Combined Low-dose Aspirin and Warfarin Anticoagulant Therapy of Postoperative Atrial Fibrillation Following Mechanical Heart Valve Replacement

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients （620 females, mean age of 36.8-4-7.7 years） admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study （warfarin plus 75-100 mg aspirin） or control （warfarin only） groups. International normalized ratio （INR） and prothrombin time were main- tained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respec- tively （P〉0.05）. The incidence of overall thromboembolic events in study group was lower than that in control group （2.16% vs. 4.35%, P=0.049）. No statistically significant differences were found in hem- orrhage events （3.53% vs. 3.95%, P=-0.722） or mortality （0.20% vs. 0.40%, P=0.559） between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Anticoagulation early after mechanical heart valve replacement

Objective： To explore the changes of coagulation activity and the characters of anticoagulation early after mechanical heart valve replacement. Methods： All patients only took warfarin orally for anticoagulation. The predicted international normalized ratio （INR） was 1.5 to 2.0. Several coagulation markers were monitored early after valve replacement. Complications associated with anticoagulation were recorded and analyzed. The patients were divided into three groups based on the number and position of mechanical valve prothesis, including group M （mitral valve replacement）, group A （aortic valve replacement） and group D （mitral and aortic valve replacement）.Comparison was made between the three groups. Results： Three events of mild cerebral embolism and five events of mild bleeding occurred during the early postoperative period. One patient suffered from mild cerebral embolism on the 4th day after operation, accompanied by large volume of pericardial drainage. Two patients with bleeding had lower INRs than predicted range. However, INR in one patient with mild cerebral embolism was in the predicted range. There was no significant difference in thrombo time （TT）, activated partial thromboplastin time （APTT） and 1NR on the 3rd day after operation compared to those before operation; meanwhile, plasma fibrinogen （FIB） concentration was higher than that before operation （P〈0.05）. 1NR had no significant changes on the 2nd day after the beginning of anticoagulation compared to that before operation; however, 1NR was significantly elevated on the 4th day （P〈0.05）. Warfarin doses and INRs were similar among the three groups, but FIB concentrations in plasma were higher in groups M and D than in group A （P〈0.01）. Conclusion： Hypercoagulabale state exists early after mechanical heart valve replacement. When anticoagulation begins is determined by the change of coagulation markers, not by the volume of chest or pericardial drainage. INR can not accurately reflect the coagulation state sometimes, especially during the first 3 days after anticoagulation. The number and position of mechanical valve prothesis could affect coagulation state. Therefore, anticoagulation therapy should be regulated accordingly.

Early Postoperative Anticoagulation by Enoxaparin after Mechanical Aortic Valve Replacement

Background: The use of low molecular weight heparin for early anticoagulation after mechanical aortic valve replacement is still a matter of debate even more that the early postoperative phase is associated with maximum of thrombo-embolic and bleeding risks. The objective of this study is to verify the efficacy and the safety of low molecular weight heparin for the early anticoagulation after mechanical aortic valve replacement. Methods and Results: It is a prospective study conducted over 6 months and interested 40 consecutive patients (32 male and 8 female) with a mean age 53.83 ± 16.93 years (19-75 years) who underwent a mechanical aortic valve replacement and received enoxaparin as bridging therapy between continuous unfractionated heparin and fully effective vitamin K antagonist therapy. There was no in-hospital death and no in-hospital thromboembolic events. We report 2 major bleeding events (5%). Conclusion: The use of low molecular weight heparin should be an alternative to explore for early anticoagulation after valve heart surgery and the results of our study must be verified by large randomized studies before drawing any hasty conclusions.

Role of thrombus precursor protein in assessment of anticoagulation in patients with atrial fibrillation after mechanical heart valve replacement

Objective: To explore the role of thrombus precursor protein (TpP) in assessment of anticoagulation and predict the risk of thromboembolism in the patients with atrial fibrillation (AF) after mechanical heart valve replacement. Methods: TpP plasma concentration and international normalization ratio (INR) were measured in 45 patients with atrial fibrillation and 45 patients with sinus rhythm both after mechanical heart valve replacement. Twenty patients with non valvular heart diseases were selected as the control. Furthermore, the patients with AF were divided into groups based on different TpP plasma concentration and TpP plasma concentration and INR were analyzed. Results: After mechanical heart valve replacement, those with AF had higher TpP plasma concentration than those with sinus rhythm. It was found that discordancy existed between INR and TpP plasma concentration in the patients with AF. There were 28 AF patients with TpP plasma concentration lower than 6 μg/ml and without bleeding, who might be at the optimal anticoagulant state. The 95% confidence of the mean INR value was 1.90-2.30 in these patients and TpP plasma concentration was between 2.84-5.74 μg/ml. Conclusion: Patients with AF might face higher risk of thromboembolism after mechanical valve replacement; INR between 1.90-2.30 and TpP plasma concentration between 2.84-6 μg/ml might be the optimal anticoagulant range for patients with AF after mechanical valve replacement.

Thrombus precursor protein for monitoring anticoagulation in patients with mechanical valve prosthesis

Objective: To evaluate the plasma concentration of thrombus precursor protein (TPP) in patients after mechanical heart valve replacement, and to explore whether it can be used as a marker for monitoring anticoagulation. Methods: Totally 60 patients who took warfarin after mitral valve replacement and 20 control patients with non-valvular heart diseases were subjected in this study. Their plasma TPP concentration and international normalized ratio (INR) were determined, and compared not only between the anticoagulant patients and the control patients, but also between the patients with atrial fibrillaiton (AF, n=37) and the patients with sinus rhythm (SR, n=23) after mechanical valve replacement. The relationship between plasma TPP concentration and INR in the 60 anticoagulant patients was analyzed with linear regression. Results: It was found that the anticoagulant therapy effectively decreased plasma TPP concentration and elevated INR. In the anticoagulant group, the patients with AF had higher plasma TPP concentration than the others with sinus rhythm (P<0.05), although there was no significant difference in INR level between these 2 groups of patients (P>0.05). No significant correlation was found between plasma TPP concentration and INR in the anticoagulant patients (P>0.05). INR did not accord with plasma TPP concentration in several patients. Conclusion: INR can’t reflect the coagulation status and guide the anticoagulation correctly sometimes; TPP may be a valuable assistant marker for monitoring anticoagulation in patients with mechanical heart valve prothesis; Patients with AF may require higher density of anticoagulation and TPP is strongly suggested to be monitored in these patients.

基于时机理论的家庭护理对瓣膜置换患者康复及效果研究

目的探讨基于时机理论的家庭护理对机械瓣膜置换患者的康复及影响。方法根据统一的诊断、纳入及排除标准,选取102例患者,按随机数字表法分为对照组(52例)与试验组(50例)。对照组患者及家属接受心胸外科常规护理与随访;试验组在心胸外科常规护理的基础上接受家庭护理干预,分别于出院时、出院后3个月及6个月时对患者生活质量、华法林服用依从性及并发症发生率进行统计。结果出院后3个月和6个月时试验组患者生活质量、华法林服药依从性均优于对照组(p<0.001);研究结束时,试验组患者华法林相关并发症低于对照组,差异有统计学意义(p<0.05)。结论基于时机理论的家庭护理在机械瓣膜置换患者的康复中应用效果显著,可以有效提高患者华法林服药依从性及生活质量,降低华法林相关并发症的发生率。

An Experimental Study on the Flexibility of Prevention against Thrombosis Following Mechanical Valve Replacement by tPA Gene Transduction

Objectives Use a gene suture immersed recombinant tissue-type plasminogen activator （r-tPA）expression plasmid to transduce myocardia to prevent the thrombosis after mechanical tricuspid valve replacement in pigs. Methods A r-tPA gene plasmid was constructed and conjugated to a novel cationic phosphonolipid and a r-tPA gene suture was made. Eighteen pigs were selected and divided into two groups at randomization. There were 9 pigs in the experimental group and 9 in the control group, all the 18 pigs＇ tricuspids were replaced with mechanical valves. The gene threads were sutured into the right ventricular walls near mechanical valves and an ultrasound was used on the surfaces of the right ventricular walls for the gene transfer in the experimental group. Coagulative function, D-dimer level of the blood and the thrombosis on the surfaces of the valves were observed. Results r-tPA gene plasmid was successfully constructed and r-tPA protein was expressed in the ventricular cells around the gene sutures. D-dimer reached its peak level （ 1.67 ±0. 79） μg · mL^-1 in 1 week after operation in two groups, but it decreased to preoperation level thereafter in control group and kept on the high level and reincreased to a new high level （ 1.89 ± 0.79 ） μg · mL^-1 until the end of the experiment in experimental group. The thromboses around the valves were found in all the control group （100%） but only 1 （ 11.11% ） case in experimental group. There were no changes in prothrombin time pre and post operation in two groups. Conclusions Using gene suture immersed r-tPA expression plasmid to transduce myocardia might be a best substitution for life long anti-coagulation therapy for the patients, who underwent operation.

Valve replacement in pediatric patients： a single center experience

Background Reconstructive surgery is the primary goal in pediatric patients with valve disease.However,in cases with irreparable valve lesions,valve replacement is the only option.This study aimed to retrospectively analyze the clinical experience of heart valve prosthesis replacement in children.Methods Between January 1990 and July 2009,35 pediatric patients （16 boys,19 girls） underwent mechanical valve replacement in Shandong University Qilu Hospital.The ages ranged from 2.5 to 14 years （mean,（8.8±3.8） years） and body weight varied from 11 to 37 kg （mean,（22.1±5.2） kg）.Mechanical valve replacement was performed because of congenital heart disease in 23 patients,rheumatic disease in ten patients and infective endocarditis in two patients.St.Jude bileaflet mechanical valves were implanted in all the 35 patients including mitral valve replacement （MVR） in 18,aortic valve replacement （AVR） in 12,tricuspid valve replacement （TVR） in two,AVR and MVR in two and MVR and TVR in one.The size of the prostheses ranged between 19 and 27 mm.All patients received long-term anticoagulation treatment with sodium warfarin,aiming to maintain an international normalized ratio between 1.5 to 2.0.Follow-up was performed in all the patients with a total follow-up of 119.4 patient-years.Results The operative mortality was 8.57% （3/35）.One patient,who underwent cardiac debridement and AVR,died 2 hours after being admitted to the intensive care unit because of severe low cardiac output syndrome and ventricular fibrillation.Two patients died of cardiogenic shock and renal failure during initial hospitalization after the operation.One patient who received replacement of a tricuspid valve developed complete heart block requiring temporary pacing and recovered sinus rhythm 4 days later.Thirty-two patients survived and their cardiac function was in New York Heart Association （NYHA） class Ⅰ to class Ⅱ when discharged.Late events included hemorrhage and endocarditis.Two patients required reoperation.No late deaths occurred during the follow-up.Conclusions Mechanical valve replacement remains an acceptable treatment option in children when the valve reparation is impossible or unsuccessful.The operative mortality and incidence of any valve-related events such as endocarditis,reoperation,thromboembolism or anticoagulation-related bleeding are acceptable.