Risk Of Bleeding Complications Research Articles

The effect of Vitamin K antagonists as anticoagulants on bleeding in patients post-dental procedures

Background: Individuals undergoing continuous treatment and taking vitamin K antagonist (VKA) and other anticoagulant medications are at a higher risk of experiencing bleeding complications during and after dental surgery procedures. Objective: To determine the effect of vitamin K antagonists in post-dental procedure patients by exploring existing literature on managing patients on vitamin K antagonist therapy as anticoagulants. Methods: This research utilized a literature review based on a database search of studies published between 2019-2024. The literature search used strategies with the terms “Tooth extraction bleeding,” “Odontectomy bleeding,” “Vitamin K Antagonist,” and “Anticoagulant,” utilizing databases such as PubMed, Science Direct, and SCOPUS related to the research topic and meeting eligibility criteria. The studies were then reviewed, summarized, and conclusions were drawn using tables to reveal all data regarding study characteristics and results. Results: Patients using anticoagulants are categorized as high risk for bleeding when undergoing invasive dentistry procedures. VKA is the most commonly used anticoagulant to prevent blood clotting. The consumption of VKA does not significantly affect bleeding post-procedure. Dental procedures can be performed on patients taking anticoagulants without discontinuing the therapy. Conclusion: Based on several studies from various literature sources, it can be concluded that dental procedures in patients taking vitamin K antagonist anticoagulants can still be performed without the risk of bleeding complications with proper local hemostatic measures and perioperative management.

Dynamics of hemostasis system parameters in assessing the risk of complications in the patients with acute myocardial infarction receiving antiplatelet therapy

Background. Current treatment of patients with myocardial infarction is based on the strategy of early invasive coronary intervention in combination with dual antiplatelet therapy - with acetylsalicylic acid and a P2Y12 blocker of platelet adenosine diphosphate receptors. In patients with thrombosis of the infarct-related artery, the phenomenon of “slow/ no reflow” (slowing of blood flow due to distal embolization of the artery), inhibitors of glycoprotein IIb/IIIa platelet receptors are administered as additional disaggregant therapy. In patients undergoing standard antiplatelet therapy in combination with glycoprotein IIb/IIIa inhibitors, there is a risk of hemorrhagic complications, therefore, monitoring of hemostasis parameters is necessary. Currently, there are no standard approaches to monitor the antiplatelet therapy.Objective. To study the dynamics of hemostatic system parameters in patients with acute myocardial infarction during antiplatelet therapy.Material and methods. We assessed platelet aggregation with 10 µmol of adenosine phosphate as an inducer in patients with ST-segment elevation myocardial infarction with different options of standard antiplatelet therapy in combination with GPIIb/IIIa inhibitors. Group 1 included 20 patients on dual antiplatelet therapy (clopidogrel 75 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor (tirofiban). Group 2 included 15 patients on dual antiplatelet therapy (ticagrelor 180 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor.Results. While on antiplatelet therapy the patients in both groups 1 and 2 demonstrated a decrease in platelet aggregation ability under the impact of adenosine phosphate, relative to the norm: 38 (21;43) % and 14 (11;15) %, respectively, the norm being 79 (73;84) % (p<0.05). Meantime, no thrombotic events in the form of stent thrombosis were noted, which indicated antiplatelet therapy efficacy. In an intragroup comparison, the decrease in the platelet aggregation ability was most pronounced in group 2 (p<0.05). By the 7th day of myocardial infarction, the platelet aggregation had continued to decrease to 26 (17;43) % in group 1, to 10 (7;11) % in group 2. The most pronounced effect of antiplatelet therapy was observed in group 2 (p<0.05), which was manifested by a statistically significant decrease in platelet aggregation ability under the impact of 10 µmol of adenosine phosphate.Conclusions. While studying the hemostasis system changes over time in patients with myocardial infarction receiving antiplatelet therapy, we have found that making the platelet aggregation ability assessment with 10 µmol of adenosine phosphate as an inducer is possible to identify the effect of medications. However, further studies including larger patient groups are needed to determine the target values of platelet aggregation with 10 µmol of adenosine phosphate and assess the therapy efficacy.

Postoperative bleeding complications in breast conserving surgery and the role of antithrombotic medications: retrospective analysis of 4712 operations

BackgroundThis study aimed to evaluate the risk and timing of postoperative bleeding complications following breast-conserving surgery (BCS), with or without axillary surgery, especially in relation to perioperative management of antithrombotic medications.MethodsData from all patients who underwent BCS for breast cancer between 2010 and 2022 at a single university hospital were collected. Medical records were reviewed for reoperations, unplanned admissions, and patient characteristics.ResultsIn total, 4712 breast-conserving surgeries and 3631 axillary surgeries were performed on 3838 patients. The risk of any bleeding complication was 1.1% (40/3571) in breast-conserving surgery, 0.3% (9/2847) in sentinel lymph node biopsy, and 0.5% (4/779) in axillary lymph node dissection. Upon arrival for treatment, 645 (17%) patients were taking antithrombotic medications. The risk of bleeding complications was not elevated in patients whose medication was discontinued at least a day before the surgery (OR 0.84, p = 0.76); but it was almost four-fold (OR 3.61, p = 0.026) in patients whose antithrombotic medication was continued. However, the absolute risk for bleeding complication was low in these patients as well (2.0%, 15/751). The majority of bleeding complications (85%, 47/55) occurred within 24 h after the surgery.ConclusionThe risk for bleeding complications was elevated, but still low, after BCS with or without axillary surgery, when antithrombotic medications were continued through the surgical period. Discontinuing antithrombotic medications is not obligatory in these patients.

Optimal Dual Antiplatelet Therapy Duration For Carotid Artery Stenting On the Basis of Angioscopic Findings

Background Dual antiplatelet therapy plays a crucial role in preventing thrombosis in the perioperative period of carotid artery stenting (CAS); however, it has been associated with a risk of hemorrhagic complications. A standard regimen for the duration and combination of antiplatelet therapy is yet to be established. Angioscopy enables direct visualization of neointimal coverage and might help determine the optimal duration of dual antiplatelet therapy through the assessment of post‐CAS neointimal coverage. Methods This prospective study enrolled 20 patients who were scheduled to undergo CAS at the Osaka Police Hospital. A 2‐month post‐CAS period was chosen for angioscopic neointima evaluation on the basis of previous evidence of reliable neointimal coverage 2 months following coronary artety stenting. Furthermore, antiplatelet therapy was initiated 1 week before CAS and continued until angioscopic examination. Angioscopic evaluation categorized the degree of neointimal coverage and was supplemented with carotid ultrasonography and biplane angiography. Results Coincidentally, a dual‐layer stent was used in all cases. The stent lumen was observed in 19 of the 20 cases. One case was difficult to evaluate owing to poor visibility. Angioscopy showed complete neointimal coverage in 18 of 19 cases and partial coverage in 1 case. Ultrasonography could detect neointima in 9 of 20 cases, and angiography showed a radiolucent gap suggestive of neointima in all cases in which neointima was confirmed via angioscopy. No post‐CAS or procedural complications occurred. Conclusion Angioscopy performed 2 months following CAS revealed large neointimal coverage, suggesting that a 2‐month duration of dual antiplatelet therapy is generally sufficient. However, as a limitation, this study was performed using the same dual‐layer stent; thus, additional studies with other stents are required.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Short term outcome of neonatal venous thromboembolism in anticoagulated versus observed patients

BackgroundAdvancements in the medical field and increased survival of premature infants have led to a rise of venous thromboembolism (VTE) in neonates. Neonatal hemostasis exists in a delicate balance with a propensity towards pro-coagulation. Current recommendations include careful observation, therapeutic anti-coagulation and in some cases thrombolysis. We hypothesize that a sub-group of neonates may not require anti-coagulation and could be safely observed thus reducing their risk of bleeding complications. MethodsWe conducted a retrospective chart review of patients with VTE admitted to the neonatal intensive care unit at the Oklahoma University Children's Hospital from October 2009–October 2019. Patients were selected if they had an ICD-9 or ICD-10 code specific for a VTE or if screening with CPT codes for diagnostic imaging including echocardiogram, venous dopplers and computed topographic/magnetic resonance venogram revealed the word ‘thrombus’, ‘clot’ or ‘venous thromboembolism’. Data were collected about demographics, medical history, co-morbidities, thrombosis characteristics, treatment and outcome. ResultsA total of 211 patients were screened and 119 patients were eligible and included in the study. The majority of patients (85 %) had a central venous catheter (CVC) associated VTE. Two-thirds of patients (n = 81, 68 %) received therapeutic anti-coagulation while one-third (n = 38, 32 %) were observed. The group that received anticoagulation had a significantly older age at diagnosis and had a higher frequency of bacteremia, congenital heart disease and presence of symptoms. There was no difference in the odds of complete resolution between patients who were treated with therapeutic anti-coagulation and those that were observed (OR: 1.37, 95 % CI: 0.59–3.20, p-value: 0.47). Univariate analysis revealed maternal preeclampsia (OR: 0.2, 95 % CI: 0.05–0.82, p-value = 0.025), maternal history of chronic hypertension (OR: 0.17, 95 % CI: 0.04–0.68, p-value = 0.01), and presence of complete occlusion (OR = 0.37, 95 % CI: 0.15–0.91, p-value = 0.03) significantly reduced the odds of complete resolution. Furthermore, having a VTE related to a CVC in an extremity versus an ECMO cannula or cardiac catheterization significantly improved the odds of VTE resolution (OR = 5.94, 95 % CI: 1.30–27.20, p-value = 0.022). Using a stepwise regression model, maternal history of chronic hypertension remained significant for a reduced odds of VTE resolution (OR: 0.14, 95 % CI 0.025–0.73, p-value: 0.02). ConclusionsThe short-term outcome of neonatal VTE does not seem to differ between those that were anticoagulated and those that were observed with serial imaging.

Urinary N-acetyl-D-glucosaminidase can predict bleeding after a percutaneous kidney biopsy

BackgroundA percutaneous kidney biopsy (PKB) allows nephrologists to make informed decisions for treating various kidney diseases; however, the risk of bleeding complications should be considered, given the vascularity of the kidney. Many studies have reported risk factors for bleeding events after a PKB. However, while urinary N-acetyl-β-D-glucosaminidase (NAG) is a useful biomarker of kidney disease severity, little is known about whether or not urinary NAG is related to the bleeding risk.MethodsMedical records of patients who underwent a PKB at the National Defense Medical College Hospital between October 2018 and October 2023 were retrospectively studied. Hemoglobin (Hb) loss ≥ 1 g/dL was defined as a bleeding event.ResultsOf the 213 patients, 110 (51.6%) were men, and the median age was 56 years old (interquartile range 40–71). The most frequent diagnosis on a PKB was IgA nephropathy (N = 72; 34.0%). Fifty-four patients (25.3%) experienced Hb loss ≥ 1 g/dL after a PKB, and urinary NAG/Cr levels before the biopsy were able to predict a bleeding event, with an area under the receiver operating characteristic curve of 0.65 (p = 0.005). Using the optimal cutoff value of 35 U/gCr, urinary NAG/Cr was found to be an independent risk factor by multiple logistic regression analysis (odds ratio 3.21, 95% confidence interval 1.42–7.27, p = 0.005). Even after adjusting for previously-reported risk factors, the elevated urinary NAG/Cr ratio remained a statistically significant variable. Compared with the pathological findings, only the severity of multilayered elastic laminae of the small muscular artery was associated with both urinary NAG/Cr levels (p = 0.008) and bleeding events (p = 0.03).ConclusionUrinary NAG successfully predicted not only the severity of kidney disorders but also bleeding events after a PKB. Arteriosclerosis in the kidneys may be the mechanism underlying these increased bleeding events.

Oral anticoagulation in supraventricular arrhythmia

Atrial fibrillation represents the most frequent persistent cardiac arrhythmia and is associated with an increased morbidity and mortality. An important component of the holistic treatment of atrial fibrillation is oral anticoagulation (OAC) for the prevention of stroke. The CHA2DS2-VASc score as a risk score is recommended for estimation of the individual stroke risk and the concomitant need of OAC in these patients. In the majority of patients the OAC is nowadays carried out with direct oral anticoagulants (DOAC), which have proved to be effective with a moderate side effect profile and have replaced vitamin K antagonists as the standard substance. In the meantime, these principles have become established as the usual practice but some issues regarding OAC in patients with atrial fibrillation are still insufficiently answered. Furthermore, it is unclear whether OACs need to be continued after successful treatment of atrial fibrillation with pulmonary vein ablation or in some cases can even be discontinued. Unanswered questions also remain regarding the treatment of subclinical atrial fibrillation and atrial high-frequency episodes detected by implanted heart rhythm devices. Especially the duration of atrial high-frequency episodes that should trigger the initiation of OAC treatment is still under debate. Therefore, currently the benefits of stroke prevention must be carefully weighed up against the risk of bleeding complications.

Oral surgery in people with inherited bleeding disorder: A retrospective study.

The objectives were to describe the peri-operative management of people with inherited bleeding disorders in oral surgery and to investigate the association between type of surgery and risk of developing bleeding complications. This retrospective observational study included patients with haemophilia A or B, von Willebrand disease, Glanzmann thrombasthenia or isolated coagulation factor deficiency such as afibrinogenemia who underwent osseous (third molar extraction, ortho-surgical traction, dental implant placement) or nonosseous oral surgery between 2014 and 2021 at Bordeaux University Hospital (France). Patients and oral surgery characteristics were retrieved from medical records. Odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression. Of the 83 patients included, general anaesthesia was performed in 16%. Twelve had a bleeding complication (14.5%) including six after osseous surgery. The most serious complication was the appearance of anti-FVIII inhibitor in a patient with moderate haemophilia A. All bleeding complications were managed by a local treatment and factor injections where indicated. No association was observed between type of surgery (osseous vs. nonosseous) and risk of bleeding complications after controlling for sex, age, disease type and severity, multiple extractions, type of anaesthesia and use of fibrin glue (OR: 3.21, 95% CI:.69-14.88). In this study, we have observed that bleeding complications after oral surgery in people with inherited bleeding disorders were moderately frequent and easily managed. However, in this study, we observed a serious complication highlighting the necessity of a thorough benefit-risk balance evaluation during the preoperative planning of the surgical and medical protocol.

#1912 Assessment of the dynamics of renal anemia in patients with atrial fibrillation and chronic kidney disease stage IIIb-V during anticoagulant therapy

Abstract Background and Aims Therapy with oral anticoagulants prevents the development of most ischemic strokes and systemic embolisms in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), and also helps to increase life expectancy, improving its quality. It should be emphasized that with CKD, the risk of hemorrhagic complications also increases, which in turn can lead to the progression of renal anemia and deterioration in the patient's general condition. The main complication of anticoagulants is an increased risk of major bleeding, including intracranial, life-threatening bleeding. The purpose of the study is to assess the benefits and risks of anticoagulant therapy in patients with renal anemia in AF and stage IIIb-V CKD. Method From February 2022 to July 2023, 2983 patients with AF were admitted to cardiology departments. The majority of patients with AF had hypertension (94%), chronic heart failure (71%), coronary heart disease (65%), and type 2 diabetes mellitus (23%). CKD was diagnosed according to KDIGO criteria, glomerular filtration rate (GFR) was calculated using the CKD-EPI formula. Indications for anticoagulant therapy (ACT) were determined according to European guidelines for AF using the scales for assessing the risk of thromboembolic complications (TEC)—CHA2DS2-VASc and the risk of bleeding—HAS-BLED. Results GFR up to 45 ml/min/1.73 m2 was detected in 2189 (73%) patients with AF, GFR less than 45 ml/min/1.73 m2 in 794 (27%) patients with AF (CKD stages IIIb–V in 516 (65%) cases, for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2 was detected in 278 (35%) cases). Among patients with AF and CKD, renal anemia was diagnosed in 23% of cases, in 63% (n = 505) of cases with AF and GFR <45 ml/min/1.73 m2. With a GFR of 45-30 ml/min/1.73 m2, renal anemia was detected in 59%, with a GFR of 30-15 ml/min/1.73 m2—in 89%, with a GFR <15 ml/min/1.73 m2—in 97%, with FISD in GFR <45 ml/min/1.73 m2—in 51%. When stratifying thromboembolic risk according to the CHA2DS2-VASc scale in patients with AF and CKD stages IIIb–V, 0-1 points were scored by 1% (n = 11), 2-5 points by 53% (n = 420), ≥6 points by 46% (n = 363) patients. The results of the analysis of the risk of bleeding according to the HAS-BLED scale showed the following data: 0-1 point—8% (n = 64), 2 points—15% (n = 118), ≥3 points—77% (n = 612). When studying the frequency of ACT prescription, it was revealed that rivaroxaban was prescribed in 21%, apixaban—22%, dabigatran—10%, warfarin—25%, low molecular weight heparins—3%, ACT not recommended—9%, ACT of choice—10% of cases (Table 1). In mild renal anemia (in 39% of patients), taking ACT led to a reduction in the risk of developing TEC—RR 0.55 with 95% CI 0.38-0.79; in case of moderate renal anemia (in 47.3% of patients), the risk of TEC did not decrease RR 1.03 with 95% CI 0.69-1.58; with severe renal anemia (in 13.7% of patients), the risk of TEC was also not reduced—RR 1.6 with 95% CI 1.17-2.2). Conclusion Every fourth patient in the cardiology department with AF showed a decrease in GFR <45 ml/min/1.73 m2, while 1/3 of them had FISD in GFR <45 ml/min/1.73 m2, and it is in these patients that the most common the dose of the prescribed anticoagulant did not correspond to the GFR; 50% of patients with GFR <45 ml/min/1.73 m2 and 32% with GFR <30 ml/min/1.73 m2 are recommended to use direct oral anticoagulants. Patients with stage V CKD were not prescribed direct oral anticoagulants; in 50% of cases, none of the anticoagulants was recommended.

Enhancing thromboresistance of neurovascular nickel-titanium devices with responsive heparin hydrogel coatings

BackgroundNeurointerventional devices, particularly laser-cut thin-strut stents made of self-expanding nickel-titanium alloy, are increasingly utilized for endovascular applications in intracranial arteries and dural venous sinuses. Preventing thrombosis and stroke necessitates systemic...

Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine’s potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Unraveling the Paradox: Can Anticoagulation Improve Outcomes in Patients With Heart Failure and Increased Bleeding Risk?

Heart failure (HF) patients frequently present with comorbidities such as atrial fibrillation (AF) or other cardiovascular conditions, elevating their risk of thromboembolic events. Consequently, anticoagulation therapy is often considered for thromboprophylaxis, although its initiation in HF patients is complicated by concomitant bleeding risk factors. This review explores the paradoxical relationship between HF, increased bleeding risk, and the potential benefits of anticoagulation. Through an examination of existing evidence from clinical trials, observational studies, and meta-analyses, we aim to elucidate the role of anticoagulation in HF patients with increased bleeding risk. Despite guidelines recommending anticoagulation for certain HF patients with AF or other thromboembolic risk factors, uncertainty persists regarding the optimal management strategy for those at heightened risk of bleeding. The review discusses the pathophysiological mechanisms linking HF and thrombosis, challenges in bleeding risk assessment, and strategies to minimize bleeding risk while optimizing thromboprophylaxis.Shared decision-making between clinicians and patients is emphasized as essential for individualized treatment plans that balance the potential benefits of anticoagulation against the risk of bleeding complications. Furthermore, it examines emerging anticoagulant agents and their potential role in HF management, highlighting the need for further research to delineate optimal management strategies and inform evidence-based practice. In conclusion, while anticoagulation holds promise for improving outcomes in HF patients, careful consideration of patient-specific factors and ongoing research efforts are essential to optimize therapeutic strategies in this population.

The Effect of ABCB1 and CES1 Polymorphisms on Plasma Levels of Dabigatran and Risk of Hemorrhagic Complications in Ischemic Stroke Patients.

Dabigatran directly inhibits thrombin and is used in primary and secondary stroke prevention in individuals with nonvalvular atrial fibrillation. The prodrug dabigatran etexilate is absorbed by enteral P-glycoprotein (ABCB1) and then activated by hepatic and intestinal carboxylesterases (CES1) to produce active metabolites. Variations in dabigatran metabolism because of genetics may affect concentration levels and clinical outcomes. We conducted a study to assess how polymorphisms in the CES1 (rs2244613) and ABCB1 (rs4148738) genes affect the through plasma level (c min ) of dabigatran and its correlation to clinical outcomes. Retrospective multicentric study of consecutive patients on dabigatran therapy. Examination of CES1 rs2244613 and ABCB1 rs4148738 polymorphisms, c min 12 hours after administration, clinical follow-up (ischemic stroke, major or clinically relevant hemorrhage, myocardial infarction, other thromboembolism, and death). A total of 432 patients received treatment for an average of 19.78 months (SD of 20.165). The sex distribution of the patients was 56.5% male, and the average age was 67.56 years (SD of 14.7). The ABCB1 variant genotype was present in 67.8% of patients, whereas 37.5% carried the CES1 polymorphism. Compared with wild-type patients, patients with the CES1 variant had significantly lower dabigatran plasma levels (with a mean difference of 16.986; 95% confidence interval, 5.794-28.178 ng/mL, P = 0.003). We also found a significant risk of major bleeding in patients carrying the ABCB1 rs4148738 allele (hazard ratio = 1.99, confidence interval 95% 1.10 to 3.59, P = 0.024). The CES1 variant genotype rs2244613 is closely linked with reduced c min of dabigatran. Carriers of the ABCB1 rs4148738 polymorphism exhibit a tendency toward higher plasma levels of dabigatran, which leads to a significantly increased risk of bleeding.

In situ formed depot of elastin-like polypeptide-hirudin fusion protein for long-acting antithrombotic therapy

Thrombosis, induced by abnormal coagulation or fibrinolytic systems, is the most common pathology associated with many life-threatening cardio-cerebrovascular diseases. However, first-line anticoagulant drugs suffer from rapid drug elimination and risk of hemorrhagic complications. Here, we developed an in situ formed depot of elastin-like polypeptide (ELP)-hirudin fusion protein with a prodrug-like feature for long-term antithrombotic therapy. Highly secretory expression of the fusion protein was achieved with the assistance of the Ffu312 tag. Integration of hirudin, ELP, and responsive moiety can customize fusion proteins with properties of adjustable in vivo retention and controllable recovery of drug bioactivity. After subcutaneous injection, the fusion protein can form a reservoir through temperature-induced coacervation of ELP and slowly diffuse into the blood circulation. The biological activity of hirudin is shielded due to the N-terminal modification, while the activated key proteases upon thrombus occurrence trigger the cleavage of fusion protein together with the release of hirudin, which has antithrombotic activity to counteract thrombosis. We substantiated that the optimized fusion protein produced long-term antithrombotic effects without the risk of bleeding in multiple animal thrombosis models.

Can the combination of antiplatelet or alteplase thrombolytic therapy with argatroban benefit patients suffering from acute stroke? a systematic review, meta-analysis, and meta-regression.

The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is presently uncertain. However, it is important to highlight the potential benefits of combining this medication with known thrombolytics or antiplatelet therapy. One notable advantage of argatroban is its short half-life, which helps minimize excessive anticoagulation and risk of bleeding complications in inadvertent cases of hemorrhagic stroke. By conducting a meticulous review and meta-analysis, we aim to further explore the common use of argatroban and examine the plausible advantages of combining this medication with established thrombolytic and antiplatelet therapies. In this study, we performed a rigorous and methodical search for both randomized controlled trials and retrospective analyses. Our main objective was to analyze the impact of argatroban on the occurrence of hemorrhagic events and the mRS scores of 0-2. We utilized a meta-analysis to assess the relative risk (RR) associated with using argatroban versus not using it. In this study, we analyzed data from 11 different studies, encompassing a total of 8,635 patients. Out of these patients, 3999(46.3%) received argatroban treatment while the remaining 4636(53.7%)did not. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score≤2) showed that the risk ratio (RR) for patients using argatroban after alteplase thrombolytic therapy compared to those not using argatroban was(RR, 1.00 ([95% CI, 0.92-1.09]; P = 0.97), indicating no statistical significance. However, for patients using argatroban after antiplatelet therapy, was (RR,1.09 [95% CI, 1.04-1.14]; P = 0.0001), which was statistically significant. In terms of hemorrhagic events, the RR for patients using argatroban compared to those not using argatroban was (RR,1.08 [95% CI, 0.88-1.33]; P = 0.46), indicating no statistical significance. The results of this study suggest that further research into combination therapy with argatroban and antiplatelet agents may be warranted, however more rigorous RCTs are needed to definitively evaluate the effects of combination treatment.

No contraindication to internal jugular central venous catheter insertion in patients at increased risk of bleeding: Results from a prospective observational study in a internal medicine department.

Implantation of centrally inserted central venous catheter (CICC) may be complicated by bleedings particularly in patients with severe coagulopathy or taking antithrombotic drugs. It has been shown that the application of the Italian Group for Venous Access Devices (GAVeCeLT) bundle reduces the incidence of bleeding in patients admitted to intensive care units (ICU), but its effectiveness has never been demonstrated in different contexts. In this study we evaluated the incidence of bleeding after urgent internal jugular CICC (J-CICC) implantation in patients with increased or no risk of bleeding complications when recommended preventive strategies are applied systematically. We included 185 patients admitted to Internal Medicine Units who underwent urgent J-CICC implantation from April 2016 to December 2018. The incidence of major and minor bleeding immediately after the procedure and in the following 30 days was recorded. None of the enrolled patients showed major bleeding. The incidence of minor bleedings was 2.1% (95% IC: 0.03-4.2) with two patients requiring line removal and repositioning (1.1%; 95% IC: -0.45 to 2.6). Bleeds were not correlated with age or sex, although they all occurred in female subjects. The incidence of bleeds was not increased in patients with increased risk of bleeding compared with those without (5.0% vs 1.3%; p = 0.16). The use of anti-thrombotic medications was significantly associated with increased risk of minor bleedings (p = 0.03). In this study we demonstrated that the application of the GAVeCeLT suggested bundle can minimize the number of bleeding complications even in patients hospitalized in Internal Medicine Units. Further data are needed in patients taking antithrombotic drugs who appear to be more prone to minor bleeding, however the benefit of completing the procedure appears to significantly outweigh the risk of mechanical complications.

Effect of CYP3A4/5, ABCB1 gene polymorphisms on the residual equilibrium concentration of apixaban and bleeding in patients with non-valvular atrial fibrillation and deep vein thrombosis

Effect of CYP3A4/5, ABCB1 gene polymorphisms on the residual equilibrium concentration of apixaban and bleeding in patients with non-valvular atrial fibrillation and deep vein thrombosis

Safety of antiplatelet therapy during the perioperative period of revascularization surgery for moyamoya disease patients with ischemic onset.

For patients with moyamoya disease, antiplatelet agents are often used during the perioperative periods of revascularization surgeries to prevent ischemic events. However, antiplatelet therapy is associated with the risk of hemorrhagic complications. Further, the influence of antiplatelet therapy on perioperative ischemic or hemorrhagic complications has not been investigated. This study aimed to determine the impact of antiplatelet agents on adult moyamoya disease patients with ischemic onset during the perioperative period. From January 2016 to December 2020, 183 consecutive combined (direct and indirect) revascularization surgeries for moyamoya disease patients were performed. Among these surgeries, 96 consecutive combined revascularization surgeries for adult moyamoya disease patients with ischemic onset were analyzed and perioperative ischemic and hemorrhagic complications were reviewed. Antiplatelet agents were continued during the perioperative period including on the day of surgery and the day after the surgery. Among 96 surgeries, no hemorrhagic complications occurred postoperatively. Infarction occurred in five cases (5.2%). Among the five cases, neurological deficits persisted in two cases and improved in three. The median value of bleeding volume was 112.5 mL (interquartile range, 80.0 - 200.0). Twenty-five cases (26.0%) needed blood transfusion. The modified Rankin Scale score deteriorated in two cases due to cerebral infarction. The incidence of hemorrhagic and ischemic complications after combined revascularization surgery in patients with ischemic moyamoya disease under antiplatelet therapy was low, indicating the safety of continued antiplatelet therapy.

Stroke and Bleeding Risks of Endocardial Ablation for Ventricular Arrhythmias

BackgroundRisks of radiofrequency catheter ablation for ventricular arrhythmias include emboli and bleeding complications but data on antithrombotic regimens are limited and guidelines do not specify a systematic approach. ObjectivesThis study sought to assess embolic and bleeding complications in relation to pre-periprocedure and post-periprocedure antithrombotic regimens. MethodsProspective assessment for complications was performed for 663 endocardial radiofrequency catheter ablation procedures in 616 consecutive patients (median age 64 years [Q1-Q3: 54-73 years], 70.3% men, 71.6% with cardiomyopathy, 44.5% with sustained ventricular tachycardia). ResultsThere were 2 strokes (0.3%; 95% CI: 0.0%-0.8%), 1 transient ischemic attack (0.15%), and 2 pulmonary emboli (0.3%). There were 39 bleeding complications (5.9%) including 11 pericardial effusions (1.7%), and 28 related to vascular access (4.2%). Consistent with the prevalence of coronary artery disease (47.5%), atrial fibrillation (30.0%), and prior stroke (10.6%), preprocedure, 464 patients (70.0%) were taking antithrombotic agents including 220 (33.2%) taking aspirin alone (ASA), and 163 (24.6%) taking warfarin or a direct acting oral anticoagulant (DOAC). Preprocedure non-ASA antiplatelet use (OR: 2.846; P = 0.011) and DOAC use (OR: 2.585; P = 0.032) were associated with risk of bleeding complications. Following ablation, 49.8% of patients were treated with ASA 325 mg/d and 30.3% received DOACs or warfarin. New DOAC or warfarin administration was initiated in only 6.6% of patients. Overall, 39.7% of patients continued the same preprocedure antithrombotic regimen. ConclusionsStroke is a rare complication of radiofrequency catheter ablation for ventricular arrhythmia using ASA 325 mg/d as a minimal postprocedure regimen with more potent regimens for selected patients.