ObjectiveTo study the correlation between international normalized ratio (INR) and coagulation factor Ⅱ and Ⅹ in patients with pulmonary thromboembolism treated with warfarin at moderate and low intensity anticoagulation.MethodsFifty-one patients with pulmonary thromboembolism treated with warfarin orally were divided into low-intensity anticoagulation group (INR from 1.6 to 2.0) and standard-intensity anticoagulation group (INR form 2.0 to 3.0) according to their monitoring INR indices. The levels of coagulation factor Ⅱ and Ⅹ were measured, and the correlation between INR level and coagulation factor activity was compared.ResultsThe INR of the low intensity anticoagulation group was 1.69±0.2 and the standard intensity anticoagulation group was 2.55±0.46. The corresponding activity of coagulation factor Ⅱ was (48.3±28.0)% and (24.0±8.0)% respectively. The activity of coagulation factor Ⅹ was (32.8±24.0)% and (16.7±6.0)%. There was a negative correlation between the activity of INR and coagulation factor Ⅱ and Ⅹ, with correlation coefficients of –0.903 and –0.459, respectively. Coagulation factor Ⅱ activity < 40%, coagulation factor Ⅹ activity inhibitory level < 25% is defined as anticoagulation effect. When coagulation factor Ⅱ activity level reaches anticoagulation effect, the corresponding minimum INR value was 1.56 and as to coagulation factor Ⅹ, the corresponding minimum INR value was 1.66.ConclusionsINR is negatively correlated with the activity of coagulation factor Ⅱ and coagulation factor Ⅹ. With the increase of INR, the activity of coagulation factor Ⅱ and coagulation factor Ⅹ decrease. Low intensity anticoagulation could not effectively inhibit the activity of coagulation factor.
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.
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 the impact of the women taking warfarin throughout pregnancy after mechanical valve replacement on the children’s physical and mental development.Methods A total of 12 children whose mothers had taken mechanical valve replacement before pregnancy were enrolled in the experimental group in this study, for determination of their physical and mental development. The following indicators were measured: a) Physical development indexes: height, weight, sitting height, head circumference, chest circumference; b) Mental development indexes: intelligence quotient (IQ), and development quotient (DQ) which included adaptability, big movement, fine motor, language, and individual-society. According to the 1?∶?2 matching ratio, 24 children of the healthy women were selected in the control group, and then the difference of each index between the two groups was analyzed. Results In the aspects of both physical development indexes and mental development indexes, there were no significant differences in the children aged 0 to 3 yrs, 4 to 6 yrs, and 6 to 12 yrs in the two groups (Pgt;0.05). Conclusion After mechanical valve replacement, women taking oral anticoagulant warfarin in daily dose not exceeding 5mg are safe, and there are no negative effects on children’s physical and mental development.
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 explore the anticoagulant strategy of adjusting the dose of warfarin at different stages after mechanical valve replacement of mitral valve.MethodsClinical data of a total of 302 patients, including 76 males and 226 females, with an average age of 50.1±10.1 years, who underwent mechanical mitral valve replacement in the Chinese adult cardiac surgery database from 2013 to 2017 were retrospectively analyzed. According to the dose adjustment strategy of taking warfarin, the patients were divided into a D group (adjusting warfarin dose in days) and a W group (adjusting warfarin dose in weeks) to evaluate the anti-coagulation effect of warfarin.ResultsThe total follow-up time was 423277 d (1159.7 years). There was no significant difference in the overall anticoagulant strength, and the warfarin dose adjusted in days was better in the early postoperative period (P<0.05), especially in patients over 60 years. It was better to adjust warfarin dose in weeks in the middle and long periods (P<0.05), especially in patients ≤40 years. In terms of the stability of anticoagulation, it was better to adjust the dosage of warfarin in weeks (P<0.05). It was better to adjust the dosage of warfarin in weeks for early, middle- and long-term anticoagulant therapy after operation (P<0.05), especially in the females aged >40 and ≤50 years.ConclusionWithin the target range of international normalized ratio (1.5-2.5), the anticoagulant strategy of adjusting warfarin dose in days after mechanical valve replacement of mitral valve can achieve a better anticoagulant strength, and adjusting the dosage of warfarin in weeks is better in the middle- and long-term after operation. In general, the anticoagulant effect is more stable in the short term when warfarin dose is adjusted on a weekly basis.
Abstract: Objective To investigate the anticoagulation effect of warfarin on pregnant women with prosthetic mechanical heart valves during the whole course of pregnancy and their fetuses. Methods Followup survey was carried out on 103 pregnant women with prosthetic mechanical heart valves treated in the Second Xiangya Hospital of Central South University from April 1998 to June 2010. Their age ranged from 19 and 38 years (26.4±3.8 years). All the 103 pregnant women were given oral administration of warfarin during the whole course of pregnancy. The average dose of domestic warfarin was 3.30±0.43 mg/d (87 cases), while the average dose of imported warfarin was 2.90±1.05 mg/d (16 cases). Results None of the patients suffered from serious embolic events. One patient suffered from spontaneous peritoneal hemorrhage. There were 4 cases of intrauterine deaths, and 5 cases of fetal malformation including 1 case of Down’s syndrome and 4 cases of hydrocephalus. Six cases of low birth weight infants and 1 case of ABO hemolytic disease were also found. All the other neonates were healthy with normal weight. No pregnant women suffered from postpartum hemorrhage. Conclusion Oral administration of low dose warfarin (lt;5 mg/d) during the whole course of pregnancy is a relative safe and effective anticoagulation protocol.
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.
ObjectiveTo verify the reliability of Anticlot Assistant, a patient self-management system for warfarin therapy assisted by artificial intelligence.MethodsIt was a single-center, prospective cohort study. The eligible 34 participants were recruited consecutively between November 29, 2017 to September 27, 2018 and managed by warfarin therapy via Anticlot Assistant. The recommendations of Anticlot Assistant were examined and verified by the doctors to ensure the security. Medical records were exported from the the background management system. An univariate analysis compared the outcomes between accepted and overridden records and a logistic regression model was built to determine independent predictors of the outcomes. The research team analyzed 153 medical records, which were from 18 participants and were input by 19 doctors. There were 97 records with doctor accepting the suggestion and 56 records with doctor rejecting the suggestion .ResultsWhen the doctors accepted the recommendations, the percentage of the next-test international normalized ratio (INR) in the therapeutic range was higher (64.95% vs. 44.64%, RR=2.298, 95%CI 1.173 to 4.499, P=0.014). The logistic regression analysis revealed that accepting the recommendations was an independent predictor for the next-test INR being in the therapeutic range after controlling potentially confounding factors (OR=2.446, 95%CI 1.103 to 5.423, P=0.028).ConclusionThe algorithm of Anticlot Assistant is reasonable and reliable.
Objective To assess different anticoagulant regimens in pregnant women with mechanical heart valves: taking oral warfarin throughout the pregnancy, or heparin in the 1st trimester and oral warfarin for the other trimesters. The main outcome measures were major maternal complications and perinatal outcomes. Methods The MEDLINE, EMbase, CBM and CNKI were searched. The quality of the included studies was evaluated and data were extracted by two reviewers independently. Meta-analyses were performed on the results of homogeneous studies. Result Seven studies involving 629 pregnancies in 469 patients met the inclusion criteria for this review, all of which were retrospective surveys. The comparison between the administration of heparin in the 1st trimester plus oral warfarin for the other trimesters and warfarin throughout the pregnancy showed that, there are not significant different in the incidence of major maternal complications and the incidence of adverse perinatal outcomes. Conclusion Compared with the administration of warfarin throughout the pregnancy, the administration of heparin in the 1st trimester and oral warfarin for the other trimesters might increase the incidence of major maternal complications, but with a similar incidence of adverse perinatal outcomes.