Objective To investigate the role of clinical pharmacists in warfarin therapy. Methods A total of 134 patients underwent prosthetic heart valve replacement and had warfarin for life from March 2013 to October 2013 in Fujian Medical University Union Hospital. All patients were equally divided into two groups (an intervention and a non-intervention group) crosswise by sequence. There were 67 patients in each group. The anticoagulant effects of the two groups were compared. Results There was no statistical difference in the patients' demographic information between the two groups. However, the time for the patients to reach the target international normalized ratio(INR) values for the first time (7.1±3.3 dvs. 10.5±5.0 d,P=0.000) and time of INR in the therapy range (46.3%±18.8%vs.19.0%±16.2%,P=0.000) during their hospitalization, proportion of time of under anticoagulation (47.5%±19.5%vs. 71.2%±22.9%,P=0.000), proportion of time of anticoagulation overdose (5.3%±8.2%vs. 9.9%±16.7%,P=0.002) were significantly different. While there was no statistical difference in postoperative hospitalization time between the two groups (19.9±6.6 dvs. 18.1±7.0 d,P=0.137). There were 4 patients (6.0%) with minor hemorrhage and no severe complication was found in the intervention group. There were seven patients (10.4%) with mild hemorrhage, two patients with stroke, one patient with mild pulmonary embolism, and severe complication rate of 4.5% in the non-intervention group. Conclusion With clinical pharmacists involved in the whole anticoagulation therapy progress of patients after mechanical heart valve replacement, the time to achieve the therapeutic window for the first time is effectively shorten, and the time of the INR value controlled in therapeutic range is highly improved during hospitalization time. Moreover, the patients' risk of thrombosis and bleeding is eventually reduced.
ObjectiveTo investigate the influence of high activity of CYP2C9 (Cytochrome P450 proteins 2C9)and VKORC (Vitamin K epoxide reductase C)on warfarin anticoagulation of patients after heart valve replacement (HVR). MethodsFrom February 2010 to May 2013, 40 patients with high activity of CYP2C9 and VKORC underwent HVR in the Department of Cardiac Surgery, the First Affiliated Hospital of Zhengzhou University. There were 18 male and 22 female patients with their age of 40-51 (45.18±2.93)years. There were18 patients receiving mitral valve replacement (MVR), 14 patients receiving MVR and tricuspid valvuloplasty (TVP), and 8 patients receiving double valve replacement (DVR). Depen-ding on whether they received preoperative genetic polymorphism detection of CYP2C9 and VKORC1, all the patients were divided into 2 groups with 20 patients in each group. Patients in group A didn't receive preoperative genetic polymorphism detection of CYP2C9 and VKORC1, while patients in group B received preoperative genetic polymorphism detection of CYP2C9 and VKORC1. Postoperatively, periodic examination of international normalized ratio (INR)was performed to adjust warfarin dosage. Time to reach expected INR value and morbidity were collected. All the patients were followed up for 3-12 months after discharge. Monthly telephone follow-up was performed to record INR values, morbidity and general recovery. ResultsPostoperatively, in group A, 2 patients had cerebral infarction, 2 patients had popliteal artery throm-bosis, 1 patient had pulmonary embolism, and 1 patient had thrombosis in the annulus. Expected INR was achieved 15-20 days after warfarin treatment among the other 14 patients without thromboembolism. Three months after surgery, CYP2C9 and VKORC1 gene polymorphism was examined to find 17 patients with positive CYP2C9*1/*1 (*2CC/*3AA)and positive VKORC1-1639 GA, and 3 patients with positive CYP2C9*1/*1 (*2CC/*3AA)and positive VKORC1-1639 GG. In Group B, patients received aspirin (100 mg/d)and low molecular heparin (0.4 ml/d)in addition to warfarin since the second posto-perative day. Expected INR was achieved 5-9 days after warfarin treatment, and then aspirin and low molecular heparin were discontinued. During the 6 months follow-up period, no obvious thromboembolism was found, and only 1 patient had epistaxis who was cured with nasal tamponade. ConclusionPreoperative detection of genetic polymorphisms of CYP2C9 and VKORC1 can provide important guidance for warfarin anticoagulation after HVR.
ObjectiveTo investigate the effect of CYP2C9 and APOE on the dose of stable warfarin and model prediction in Hainan population.MethodsFrom August 2016 to July 2018, 368 patients who required heart valve replacement and agreed to take warfarin anticoagulation at the second department of cardiothoracic surgery in our hospital were enrolled, including 152 males aged 48.5–70.5 (60.03±10.18) years and 216 females aged 43.5–65.6 (54.24±11.35) years. CYP2C9 and APOE were amplified by polymerase chain reaction. The gene fragment was sequenced by the Single Nucleotide Polymorphisms (SNP) site. The patients' age, sex, weight, history of smoking and drinking, and the dose of stable warfarin were recorded. Regression analysis of these clinical data was made to construct a dose prediction model.ResultsAmong 368 patients, CYP2C9 genotype test results showed 301 patients (81.8%) with *1*1 genotype, and 67 patients (18.2%) with *1*3 type. For different CYP2C9 genotype patients, the difference was statistically significant in the dose of stable warfarin (P<0.05). The results of APOE genotype showed 93 patients (25.3%) with E2 genotype, 221 patients (60.1%) with E3 genotype, and 54 patients (14.7%) with E4 genotype; the dose of stable warfarin in patients with different APOE genotypes was statistically significant (P<0.05). Multiple regression analysis showed that patients' age, body weight, and CYP2C9 and APOE genotypes were correlated with the dose of stable warfarin. The correlation coefficient R2 was 0.572, and the prediction model was statistically significant (P<0.05).ConclusionCYP2C9 and APOE gene polymorphisms exist in Hainan population. There is significant difference in the dose of stable warfarin among different genotypes of patients. The model to predict stable warfarin can partly explain the difference of warfarin among different patients.
Objective To explore clinical effect and safety of rivaroxaban in treatment of acute pulmonary thromboembolism at moderate risk with deep vein thrombosis of lower limbs. Methods The clinical data of 60 patients with acute pulmonary thromboembolism at moderate risk with deep vein thrombosis of lower limbs, collected from January 2010 to March 2017 in Hunan Provincial People’s Hospital, were retrospectively analyzed. According to the different treatment, these patients were randomly divided into a rivaroxaban group and a control group (traditional warfarin anticoagulation), with 30 patients in each group. The clinical effect and safety were compared between two groups on the 10th day, 20th day and 30th day after treatment. Results Compared with the control group, maximum short axis diameter, ratio of right and left ventricles, systolic pulmonary artery pressure, and main pulmonary artery diameter measured by CTPA and echocardiography in the rivaroxaban group were not significantly different on the 10th day, 20th day and 30th day after treatment. However, the intragroup differences were statistically significant at different timepoint (P<0.05). Levels of N-terminal-pro-brain natriuretic peptide of two groups after treatment were significantly reduced on the 10th day, 20th day and 30th day after treatment, and the values of PO2 were significantly increased on the 10th day and 20th day after treatment (P<0.05), but no significant differences were found in the values of PO2 on 20th day and 30th day after treatment. D-dimer in the two groups was obviously increased on the 10th day after treatment but significantly declined on the 20th day and 30th day after treatment (all P<0.05). These changes were predominant in the rivaroxaban group. Conclusion Rivaroxaban is effective and safe for acute pulmonary thromboembolism at moderate risk with deep vein thrombosis of lower limbs, and worthy of clinical implementation and application.
Objective To systematically review the effect of discontinuous warfarin on the risk of postoperative bleeding complications after tooth extractions. Methods PubMed, EMbase, The Cochrane Library (Issue 9, 2016), CNKI, VIP, WanFang Data, China Food and Drug Administration and the ADR supervision system of FDA were electronically searched to collect randomized controlled trials (RCTs) and cohort studies about the effect of discontinuous warfarin on risk of postoperative bleeding complications after tooth extractions in patients until September 30th, 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 8 studies were included, involving 3 RCTs and 5 cohort studies. The results of meta-analysis showed that: there was no significant difference between the discontinuous or reduced warfarin group and the continuous warfarin group (RCTs: RR=0.86, 95%CI 0.49 to 1.51,P=0.60; cohort studies: RR=0.67, 95%CI 0.45 to 1.01,P=0.06). Conclusions Current evidence indicates that there is no statistically significant correlation between whether discontinuous warfarin and the risk of postoperative bleeding complications after tooth extractions. Due to the limited quantity and quality of included studies, the above conclusions are needed to be further verified by more high quality studies.
Objective To investigate the diagnosis and treatment of pulmonary thromboembolism (PTE) after thoracotomy. Methods We analyzed the clinical data of 10 patients with PTE after thoracotomy treated from January 2011 to March 2015. Among them were 8 males and 2 females, with their age ranging from 51 to 73 years old, averaging 61. Six patients had lung cancer lobectomy, and 4 had esophagus carcinoma resection. All the 10 patients suffered sudden shortness of breath, chest pain and palpitation within the first 40 hours to 128 hours after surgery, and the physical examinations revealed tachypnea, drop of blood pressure and tachycardia. The PTE diagnosis was confirmed after using echocardiography, three-dimensional imaging of CT pulmonary angiography. All the patients accepted the treatment combination of low molecular weight heparin and warfarin. Results All the patients were cured without complications like chest or wound bleeding. Follow-up checks 3 months after the surgery showed no relapses. Conclusions Thoracotomy patients are of high risks of PTE. The diagnosis should be based on imaging examinations. Treatment combination of low molecular weight heparin and warfarin has a remarkable effect in treating PTE patients after thoracotomy, which also has a low rate of bleeding complications.
Objective To investigate the effects of antiepileptic drugs (AEDs) with warfarin functions and blood coagulation system, to provide the reference for clinicians of the selection of AEDs under the combination therapy with warfarin. Methods Analyse the clinical data of the patient with symptomatic epilepsy from the Second Clinical Medical College of Guiyang University of Chinese Medicine on April 1, 2017, whom taking AEDs and warfarin at the same time, clear the drug adverse reactions, and analysed related literature. Results After the treatment with valproate, abnormal blood coagulation, a danger and emergency data appeared, so we stopped using warfarin immediately, and reduce the dosage of valproate gradually, insteadly, we used levetiracetam as antiepileptic therapy. Monitoring blood coagulation function, when it returned to normal, restart warfarin anticoagulant therapy. Conclusions When start antiepileptic treatment in relevant basic diseases of symptomatic epilepsy, for a variety of combination reactions, AEDs can affect the anticoagulant effect of warfarin, so we need to consider the interaction between drugs and avoid adverse reactions.
ObjectivesTo compare different formula calculated dosages with the actual doses of warfarin from patients in Beijing Hospital so as to investigate suitable warfarin dosing models for Chinese patients.MethodsOne hundred and three Chinese patients with long-term prescription of warfarin were randomly selected from Beijing Hospital from July 2012 to May 2013. The CYP2C9 and VKROC1 genotypes and basic statistical information were collected. SPSS 18.0 software was used to compare the differences between different formula calculated dosages and the actual dosages of warfarin.ResultsFive genotypes were found in 103 patients, including: CYP2C9 AA genotype + VKORC1 AA genotype (n=72, 69.9%), CYP2C9 AA genotype + VKORC1 AG genotype (n=17, 16.5%), CYP2C9 AC genotype + VKORC1 AA genotype (n=10, 9.7%), CYP2C9 AC genotype + VKORC1 AG genotype (n=3, 2.9%) and CYP2C9 AA genotype + VKORC1 GG genotype (n=1, 1%). Compared with the actual dosages of warfarin, the degree of coincidence was highest for dosages calculated by Jeffrey’s formula.Conclusions Using Jeffrey’s formula to calculate warfarin dosages may be more suitable for Chinese patients with using long-term warfarin. Due to limited sample size, prospective and large sample size studies are required to verify the above conclusion.
Warfarin, a classic oral anticoagulant, is characterized by a narrow therapeutic window and considerable interindividual variability in dosing requirements. This makes precise dose adjustment challenging in clinical practice and increases the risk of bleeding or thrombosis. To improve dose prediction, this study developed a streamlined multilayer perceptron (MLP) model using real-world data from the International Warfarin Pharmacogenomics Consortium (IWPC) database. The LASSO-proj algorithm was applied for high-precision feature selection prior to model construction. The resulting model demonstrated strong predictive performance on the test set, achieving a coefficient of determination (R2) of 0.456, a mean absolute error (MAE) of 8.92 mg/week, and 48.522% of its predictions falling within ±20% of the actual stable therapeutic dose. Through SHAP-based interpretation using DeepExplainer, key features influencing warfarin dosing were identified, including the VKORC1 genotype, body weight, age, and ethnicity. The interpretable MLP framework incorporating LASSO-proj not only maintains high predictive accuracy, but also significantly enhances model transparency, providing a valuable tool for guiding warfarin therapy.
Objective To investigate the influence of CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms on warfarin dosages of patients after heart valve replacement. Methods A total of 133 patients undergoing heart valve replacement in the Department of Cardiovascular Surgery of Fujian Provincial Hospital from November 2011 to August 2012 were included in this study. Polymerase chain reaction（PCR）gene sequencing was performed to detect CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphism of these 133 patients. Patients were grouped according to their genotypes，and average warfarin dosages were compared between different genotype groups. Results The frequencies of CYP2C9 3 AA，AC and CC were 127 patients，6 patients and 0 patient respectively，and average daily warfarin dosages were 3.75 mg and 2.13 mg respectively which were statistically different between differentCYP2C9 3 genotypes （P＜0.05）. The frequencies of VKORC1-1639 G＞A GG，GA and AA were 3 patients，32 patientsand 98 patients respectively，and average daily warfarin dosages were 6.00 mg，4.50 mg and 3.00 mg respectively which were statistically different between different VKORC1-1639 G＞A genotypes （P＜0.05）. The frequencies of CYP4F2 rs 2108622 CC，CT and TT were 67 patients，59 patients and 7 patients respectively，and average daily warfarin dosages were 3.00 mg，3.75 mg and 4.50 mg respectively which were statistically different between different CYP4F2 rs2108622 genotypes（P＜0.05）. Conclusion CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms are associated with individual difference of warfarin dosages of patients after heart valve replacement.