The fine structure of enoxaparin sodium samples with different degree of 1,6-anhydro derivatives were analyzed with polyacrylamide gel electrophoresis, high performance liquid chromatography, ultraviolet spectroscopy, infrared spectroscopy and nuclear magnetic resonance spectroscopy. A further study of anticoagulation activity of enoxaparins was performed, including those on their inhibition activities of coagulation factor Xa (FXa) and thrombin (FIIa). The results showed that the anti-FXa and -FIIa activities of enoxaparins with different degree of 1,6-anhydro derivatives (20.0%-39.7%) with similar structure characteristics, had decreasing tendency when the degree of 1,6-anhydro derivatives increased. Especially, the anti-FXa activity was sensitive to the change of the degree of 1,6-anhydro derivatives.
Anticoagulants ; chemistry ; Enoxaparin ; chemistry ; Factor Xa Inhibitors ; chemistry ; Thrombin ; antagonists & inhibitors

Regulatory approvals of non-vitamin K antagonist oral anticoagulants (NOACs) have been based on large randomized phase III trials evaluating dabigatran, rivaroxaban, apixaban, or edoxaban relative to warfarin for atrial fibrillation (AF). The results of the trials showed that all NOACs were at least non-inferior to warfarin in the prevention of stroke/thromboembolism and showed lower rates of intracranial bleeding than those associated with warfarin. However, the trials were designed differently, varied in the inclusion/exclusion criteria, and used either one dose or a low/high dose of the NOAC drug. Some of these differences have challenged the ability to directly compare various NOACs, and comparative data on effectiveness and intracranial bleeding are sparse in “real-world” patients. Real-world data complement data from large randomized phase III trials by providing new aspects of the “real-world” absolute risks of ischemic and hemorrhagic stroke associated with NOACs vs. warfarin. Moreover, “real-world” fragile patients might have been included (e.g., patients with increased risk of bleeding, liver disease, and chronic kidney disease), although these patients would be less represented in trials. This paper introduces recently published real-world data of NOACs and further suggests the recommended dosage of NOACs for Korean patients.
Anticoagulants* ; Atrial Fibrillation ; Complement System Proteins ; Dabigatran ; Factor Xa Inhibitors ; Hemorrhage ; Humans ; Kidney ; Liver Diseases ; Rivaroxaban ; Stroke ; Warfarin

Anticoagulant agents are used to reduce the risk of thromboembolic complications in patients with atrial fibrillation or deep vein thrombosis. Several new generation of oral anticoagulants have been approved. These novel oral anticoagulants (NOACs) include direct thrombin inhibitors, dabigatra etexilate, and the direct factor Xa inhibitors, rivaroxaban, apixaban and edoxaban. This review evaluates NOACs-related gastrointestinal bleeding and summarizes the ideal management strategies based on the guideline suggested by American Society for Gastrointestinal Endoscopy.
Anticoagulants* ; Antithrombins ; Atrial Fibrillation ; Endoscopy ; Endoscopy, Gastrointestinal ; Factor Xa Inhibitors ; Gastrointestinal Hemorrhage ; Hemorrhage ; Humans ; Rivaroxaban ; Thromboembolism ; Venous Thrombosis

Chronic Limb-Threatening Ischemia ; Factor Xa Inhibitors/adverse effects* ; Humans ; Platelet Aggregation Inhibitors/adverse effects* ; Rivaroxaban/adverse effects* ; Singapore ; Treatment Outcome

BACKGROUNDLow molecular weight heparin (LMWH) was more effective than unfractionated heparin (UFH) in treating acute coronary syndrome (ACS). However, it remains uncertain whether LMWH can be used in patients undergoing percutaneous coronary intervention (PCI) instead of UFH. This study aimed to evaluate the efficacy and safety of using enoxaparin instead of UFH in the intervention treatment of patients with coronary heart disease (CHD).

METHODSFrom October 2003 to Febuary 2005, 966 patients with CHD were enrolled into this study. Among 966 patients, 455 patients received the PCI, including 283 patients with Non-ST segment elevation ACS (NSTEACS), 511 patients did not received PCI due to mild, moderate lesions or were suitable for coronary artery bypass graft (CABG). The 966 patients were randomized to enoxaparin group (484 patients) and UFH group (482 patients). Patients in the enoxaparin group were given enoxaparin at least twice subcutaneously (1 mg/kg, q12 h) before catheterization. Plasma anti-Xa activity was determined 1 - 8 hours after the last dose of enoxaparin was determined. The catheterization was performed within 8 hours after the last dose of enoxaparin. The sheath was removed immediately after the procedure. Patients in the UFH group were given UFH 25 mg intravenously before coronary angiography. Additional 65 mg was given intravenously if PCI was to be performed. The sheath was removed 4 hours after the procedure.

RESULTSA total of 227 patients in the enoxaparin group and 228 patients in the UFH group received PCI. In the enoxaparin group, one patient developed acute thrombosis during PCI and resulted in acute myocardial infarction (AMI), no acute or subacute thrombosis was found during hospitalization. In the UFH group, no acute or subacute thrombosis occurred during PCI procedure and hospitalization. Therefore, the incidence of major adverse cardiovascular events (MACEs) during the hospitalization was 0.44% in the enoxaparin group and 0 in the UFH group. In the enoxaparin group, the sheath was removed immediately after the procedure and 8 patients had hematoma on the puncture site. In the UFH group, the sheath was removed 4 hours after the procedure and 20 cases had hematoma on the puncture site. The incidence of hematoma on the puncture site was significantly higher in the UFH group than that in the enoxaparin group (P < 0.05). Anti-Xa activity was determined in 174 patients in LMWH group. The mean anti-Xa activity was (0.87 +/- 0.23) U/ml, and 94.8% of them had anti-Xa activity >0.5 U/ml and 6.9% of the patient >1.2 U/ml. There was no death and AMI occurred in enoxaparin group, but one patient had AMI caused by subacute thrombosis in UFH group during 30-day follow-up. MACE rate at 30-day follow-up was 0 in enoxaparin group and 0.43% in UFH group.

CONCLUSIONSThe results of the study suggest that it is safe and efficient to give enoxaparin at least twice before the PCI procedure, and the sheath can be removed immediately after PCI. For NSTEACS patient who has received enoxaparin more than twice during the hospitalization can undergo PCI directly and no UFH is necessary before or during PCI.

Angioplasty, Balloon, Coronary ; Anticoagulants ; therapeutic use ; Coronary Disease ; therapy ; Enoxaparin ; adverse effects ; therapeutic use ; Factor Xa Inhibitors ; Female ; Heparin ; therapeutic use ; Humans ; Male ; Middle Aged

OBJECTIVETo evaluate the effectiveness and safety of subcutaneous low molecular weight heparin (LMWH) used in acute management of patients with non-ST segment elevation acute coronary syndrome (ACS).

METHODSA total of 102 patients with non-ST segment elevation ACS were treated for at least 48 hours ( > or =5 times) with subcutaneous nadroparin (1 mg/kg each 12 hours). All 102 patients underwent coronary angiographies (CAG) within 8 hours after LMWH injection, followed by immediate percutaneous coronary intervention (PCI).

RESULTSAnti-Xa activity at the time of catheterization was (0.62 +/- 0.18) IU/ml, and 90% of the patients had anti-Xa activity > 0.5 IU/ml. No death, myocardial infarction relapse or emergent revascularization occurred after PCI. Thrombosis and/or embolism occurred in 2 patients (3.5%) during PCI. Mild hemorrhage was observed in 4 patients (3.9%) of PCI group and in 2 patients (4.4%) in CAG group. No major hemorrhage occurred.

CONCLUSIONPCI within 8-12 hours of the last dose after > or =48 hours nadroparin subcutaneous injection seems to be effective and safe.

Acute Coronary Syndrome ; blood ; therapy ; Angioplasty, Balloon ; Anticoagulants ; adverse effects ; therapeutic use ; Factor Xa Inhibitors ; Humans ; Nadroparin ; adverse effects ; therapeutic use

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031–3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.
Colorectal Neoplasms ; Drug Therapy ; Factor Xa Inhibitors ; Gastrointestinal Tract ; Hemorrhage ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Mortality ; Neoplasm Metastasis ; Recurrence ; Retrospective Studies ; Rivaroxaban ; Stomach Neoplasms ; Venous Thromboembolism

Objective: This analysis was performed to evaluate the efficacy and the safety of rivaroxaban-aspirin combination therapy in secondary prevention of major adverse cardiovascular events in Chinese patients enrolled in the COMPASS trial. Methods: COMPASS was a prospective, international multi-center and randomized controlled trial. From September 2014 to February 2017, 1 086 patients with stable coronary artery disease and peripheral artery diseases were recruited from 31 centers in China. Patients were randomly assigned to separately receive the therapy of rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day,) group (n=366), rivaroxaban (5 mg twice a day) alone group (n=365), and aspirin (100 mg once a day) alone group (n=355). Baseline information such as age, sex, etc. of all three groups was collected. Finally, 1 081 patients were followed up successfully, with the follow-up rate 99.5% and the average follow-up time was 19 months. The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction and stroke. The primary safety endpoint was major bleeding evaluated by modified International Society on Thrombosis and Haemostasis criteria. Results: Age of patients was (64.2±8.3) years and there were 293 male in rivaroxaban plus aspirin group. Age of patients was (63.8±9.0) years, and there were 301 male patients in rivaroxaban alone group. Age of patients was (63.6±8.8) years, and there were 282 male patients in the aspirin alone group. The incidences of primary efficacy endpoint occurred in 9 cases (1.5%) in rivaroxaban with aspirin group, 21 cases (3.7%) in rivaroxaban alone group and 14 cases (2.5%) in aspirin alone group. Meanwhile, the incidences of primary safety endpoint occurred in 6 cases (1.0%) in rivaroxaban with aspirin group, 9 cases (1.6%) in rivaroxaban alone group and 7 cases (1.2%) in aspirin alone group. The net clinical benefit events were 10 cases (1.7%) in rivaroxaban with aspirin group, 22 cases (3.9%) in rivaroxaban alone group and 15 cases (2.7%) in aspirin alone group (P>0.5%). Conclusions: The combination of rivaroxaban with aspirin can be safe and effectively used for the secondary prevention in Chinese patients with stable coronary artery disease and peripheral artery diseases.
Aged ; Aspirin/therapeutic use* ; Cardiovascular Diseases/prevention & control* ; China ; Drug Therapy, Combination ; Factor Xa Inhibitors/therapeutic use* ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Rivaroxaban/therapeutic use* ; Secondary Prevention

Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.
Administration, Oral ; Factor Xa Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Middle Aged ; Portal Vein ; Recurrence ; Rivaroxaban/*therapeutic use ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/diagnostic imaging/*drug therapy

INTRODUCTIONDirect oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation.

MATERIALS AND METHODSLaboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations.

RESULTSProthrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing.

CONCLUSIONKnowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.

Antithrombins ; therapeutic use ; Blood Coagulation Tests ; Dabigatran ; therapeutic use ; Factor Xa Inhibitors ; therapeutic use ; Humans ; Partial Thromboplastin Time ; Practice Guidelines as Topic ; Prothrombin Time ; Pyrazoles ; therapeutic use ; Pyridones ; therapeutic use ; Rivaroxaban ; therapeutic use ; Singapore