transplant in JWs. We plan to give a JW patient romiplostim 4 mcg/kg weekly on day +2 post-ASCT to enhance platelet recovery and decrease risk of thrombocytopenia related bleeding, in addition to standard-of-care conservative bleeding risk reduction techniques. Additionally, we plan to judiciously use aminocaproic acid, erythropoietin, desmopressin and vitamin K in conjunction with romiplostim to keep hemoglobin stable and minimize bleeding risk. Conclusion: The majority of multiple myeloma patients with a baseline hemoglobin ≥ 10 g/dL and platelet > 100 × 109/L s only require platelet transfusion after ASCT. The frequency of severe thrombocytopenia is a limitation for JWs who would benefit from this procedure. We propose using romiplostim as an adjunct to conservative bleeding risk reduction techniques in a JW patient.

A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery.

The aim of this study was to determine the bleeding risks associated with single (aspirin) and dual (aspirin + clopidogrel) antiplatelet therapy (DAPT) versus placebo or no treatment in adults undergoing noncardiac surgery. The impact of antiplatelet therapy on bleeding during noncardiac surgery remains controversial. A meta-analysis was performed to examine the risk associated with single and DAPT. A systematic review of antiplatelet therapy, noncardiac surgery, and perioperative bleeding was performed. Peer-reviewed sources and meeting abstracts from relevant societies were queried. Studies without a control group, or those that only examined patients with coronary stents, were excluded. Primary endpoints were transfusion and reintervention for bleeding. Of 11,592 references, 46 studies met inclusion criteria. In a meta-analysis of >30,000 patients, the relative risk (RR) of transfusion versus control was 1.14 [95% confidence interval (CI) 1.03-1.26, P = 0.009] for aspirin, and 1.33 (1.15-1.55, P = 0.001) for DAPT. Clopidogrel had an elevated risk, but data were too heterogeneous to analyze. The RR of bleeding requiring reintervention was not significantly higher for any agent compared to control [RR 0.96 (0.76-1.22, P = 0.76) for aspirin, 1.84 (0.87-3.87, P = 0.11) for clopidogrel, and 1.51 (0.92-2.49, P = 0.1) for DAPT]. Subanalysis of thoracic and abdominal procedures was similar. There was no difference in RR for myocardial infarction [1.06 (0.79-1.43)], stroke [0.97 (0.71-1.33)], or mortality [0.97 (0.87-1.1)]. Antiplatelet therapy at the time of noncardiac surgery confers minimal bleeding risk with no difference in thrombotic complications. In many cases, it is safe to continue antiplatelet therapy in patients with important indications for their use.

Aspirin Thromboprophylaxis in Joint Replacement Surgery

Introduction. Total knee replacement (TKR) and total hip replacement (THA) surgeries have historically been felt to carry a high risk of post-operative venous thromboembolism (VTE) events thereby warranting anticoagulant prophylaxis. This risk however was based on composite endpoints in which asymptomatic DVT on venography, as opposed to symptomatic VTE or VTE-related mortality, constituted the majority of the events. Furthermore, current day orthopedic practices have likely led to a reduction in risk of VTE, thought to be 3-5% in the absence of prophylaxis. While the American College of Chest Physicians (ACCP) guidelines recommend the use of an anticoagulant for prophylaxis for all patients undergoing TKR and THR over aspirin, American Academy of Orthopaedic Surgeons (AAOS) guidelines classify patients without a prior history of VTE, and those not meeting their high risk criteria (significant cardiovascular disease; BMI &amp;gt; 40; smoking + DM + BMI &amp;gt; 35; and recent cancer) as low-risk; aspirin (325 mg twice daily) is a recommended alternative for post-operative VTE prophylaxis in these patients. As a result, many orthopedic surgeons in the US use aspirin for patients without major risk factors for VTE other than the surgery itself, accounting for over 40% joint replacement surgery cases in the US. The risk of symptomatic VTE in this patient population outside of small and primarily retrospective studies remains unknown. We conducted a prospective cohort study of patients receiving aspirin thromboprophylaxis following TKR and THR surgery at a large orthopedic specialty hospital to assess the risk of clinically symptomatic VTE and bleeding events. This is a preliminary analysis of planned total accrual of 500 subjects (assuming 2% VTE event rate in aspirin-treated patients, as compared to 1% in anticoagulant-treated, with alpha and beta error levels of 5% and 50%, respectively, and accounting for attrition rate of at least 10%). Methods. All TKR and THR patients prescribed aspirin for VTE prophylaxis by the surgical team and not on any anticoagulant medications were eligible for the study. Study subjects were identified and consented post-operatively prior to their hospital discharge. Enrolled subjects were followed for symptomatic VTE and bleeding events during their hospitalization, and then contacted at 30 and 90 days postoperatively for a telephone survey. Symptomatic VTE and bleeding events were captured using a questionnaire and outside records obtained to confirm VTE or major bleeding events. Three-month risk of symptomatic VTE and major bleeding events associated with aspirin thromboprophylaxis were estimated. Results. A total of 300 patients, 199 TKR and 101 THR, have been enrolled in this ongoing study so far. Table 1 shows the baseline characteristics of the patients. A total of 6 symptomatic VTE (4 pulmonary emboli, 1 proximal deep vein thrombosis (DVT) and 1 isolated-distal DVT) occurred during the follow up period. (3-month post-op VTE event rate of 2%). 3 events were diagnosed during hospitalization, whereas the remaining 3 occurred following hospital discharge (within 7-10 days). Bruising was a common side effect affecting nearly 3% of the patients, but major bleeding events were rare, only 1 major upper gastrointestinal bleeding, giving a 3-month risk of 0.33%. There were no surgical bleeds reported. Conclusions. In this single-center prospective cohort study of TKR and THR patients considered to be at lower risk for VTE, the use of aspirin for thromboprophylaxis was associated with a 2% symptomatic VTE event rate over three months of follow up with minimal bleeding risk. This result, together with those of the EPCATII study from Canada showing that low-dose aspirin was as effective (~0.7% event rate) following 5 days of rivaroxaban following TKR and THR in lower risk patients, argues for a large randomized trial evaluating aspirin as monotherapy for VTE prophylaxis in such patients. Disclosures No relevant conflicts of interest to declare.

Elongated Plant Virus-Based Nanoparticles for Enhanced Delivery of Thrombolytic Therapies.

Thrombotic cardiovascular disease, including acute myocardial infarction, ischemic stroke, and venous thromboembolic disease, is the leading cause of morbidity and mortality worldwide. While reperfusion therapy with thrombolytic agents reduces mortality from acute myocardial infarction and disability from stroke, thrombolysis is generally less effective than mechanical reperfusion and is associated with fatal intracerebral hemorrhage in up to 2-5% of patients. To address these limitations, we propose the tobacco mosaic virus (TMV)-based platform technology for targeted delivery of thrombolytic therapies. TMV is a plant virus-based nanoparticle with a high aspect ratio shape measuring 300 × 18 nm. These soft matter nanorods have favorable flow and margination properties allowing the targeting of the diseased vessel wall. We have previously shown that TMV homes to thrombi in a photochemical mouse model of arterial thrombosis. Here we report the synthesis of TMV conjugates loaded with streptokinase (STK). Various TMV-STK formulations were produced through bioconjugation of STK to TMV via intervening PEG linkers. TMV-STK was characterized using SDS-PAGE and Western blot, transmission electron microscopy, cryo-electron microscopy, and cryo-electron tomography. We investigated the thrombolytic activity of TMV-STK in vitro using static phantom clots, and in a physiologically relevant hydrodynamic model of shear-induced thrombosis. Our findings demonstrate that conjugation of STK to the TMV surface does not compromise the activity of STK. Moreover, the nanoparticle conjugate significantly enhances thrombolysis under flow conditions, which can likely be attributed to TMV's shape-mediated flow properties resulting in enhanced thrombus accumulation and dissolution. Together, these data suggest TMV to be a promising platform for the delivery of thrombolytics to enhance clot localization and potentially minimize bleeding risk.

Incorporating Comprehensive Management of Direct Oral Anticoagulants into Anticoagulation Clinics.

Anticoagulation clinics emerged as a means to optimize warfarin effectiveness and minimize bleeding risks. Anticoagulation clinics have traditionally been warfarin-based models due to the need for frequent blood-level monitoring, drug interactions, dietary considerations, and periprocedural management with warfarin. These models have demonstrated improved anticoagulation control and reduced bleeding complications for patients taking warfarin. Direct oral anticoagulants (DOACs) emerged with the perception of improved convenience due to the lack of blood-level monitoring and lack of dietary considerations. Despite the advantages of DOAC therapy, new challenges exist with their management, warranting ongoing monitoring. Such challenges include prescribing and dosing issues, drug adherence, drug interactions, and high drug cost. Comprehensive anticoagulation centers are needed to manage and monitor all oral anticoagulants including DOACs. The objectives of this review are to describe the challenges and opportunities that exist in the management of DOACs and to describe a practice model that integrates a DOAC management service into the traditional anticoagulation clinic.

Is it safe to consider anticoagulation in cirrhotic patients with venous thromboembolism?

Venous thromboembolism (VTE) increases the morbidity and mortality of the hospitalized patients. VTE can be seen in two different groups of people admitted to the hospitals. One group of patients is at very high risk of bleeding and the second group of patients is those without or with minimal risk of bleeding. When we plan thromboprophylaxis or treatment for VTE with the anticoagulants we are concerned about the risk of bleeding in special patients. Therefore, one should be aware of the number needed to harm (NNH) while considering the anticoagulation. In one population-based cohort of Coumadin patients 2% experienced a fatal bleeding event (NNH =50) and the overall major bleeding rate was 12% (NNH =8) (1).

P828Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in patients with atrial fibrillation: from asian perspectives

P828Optimal dose of dabigatran for the prevention of thromboembolism with minimal bleeding risk in patients with atrial fibrillation: from asian perspectives

Risk-adapted management of pulmonary embolism

The presence and severity of right ventricular (RV) dysfunction is a key determinant of prognosis in the acute phase of pulmonary embolism (PE). Risk-adapted treatment strategies continue to evolve, tailoring initial management to the clinical presentation and the functional status of the RV. Beyond pharmacological and, if necessary, mechanical circulatory support, systemic thrombolysis remains the mainstay of treatment for hemodynamically unstable patients; in contrast, it is not routinely recommended for intermediate-risk PE. Catheter-directed pharmacomechanical reperfusion treatment represents a promising option for minimizing bleeding risk; for reduced-dose intravenous thrombolysis, the data are still preliminary. Non-vitamin K-dependent oral anticoagulants, directly inhibiting factor Xa (rivaroxaban, apixaban, edoxaban) or thrombin (dabigatran), have simplified initial and long-term anticoagulation for PE while reducing major bleeding risk. Use of vena cava filters should be restricted to selected patients with absolute contraindications to anticoagulation, or PE recurrence despite adequately dosed anticoagulants.