Conventional Anticoagulant Therapy Research Articles

Formulation and Evaluation of Logenzes for Anticoagulantion

Cardiovascular diseases represent a significant global health burden, necessitating effective prevention and treatment strategies to mitigate their impact. Anticoagulant therapy plays a crucial role in managing these diseases by preventing the formation of blood clots, which can lead to life-threatening complications such as heart attacks and strokes. However, conventional anticoagulants are associated with limitations, including the risk of bleeding complications and the need for frequent monitoring. In recent years, there has been increasing interest in exploring natural alternatives to conventional anticoagulants, with Cayenne pepper (Capsicum annuum) emerging as a potential candidate due to its bioactive compound, capsaicin. This paper aims to review the existing literature on the anticoagulant properties of Cayenne pepper lozenges. By examining the pharmacological mechanisms of capsaicin and summarizing preclinical and clinical studies, this paper evaluates the efficacy, safety, and therapeutic potential of Cayenne pepper as an alternative or adjunctive therapy for cardiovascular diseases. The findings suggest that Cayenne pepper lozenges may hold promise as a novel anticoagulant agent, offering potential benefits in terms of cardiovascular health and reducing the burden associated with conventional anticoagulant therapy

Fucoidan-incorporated dissolving microneedles: A novel approach to anticoagulant transdermal delivery

Cardiovascular disease (CVD) is the leading cause of global mortality, particularly in Indonesia. Vascular disorders, including thrombosis and atherosclerosis, have been implicated as potential contributors to the development and progression of CVDs. Anticoagulant agents, such as heparin, have been commonly used to treat vascular disorders. Nevertheless, this agent may result in a hazardous adverse effect. Bioactive substances like fucoidan (FC) have emerged as an alternative, with anticoagulant and antithrombotic properties similar to heparin. However, FC was often found in oral, injectable, and transdermal dosage forms, which has considerable limitations due to its low bioavailability alongside with poor patient comfort and compliance. To overcome these issues, FC was further incorporated into dissolving microneedles (DMN) that can facilitate transdermal delivery of FC by penetrating the stratum corneum. Fucoidan Dissolving Microneedle (FC-DMN) was fabricated using gelatin and polyvinyl pyrrolidone (PVP) as polymers with various concentrations. Following several evaluations, FC-DMN exhibited good stability, mechanical resistance, and penetration ability. Ex vivo permeation study revealed that 91.23 ± 0.12 % of FC was released from the optimum formula. Furthermore, the hemolytic activity demonstrated that FC-DMN did not induce notably hemolytic, confirming its safe applicability. The in vivo anticoagulant activity test showed increased aPTT and PT values following a 7-day regimen of FC-DMN application. Interestingly, there were no significant differences (p > 0.05) were observed between FC-DMN and heparin injection (dosage 200 IU/Kg). In contrast, significant differences (p < 0.05) were observed when comparing FC-DMN to healthy controls, negative controls, and heparin gel. These findings suggested that FC-DMN offers a promising alternative to conventional anticoagulant therapies and can effectively deliver FC into systemic circulation. This study successfully developed a safe, painless, and nonirritating FC-DMN with promising results for enhancing the efficacy of anticoagulant therapy through the transdermal route.

Anticoagulant therapy without bleeding: A novel molybdenum‐based nanodots alleviate lethal coagulation in bacterial sepsis by inhibiting ROS‐facilitated caspase‐11 activation

AbstractSepsis is a leading cause of death worldwide. This syndrome is commonly accompanied by overactivation of coagulation, excessive reactive oxygen species (ROS), and inflammatory cytokine storm. Notably, disseminated intravascular coagulation (DIC) accounts for around 40% of sepsis‐associated deaths. However, anticoagulant therapy is still difficult for sepsis treatment because of the lethal bleeding side effects. Although the relationship between ROS and inflammatory cytokine storm has been described clearly, the pathogenic role of ROS in DIC, however, is still unclear, which renders novel therapeutic approaches hard to achieve bedside for inhibiting DIC. Herein, our new finding reveals that ROS greatly facilitates the entry of lipopolysaccharide (LPS) into the macrophage cytoplasm, which subsequently activates the caspase‐11/gasdermin D pathway, and finally induces DIC through phosphatidylserine exposure. Based on this finding, novel gallic acid‐modified Mo‐based polyoxometalate dots (M‐dots) with outstanding antioxidant activity are developed to provide ideal and efficient inhibition of DIC. As expected, M‐dots are capable of markedly inhibiting sepsis‐caused coagulation, organ injury, and death in sepsis. This therapeutic strategy, blocking the upstream pathway of coagulation rather than coagulation itself, can avoid the side effects of extensive bleeding caused by conventional anticoagulation therapy, and will provide a new avenue for the efficient treatment of sepsis.

АНАЛИЗ МАРКЕРОВ СИСТЕМЫ ГЕМОСТАЗА У ПАЦИЕНТОВ С ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ НЕКЛАПАННОГО ГЕНЕЗА С ТРОМБОЭМБОЛИЧЕСКИМИ ОСЛОЖНЕНИЯМИ

Introduction. Atrial fibrillation (AF) is one of the most common heart rhythm disorders. The risk of developing thromboembolic complications, including ischemic stroke, in patients with AF is 5 times higher than that in patients with sinus rhythm; therefore, one of the main directions in the treatment of patients with this rhythm disorder is the prevention of thromboembolic complications. Objective: to study the markers of monitoring the blood coagulation system in the blood serum of patients with non-valvular AF receiving anticoagulant therapy and having a history of thrombotic and thromboembolic complications. Materials and methods. The study included 31 healthy volunteers (without a history of AF, thrombosis) and 31 patients over 18 years of age with a diagnosis of AF (mean age 66.2±8.1), receiving anticoagulant therapy and having a history of thrombotic and thromboembolic events. complications. Therapy taken by patients at the time of inclusion in the study was in line with current recommendations and included standard conventional antiarrhythmic and anticoagulant therapy, as well as therapy for the underlying cardiovascular disease. Biomarkers of thrombus formation and pro-inflammatory activation (L-selectin, thrombomodulin) were determined by enzyme immunoassay using diagnostic kits from BiomedicaGmbH, Austria. Results. During the screening of 2820 patients treated in the Department of CHLSRS&amp;EX for the nosology of AF in the period 01.2020-01.2023, 31 patients were included in the study, who were diagnosed with thrombotic and thromboembolic complications (0.01% of the total number of screened patients) against the background of regular anticoagulant therapy . Among all patients included in the study, thrombotic complications in AF were as follows: thrombosis of the left atrial appendage was noted in 17 patients (54%), spontaneous echo contrast of grade II or more in 5 patients (16%), cardioembolic stroke - in 3 patients (10%) , thrombosis of peripheral arteries (2 (6%)), thrombosis on EKS electrodes (2 (6%)). The concentration of soluble thrombomodulin in the blood serum of patients with thrombotic and thromboembolic complications was reduced compared with the group of healthy volunteers (2073.0±548.6 vs. 2845.3±726.4 pg/ml; p=0.004). Serum levels of L-selectin in patients with thrombotic and thromboembolic complications were reduced compared to healthy volunteers (1.5±0.6 vs. 2.4±1.3 µg/mL; p=0.04). Conclusion. In patients with thrombotic and thromboembolic complications that occurred against the background of adequate anticoagulant therapy, there was a decrease in serum soluble thrombomodulin and L-selectin, which may indicate damage to the endothelium, activation of thrombus formation and inflammation.

A Comparative Study between Conventional and Recent Anticoagulant Therapies in Atrial Fibrillation

A Comparative Study between Conventional and Recent Anticoagulant Therapies in Atrial Fibrillation

Clinical Observation and Value Analysis of Endovascular Interventional Therapy for Intracranial Venous Sinus Thrombosis.

The main aim of this study was to investigate the therapeutic effect of endovascular interventional therapy on cerebral venous sinus thrombosis (CVST). 137 patients with CVST were included, 92 patients were treated with interventional therapy, and 45 patients were treated with conventional anticoagulant therapy. Through endovascular therapy (EVT) combined with therapy, the patients were treated with EVT in combination with conventional anticoagulant therapy, and the prognosis of the two groups of patients was evaluated. The results showed that 26 patients were complicated with female-specific infections in the combined EVT group, and 7 patients had female-specific infections in the simple anticoagulant therapy (LMWH) group. In terms of central nervous system infections, the EVT group was significantly lower than the LMWH group, P < 0.001, and the difference was statistically significant. There were 2 cases of EVT involving the inferior sagittal sinus and 12 cases of LMWH involving the inferior sagittal sinus, P < 0.001, and the difference had statistical significance. Through the RANKIN scale (mRS) score, it was classified as complete recovery and good prognosis (dependent variable). The patients receiving EVT with good prognosis (96.7%) were more than those receiving simple anticoagulant therapy (84.4%), and 78.3% were completely recovered after EVT, and 77.5% were completely recovered after anticoagulant therapy. Therefore, it can be concluded that gender, malignant tumors, thrombosis, and sinuses are all risk factors affecting the prognosis of patients; both endovascular interventional therapy and anticoagulant therapy can significantly improve the prognosis of patients.

Cerebral Venous Thrombosis as The Sole Presenting Manifestation of Human Immunodeficiency Virus and Hepatitis B Virus Co-Infection.

Cerebral venous thrombosis (CVT) following either human immunodeficiency virus (HIV) infection or hepatitis B virus (HBV) infection is a very rare condition. Moreover, it has never been reported as the presenting manifestation of HIV and HBV co-infection, even more so when the patient had a normal CD4 count and no demonstrable opportunistic infections. We aimed to report the first case of an adult Indian male, an intravenous drug abuser who developed CVT as the presenting manifestation of HIV-HBV co-infection. Patient data were obtained from medical records from the Bangur Institute of Neurosciences, Institute of Post Graduate Medical Education and Research & SSKM Hospital, Kolkata, West Bengal, India. A 25-year-old male with a history of intravenous drug abuse and a normal CD4 count developed CVT as the presenting manifestation of HIV-HBV co-infection. His CD4 count was normal, and he had no demonstrable opportunistic infections. He had an uneventful recovery of the condition (CVT) following the institution of conventional anticoagulation therapy alongside anti-retroviral therapy. Whether illicit drug abuse or HIV/HBV infection itself or all in combination led to this thrombotic event cannot be precisely established. Notwithstanding, we recommend serologic testing for HIV and HBV in patients suffering from CVT with high-risk behavior.

Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Patients With Active Cancer.

Although direct oral anti - coagulants (DOACs) are as safe and effective as conventional anticoagulants for treating venous thromboembolism (VTE), we have insufficient evidence justifying their use in patients with active cancer. We investigated the safety and effectiveness of DOACs in patients with active cancer. To investigate the safety and efficacy of DOACs, we retrospectively extracted 312 consecutive patients with active cancer who were prescribed edoxaban, rivaroxaban or apixaban for VTE. The most common primary cancer sites were the lung, stomach, colon/rectum, hematology, ovary, and pancreas. Fifty patients (16%) discontinued DOACs due to clinically relevant bleeding; major bleeding events occurred in 18 patients (5.4%). Thrombosis reduced or resolved in 144 of 167 evaluable patients (86%). In particular, pulmonary embolism was reduced or resolved in 46 of 50 patients (92%). Our findings revealed that DOACs for cancer-associated VTE are as safe and effective as conventional anticoagulation therapy.

Anticoagulation in Italian patients with venous thromboembolism and thrombophilic alterations: findings from START2 register study.

Randomised control trials have assessed the efficacy and safety of direct oral anticoagulants in the prophylaxis and treatment of venous thromboembolism (VTE). Positive but limited results have been reported in patients with inherited thrombophilia. Using an Italian, multicentre, prospective registry of consecutive patients presenting with symptomatic, acute VTE, we aimed to assess which factors are involved in making the choice of the drug that best fits the patient's risk profile in a large real-world setting of VTE patients. We investigated 4,866 VTE patients who took oral anticoagulants in the period between 2012 and April 2018 to prevent a new thromboembolic episode. The large majority of patients who underwent thrombophilic screening, regardless of the results obtained, were prescribed direct oral anticoagulants rather than conventional anticoagulant therapy (p<0.001). During anticoagulation, bleeding events occurred more frequently in patients on conventional anticoagulant therapy (4.2%) than in those receiving direct oral anticoagulants (1.8%) and an increase in bleeding events was observed in patients who tested positive at the thrombophilic screening. Overall, a higher number of recurrent VTE was observed in patients not screened for thrombophilia (n=36; 1.7%) than in those screened (n=20; 0.7%; adjusted odds ratio: 2.2; 95% confidence interval: 1.2-4.1). The present data confirm previous findings from other post-marketing registries and suggest that the choice of oral anticoagulation is strongly driven by patients' characteristics and VTE manifestations. Factors leading to the prescription of thrombophilic screening may identify a patient with a lower risk of VTE recurrence during anticoagulation.

High-sensitive cardiac troponin T as a marker of hemorrhagic complications in elderly patients anticoagulated for non-massive pulmonary embolism

BackgroundRecent data have raised concerns about the risk/benefit ratio of thrombolysis in non-high risk pulmonary embolism patients due to increased serious bleeding events. Whether cardiac biomarkers could be of help for bleeding risk stratification in this setting remains elusive. ObjectivesTo determine the prognostic accuracy of hs-cTnT, NT-proBNP, RIETE and PESI score for the occurrence of clinically relevant bleeding (CRB) in elderly patients under conventional anticoagulation therapy for non-massive pulmonary embolism (NMPE). MethodsWe evaluated 230 elderly patients with available blood sample taken within one day from diagnosis. The primary study endpoint was CRB at 1, 3 and 24 months. Prognostic accuracies and associations were determined using C-statistics and subhazard ratios (SHR), respectively. Resultshs-cTnT displayed the highest discriminatory power at 1 month (C-statistics: 0.77, 95% CI: 0.68–0.88) which remained stable over time. Although C-statistics comparison indicated that hs-cTnT was not statistically superior to RIETE score (0.77 vs 0.67, p = 0.11), adding hs-cTnT to RIETE score significantly improved the C-statistics from 0.67 to 0.78 (p = 0.02). SHRs indicated that for each hs-cTnT log-unit increase, there was a 58% increase in the risk of CRB independently of the RIETE score (adjusted SHR: 1.58, 95% CI: 1.31–1.92). At the pre-specified cut-off of 14 ng/l, the negative predictive value of hs-cTnT was 96.9% (95% CI: 91.4–99.0) and 94.9 (95%CI: 88.6–97.8) at 1 and 3 months, respectively. ConclusionIn elderly, hs-cTnT provides incremental prognostic information over the RIETE score and could represent a valuable tool to identify NMPE patients at low risk of bleeding.

Safety of direct oral anticoagulants versus traditional anticoagulants in venous thromboembolism.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. For decades, low molecular weight heparins (LMWH) and vitamin K-antagonists have been the gold standard of anticoagulation for VTE. Recently, direct oral anticoagulants (DOACs) that can be administered in fixed doses, without laboratory monitoring and dose adjustment have revolutionized anticoagulation management in VTE. Here, we report on recent evidence regarding the safety of DOACs compared to traditional anticoagulants in surgical and medical prophylaxis as well as in acute and extended treatments of VTE. Additionally, we provide data on special situations such as elderly, cancer and renal impairment patients. Regarding antithrombotic prophylaxis, data are lacking on DOAC use in general surgical patients, while DOACs appear to be more effective than and as safe as LMWHs in VTE prophylaxis for major orthopedic surgical patients. Whether a medically ill patient may benefit from extended VTE prophylaxis remains unclear. In fact, in these patients, DOACs showed an increased risk of bleeding compared to conventional therapy. In the acute treatment of VTE, DOACs were non-inferior and probably safer than conventional anticoagulation therapy while in the extended VTE treatment DOACs were more effective than placebo or aspirin with a comparable risk of major bleeding. These favorable results were also confirmed in elderly, cancer and renal impairment patients. However, further investigations are needed in order to generalize the safe use of DOACs in these specific subgroups of patients.

A prospective study on the time course and outcome of perioperative deep venous thrombosis in hip fracture patients

Objective To investigate the time course and prognosis of perioperative deep venous thrombosis in hip fracture patients. Methods A prospective study was conducted to analyze the clinical data of 88 patients with hip fractures who were injured within 24 h in the Department of Traumatic Orthopedics, Honghui Hospital, Xi′an Jiaotong University from September 2017 to March 2018. The patients were divided into anticoagulant group (n=53) (low molecular weight heparin combined with physical prevention) and non-anticoagulant group (n=35) (physical prevention only). The patients were examined by deep venous examination of the lower limbs every 24 h after they were admitted to hospital. The number and incidence of new thrombosis within 4 d after injury and 7 d after operation were recorded. The histogram was recorded. The prognosis of thrombosis and the occurrence of thrombosis in different fracture sites were also recorded. Counting data were expressed by percentage (%), and χ2 test was used for comparison between groups. Results In the anticoagulant group, 33 cases of deep venous thrombosis occurred in 53 cases, and the incidence rate was 62.26%. Deep venous thrombosis occurred in 29 of 35 patients in non-anticoagulant group (82.86%). The difference between the two groups was statistically significant (P 0.05). Conclusions Despite routine prophylactic anticoagulation therapy, the incidence of deep venous thrombosis is still high in hip fracture patients. The peak time of perioperative deep venous thrombosis in hip fracture patients was 2 d after injury and 2 d after operation. There was no significant change in thrombus after conventional anticoagulation therapy in patients with deep venous thrombosis during perioperative period, and even some of the thrombus changed from unilateral to bilateral. Key words: Hip; Fracture; Venous thrombosis; Time law

Protocolo diagnóstico y terapéutico del tromboembolismo pulmonar

Pulmonary thromboembolism (PTE) is a condition characterized by a wide range of clinical manifestations with different prognosis and treatment. In absence of any specific diagnostic test, diagnosis of acute and symptomatic PTE relies on clinical suspicion, D-dimer results and imaging tests. Approved diagnostic algorithms improve the prognosis in patients suspected of PTE. Early treatment goals are to stabilize the patient, to improve symptoms, to restore vascular permeability and to prevent relapses. In most cases, those goals are achieved by the use of conventional anticoagulation therapy, which avoids thrombus progression. On the other hand, endogenous fibrinolytic system resolves vascular obstruction and develops collateral circulation. Anticoagulant therapy has to be stablished quickly regardless diagnostic process. Hemodynamic status at the time of diagnosis is the most important prognostic factor in PTE.

The prevalence and risk factors of venous thromboembolism in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease.

Venous thromboembolism (VTE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is not rare, which would affect the patient's prognosis. To examine the prevalence, risk factors and clinical characteristics of AECOPD patients with VTE. We performed this multi-center, prospective, observational study that involved 16 hospitals in China. Patients admitted to hospital due to AECOPD were consecutively enrolled. Baseline characteristics, VTE risk factors, symptoms, signs and auxiliary examination results were collected. Lower limb venous ultrasound and computed tomography pulmonary angiography were examined. Between June 2009 and October 2010, a total of 1144 AECOPD patients (the average age 72.0±9.1 years, 761 males) were enrolled in this study. Seventy-eight (6.8%) were diagnosed with VTE, including 24 PE, 64 DVT, 10 combined PE and DVT. VTE patients were older than non-VTE patients. History of venous thromboembolism and lower extremity varicose vein, and presence of longer immobility (≥3days), lower limbs problems of swelling, pain and walking difficulties, diuretics use, fever, syncope, higher d-dimer and lower hemoglobin were more common in VTE patients than in non-VTE patients. After adjusting the covariates, venous thrombosis history, prolonged immobility (≥3days), lower limb pain before hospitalization, higher d-dimer independently associated with VTE development. Regular glucocorticoid use was not associated with increased risk of VTE in this set of patients. VTE is relatively common among hospitalized AECOPD patients. Conventional prophylactic anticoagulant therapy may be considered for those hospitalized AECOPD patients with risk factors.

A Review of the Role of Non-Vitamin K Oral Anticoagulants in the Acute and Long-Term Treatment of Venous Thromboembolism.

Venous thromboembolism (VTE), which includes both deep vein thrombosis and pulmonary embolism (PE), is a very common disorder with high risk for recurrence and is associated with significant morbidity and mortality. The non-vitamin K oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, have been shown to be noninferior to conventional anticoagulant therapy for the prevention of recurrent VTE and are associated with more favorable bleeding risk. Evidence from the treatment of VTE with traditional therapy (low molecular weight heparin and vitamin K antagonists) implies that extended or indefinite treatment reduces risk of recurrence. Recently, mounting evidence suggests a role for the extended use of NOACs to reduce the risk of VTE recurrence. This review summarizes the existing evidence for the extended use of NOACs in the treatment of VTE from phase III extension studies with dabigatran, rivaroxaban, and apixaban. Additionally, it examines and discusses the major society guidelines and how these recommendations may change physician practices in the near future.

The fibrogenic actions of the coagulant and plasminogen activation systems in pulmonary fibrosis.

Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis. The coagulants, thrombin and factor Xa (FXa) evoke fibrogenic effects via cleavage of the N-terminus of protease-activated receptors (PARs). Whilst the formation and activity of plasmin, the principle plasminergic mediator is suppressed in the airspaces of patients with IPF, localized increases are likely to occur in the lung interstitium. Plasmin-evoked proteolytic activation of factor XII (FXII), matrix metalloproteases (MMPs) and latent, matrix-bound growth factors such as epidermal growth factor (EGF) indirectly implicate plasmin in pulmonary fibrosis. Another plasminergic protease, urokinase plasminogen activator (uPA) is associated with regions of fibrosis in the remodelled lung of IPF patients and elicits fibrogenic activity via binding its receptor (uPAR). Plasminogen activator inhibitor-1 (PAI-1) formed in the injured alveolar epithelium also contributes to pulmonary fibrosis in a manner that involves vitronectin binding. This review describes the mechanisms by which components of the two systems primarily involved in fibrin homeostasis contribute to interstitial fibrosis, with a particular focus on IPF. Selectively targeting the receptor-mediated mechanisms of coagulant and plasminergic proteases may limit pulmonary fibrosis, without the bleeding complications associated with conventional anti-coagulant and thrombolytic therapies.

535P - Safety and effectiveness of oral rivaroxaban for the treatment of venous thromboembolism in cancer patients

Background: Cancer patients are at an increased risk of venous thromboembolism (VTE), even in the absence of traditional VTE risk factors. Cancer patients account for 20% of the patients with VTE. Although direct oral anticoagulants (DOACs) are as safe and effective as conventional anticoagulation (heparin followed by vitamin K antagonists) for treating VTE, the use of DOACs for cancer patients is less common. DOACs do not require monitoring and have little drug interaction with other drugs. We aimed to assess the safety and effectiveness of oral rivaroxaban, a DOAC, in patients with a history of intravenous (IV) antineoplastic drug administration in our hospital. Methods: We retrospectively extracted data of patients prescribed rivaroxaban and IV antineoplastic drugs from July 2011 to March 2017 at Kobe city medical center general hospital, and investigated adverse events during the administration period with the electronic medical record. Results: Of 76 patients, 39 had VTE, 37 had atrial fibrillation (Af), 2 had other diseases, and 2 had both VTE and Af. Of 39 patients with VTE, 38 were active cancer patients (11 had pulmonary embolism: PE). The characteristics of the 38 active cancer patients with VTE were as follows: median age (range), 66.5 (45-79); male/female, 17/21; and creatinine clearance [mean±SD], 85.7±28.1 mL/min. The most common primary site in the 38 patients was the colon (7), stomach (6), and ovary (6). The starting dose was 30 mg/day (13), 20 mg/day (1), 15 mg/day (21), 10 mg/day (2), and unknown (1). Nine patients discontinued rivaroxaban due to hematuria (2), bleeding from the uterus (1), epigastric discomfort (1), patient’s request (2), and unknown reasons (3). Two patients required dose reduction due to deterioration of renal function or significant weight loss. With a median follow-up of 5.9 months (range, 4 days-13.9 months), bleeding events was seen in 17 patients, of which 3 (8%) were clinically relevant; however, no severe bleeding was observed. Thrombosis reduced or disappeared in 29 of 30 evaluable patients (97%). PE were disappeared in 9 of 11 patients (82%). Conclusions: Using oral rivaroxaban for cancer-associated VTE is as safe and effective as conventional anticoagulation therapy. Legal entity responsible for the study: Kobe City Medical Center General Hospital Funding: None Disclosure: All authors have declared no conflicts of interest.

Diabetes mellitus is associated with increased bleeding in pulmonary embolism receiving conventional anticoagulant therapy: findings from a "real-world" study.

Bleeding refers to the most important complication during anticoagulation therapy in patients with pulmonary embolism (PE). However, the incidence and risk factors of bleeding in Chinese population with anticoagulant therapy remains unknown. Although diabetes mellitus (DM) has been demonstrated to increase the risk of PE, little information of its influence on anticoagulation-associated bleeding risk can be available. In our study, 563 acute PE patients, who fulfilled the including criteria were enrolled from a single center and received conventional anticoagulant therapy. And there were 539 patients completed the 3 months following-up. The cumulative incidences of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) were 3.0% (95% CI 1.01-3.05) and 14.0% (95% CI 1.47-5.21), respectively. Besides, anemia (OR 3.52, 95% CI 1.12-11.41) and recent history of MB (OR 8.14, 95% CI 1.41-31.95) were independently associated with MB. Age >65year (OR 1.51, 95% CI 1.12-3.11), cancer (OR 2.01, 95% CI 1.12-4.01) and therapeutic range (TTR) during 3 months (OR 0.93, 95% CI 0.91-0.98) were independently associated with CRNMB. Additionally, DM was an independent risk factor for both MB (OR 2.11, 95% CI 1.10-4.12) and CRNMB (OR 2.11, 95% CI 1.10-4.12). Notably, the incidence of MB or CRNMB was significantly higher in DM patients than non-DM patients. At the end of 3-month follow-up, the HbA1C in CRNMB group was 8.3%, yet it was 7.0% in non-CRNMB group among diabetic patients (p = 0.04). In conclusions, the bleeding rates are high in patients with acute PE who receive anticoagulant therapy. In addition to the already known bleeding risk factors, DM can also increase the bleeding risk significantly. Thus, good glycemic control may be essential after prescription of anticoagulant therapy.

Clinical Study on efficacy of allopurinol in patients with acute coronary syndrome and its functional mechanism

ObjectiveTo investigate the therapeutic effect of allopurinol treatment on acute coronary syndrome and to elucidate its possible mechanism. MethodsPatients with acute coronary syndrome (n = 100) were recruited as research subjects in our hospital. The patients were randomly divided into two groups, an allopurinol group (n = 50) and a control group (n = 50). These two groups were treated with conventional antiplatelet, anticoagulation and anti-ischemic therapy; allopurinol therapy was added to the allopurinol group based on conventional treatment indications. Biochemical markers such as serum creatinine, uric acid, BNP, blood glucose and blood lipid were compared between the two groups. Indicators of oxidative stress and inflammatory response (MDA, OX-LDL, NO, hs-CRP and TNF-α), as well as cardiovascular events during 2-years follow-up, were recorded. ResultsOn admission, there was no difference in serum creatinine, uric acid, BNP, blood glucose or lipid levels between the two groups (P > 0.05). However, after 1 month of treatment, these levels were improved in patients in the allopurinol group compared to the control group (P < 0.05). MDA, OX-LDL, hs-CRP and TNF-α decreased after treatment periods of 14 days and 1 month. They were also decreased at 3 month, 6 month, 1 year, and 2 year follow-up visits. However, data from the allopurinol group demonstrated significantly lower levels than in the control group (P < 0.05). Additionally, compared with the control group, allopurinol treatment significantly elevated the level of NO (P < 0.05). The total effective rates of the allopurinol group are much higher than in the control group for both angina pectoris (93.2% and 76%, respectively) and ECG (96% and 82%, respectively). Most patients in the allopurinol group (n = 40) and the control group (n = 41) received stent implantation with no significant difference shown between them. The incidence of cardiovascular events during 2 years of follow-up in the allopurinol group was 10%; it was 30% in the control group. ConclusionAllopurinol has a remarkable effect in the treatment of ACS and can improve the oxidative stress and inflammatory reaction indicators of patients. The protective mechanism of allopurinol might be achieved by suppressing the secretion and release of inflammatory mediators such as TNF-α, hs-CRP, OX-LDL and MDA while increasing levels of NO.

Control of IBMIR Induced by Fresh and Cryopreserved Hepatocytes by Low Molecular Weight Dextran Sulfate versus Heparin

Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 μg/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze–thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze–thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 μg/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.