Clinical Research On Activation Of Platelet And Prothrombin After Transcatheter Closure Of Atrial Septal Defects

Background and objectiveDevice-related thrombus is one of the serious complications after transcatheter closure of atrial septal defects(ASD).It has been recommended to anticoagulate with unfractionated heparin(UFH) for 24 hours and antiplatelet with asprin for 6 months following transcatheter closure of ASD,according to the present "guidelines for trangcatheter intervention treatment of congenital heart disease".But to our knowledge,the clinical anticoagulant practices remain controversial.Activation of platelet and prothrombin is important process during thrombogenesis.β-TG and PF4 is released after platelet activation,Prothrombin fragment 1+2(F1+2),N-terminal components of prothrombin,is formed during thrombin generation.Changes of the levels ofβ-TG,PF4 and F1+2 in plasma are the markers reflecting activation of platelet and prothrombin.All the patients with ASD were divided into 3 groups according to gender,age and defect size:group A(n=16),who was intravenous drop infusion with UFH for 24 hours after occlusion of ASD,group B(n=20),who was administered low molecular weight heparin(LMWH) twice through subcutaneous injection in abdominal wall after occlusion of ASD,and group C(n=20),who was given LMWH for 3 days after occlusion of ASD. The research work was divided into two parts.The first part was designed to observe the changes of activation of platelet and prothrombin after transcatheter closure of ASD,and the second part was to explore the influence of different anticoagulant protocols,and to evaluate the effect and safety of the anticoagulant protocols. MethodsPartⅠ:Changes of Activation of Platelet and Prothrombin after Transcatheter Closure of ASD20 patients underwent successful transcatheter closure of ASD at our institution were investigated in the study(group B).20 healthy subjects matched by gender and age were included as the control group.Domestic atrial septal occluders were implanted for occlusion of ASD,and they were loaded by a long 10F to 14F introducer sheath.The occluders were selected to be 2～6mm larger than the measured stretched diameter,according to the residual edge.Two additional doses of 1 mg/kg of LMWH were administered within 24 hours after removement of introducer sheath.Patients were instructed to take aspirin 3 to 5 mg/kg daily for 6 months.All the patients underwent clinical follow-up after occlusion for 3 months. Transthoracic chocardiograph(TTE) were performed in the 1^st and 3^rd month after occlusion of ASD.RBC and platelet count,hematocrit and activated partial thromboplastin time(APTT) were determined before occlusion of ASD and at 4 days after occlusion. Fasting blood samples were obtained before occlusion and at 4,7,30,90 days after device implantation.A commercial ELISA was used to measure the levels ofβ-TG,PF4 and F1+2 in the plasma.PartⅡ:Effect of Different Anticoagulant Protocols on Activation of Platelet and Prothrombin after Transcatheter Closure of ASD56 patients with ASD who underwent successful transcatheter closure of the ASD at our centre from May 2006 to February 2008 were included in this study.All the patients were stratified into 3 groups as mentioned above,namely group A,group B and group C.Occlusion procedure,clinical follow-up,TTE and blood samples test were performed the same with those shown in partⅠ.Results1.Levels ofβ-TG and PF4 increased signicantly 4 days after occlusion from the baseline values before occlusion(P＜0.01),and returned to the baseline 7 days after occlusion(P＞0.05). 2.Levels of F1+2 at 4 and 7 days after occlusion were significantly higher than the baseline values before occlusion(P＜0.01).Levels of F1+2 at 30 days after occlusion were slightly higher than the baseline values(P＜0.01),and returned to the baseline values by 90 days(P＞0.05).3.There were no thromboembolic events or serious hemorrhage complications in all the patients.All the patients were free of thrombus evaluated by TTE in the 1^st and 3^rd month after occlusion.4.There were no significant difference among group A,B,and C before occlusion or after 4 days following occlusion in RBC,platelet count,hematocrit and APTT(P＞0.05). Levels of APTT among the three groups kept within normal range.5.No significant differences were revealed between group A and group B in levels ofβ-TG,PF4 and F1+2 before occlusion or at 4,7,30 and 90 days after device implanted (P＞0.05).Levels of F1+2 were lower in group C than group A or group B at the 4^th day after occlusion of ASD(P＜0.01).Conclusions1.With the present clinical anticoagulant protocols,transcatheter closure of the ASD can activate platelet and prothrombin at 4 days after occlusion.Activation of platelet returned to the state of preoperation by 7 days after occlusion,however,activation of prothrombin gradually returned to the state of preoperation by 90 days after occlusion.2.It is necessary to perform further prospective research on the hemostatic changes following transcatheter closure of ASD.It may be considered to be prescribed aspirin 2 days before transcatheter closure of ASD,and anticoagulated with LMWH for 3 days after occlusion.