ObjectivesTo systematically review the efficacy and safety of direct oral anticoagulants (DOAC) on preventing venous thromboembolism (VTE) after major orthopedic surgery (MOS).MethodsThe Cochrane Library, PubMed, EMbase, CNKI, WanFang Data and CBM databases were electronically searched for randomized controlled trials (RCTs) on the efficacy and safety of DOAC on preventing VTE after MOS from inception to March 2019. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 22 RCTs involving 41 244 patients were included. The results of meta-analysis showed that: the rate of symptomatic deep vein thrombosis (DVT) after MOS in rivaroxaban (Peto OR=0.54, 95%CI 0.35 to 0.82, P=0.004) and apixaban (Peto OR=0.49, 95%CI 0.26 to 0.92, P=0.03) were lower than enoxaparin. Additionally, the rate of symptomatic pulmonary embolism (PE) after MOS in rivaroxaban was lower than enoxaparin (Peto OR=0.53, 95%CI 0.29 to 0.96, P=0.04), however, in major bleeding after MOS rivaroxaban was significant higher than enoxaparin (Peto OR=1.98, 95%CI 1.30 to 3.01, P=0.001).ConclusionsCurrent evidence shows that rivaroxaban and apixaban is superior to enoxaparin on preventing symptomatic DVT after MOS. Rivaroxaban is superior to enoxaparin on preventing symptomatic PE, however, the risk of major bleeding is higher than enoxaparin. Due to limited quality and quantity of the included studies, more high quality studies are required to verify the above conclusions.
Objective To review current status of clinical application and research progress of different anticoagulants in perioperative period of free flap transplantation. Methods A comprehensive review of recent relevant literature was conducted, focusing on clinical research concerning the application of anticoagulants in the perioperative period of free flap transplantation. The administration route, timing, dosage selection, effectiveness, and safety of commonly used and novel anticoagulants were summarized. Results At present, the anticoagulants mainly used in the perioperative period of free flap transplantation include drugs for venous thrombosis prophylaxis, drugs for arterial thrombosis prophylaxis, and physical/colloidal anticoagulants, etc. The administration strategies can be classified into two major categories: single-agent anticoagulation and combined anticoagulation. Single-agent anticoagulation mainly includes unfractionated heparin, low-molecular-weight heparin, aspirin, and novel anticoagulants. Combined anticoagulation is commonly a synergistic anticoagulation regimen dominated by heparin drugs, combined with aspirin, different antiplatelet drugs, and expansion agents. Studies indicate that perioperative anticoagulant administration can effectively reduce the risk of thrombosis in free flaps and improve the overall flap survival rate. However, significant differences exist in the impact of drug types, administration routes, initiation timing, and dosage intensity on efficacy and bleeding risk. A unified, standardized application protocol has not yet been established. In addition, there has been a growing number of studies on novel anticoagulant drugs. However, their superiority and optimal application strategies in the field of free flap transplantation still necessitate more high-quality evidence. Conclusion Perioperative anticoagulation therapy represents one of the key strategies for improving the survival rate of free flaps. However, there is still a lack of high-level evidence to establish a standard protocol. Future research should focus on the optimization of individualized anticoagulation strategies, the validation of the effectiveness of new anticoagulants, and the exploration of the advantages of different anticoagulation strategies. At the same time, attention should be paid to balancing anticoagulation and bleeding risks to promote the standardization of clinical practice and the improvement of treatment safety.
Objective To explore the safety and efficacy of mobile APP in telemanagement for patients who received oral warfarin anticoagulant therapy after mechanical heart valve replacement. Methods A prospective cohort study was performed. According to the inclusion and exclusion criteria, a total of 80 patients who underwent mechanical heart valve replacement for more than half a year and received oral warfarin anticoagulant therapy in outpatient department were included in our hospital from January 1, 2017 to December 31, 2017. These patients were divided into a telemanagement group (40 paitents, telemanagement using mobile APP) and a control group (40 patients, anticoagulant management in outpatient clinics) according to patients' wishes and local hospital international normalized ratio (INR) monitoring conditions. After 12-month follow-up, clinical effect of the two groups was compared. The INR, time in therapeutic range (TTR), fraction in therapeutic range (FTTR), anticoagulation-related complications and patient satisfaction were analyzed. Results During the follow-up period of anticoagulation, there was no significant difference in INR between the two groups (P=0.732). The average interval of INR monitoring in the telemanagement group was 3-65 (21.4 ± 12.5) days, while that in the control group was 7-93 (39.6 ± 14.7) days (P=0.012). TTR was 42.7% (6 027.6 d/14 116.0 d) in the control group and 67.9% (10 168.6 d/14 972.0 d) in the telemanagement group (P=0.018). And FTTR in the two groups was 45.6% (144/316) and 67.1% (432/644), respectively (P=0.015). No serious thromboembolism or hemorrhage events occurred in the 80 patients during the 12-month follow-up period. There was no significant difference in the incidence of anticoagulation-related complications, general bleeding and embolism between the two groups (P>0.05). Conclusion For patients with stable anticoagulation after cardiac mechanical valve replacement, it is safe and effective to telemanagement by mobile APP. Telemanagement can increase the frequency of anticoagulation monitoring without increasing anticoagulation risk, meanwhile, it also could obtain more convenient and rapid consultation, save time and economic costs,and improve the quality of life and patient satisfaction.
ObjectiveTo evaluate the anticoagulation efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in patients with high-risk atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI). MethodsA computer-based search was conducted on PubMed, EMbase, The Cochrane Library, CNKI, SinoMed, and VIP databases to identify studies on the application of NOACs and VKAs in high-risk AF patients after TAVI. The search period was from database inception to January 2023. The quality of the included studies was assessed using the Cochrane risk assessment tool and the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4 software. ResultsA total of 7 studies involving 24 592 patients were included. The meta-analysis results showed that compared to patients using VKAs, those treated with NOACs had a significantly lower risk of all-cause mortality [RR=0.74, 95%CI (0.58, 0.94), P=0.01]. Subgroup analysis indicated that when the follow-up period was less than 1 year, there was no significant difference in all-cause mortality between the NOAC and VKA groups [RR=0.57, 95%CI (0.17, 1.88), P=0.35]; however, when the follow-up period was ≥1 year, the VKA group had a higher all-cause mortality rate than the NOAC group, with a statistically significant difference [RR=0.73, 95%CI (0.57, 0.95), P=0.02]. No significant differences were found between the two groups regarding early stroke [RR=0.50, 95%CI (0.19, 1.28), P=0.15], stroke during follow-up [RR=1.04, 95%CI (0.88, 1.22), P=0.64], bleeding [RR=0.94, 95%CI (0.73, 1.21), P=0.61], major or life-threatening bleeding [RR=0.80, 95%CI (0.49, 1.31), P=0.38], or acute kidney injury [RR=0.51, 95%CI (0.16, 1.59), P=0.24]. Conclusion Compared to VKAs, the use of NOACs in patients with high-risk AF undergoing TAVI may reduce the risk of all-cause mortality, especially during long-term anticoagulation therapy, potentially offering greater benefits. However, further evidence from randomized controlled trials is needed to confirm these findings.
ObjectivesTo investigate the correlation of warfarin dose genetic and polymorphism of Han-patients after heart valve replacement, to forecast the anticoagulation therapy with warfarin reasonable dosage, and to realize individualized management of anticoagulation monitoring. MethodsWe selected 103 patients between January 1, 2011 and December 31, 2012 in West China Hospital of Sichuan University who were treated by oral warfarin after heart valve replacement with monitoring anticoagulation by international normalized ratio (INR) in Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. There were 32 males and 71 female at age of 21-85 (48.64± 11.66) years. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method and gene sequencing technology. Warfarin concentration in plasma was determined by high performance liquid chromatography (HPLC) method. The activity of coagulation factorⅡ, Ⅶ, Ⅸ, Ⅹwas determined by Sysmex CA7000 analyzer. ResultsThe multivariate linear regression analysis showed that age, body surface area, and coagulation factor activity had no significant effect on warfarin dosage. While the gene polymor-phisms of CYP2C9 and VKORC1, warfarin concentration, and age had significant contributions to the overall variability in warfarin dose with decisive coefficients at 1.2%, 26.5%, 43.4%, and 5.0% respectively. The final equation was:Y=1.963-0.986× (CYP2C9* 3) +0.893× (VKORC1-1639) +0.002× (warfarin concentration)-0.019× (age). ConclusionMultiple regression equation including gene polymorphisms of CYP2C9 and VKORC1, non-genetic factors of coagulation factor activity, warfarin concentration, age, and body surface area can predict reasonable dosage of warfarin for anticoagulation to achieve individualized management of anticoagulation monitoring and reduce the anticoagulation complications.
Resuming oral anticoagulant (OAC) after intracerebral hemorrhage (ICH) is still a dilemma to clinical decision. To date, no high-quality randomized controlled trials demonstrate the timing and mode of safely resuming OAC. In recent years, some moderate-quality researches have suggested that OAC resuming after ICH can decrease the incidence of thromboembolic events and long-term mortality, without significantly increasing the risk of ICH; it is safer to resuming OAC in patients with non-lobar ICH than in patients with lobar-ICH; new OACs are superior to vitamin K antagonists; patients with high thromboembolic risk should resume OAC 2 weeks or even earlier after ICH, otherwise, a time-window for optimal resumption is between 4-8 weeks; meanwhile, individual patient characteristics should be considered and blood pressure should be strictly controlled.
ObjectiveTo evaluate the quality of warfarin anticoagulant therapy in patients with stable stage after mechanical valve replacement surgery, to observe the effect of compound salvia miltiorrhiza tablet on the anticoagulant effect of warfarin in patients after mechanical valve replacement, and to understand the impact of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 on warfarin resistance in patients with mechanical valve replacement in the stable period.MethodsFrom July 2011 to February 2014, 1 831 patients who had ≥ 6 months after mechanical valve replacement surgery were enrolled at the outpatient follow-up. The basic clinical data were recorded. Anticoagulant therapy uses a target international normalized ratio（INR, 1.60–2.20) and a weekly warfarin dose adjustment strategy. Forty-six patients who needed compound salvia miltiorrhiza tablet were screened and the INR values. Before and after taking tablets were recorded and compared. The patients were divided into three groups according to the percentile of warfarin dosage including a warfarin sensitive patients group, a control patients group, and a warfarin resistance patients group. And 101 of them were selected. TIANGEN blood DNA Kit blood genomic DNA extraction kit was used to extract samples and polymerase chain restriction fragment length polymorphism (PCR-RELP) was used to determine the genotypes of patients. The detected gene loci included CYP4F2: rs2108622C>T locus; VKORC1:1639G>A locus; VKORC1:1173C>T locus; CYP2C9*2: rs1799853C>T locus; CYP2C9*3:1061A>C locus.ResultsThe time in therapeutic range (TTR) and fraction of time in therapeutic range (FTTR) in the target INR range of the patients included in the study period was 27.2% and 49.4%, respectively, and the TTR and FTTR in the acceptable INR range was 34.25% and 63.36%, respectively. Before and after the addition of compound salvia miltiorrhiza tablets, the INR value was 1.55±0.03 and 1.69±0.30, respectively, and the difference was statistically different (P<0.05). A total of 101 patients with genetic testing, in which the C/T composition of the VKORC1: 1173C>T locus increased in the warfarin sensitivity, contrast and warfarin resistance patients, while the ratio of allelic loci of C/T in CYP2C9*3: 1061A>C loci decreased in turn. There was no difference in the CYP4F2 gene, VKORC1639 gene, and CYP2C9*2 locus. The IWPC model predicts that warfarin dose is only consistent with the actual warfarin dose in warfarin sensitive patients.ConclusionRelatively low TTR and FTTR are acceptable in patients with stable stage after mechanical valve replacement. It is beneficial to the patients with compound salvia miltiorrhiza tablets in terms of some appropriate patients. VKORC1: 1173C>T site and CYP2C9*3: 1061A>C site mutation is the main pharmacological gene factor of warfarin dose sensitivity and warfarin resistance in stable period after mechanical valve replacement. The IWPC dose prediction model is only consistent with the actual dose of warfarin sensitive patients.
ObjectivesTo systematically review the efficacy and safety of new oral anticoagulants (NOACs) for cancer-associated venous thromboembolism.MethodsStudies about the efficacy and safety of NOACs versus low molecular weight heparins (LMWHs) or vitamin K antagonists (VKAs) for cancer-associated venous thromboembolism were collected by searching PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data and CBM databases from inception to August, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was then performed by RevMan 5.3 software.ResultsA total of 8 studies involving 2 448 patients were included. The results of meta-analysis showed that: there was no significant difference in the recurrent VTE rate (OR=0.74, 95%CI 0.49 to 1.11, P=0.15) or bleeding rate (OR=0.80, 95%CI 0.57 to 1.13, P=0.21) between NOACs group and VKAs group. The major bleeding rate was significantly higher in the VKAs group than in the NOACs group (OR=0.47, 95%CI 0.27 to 0.84, P=0.01). The incidences of recurrent VTE (OR=0.84, 95%CI 0.16 to 4.14, P=0.83), bleeding (OR=0.46, 95%CI 0.18 to 1.20, P=0.11), major bleeding (OR=0.45, 95%CI 0.12 to 1.60, P=0.21) were similar between NOACs group and LMWHs group.ConclusionsThe current evidence indicates that for cancer patients with VTE, NOACs are superior to warfarin and comparable to LMWHs. Due to limited quantity and quality of the included studies, more high quality studies are required to verify the above conclusion.
ObjectiveTo realize the application status and development trend of oral anticoagulant drugs used in respiratory diseases in 72 hospitals in 6 cities from the year 2013 to 2017.MethodsFrom January 2013 to December 2017, we randomly selected the electronic information from 10 working days per quarter in 6 cities including Beijing, Guangzhou, Shanghai, Chengdu, Shenyang, and Zhengzhou, with 12 hospitals in each city, and summarized the information into the prescription database of the hospital prescription analysis project. Through the hospital information system, we screened out the information of outpatient prescriptions and inpatient medical records which used oral anticoagulants. The prescriptions with respiratory diseases related-diagnosis were selected as the research objects by manual screening. The application of oral anticoagulant drugs used in respiratory diseases was statistically analyzed by drug amount, prescription amount, prescribed daily dose (PDD), and defined daily dose (DDD).ResultsFrom 2013 to 2017, the number of warfarin sodium prescriptions was successively 4 769, 5 747, 7 549, 7 261, and 7 151, which had been always ranked the first in the five years, but decreased year by year since 2015. The proportion of warfarin sodium drug use amount decreased year by year from 32.52% in 2013 to 5.03% in 2017. The proportion of prescription and drug consumption sum of new oral anticoagulants increased year by year in the past five years. The PDD/DDD of warfarin sodium, dabigatran etexilate, rivaroxaban, and apixaban were 0.41, 0.73, 0.68, and 0.33, respectively. There were off lable use of new oral anticoagulants.ConclusionsWarfarin still dominates the proportion of oral anticoagulants prescribed in the 72 hospitals in the 6 cities in the five years. The clinicians have made a comprehensive judgment after fully considering the safety, effectiveness, and economy of drug use when formulating drug treatment programs.
ObjectiveTo summarize the occurrence and development of hepatocirrhosis complicated with portal vein thrombosis (PVT), and summarize the status and prospect of anticoagulant treatment.MethodThe literatures and guidelines on the treatment of hepatocirrhosis complicated with PVT were collected and reviewed.ResultsPVT was one of the most common complications in patients with hepatocirrhosis. Its pathogenesis was complicated, and the coagulation function of patients with hepatocirrhosis was poor. In addition, patients with severe complications such as esophageal and gastric varicose bleeding (EVB) were often complicated. According to the current study, the formation of PVT was mainly related to the coagulation mechanism of patients, hemorheology changes of blood vessels, and their own factors. Treatment methods included drug therapy, interventional therapy, and surgical treatment. However, there was still controversy on anticoagulant therapy for hepatocirrhosis with PVT, and there was no complete consensus on anticoagulant indications, drug selection, course of treatment, and safety monitoring.ConclusionPVT should be treated with anticoagulant therapy under certain indications, but to ensure its safety and effectiveness, prospective large sample randomized controlled trials are still needed.