Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer’s Disease Mice

Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

Underdosed Direct Oral Anticoagulants in Atrial Fibrillation Patients Reduce Stroke Severity and Improve Outcome

<b><i>Background and Purpose:</i></b> Anticoagulant drugs, including vitamin K antagonist (VKA) and direct oral anticoagulants (DOACs), can reduce stroke severity and are associated with good functional outcomes. Some patients are prescribed lower-than-recommended doses of DOACs; whether these have similar effects has not been clarified. <b><i>Methods:</i></b> We retrospectively evaluated 1,139 consecutive ischemic stroke and transient ischemic attack patients with atrial fibrillation. Patients were divided into 5 groups according to their preceding anticoagulant drug therapies: no anticoagulant therapy (AC_n), undercontrolling VKA doses (VKA_uc), recommended, controlling VKA doses (VKA_rec), prescribed underdoses of DOAC (DOAC_ud), and recommended doses of DOAC (DOAC_rec). We investigated the associations between these anticoagulant drug therapies and patients’ initial stroke severity and 3-month outcomes. <b><i>Results:</i></b> Median National Institutes of Health Stroke Scale scores at admission were as follows: AC_n: 16, VKA_uc: 15, VKA_rec: 9, DOAC_ud: 5, and DOAC_rec: 7. When the AC_n group was used as a reference, regression analysis showed that VKA_rec (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.01–2.21), DOAC_ud (OR 2.84, 95% CI: 1.47–5.66), and DOAC_rec (OR 1.83, 95% CI: 1.23–2.74) were associated with milder stroke severity, while VKA_uc was not. Median 3-month modified Rankin Scale scores were 2 in the DOAC_ud and DOAC_rec groups and 4 in all other groups. After adjusting for confounding factors, DOAC_ud (OR 3.14, 95% CI: 1.50–6.57) and DOAC_rec (OR 1.67, 95% CI: 1.05–2.64) were associated with good 3-month outcomes while VKA_uc and VKA_rec were not. <b><i>Conclusions:</i></b> In patients with atrial fibrillation, recommended doses and underdoses of DOACs reduced stroke severity on admission and were associated with good 3-month outcomes.

Acute spinal cord compression due to spinal subdural hematoma after spinal anaesthesia in-patient under anticoagulant drug

Background Subdural spinal cord hematomas are very rare condition. They most often occur in patients with primary or secondary blood haemostasis disorders and following lumbar punctures. Early diagnosis and management preserve functional prognosis. Case description We report the case of a female 69-year-old patient on oral anticoagulant, Acenocoumarol 4 mg (SINTROM) for previous aortic prosthesis. The patient had undergone surgery for appendicitis under spinal anaesthesia 2 days before her admission in neurosurgery department. She was admitted in emergency for 1/5 central flaccid paraplegia with sensitive umbilical level. A spinal MRI performed showed a collection intradural in intermediate signal in T1 and hyposignal in T2 with echo gradient of 8 mm thickness extended from D8 to L2 compressing the marrow with anomalies of intramedullary signal extended from D8 to the conus medullaris. We retained indication to operate the patient early in emergency because of acute spinal cord compression. We performed T12-L2 laminectomy, durotomy and evacuated hematoma. Postoperative marked by an immediate recovery of sensitivity and an onset of motor recovery from 1/5 to 2/5 and 4/5 follow up at on year with physiotherapy. Conclusion Spinal cord compression due to subdural spinal hematomas not often described especially in patients with haemostasis blood disorders due to anticoagulants drugs. In addition, we should pay attention with lumbar puncture in these patients. Emergency surgery allows a good prognosis about recovery of neurological disorders.

Current Anticoagulation Recommendation for COVID-19 Patients

Thromboembolic events in COVID-19 patients can be one of the factors that aggravate the disease and increase mortality. When severe hypoxemia and hypotension occur in COVID-19 patients, the possibility of embolism should be considered. As a result, anticoagulant therapy in COVID-19 patients has an essential role in lowering disease severity and mortality. Many studies report that giving anticoagulants to COVID-19 patients can reduce mortality. Therefore, it is important to understand the role and use of anticoagulant therapy in cases of COVID-19. Several guidelines that have been issued by several health organizations in the world and Indonesia can be used as guidelines for clinicians to start anticoagulant therapy in cases of COVID-19. Various anticoagulant drug regimens have also been recommended to be used both as prophylaxis and as therapy for thromboembolism that can occur after COVID-19 cases.

Comparison of seasonal pattern in patients with warfarin overdose

Objectives: The most common anticoagulant drug in the world is warfarin. Overdoses of warfarin may follow seasonal patterns, but the information is scarce. This study investigated possible seasonal variations in warfarin overdose among various age groups living in cold climates. Results: Seasonal patterns were observed in warfarin overdoses. Warfarin overdoses were more common among the patients under 65 years old during winter (P-value = 0.03), whereas almost identical findings were found among the patients 65 and older, although numerically more cases were seen during the summer season (P-value = 0.8). Conclusions: The results of the current study showed that warfarin overdoses in the patients younger than 65 years showed a seasonal pattern peaking in the winter months. However, these findings did not have any relation with older patients. To confirm the results of the present study, larger prospective multicenter studies in a variety of climate settings are needed.

Current therapeutic approaches to haemostasis correction in covid-19: a systematic review

Background. The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has swept across countries worldwide. Despite an unprecedented volume of research, few drug therapies have been proved effective. The lack of evidence-based strategies entailed many practical treatments. Hypercoagulability observed in COVID-19 patients has sparked a debate in the medical community on therapeutic value of anticoagulants.Objectives. A review of up-to-date evidence supporting the therapeutic effect of unfractionated and low molecular-weight heparin as anticoagulant in treatment for COVID-19. Methods. Russian-language and foreign literature was mined in the RSCI, Scopus, PubMed, medRxiv and eLibrary databases for the years 2020–2021, with considering selected impactive publications within 1991–2019 as well. The query keywords were COVID-19, heparin [гепарин], hemostasis [гемостаз], thromboembolism [тромбоэмболия]. Peer-reviewed scientific journals received priority. Content and descriptive analytics were used as research tools.Results. The review surveyed 84 literature sources, with 51 articles selected for downstream analysis. We highlight usage of heparin and its fractions in treatment for COVID-19 and preclinical evidence verifying the antiviral and anti-inflammatory properties of heparin and synthetic heparin-like drugs in COVID-19. The known and plausible side effects demanding additional prospective randomised controlled trials on anticoagulant application in COVID-19 are reviewed, with an assessment of oral direct-acting anticoagulant drug efficiency.Conclusion. Drug-based therapies for haemostasis correction in COVID-19 are currently limited. The paucity of evidence warrants heparin usage as a safer therapy in acute COVID-19 compared to oral anticoagulants. However, the balance of its potential benefits vs. risks must be observed. The benefits and risk uncertainty in heparin treatment require randomised clinical trials and further studies to evaluate safety of direct-acting oral anticoagulants after the patient’s discharge in COVID-19.

Characteristics and Surgical Outcomes of the Patients With Atraumatic Splenic Rupture

Background: Although splenic emergencies are rare in the case of the absence of trauma, late-diagnosed atraumatic splenic ruptures (ASR) may result in mortality. Methods: All consecutive adult patients who underwent emergency splenectomy due to ASR between January 01, 2015, and January 01, 2021, were reviewed.Results: 203 patients underwent splenectomy, 83 electively, 120 emergency splenectomy, and amongst them 15 for atraumatic reasons.The median age of patients with ASR was 55 years (34- 90), and 10 patients (66. 6%) were male. The most pre-existing medical diseases are heart valve replacement (n=5, 33. 3%) and diabetes mellitus (n=6, 40 %). Eight (46. 6%) patients had more than one comorbid disease. Ten patients (66. 6 %) had splenic rupture due to splenic infarction and abscess. Two patients were diagnosed with diffuse large B cell lymphoma (DLBCL) postoperative by histological assessment. Two patients were diagnosed with lung cancer with spleen metastasis. One patient had aortic and mitral valve replacement and was receiving an oral anticoagulant drug. The median length of hospital stay was 6 (2- 24) days and the intensive care unit stay was 2 (0- 20) days. Three patients (20%) died in hospital.Conclusion: Male sex, previous splenic infarctions, hematological malignancies, lung cancer spleen metastases, underlying cardiac diseases (valve replacement, endocarditis, atrial fibrillation) may increase the risk for ASR.

Possibilities of the efficiency and safety control of rivaroxaban application in patients with atrial fibrillation

The results of a study of the concentration of rivaroxaban in the peripheral blood in patients with atrial fibrillation, receiving different doses of rivaroxaban, as well as in the case of developing hemorrhagic complications, are presented. 65 patients admitted for treatment for atrial fibrillation were examined. As an anticoagulant drug, rivaroxaban was prescribed at a dose of 15 or 20 mg once a day, depending on the state of renal function. The patients were divided into 3 groups depending on the prescribed dose of rivaroxaban and the presence or absence of hemorrhagic complications. At the same time, each patient underwent therapeutic drug monitoring of the drug. It was found that in patients, who received rivaroxaban at a dose of 15 mg, in 35% of cases its concentration in the blood was below the average minimum values. In patients, who received the drug at a dose of 20 mg, in 16% of cases its concentration in the blood serum exceeded the average maximum values. Patients treated with 15 mg of rivaroxaban lacked any hemorrhagic complications. In the group of patients with advanced hemorrhagic complications who received rivaroxaban at a dose of 20 mg, its serum concentration at all stages of therapeutic drug monitoring was significantly higher than the average maximum values and more than 4 times higher than in the control group (without hemorrhagic complications). The results of the study indicate the advisability of conducting therapeutic drug monitoring with the determination of rivaroxaban concentrations in the blood serum of patients receiving the drug, especially when they develop hemorrhagic complications.