Long-term risk of major bleeding after discontinuing anticoagulation for unprovoked venous thromboembolism: a systematic review and meta-analysis

Background: The long-term risk of major bleeding after discontinuing anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. Objectives: To determine the incidence of major bleeding up to 5 years after discontinuing anticoagulation for a first unprovoked VTE. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL (from inception to January 2021) to identify relevant randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE who had completed ≥3 months of initial treatment. Unpublished data on major bleeding events and person-years were obtained from authors of included studies to calculate study-level incidence rates. Random-effects meta-analysis was used to pool results across studies. Results: Of 1123 records identified by the search, 20 studies (17 RCTs) and 8740 patients were included in the analysis. During 13 011 person-years of follow-up after discontinuing anticoagulation, the pooled incidence of major bleeding (n=41) and fatal bleeding (n=7) per 100 person-years was 0.35 (95% confidence interval [CI], 0.20-0.54) and 0.09 (95% CI, 0.05-0.15). The 5-year cumulative incidence of major bleeding was of 1.0% (95% CI, 0.4%-2.4%). The case-fatality rate of major bleeding after discontinuing anticoagulation was 19.9% (95% CI, 10.6%-31.1%). Conclusions: Patients with a first unprovoked VTE have a non-trivial risk of major bleeding once anticoagulants are discontinued. Estimates from this study can help clinicians counsel patients about the incremental risk of major bleeding with extended anticoagulation to guide decision making about treatment duration for unprovoked VTE.

A new insight into the treatment of factor V deficiency.

Inherited factor V deficiency is an extremely rare bleeding disorder with no proper treatment currently available and can result in fatal bleeding episodes for the most severe cases. It is characterized by mutations on the F5 gene and provokes reduced levels and activity of factor V (FV) , a critical protein involved in the coagulation process. One of the most promising biotechnologies in the medical field to tackle similar genetic disorders is the use of messenger RNA, being studied for the management of several conditions. Messenger RNA can be encapsulated into lipid nanoparticles, another promising non-viral delivery system. This present article will detail the possible therapeutic effects of a composition of FV mRNA encapsulated in LNPs, by hypothesizing its details, evaluating the possible treatment and suggesting a possible experimental study that may provide further data about this treatment.

Case report: fatal bleeding from a duodenal ulcer—Dieulafoy’s lesion?

A 46-year-old man was admitted to the hospital by ambulance due to syncope. A standard blood screening showed a normal Hb value. The man had known hemorrhoids and a single fresh rectal bleeding earlier at home. On the following morning, the patient suddenly required resuscitation within a few minutes and subsequently died. Autopsy revealed a fatal hemorrhage with blood loss in the stomach and small and large intestines and a mucosal defect of the duodenum. After autopsy, the question arose whether the cause of death might have been a rare Dieulafoy’s lesion—aim of this case report was to clarify the diagnosis.

Bleeding risks with novel oral anticoagulants especially rivaroxaban versus aspirin: a meta-analysis

Background This pairwise meta-analysis determines the difference in bleeding risks associated with the use of novel oral anticoagulants (NOACs) and aspirin. Methods PubMed, the Cochrane Library database, clinicaltrial.gov, and related studies were searched for randomized control trials (RCTs) comparing NOAC and aspirin published between January 1, 2000 and May 10, 2021. The primary endpoint was intracranial hemorrhage (ICH). Results Eleven studies involving 57,645 patients were included. Compared to aspirin, rivaroxaban (5 mg/day) had a similar risk of ICH, major bleeding, and fatal bleeding; rivaroxaban (10 mg/day) had higher risks of gastrointestinal hemorrhage (OR: 1.41; 95% CI: 1.03–1.94; P = 0.032; I2 = 0%) and a similar risk of ICH, major bleeding, and fatal bleeding; and rivaroxaban (15–20 mg/day) had higher risks of ICH (OR: 3.21; 95% CI: 1.36–7.60; P = 0.008; I2 = 0%), major bleeding (OR: 2.64; 95% CI: 1.68–4.16; P < 0.001; I2 = 0%), and fatal bleeding (OR: 2.26; 95% CI: 1.25–4.08; P = 0.007; I2 = 0%) and a similar risk of gastrointestinal hemorrhage. Bleeding outcomes between other NOACs (apixaban and dabigatran etexilate) and aspirin were not different. Conclusions The bleeding risks associated with NOACs depend on drug type and dosage. For ≥15 mg/day of rivaroxaban, the risk of ICH was significantly higher than that with aspirin. However, further studies comparing dabigatran etexilate and apixaban versus aspirin are warranted to draw a definite conclusion.

Safety and Efficacy of Direct Oral Anticoagulants in Patients With Moderate to Severe Cirrhosis

Background: Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. Objective: To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. Methods: This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. Results: A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group ( P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population ( P = 0.55). No fatal bleeding or thromboembolic events occurred. Conclusion and Relevance: DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

Potential benefits of anticoagulant doses of low molecular weight heparin in COVID-19: An observational retrospective study

Hypercoagulability is a common complication of the systemic inflammation related to coronavirus disease 2019 creating debate within the critical care community on the therapeutic utility of Low Molecular Weight Heparin (LMWH). We collected data on consecutive patients with COVID-19 admitted to the Emergency Department of Castel San Giovanni Hospital, between February 29th and April 7th, 2020. Exclusion criteria were age <18 years, hospital stay <7 days, patients on dialysis and patients who had been transferred to other centers for which we could not collect data. Of the 257 patients included in the study, 49 (19.1%) died during hospitalization. We considered a wide set of variables as independent variables (age, sex, comorbidities and in-hospital treatments). We used a multivariate logistic regression model and, being heparin the only one therapy affecting survival rate, we compared prophylactic LMWH (p-LMWH) and Therapeutic LMWH (T-LMWH) groups. Kaplan Meier curve showed a higher survival probability in the T-LMWH and the difference between the two groups was statistically significant according to the log-rank or Mantel- Haenszel test (p< 0.0001). In a stratified analysis by ventilation type, the subgroup of patients who benefited from therapeutic LMWH was that in non-invasive mechanical ventilation. Using a multivariate analysis and adjusting for the drugs intake, TLMWH was the only therapy impacting on survival (HR 0.293, p <0.001). No fatal bleeding was observed. Therapeutic dose of LMWH in patients admitted to hospital with COVID-19 pneumonia was 70 associated with a decrease risk of intra-hospital mortality.

Video mediastinoscopy-assisted superior mediastinal dissection in the treatment of thyroid carcinoma with mediastinal lymphadenopathy: preliminary results

Background Mediastinal lymph node metastases (MLNM) are not rare in thyroid cancer, but their treatment has not been extensively studied. This study aimed to explore the preliminary application of video mediastinoscopy-assisted superior mediastinal dissection in the diagnosis and treatment of thyroid carcinoma with mediastinal lymphadenopathy. Materials and methods We retrospectively reviewed the clinical pathologic data and short-term outcomes of thyroid cancer patients with suspicious MLNM treated with video mediastinoscopy-assisted mediastinal dissection at our institution from 2017 to 2020. Results Nineteen patients were included: 14 with medullary thyroid carcinoma and five with papillary thyroid carcinoma. Superior mediastinal nodes were positive in nine (64.3%) patients with medullary thyroid carcinoma and in four (80.0%) patients with papillary carcinoma. No fatal bleeding occurred. There were three cases of temporary recurrent laryngeal nerve (RLN) palsy postoperatively, one of which was bilateral. Four patients had temporary hypocalcemia requiring supplementation, one had a chyle fistula, and one developed wound infection after the procedure. Postoperative serum molecular markers decreased in all patients. One patient died of cancer while the other 18 patients remained disease-free, with a median follow-up of 33 months. Conclusion Video mediastinoscopy-assisted superior mediastinal dissection can be performed relatively safely in patients with suspicious MLNM. This diagnostic and therapeutic approach may help control locoregional recurrences.

Effect of Rivaroxaban and Aspirin in Patients with Peripheral Artery Disease Undergoing Surgical Revascularization: Insights from the VOYAGER PAD Trial

Background: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. Methods: The VOYAGER PAD trial randomized patients with PAD after surgical and endovascular LER to rivaroxaban 2.5mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary endpoint was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. International Society on Thrombosis and Haemostasis (ISTH) bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. Results: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared to placebo, rivaroxaban reduced the primary endpoint consistently regardless of LER method (p-interaction 0.43). Following surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (HR 0.81, 95% CI 0.67 - 0.98; p=0.026). In the overall trial, TIMI major bleeding and ISTH major bleeding were increased with rivaroxaban. There was no heterogeneity for TIMI major bleeding (p-interaction 0.17) or ISTH major bleeding (p-interaction 0.73) based on LER approach. Following surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence 1.3% and 1.4% respectively (HR 0.88, 95% CI 0.39-1.95; p=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (p=0.95) and postprocedural bleeding requiring intervention (p=0.93) were not significantly increased. Conclusions: The efficacy of rivaroxaban is associated with a benefit in surgical LER patients. While bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage or postprocedural bleeds requiring intervention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02504216

Fatal bleeding in a 1.5-year-old child with aortoesophageal fistula: case report and review of the literature

Aortoesophageal fistula in children is a very uncommon disease, which in most cases leads to death during the first days from the moment it occurs. Its high mortality is due to the lack of knowledge among doctors about the similarity of the disease in children and the lack of experience treating it. This paper presents the case history of a 1.5-year-old child who was admitted with bleeding from the upper gastrointestinal tract and died 36 hours after admission due to continued massive bleeding at the diagnostic measure stages. An autopsy revealed an aortic aneurysm with a diameter of 1.5 cm, which penetrated the esophageal lumen and formed an aortoesophageal fistula. This article analyzes the treatment results of 17 cases of successfully treating children with aortoesophageal fistula, which we found in the literature. It describes the leading causes and mechanisms of the development of this pathology in children. Also, the article describes the diagnostic and treatment methods for children with aortoesophageal fistula.