Clinical Value Of Platelet Membrane Glycoprotein Ⅱb/Ⅲa For Evaluating Thromboembolic Risk In Patients With Persistent Atrial Fibrillation

Backgroud and Objective: Atrial fibrillation (AF) is the most common clinical sustained cardiac arrhythmia which have a high thromboemobolic risk . it has been being a crucial problem in the research field of AF to select the high-risk embolism group from patients with AF and to make reasonable anticoagulant theraphy to decrease complications of cerebral embolism and hemorrhage.The thrombosis of AF mainly locate in the left atrium/left atrial appendage,transesophageal echocardiography (TEE) can view and predict the thrombosis in the left atrium /left atrial appendage. AF is a disease of the prothrombotic state .Platelet being activated play a significantly role in the cause of AF patients result in cerebral embolism . Platelet membrane glycoprotein Ⅱ b/Ⅲa (GP Ⅱ b/Ⅲa) is a parameter which can indicate sensitively the degree of platelet being activated. GP II b/IIIa binding the fibrinogen is the impromant step in the thrombosis . Flow cytometry can analysis accuately and sensitively the expression levels of Platelet membrane glycoprotein Ⅱ b/Ⅲa in the vivo background .In this study ,we measured the the alteration of GP Ⅱ b/Ⅲa by flow cytometry ,combining with TEE parameters and other coagulative parmeters , our research purpose is to expolore :Clinical value of platelet membrane glycoprotein Ⅱ b/Ⅲa for evaluating thromboembolic risk in patients with persistent atrial fibrillation.Patients and methods: the consecutive patients consisted of 128 persons ,which were divided into three groups including AF group,sinus rhythm,and normal control subjects.76 patients with AF group, 38males,38females, mean age 58.14±13.66 years; 35 patients with various heart disease and sinus rhythm ,20 males,15 females,mean age 61.91±11.84 years,17 nonnal control subjects(CS group),9 males,8 females,mean age 59.12±15.65 years. 76 patients with AF were divided into throboembolism positive group,21 patients, 8males,13females,mean age 55.71±9.02 years, included 12 patients who has thrombi in left atrium through TEE examination and other 9 patients who suffered from the complications of thromboembolism, and throboembolism negative group,55 patients,30 males,25females,mean age 58.30±15.13 years. 48 patients of the AF patients underwent transesophageal echocardiography(TEE),the left atrium thrombi or left atrial appendage thrombi were found in 12 patients(defined thrombosis positive group) ,5males,7females,mean age 55.75±8.17 years,other 36 patients ,17 males, 19 females, mean age 58.25±15.31, who had no thrombus in left atrium /left atrial appendage according to the detection of TEE(defined thrombosis negative group). The longest outbreak times were 66 months,the shortest outbreak times were 11 months, the mean outbreak time of persisting atrial fibrillation is 40.22±14.43 months.standard TTE and TEE examination were performed on 48 patients using a 5 MHz phased array transducer(VIVID 7 ,USA,GE).ultrasonical parameters were recorded as follow.(l) LA diameter ,(2)left ventricular ejection fraction(LVEF),(3)severity of left atrial spontaneous echo contrast(LASEC,grade from 0-degree to 3 dregree),(4)LAA blood flow emptying velocity(obtained by placing the pulsed Dopier sample volume into the appenadage cavity=lcm away from the atrial cavity),(5)LAA blood flow filling velocity( at the same site obtained by placing the pulsed Dopier sample volume into the appenadage cavity=lcm away from the atrial cavity),(6)LAA area(measured by multiplying the maximal LAA longitudinal diameter and transeverse diameter in ventical view).Coagulative parameters were determined in all study subjects.plasma levels of D-dimer,platelet a-granule external membrane protein (GMP-140),and von Willebrand factor (vWF) were measured using an enzyme linked immunosorbentassay(ELISA);and the whole blood Platelet membrane glycoprotein II b /HI a (GPII b/IIIa) expression level was analyzed by using flow cytometry.Results:(l)the whole blood GP II b/IIIa expression levels (31.63±6.42% ) and plasma levels of vWF( 193.62±45.74%), D-dimer(346.90±87.93 ng/ml),GMP-140( 19.03+1.93 ng/ml) were significantly higher in AF group than the sinus rhythm group(7.43+3.46% > 100.99123.86%. 215.15+39.04 ng/mh 12.14+1.78 ng/ml,respectively) (P<0.05) and CS group (7.43+3.46%, 100.99+23.86%, 215.15i39.04ng/mk 12.14±1.78 ng/ml,respectively) (P<0.05), above parameters of GP II b/IIIa (36.56+4.742%), vWF( 251.29+31.17%), D-D (414.64±93.62 ng/ml) , GMP-140 (20.61ll.83 ng/ml) in throboembolism positive group were higher than thrombosis negative group(29.74+5.98%, 171.60+27.54%, 321.03170.90 ng/ml, 18.43±1.61ng/ml,respectively) (P<0.05) .(2) AF patients through TEE examination were subdivided into two group : low flow group (<0.20m/s)and high flow group (^0.20m/s).to compare low flow group with high flow group,the measure numbers of incididencesof thrombus (34.4%) , LAA area (12.59+3.48cm2), positive incididece of LASEC2?2-grade(37.5%) , GMP-140 (19.58ll.62 ng/ml), G P II b /III a (34.17±5.34%)in low flow group were significantly higher than the numbers of levels of incididencesof thrombus (6.3%) , LAA area(8.61+3.08cm2), positive incidience of LASEC ^ 2-grade (6.3%). GMP -140 (17.11+1.37 ng/ml), G P II b /III a (27.58+6.12%) in high flow group (P<0.05). But the numbers of LVEF(55.37+12.77%) in low flow group was lower than the numbers of LVEF(62.00±7.59%) in high flow group (P<0.05),the LAA area(14.80±3.51cm2), GMP-140(20.69ll.75 ng/ml). G P II b /III a (37.55+5.14%)and the positive incidence of LASEC^2-grade(66.7%) in positive thrombus group underwent TEE were higher than the LAA area(10.09l3.17cm2) , GMP-140(18.12ll.52ng/ml), GPU b/IIIa (29.76+5.50%), and the positive incidence of LASEC^2-grade (13.9%) in negative group underwent TEE(P < 0.05), but the numbers of LVEF(44.00+11.76%) * LAA-PFV(0.12+0.04m/s) > LAA-PEV(O.13iO.O5m/s) in positive thrombus group underwent TEE were lower than the numbers of LVEF(62.11l7.41%) xLAA-PFV(0.22±0.14m/s) n LAA-PEV(0.24±0.14m/s) in negative thrombus group underwent TEE (P<0.05) .(3) All the AF patients were subdivided into two groups, according to the number >or^the numbers of mean (31.63%),the numbers >31.63%was defined as "high expression GP II b/IIIa group" , ^31.63%was defined as "low expression GP II b/IIIa group".outcomes revealed:the incidence of thrombus event (41.9%) was higher than it (9.1%) in "low expression GP II b/IIIa group". Use crosstabs analysis the date, Odds ratio is 7.20. the numbers of D-D(369.09±91.38ng/rm> vWF (207.28+50.32%), GMP -140(19.43±2.05ng/ml)> LAA-A(15.98±5.12cm2), LA-D(53.92±6.88mm)and positive incidences of LASEC^2-grade (39.3%) in "high expression GP II b/IIIa group" were higher than those of D-D(317.98±75.08 ng/ml), vWF(175.81±31.65%), GMP -140 (18.51+1.63 ng/ml), LAA-A(10.18±3.16cm2), LA-D(45.10±7.159mm), positive Incidences of LASEC^2-grade(10.0%) in "low expression GP II b/IIIa group"(P<0.05), meanwhile,the numbers of LAA-PFV(0.17±0.09m/s), LAA- PEV (0.16 + 0.087 m/s). LVEF(53.82±12.47%) in "high expression GP II b/IIIa group" were lower than the numb -ers of LAA-PFV (0.27 ±0.16 m/s) > LAA-PEV(0.24±0.166m/s), LVEF (62.85+ 8.09%) in "low expression GP II b/IIIa group" (P<0.05) .(4) statistical analysis result revealed: levels of GP II b/IIIa have the linear relation withGMP-140 (r=0.690\ vWF (r=0.513\ LVEF (r=-0.303) ^ LA-D (r=-0.387)> D-D (r=0.445), LAA-A (r=0.440) (P<0.05) .these results cann't reveal that the levels of GP II b/IIIa has linear correlation with LAA blood flow filling velocity -, LAA blood flow emptying velocity (P>0.05) .Conclusion: (1) The expressions of GP II b/IIIa in patients with persistent AF are higher than the levels of patients with sinus rhythm; The expressions of GP II b/IIIa in AF patients with throboembolism complications are higher than the levels of AF patients without throboembolism complications; The expressions of GP II b/IIIa in AF patients with thrombosis in LA and/or LAA underwent TEE detecting was higher than AF patients without thrombosis in LA and/or LAA underwent TEE detecting; It indicated that GP II b/IIIa is a risk factor for predicting thromboembolism complication in AFpatientsjt has important clinical value GPII b/IIIa for evaluating thromboembolic risk in patients with atrial fibrillation.(2) high expression GP II b/IIIa group(the expressions levels of GPlIb/IIIa>31.63 %) has a higher incidence of throboembolism event than it in low expression GP II b/IIIa group(the expressions levels of GP II b/IIIa ^ 31.63%), combining with other coagulative parmeters and TEE parameters, which can classify the thromboembolism risks in AF patients, it has important value for filtrating the higher risk patients with AF and guiding anticoagulant therapy in AF patients.(3) there were significant correlations between GP II b/IIIa and GMP-140 n vWF respectively , Especially GP II b/IIIa has tightly correlation with GMP-140 ,GP II b/IIIa and GMP-140 are sensitive and accurate parameters indicating platelet activation, these mechanisms still need further expolore.