Minor Bleeding Research Articles

Two different hybrid vascular access closure strategies post transcatheter aortic valve implantation

Abstract Background The hybrid strategy combining plug-based and suture-based vascular closure devices (VCD) was introduced as a promising technique for vascular access hemostasis after transcatheter aortic valve implantation (TAVI) with satisfactory outcomes. However, data comparing two plug-based VCDs each in the combination with a suture-based VCD, namely ProGlide/FemoSeal (P/FS) with ProGlide/AngioSeal (P/AS) VCDs, is still lacking. Aim To compare the 30-day outcome of the hybrid strategy using P/AS versus P/FS for vascular access site closure after TAVI. Methods A retrospective single Centre observational study included 608 patients recruited from a prospective TAVI registry between 2016 and 2022. The composite endpoint was defined as any VCD related major vascular complications and/or bleeding more than type 1 according to Valve Academic Research Consortium (VARC-3) criteria. Results The current study reported a significantly higher rate of composite endpoint in P/AS group, which was driven by higher rate of major bleeding (5.4% vs 1.4%, p=0.036). We also found a higher rate of VCD related minor bleeding in P/AS group (16.3% vs 8.1%, p=0.013). Successful access site hemostasis was achieved in 83.1% of P/FS group versus 71.7% in P/AS group (p=0.006). The presence of anterior wall calcification at the access site was significantly associated with the composite endpoint (adj OR 2.49; 95% CI (1.08 – 5.75), p=0.032). Conclusions The hybrid strategy for large bore vascular access closure using P/FS showed a potentially better 30-day outcomes compared with P/AS. The presence of anterior calcification at the access site carries a significant risk of VCD related complications.

Bleeding and Thrombotic Events in Hemodialysis Patients with Atrial Fibrillation on Anticoagulation and Antiplatelet Therapy: A 24-Month Cohort Study

Background and Objectives: Patients undergoing chronic hemodialysis (HD) are predisposed to both thrombotic and bleeding complications due to the complex interplay of end-stage renal disease (ESRD), cardiovascular comorbidities, and the routine use of anticoagulant and antiplatelet therapies. This study aimed to investigate the incidence of bleeding and thrombotic events in chronic HD patients receiving anticoagulant and antiplatelet therapy, with a specific focus on those with atrial fibrillation (AF). Materials and Methods: A total of 224 patients, with 43 (19%) of them diagnosed with AF, were included in this single-center, observational cohort study conducted over 24 months. The cohort was divided into three groups: patients without anticoagulation, those on warfarin monotherapy, and those on combined warfarin and aspirin therapy. Bleeding events were classified as major, clinically relevant non-major bleeding (CRNMB), or minor bleeding, while thrombotic events included ischemic stroke, myocardial infarction, pulmonary embolism, and arteriovenous fistula thrombosis. Results: Overall, 35.7% of patients experienced a bleeding event, with major bleeding occurring in 9.4%. Patients with AF had significantly higher rates of major bleeding (18.6%) compared to those without AF (7.18%; p = 0.043), especially in the combined therapy group. Mortality due to bleeding was also higher in AF patients (14%). In contrast, thrombotic events occurred in 26.8% of patients, with AF patients experiencing significantly more events (48.8%) compared to non-AF patients (21.5%; p = 0.0006). The hazard ratio (HR) for major bleeding in patients on combined warfarin and aspirin therapy was 2.56 (p = 0.016), while the HR for thrombotic events was 2.34 (p = 0.0202). Conclusions: These findings highlight the increased risks of both bleeding and thrombosis in chronic HD patients with AF, particularly those on combined anticoagulation and antiplatelet therapy.

Pharmacological Thromboprophylaxis Effectiveness in Low-Risk Patients Undergoing Arthroscopic Anterior Cruciate Ligament Reconstruction: A Randomized Clinical Trial

Background: There is a paucity of evidence and controversies regarding prophylaxis strategies in low-risk patients undergoing knee arthroscopy. This study aims to evaluate the effectiveness and safety of aspirin and low-molecular-weight heparin (LMWH) in an arthroscopic anterior cruciate ligament (ACL) reconstruction for low-risk patients. Methods: We performed a preoperational evaluation a week before surgery for any sign of pulmonary embolism (PE) and deep vein thrombosis (DVT). For this purpose, we used single limited compression Doppler ultrasonography (CUS) of the lower extremities. Rehabilitation started before the time of the surgery to improve the range of motion (ROM) and quadriceps muscle function. A team of 3 orthopedists performed the procedures. The same surgical technique and graft were used with spinal anesthesia, and operation time was recorded. Results: The mean age of participants was 31.4 ± 5.6 years, with 93 individuals (67%) being men and 23% women. No cases of DVT or PE were observed. Three cases in the LMWH group and one case in the aspirin group experienced minor surgical site bleeding. One case of hemarthrosis with normal ultrasonography occurred in the LMWH group. Regarding safety and effectiveness, there was no statistically significant difference between the parallel arms. Conclusion: The use of LMWH or aspirin after simple arthroscopic ACL reconstruction in low-risk patients showed no difference in effectiveness. Hence, the routine use of thromboprophylaxis in this setting is questionable although adverse events are rare

Analysis of risk factors for bleeding as a complication of ultrasound-guided percutaneous liver biopsy examination

Objective: To explore the independent risk factors for bleeding in patients following percutaneous liver biopsy examination. Methods: The clinicopathological data of patients who underwent percutaneous liver biopsy examination at Nanjing Second Hospital from January 2012 to December 2021 were retrospectively collected. Univariate and multivariate logistic regression analysis were used to investigate the effect of age, gender, lesion type (diffuse liver parenchymal lesions, focal liver lesions), number of biopsies, tissue length, presence or absence of cirrhosis, presence or absence of portosystemic shunt, erythrocytes, white blood cells, hemoglobin, platelets, prothrombin time, fibrinogen, international normalized ratio, and liver biochemical indicators on bleeding following liver biopsy, as well as to screen independent risk factors. Results: A total of 3 331 patients were examined by percutaneous liver biopsy, and 3 060 cases were actually included by excluding 271 cases who took consultation from other hospitals. The overall postoperative hemorrhagic rate was 1.6% (49/3 060). Of which, forty-four cases (1.4%) had overt bleeding (hemodynamic changes or hemoglobin decreased by more than 20 g/L), five cases (0.2%) had minor bleeding, three cases had subcapsular hepatic hemaotma, and two cases had local bleeding from liver biopsy. Among the overt bleeding cases, two cases were in the off-label group (platelet<50×109/L or international normalized ratio>1.5), and the rest were in the non-off-label group. The results of univariate analysis showed that factors such as focal liver lesions, portosystemic shunt, prolonged prothrombin time, increased international normalized ratio, bilirubin, and alkaline phosphatase were associated with bleeding after liver biopsy in the non-off-label group. The multivariate collinearity diagnosis revealed statistically significant differences for the indicators. Multivariate logistic regression analysis finally included factors such as lesion type, portosystemic shunt, international normalized ratio, total bilirubin, and alkaline phosphatase. The results showed that patients with focal liver lesions were more prone to bleed after surgery than patients with diffuse liver parenchymal lesions (OR=3.396, P=0.002, 95%CI: 1.596-7.228). Patients with portosystemic shunt were more prone to bleed than those without portosystemic shunt (OR=3.301, P=0.018, 95%CI: 1.232-8.845). Patients were more likely to experience bleeding following liver biopsy when their total bilirubin levels were elevated (OR=1.006, P<0.001, 95%CI:1.003-1.008). Conclusion: Focal liver lesions, portosystemic shunts, and elevated total bilirubin are independent risk factors for bleeding after percutaneous liver biopsy.

Streptokinase or Alteplase for Acute Limb Ischemia? A Meta-Analysis

Background: Acute limb ischemia (ALI) is a vascular emergency that necessitates prompt and effective treatment to restore blood flow and prevent limb loss. Thrombolytic therapy, particularly with agents like streptokinase and alteplase, plays a pivotal role in ALI management. This meta-analysis and systematic review aimed to compare the efficacy and safety of streptokinase and alteplase in treating ALI. Methods: A comprehensive search of PubMed, Embase, Science Direct, and the Cochrane Library databases was conducted up to August 13, 2024, to identify relevant studies. The inclusion criteria encompassed clinical trials involving patients diagnosed with ALI who received either streptokinase or alteplase as the initial thrombolytic treatment. The quality of the included studies was rigorously assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and the Methodological Index for Non-Randomized Studies (MINOR) criteria. A meta-analysis was performed using the Mantel-Haenszel random-effects model to calculate risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). Results: The final analysis included 20 studies, encompassing both qualitative and quantitative assessments. A comparative analysis of streptokinase and alteplase for limb salvage at 30 days revealed a significant advantage in favor of alteplase, with a relative risk ratio (RR) of 0.78 (95% CI 0.69-0.88, I² = 0%). Furthermore, streptokinase was associated with a higher rate of primary amputation, with an RR of 2.54 (95% CI 1.50-4.32, I² = 0%) compared to alteplase. The use of streptokinase also correlated with a higher risk of complications, including major bleeding (RR 1.75, 95% CI 0.04-84.30, I² = 77%) and minor bleeding (RR 1.41, 95% CI 0.60-3.32, I² = 0%). Conclusion: The findings of this meta-analysis underscore the superior efficacy of alteplase in achieving limb salvage in ALI, coupled with a more favorable safety profile. The preferential use of alteplase in clinical practice is recommended, particularly in patients with severe ischemia. However, careful patient selection and close monitoring are crucial when streptokinase therapy is considered.

Safety and Effectiveness of Oral Anticoagulants in Atrial Fibrillation: Real-World Insights Using Natural Language Processing and Machine Learning.

Background/Objectives: We assessed the effectiveness and safety of vitamin K antagonists (VKAs) versus direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) using artificial intelligence techniques. Methods: This is a retrospective study in 15 Spanish hospitals (2014-2020), including adult AF patients with no history of anticoagulation, thrombosis events, rheumatic mitral valvular heart disease, mitral valve stenosis, or pregnancy. We employed EHRead® technology based on natural language processing (NLP) and machine learning (ML), along with SNOMED-CT terminology, to extract clinical data from electronic health records (EHRs). Using propensity score matching (PSM), the effectiveness, safety, and hospital mortality of VKAs versus DOACs were analyzed through Kaplan-Meier curves and Cox regression. Results: Out of 138,773,332 EHRs from 4.6 million individuals evaluated, 44,292 patients were included, 79.6% on VKAs and 20.4% on DOACs. Most patients were elderly [VKA 78 (70, 84) and DOAC 75 (66, 83) years], with numerous comorbidities (75.5% and 70.2% hypertension, 47.2% and 39.9% diabetes, and 40.3% and 34.8% heart failure, respectively). Additionally, 60.4% of VKA and 48.7% of DOAC users had a CHA2DS2-VASc Score ≥4. After PSM, 8929 patients per subgroup were selected. DOAC users showed a lower risk of thrombotic events [HR 0.81 (95% CI 0.70-0.94)], minor bleeding [HR 0.89 (95% CI 0.83-0.96)], and mortality [HR 0.80 (95% CI 0.69-0.92)]. Conclusions: Applying NLP and ML, we generated valuable real-world evidence on anticoagulated AF patients in Spain. Even in complex populations, DOACs have demonstrated a better safety and effectiveness profile than VKAs.

Comparative Efficacy and Safety of Novel Antiplatelets and Standard Therapy in Patients With Coronary Artery Disease.

Coronary artery disease (CAD) is a significant health concern that has affected approximately 110 million people worldwide. CAD is defined as persistent narrowing of the coronary arteries as a result of atherosclerotic plaque build-up. Acute coronary syndrome (ACS), which encompasses ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina, often results from plaque ruptures. Platelets are crucial for atherogenesis, vascular inflammation, and oxidative stress. Antiplatelet therapy aimed at reducing thrombotic events is vital for ACS treatment. Clinical guidelines advise the use of dual antiplatelet therapy (DAPT) that combines aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor) in ACS patients undergoing percutaneous intervention (PCI). This study aimed to assess comprehensively the effectiveness and safety of ticagrelor and prasugrel in comparison to clopidogrel in patients with ACS. An extensive literature search was conducted using PubMed, PubMed Central (PMC), ScienceDirect, and EBSCO databases. The search revealed studies that compared ticagrelor and prasugrel to clopidogrel in ACS patients, and we selected these studies based on specific inclusion and exclusion criteria, which included observational studies, clinical trials, literature reviews, and meta-analyses involving adult ACS patients treated with ticagrelor, prasugrel, or clopidogrel. The efficacy outcomes were defined as major adverse cardiovascular events (MACE) and thrombotic events, whereas the safety outcomes were measured by major and minor bleeding and hemorrhagic stroke. After a rigorous quality assessment to minimize bias, 23 studies were selected for analysis. The findings indicated that novel antiplatelets reduced MACE but increased bleeding complications, with ticagrelor consistently associated with dyspnea.In conclusion, novel P2Y12 inhibitors provide cardiovascular benefits but require careful patient selection and monitoring due to gastrointestinal bleeding (GIB) risks. Future research should standardize bleeding definitions and assess long-term outcomes. Ticagrelor and prasugrel may be more effective and safer than clopidogrel in ACS patients. Given the high risk of GIB, especially among older individuals or those with a past stroke, it is advisable to suggest a lower prasugrel dose without raising the bleeding rates. Since fewer patients use the novel antiplatelet regimen compared to clopidogrel, future clinical trials should include a broader patient population and compare these regimens.

Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.

Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5mg BID or rivaroxaban 10mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14-p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.

ProGlide-AngioSeal versus ProGlide-FemoSeal for vascular access hemostasis posttranscatheter aortic valve implantation.

The hybrid strategy combining plug-based and suture-based vascular closure devices (VCD) was introduced as a promising technique for vascular access hemostasis after transcatheter aortic valve implantation (TAVI) with satisfactory outcomes. However, data comparing two plug-based VCDs each in the combination with a suture-based VCD, namely ProGlide/AngioSeal (P/AS) with ProGlide/FemoSeal (P/FS) VCDs, is still lacking. To compare the 30-day outcome of the hybrid strategy using P/AS versus P/FS for vascular access site closure after TAVI. A retrospective single-center observational study included 608 patients recruited from a prospective TAVI registry between 2016 and 2022. The composite endpoint was defined as any VCD-related major vascular complications and/or bleeding more than type 1 according to Valve Academic Research Consortium criteria. The current study reported a significantly higher rate of composite endpoint in P/AS group, which was driven by a higher rate of major bleeding (5.4% vs. 1.4%, p = 0.036). We also found a higher rate of VCD-related minor bleeding in P/AS group (16.3% vs. 8.1%, p = 0.013). Successful access site hemostasis was achieved in 71.7% of P/AS group versus 83.1% in P/FS group (p = 0.006). The presence of anterior wall calcification at the access site was significantly associated with the composite endpoint (adj odds ratio 2.49; 95% confidence interval (1.08-5.75), p = 0.032). The hybrid strategy for large bore vascular access closure using P/FS showed a potentially better 30-day outcomes compared with P/AS. The presence of anterior calcification at the access site carries a significant risk of VCD-related complications.

Risk of venous thromboembolism after discontinuing prophylactic or therapeutic anticoagulation in patients with haematologic malignancies because of thrombocytopenia.

Although the rates of thrombocytopenia in patients with hematologic malignancies are well known, clinical reports of patients with haematological malignancies presenting with thrombocytopenia who developed venous thromboembolism (VTE) are rare. Defining the risk of VTE in patients with hematologic malignancies in whom anticoagulation is discontinued could help to individualize concepts of anticoagulation. We performed a retrospective analysis of medical records of patients with hematologic malignancies and thrombocytopenia grade 3 (25 × 109/L to < 50 × 109/L) or more severe in 2019-2022 in the Department of Haemato-Oncology at HELIOS Klinikum Krefeld. Data from 67 patients (34 (51%) males, 33 (49%) females) aged between 22 and 82years (38 leukaemia, 23 lymphoma, 6 other) were included. Prophylactic anticoagulation was performed in 59 (88%) patients and therapeutic due to atrial fibrillation in 8 (12%). Anticoagulation was discontinued in 37 (55%) patients due to thrombocytopenia. Thrombotic events occurred in eight (12%) and minor bleeding in two (3%) patients. Seven patients developed a deep vein thrombosis (DVT) or superficial vein thrombosis (SVT) of the upper limbs, only one patient had a thrombosis of the femoral veins. Thrombotic event were much more frequent in patients suffering from leukaemia compared to lymphoma. Two thrombotic events occurred despite continued prophylaxis (2 of 30, 6.6%), the other six after discontinuing of anticoagulation (6 of 37, 16.2%). Both bleedings occurred in the group with continued anticoagulation. Five of the six patients with a thrombotic event, but without anticoagulation, received anticoagulation again despite a low platelet count and no bleeding was observed. Only one patient with jugular vein thrombosis and a platelet count around 4 × 109/L remained without anticoagulation and no thrombus formation was observed. Risk of VTE in our patients with haematologic malignancies in whom anticoagulation is discontinued due to thrombocytopenia grade 3 is about 2.5 times higher than in patients in whom anticoagulation is continued and predominantly affects patients with leukaemia and upper extremity.

Clinical outcomes of Asian patients with newly diagnosed atrial fibrillation and previously diagnosed atrial fibrillation: Insights from the CODE-AF registry

BackgroundAtrial fibrillation (AF) may have different clinical features in its early phase. Objective: This study compared the characteristics and clinical outcomes of early-phase AF with later-phase AF using a large multicenter prospective registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF]). MethodsPatients enrolled between June 2016 and March 2021 were divided into two groups based on AF duration: (1) newly diagnosed (AF duration ≤90 days) and (2) previously diagnosed (AF duration >90 days). The baseline characteristics and clinical outcomes were compared. ResultsAmong the 10,001 study participants (mean age 67.0±14.5 years, and 64% men), 22% were defined as newly diagnosed and 78% as previously diagnosed. Newly diagnosed patients had fewer comorbidities and more unhealthy social behaviors. Despite lower prescription rates of oral anticoagulant, direct oral anticoagulants were more frequently used. The newly diagnosed group also had a higher composite clinical outcome risk within 90 days (adjusted HR 1.81, 95% CI 1.30–2.53, P<0.001) and revealed a higher risk of all bleeding and heart failure admission within 90 days. No significant differences remained between the groups over a 36-month follow-up. ConclusionsPatients with early-stage AF were younger and had fewer comorbidities. While there was a higher risk of heart failure admissions and minor bleeding, the risk of death, stroke, and major bleeding was not significantly increased. Structured monitoring and management during the initial months are essential to address these risks.

Hemophilia A in a male cat with intermittent lameness

A 3-month-old domestic shorthair tomcat born on a farm was unsuccessfully treated with meloxicam for alternating lameness, fever and inappetence. On presentation, there was lameness (grade 2/4) of the right forelimb with mild swelling of the soft tissue. Rectal temperature was 39.9°C, a moderate anemia developed. Inadequate bleeding occurred during arthrocentesis performed on suspicion of polyarthritis. Coagulation tests revealed an isolated prolonged activated partial thromboplastin time (aPTT). Activity of factor VIII was 5% (reference range: 70-125%), of factor IX 55% (80-130%), and of factor XII 73% (50-140%).In a genetic study, exons and adjacent intron sequences of the feline F8-gene were sequenced and compared with the reference (ENSFCAT000078256.1). While no non-synonymous variants were found in coding sequences, intron 19 revealed the variant c.6073+2 T>C. This variant likely results in splice site alteration, atypical splicing, and thus an altered mRNA for FVIII.The patient was treated symptomatically (metamizole, buprenorphine, tranexamic acid) and clinical signs improved. Chemical castration with a GnRH implant was performed at 8 and 18 months of age, whereby minor bleeding at the implantation site occurred after the second implantation. After 3.5 years, the cat lives nearly without clinical signs of bleeding.aPTT prolongation with normal PT indicated a factor deficiency. Determination of factor activity led to the diagnosis of hemophilia A. Genetic testing detected a splice variant in the F8-gene.

An Evaluation of the Safety of Half-Dose Direct Oral Anticoagulants Following Total Joint Arthroplasty: A Pilot Study.

Background Total joint arthroplasty (TJA) patients on preoperative anticoagulation therapy present a challenge for adult reconstructionsurgeons. The goal in managing such patients is to limit bleeding complications associated with administering the medications while preventing medical complications from withholding them. At our institution, we began a protocol in 2017 that utilizes a half-dose direct oral anticoagulant (DOAC) regimen for one week followed by resuming of the full-dose regimen in select patients who underwent TJA. This study investigated the 90-day safety profile associated with this protocol compared to previous literature. Methodology A retrospective review of 898 patients from a single institution was conducted including allpatients receiving a half-dose DOAC protocol for one week followed by resuming of the full-dose regimen after total knee and total hip arthroplasty between 2017 and 2022. Data were collected on patient demographics, type of surgery, and DOAC dosage. Ninety-day complications were collected and separated into reduced dose complications of DOAC (such as cerebrovascular accidents (CVAs) or venothrombotic events (VTEe)) and DOAC therapy-related complications (including wound and bleeding complications). Results In the total hip arthroplasty (THA) subgroup (n = 396, 44.10%), there were four major VTE occurrences, aligning with therange seen in historical protocols. Deep vein thrombosis (DVT) and pulmonary embolism (PE) incidents were three and one, respectively, both within the historical range. In the total knee arthroplasty (TKA) subgroup of 502 (55.90%) patients, there were seven major VTE events, with five DVTs and two PEs, also aligning with historical ranges. Medical complications in the THA group included no CVA events and one myocardial infarction, with the latter slightly higher than the historical range. In the TKA group, there were two medical complications, both being CVAs. Regarding bleeding complications, THA patients showed four major bleeding incidents, two blood transfusions, and two hemorrhages, with these numbers comparable to or lower than historical ranges. There were seven minor bleeding events. For TKA, there were two major bleeding events, two blood transfusions, no hemorrhages, and five minor bleeding events. Wound complications in THA included five surgery-related complications, two cases of wound dehiscence, and three infections. TKA patients experienced 17 surgery-related complications, six cases of wound dehiscence, and 11 infections. Conclusions This study suggests that the half-dose DOAC protocol in patients undergoing TJA is non-inferior to historical full-dose DOACprotocolswarranting further investigation to generalize across broader populations.

Safety of Sofosbuvir-Based Direct-Acting Antivirals for Hepatitis C Virus Infection and Direct Oral Anticoagulant Co-Administration.

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit.

Antithrombotic Strategies After Transcatheter Aortic Valve Replacement in Patients Without an Indication of Oral Anticoagulants: A Network Meta-Analysis of Randomized Controlled Trials.

Single-antiplatelet therapy (SAPT) has been a standard of care posttranscatheter aortic valve replacement with no clear evidence exist using direct oral anticoagulants (DOACs), vitamin K antagonists (VKA), or dual antiplatelet agents (DAPT); thus we aim to compare the safety and efficacy of the various antithrombotic strategies after transcatheter aortic valve replacement. We performed a network meta-analysis using a frequentist framework, pooling dichotomous outcomes using risk ratio (RR), and continuous data using mean difference, along with the corresponding 95% confidence interval (CI). Nine randomized controlled trials with 4193 patients were included, 567 patients were in the VKA group, 591 patients in the SAPT group, 1571 patients in the DAPT group, and 1464 patients in the DOACs group. Only DOAC showed a statistically significant higher risk of all-cause mortality [RR of 1.88 (95% CI: 1.07-3.28)] with no statistically significant difference between our arms in terms of mortality. For minor bleeding, DAPT had a significant higher risk with RR of 1.53 (95% CI: 1.04-2.25), while for major bleeding, DAPT and DOAC had a significant higher risk with RR of 2.36 (95% CI: 1.27-4.40) and 4.74 (95% CI: 2.05-10.92), respectively. There was no significant difference in terms of stroke and life-threatening bleeding. Moreover, only DOAC showed a significantly lower risk for valve thrombosis, when compared to other strategies [RR: 0.24 (95% CI: 0.13-0.46)]. Overall, SAPT had lower major bleeding events compared to other arms. There were no differences in the outcomes of stroke, myocardial infarction, or life-threatening bleeding outcomes. However, DOACs significantly reduced valve thrombosis compared to VKAs.

A new strategy for monitoring of direct oral anticoagulants in patients with cyanotic and complex congenital heart disease

BackgroundPatients with congenital heart disease (CHD) often require an oral anticoagulation. Vitamin K antagonists (VKA) are the standard treatment, however, an increased hematocrit in patients with secondary erythrocytosis due to cyanosis complicates the correct measurement of the international normalized ratio. Direct oral anticoagulants (DOAC) could be an alternative, but data on their efficacy and safety in complex and cyanotic CHD patients are scarce. This study proposes a new strategy of DOAC monitoring in these patients using D-dimers and DOAC trough levels. MethodsThis is a retrospective study including cyanotic and complex CHD patients requiring oral anticoagulation. Clinical, cardiac imaging and laboratory data were collected before and after start of DOAC. The new monitoring strategy consists of determination of D-dimers and DOAC trough levels at 1–4 weeks, 1–6 months, 6–12 months, >1 year after start of DOAC. ResultsEleven patients were included. For 10 patients D-dimers and DOAC trough levels were in target range. In one patient, D-dimers increased continuously after start of DOAC despite dose escalation, suggesting insufficient DOAC efficacy and finally requiring a switch to VKA. D-dimers subsequently decreased under VKA to the therapeutic range. In three patients, one thromboembolic and two minor bleeding complications occurred. No major complications were observed. ConclusionsWe propose a new strategy of monitoring of oral anticoagulation with DOAC and report its implementation in clinical routine. Highlighting the importance of pharmacokinetic and -dynamic monitoring, this strategy could improve safety and efficacy of DOAC in cyanotic and complex CHD which, however, requires a prospective validation.

COVID-19 venous thromboembolism prophylaxis guidelines in pediatrics

IntroductionSARS-CoV-2 (COVID-19) infection and multisystem inflammatory syndrome in children (MIS-C) are risk factors for venous thromboembolism (VTE). Guidelines for VTE prophylaxis were established at our institution at the beginning of the pandemic. Patients who had any VTE risk factors in addition to COVID-19 met criteria for anticoagulation prophylaxis. Patients who were diagnosed with MIS-C met criteria regardless of additional risk factors. Materials and methodsWe conducted a retrospective review of patients admitted with COVID-19 or MIS-C to determine compliance with VTE prophylaxis guidelines and to evaluate the incidence of VTE and bleeding events in our population. Results and conclusionsAmong a total of 678 patients admitted with COVID-19 or MIS-C, 519 (76 %) patients met criteria for VTE prophylaxis and 348 (65.6 %) started prophylaxis. Logistic regression analysis identified a personal or family history of thrombosis or thrombophilia, diagnosis of MIS-C, admission to the intensive care unit, and presence of a central venous catheter as significantly associated with starting VTE prophylaxis. There were 18 patients who developed VTE. Minor bleeding events occurred in 19 patients (5 %), patient important bleeding, no intervention occurred in 8 patients (2 %), clinically relevant nonmajor bleeding in 8 patients (2 %), and major bleeding in 10 patients (3 %). The incidence of VTE in our patients with COVID-19 and MIS-C is similar to VTE rates at other institutions. We found that universally recognized VTE risk factors were appropriate to include as risk factors for thrombosis in hospitalized children with COVID-19 and MIS-C.

COMPARATIVE STUDY OF CLOPIDOGREL VS PRASUGREL IN PATIENTS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION (PCI)

Antiplatelet therapy is a cornerstone in managing patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic complications. Prasugrel and clopidogrel are two commonly used agents, but their comparative efficacy and safety remain a subject of ongoing research, particularly in elective PCI cases. Objective: This study aimed to compare the safety and efficacy of prasugrel and clopidogrel in patients undergoing elective PCI, focusing on clinical outcomes such as minor and major bleeding, stent thrombosis, and mortality. Methods: This retrospective cohort study was conducted at a tertiary care hospital in Pakistan between January and July 2024. A total of 200 patients undergoing elective PCI were included in the study. Patients received either clopidogrel (300 mg or 600 mg) or prasugrel (60 mg) as part of their antiplatelet therapy. Clinical outcomes were assessed, including minor and major bleeding, thrombosis, and death. Statistical analyses were performed using Pearson correlations, chi-square tests, and regression analysis. SPSS software (version 25.0) was used for data analysis, with statistical significance set at p &lt; 0.05. Results: Of the 200 patients, 48.5% were male, and 51.5% were female, with the majority aged between 61 and 70. Prasugrel (60 mg) was the most commonly used loading dose (35.5%). Minor bleeding events were significantly higher in the prasugrel group compared to the clopidogrel group (p = 0.05). However, no significant differences were observed in major bleeding, stent thrombosis, or mortality between the two groups. A positive correlation between minor bleeding and stent thrombosis was noted (p = 0.048), while regression analysis confirmed that prasugrel did not significantly increase the risk of major bleeding or death. Conclusion: Prasugrel was associated with a higher incidence of minor bleeding compared to clopidogrel, but both agents exhibited comparable safety profiles in terms of major bleeding, thrombosis, and mortality in patients undergoing elective PCI. The findings suggest that prasugrel can be considered a safe and effective alternative to clopidogrel in elective PCI, with careful patient selection to minimize bleeding risks.

Low Versus Standard Intensity Heparin Protocols in Adults Maintained on Extracorporeal Membrane Oxygenation: A Retrospective Cohort Study

Background: Patients maintained on extracorporeal membrane oxygenation (ECMO) often require systemic anticoagulation to prevent circuit clotting and systemic thromboembolic complications. The optimal intensity of anticoagulation to balance the risk of bleeding and prevention of thrombotic complications in this patient population is not well described. Objective: To compare bleeding events in patients on ECMO anticoagulated with standard vs low intensity heparin protocols. Methods: This single-center, retrospective cohort study included adult patients on VA- or VV-ECMO and anticoagulated with low or standard intensity heparin protocols. The primary outcome was the incidence of major bleeding; secondary outcomes included the incidence of minor bleeding, thrombotic complications, heparin-induced thrombocytopenia, in-hospital mortality, time in therapeutic range, anti-Xa correlation with aPTT, intensive care unit and hospital lengths of stay, oxygenator exchanges, and rate of protocol switching. Results: A total of 27 patients (14 low intensity, 13 standard intensity) were included. There were six major bleeding events in the low intensity group and four in the standard intensity group ( P = 0.69); there were four minor bleeding events in the low intensity group and five in the standard intensity group ( P = 0.69). Seven patients in the standard intensity group switched protocols; zero patients in the low intensity group switched protocols ( P = 0.002). There were no differences in any other outcomes. Conclusions: There was no difference in the incidence of any bleeding or thrombotic events when using a low vs standard intensity heparin protocol in patients on ECMO. A low intensity heparin strategy for patients on ECMO may be feasible and safe.

Cartilage-sparing otoplasty – 288 ears in 3 years

BackgroundStandard methods of otoplasty may risk anatomical distortion. Previous work showcased a novel, cartilage-sparing technique. This study aimed to confirm the safety and effectiveness of the method in a larger cohort. MethodsThis retrospective study included patients undergoing otoplasty by a single surgeon using a single technique between January 2021 and December 2023. Eligible patients were aged above 5 years and had prominent or constricted or cup ears, forming a 2cm distance from the mastoid. Surgical techniques included novel key-point sutures. Minimum follow-up was 6 months. Data on demographics, risk factors, perioperative management, and complications were collected from patient records. ResultsA total of 288 operated ears (147 patients) were included. The mean age was 17 years and 91 (61.9%) were female. The mean duration of follow-up was 24.3 months. Postoperative complications were generally minor and included PDS suture exposure (n=16, 5.5%), manageable postoperative pain (n=8, 2.7%), self-resolving swelling (n=8, 2.7%), minor bleeding (n=7, 2.4%), and superficial skin complications (n=4, 1.3%). Infections occurred in 4 ears (1.3%) and were treated effectively with topical/oral antibiotics. Cases of partial release of the ear resolved without intervention (n=4, 1.3%). Only 4 (1.3%) ears experienced loss of correction, with options for reoperation available as needed. Analysis showed no significant age differences in postoperative complications, and a nonsignificant trend towards higher postoperative swelling in males compared to females (10.7% vs 2.2%; P=0.054). ConclusionsThe data confirms that this technique offers a safe and rapid cartilage-sparing otoplasty with minimal complications and low recurrence rates. It ensures long-lasting and aesthetically pleasing results for prominent ear deformities. Level of evidenceLevel III