CO_2气腹腹腔镜手术对凝血/纤溶系统的影响
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摘要
目的:观察在靶控瑞芬太尼异丙酚全凭静脉麻醉下,CO_2气腹腹腔镜子宫切除术与开腹子宫切除术,手术前后患者凝血和纤溶系统的变化,通过特异性分子标志物的检测,评估机体发生深静脉血栓(DVT)的危险性。
     方法:选择30例行CO_2气腹腹腔镜子宫切除术病人作为观查组, 30例开腹子宫切除术病人作为对照组。ASAⅠ或Ⅱ级,心功能Ⅰ或Ⅱ级,年龄40~50岁,体质量指数(BMI)18.5~23kg/m2,无血栓形成高危因素(肥胖、高血压、冠心病、糖尿病等疾病)。术中常规血压、心率、心电图、脉搏血氧饱和度、体温、呼气末二氧化碳分压(PETCO_2)监测。腹腔冲洗液使用温盐水,手术室温度保持在25℃。两组病人均采用头低脚高+膀胱截石体位。手术时间控制在2~3h之间,术中出血量小于400ml,无术中输血。围手术期均未使用促凝血药。
     两组病人术前用药为咪唑安定5mg,阿托品0.5mg,术前30min肌肉注射。麻醉诱导用靶控瑞芬太尼4ng/ml,咪唑安定0.1mg/kg,异丙酚1mg/kg,维库溴铵0.1mg/kg,气管插管后行机械通气,潮气量8~10ml/kg,呼吸频率12~14次/分。麻醉维持用靶控瑞芬太尼4~8ng/ml,异丙酚2~4μg/ml,根据血压心率的变化随时调整药物剂量,使术中血流动力学平稳。根据PETCO_2随时调整麻醉机呼吸参数使其始终在30~35mmHg的范围内波动。观察组用气腹机充入CO_2,压力维持在12mmHg。两组病人输液量,输液种类大致相同。所有患者均于术前1h(T_1)、术后24小时(T_2)及术后72小时(T3)抽取静脉血检测以下指标:1.血小板α颗粒膜蛋白(GMP-140),2.组织纤溶酶原激活物(t-PA),3.组织纤溶酶原激活物抑制剂-1(PAI-1)。GMP-140亦称P-选择素,定位于血小板α颗粒和内皮细胞Weibel-Palade小体内。当血小板被激活时,α颗粒可与细胞膜迅速融合,在细胞膜表面表达GMP-140。血小板活化是血栓形成的重要条件,GMP-140的血浆浓度能直接反映血小板活化程度,是血小板活化时特异性分子标志物。t-PA和PAI-1是纤溶系统的重要组成部分。其水平的高低对血栓的形成有重要的调节作用。t-PA能使纤溶酶原转变成纤溶酶,降解和消除纤维蛋白,在溶解血栓中起重要作用。PAI-1是t-PA的抑制物,可使有活性的纤溶酶生成减少,导致纤维蛋白降解障碍,有利于血栓形成。正常情况下,血浆t-PA及PAI-1处于动态平衡状态,对于人体起着保护血管完整性和保持血管通畅的作用。t-PA/PAI-1可以反映纤溶系统的活性,一旦t-PA降低,PAI-1升高,打破了两者之间的平衡,就有可能导致血栓形成。
     结果:1.观察组(LH)与对照组(OH)组间比较,反映凝血和纤溶系统活性的特异性分子标志物(GMP-140、t-PA、PAI-1)的浓度差异无统计学意义(P>0.05)。2.GMP-140的变化:两组GMP-140术后24h较术前1h均明显增高(P<0.01),术后72h恢复到接近术前1h水平。3.t-PA的变化:两组t-PA术后24h较术前1h均明显升高(P<0.01),术后72h恢复到术前1h水平。4.PAI-1的变化:两组PAI-1术后24h较术前1h均升高(P<0.05),术后72h恢复到术前1h水平。5.t-PA/PAI-1的变化:两组t-PA/PAI-1术后24h较术前1h均升高(P<0.05),术后72h恢复到术前1h水平。
     结论:应用靶控瑞芬太尼异丙酚全凭静脉麻醉,CO_2气腹腹腔镜子宫切除术与开腹子宫切除术在术后凝血和纤溶系统活性变化方面无差异,CO_2气腹腹腔镜子宫切除术未增加术后DVT的危险性。
Objective: To observe the changes of coagulation and fibrinolysis system in patients undergoing laparoscopic (LH) and open hysterectomy (OH),under total intravenous anaesthesia of target-controlled infusion of remifentanil in combination with propofol,and assess the risk rate of deep vein thrombosis,by detecting the concentration of specific molecule markers.
     Methods: To choice thirty patients,who were submitted to laparoscopic hysterectomy group(observe group),and other thirty patients,who were submitted to open hysterectomy group(contrast group).All patients were classified as grade I or II,according to the American Society of Anesthesiologists (ASA) grading system, heart function grade I or II,age 40~50 years, body mass index 18.5~23kg/m2. No high risk factors of thrombogenesis (obesity, hypertension, coronary heart disease, diabetes and other diseases). Blood pressure,heart rate,pulse oxygen,temperature and end-tidal carbon dioxide partial pressure were monitored conventionally in the operation. Bathing abdominal cavity used warmed-brine. To maintain the temperature at 25℃in the operating room.This procedure of either group was performed under genenal anesthesia with Trendelenburg position.The time of operation was claimed between 2~3h.The bleeding amount was less than 400ml, no blood transfusion. During Perioperative the patients were not given coagulant drugs.
     The two groups of patients used midazolam (5mg) and atropine (0.5mg) by intramuscular injection 30 minutes before operation. Induction of anesthesia used target-controlled infusion of remifentanil (4ng/ml), intravenous injection of midazolam (0.1mg/kg) ,propofol (1mg/kg), vecuronium (0.1mg/kg), then tracheal intubation and assisted ventilation. Tidal volume (8~10ml/kg), respiratory frequency (12~14times/min).Using target-controlled infusion of remifentanil (4~8ng/ml) plus propofol (2~4μg/ml), according to the changes of blood pressure and heart rate at any time,adjusted the dose of durgs to make sure intraoperative hemodynamic stability.Readjusting the respiratory parameters of anesthesia machine, to make sure the index of PETCO_2 always in 30~35 mmHg.Observe Group(LH) used the pneumoperitoneum be filling with CO_2, the pressure maintained at 12 mmHg.The quantity and type of infusion in the two groups were approximately same.
     Venous blood samples for determination of coagulation and fibrinolytic parameters were collected preoperatively 1h and at 24h and 72h postoperatively.The following parameters were measured:
     1.platelet granular membrane protein 140 (GMP-140) ,
     2.tissue plasminogen activator(t-PA),
     3.plasminogen activator inhibitor-1(PAI-1).
     GMP-140 also called P-selectin, was found in the plateletα-granule and Weibel–Palade body membrane of endothelial cells, which was expressed on the platelet surface membrane and shed into the plasma on platelet activation. Platelet activation had an important role in the process of thrombogenesis. the plasma level of GMP-140 could reflec the degree of platelet activation directly,was the specific molecular markers of platelet activation.t-PA and PAI-1 were important components of fibrinolysis system. The value of them played an important role in the formation of thrombus. t-PA could convert plasminogen into plasmin,which can eliminate fibrin, and played an important role in dissolving the thrombus. PAI-1 was the inhibitor of t-PA,which could result in the generation of activatory plasmin reduction and lead to the obstacle of fibrin degradation, in favor of thrombogenesis. Under normal circumstances, fibrin was lysed rapidly by the fibrinolysis system. t-PA/PAI-1 could reflect the activity of fibrinolysis system.Once the value of t-PA decreased or the value of PAI increased ,disturbing the equilibrium between coagulation and fibrinolysis meight lead to thrombosis.
     Results: 1.The comparison of LH and OH, the concentration of specific molecule markers (GMP-140, t-PA, PAI-1),which reflecting the activity of coagulation and fibrinolysis system, have no statistical difference(P>0.05).
     2.The change of GMP-140:In both groups, the concentration of GMP-140 at T2 was significantly higher than at T_1(P<0.01), the concentration at T3 restored to closely at T_1.
     3.The change of t-PA: In both groups, the concentration of t-PA at T2 was higher than at T_1(P<0.01), the concentration at T3 restored to nearly at T_1.
     4.The change of PAI-1: In both groups, the concentration of PAI-1 at T2 was higher than at T_1(P<0.05), the concentration at T3 restored to nearly at T_1.
     5.The change of t-PA /PAI-1: In both groups, the concentration of t-PA /PAI-1 at T2 was higher than at T_1(P<0.05), the concentration at T3 restored to nearly at T_1.
     Conclusion: Using total intravenous anaesthesia of target-controlled infusion of remifentanil in combination with propofol,the activation of coagulation and fibrinolysis system between LH and OH is similar,The laparoscopic surgery of carbon dioxide Pneumoperitoneum did not enhance the risk rate of DVT,by detecting the concentration of specific molecule markers.
引文
1 Patel MI,Hardman DT,Nicholls D.The incidence of deep venous thrombosis after laparoscopic cholecystectomy.Med J Aust, 1996,164(11):652~654
    2 Gonzalez QH,Tishler DS,Plata Munoz JJ.Incidence of clinically evident deep venous thrombosis after laparoscopic Roux-en-Y gastric bypass.Surg Endosc,2004,18(7): 1082~ 1084
    3 Gulec B,Oner K,Yigitler C.Lower extremity venous changes in pneumoperitoneum during laparoscopic surgery.Anz J Surg,2006,76(10):904~906
    4 Jorgensen J,Hanel K,Lalak NJ,et al.Thromboembolic complications of laparoscopic cholecysetcomy.Br Med J,1993,30(6):518
    5 Lindberg F,Rasmussen I,Siegbahn A.Coagulation activation after laparoscopic cholecystectomy in spite of thromboembolism prophylaxis.Surg Endosc,2000, 14,(9):858~861
    6 Pier Luigi Vannacchi,Bice Ridolfi,Gino Biliotti,et al.Evaluation of Prothrombin F1+2 Fragament after videolaparoscopic surgery.Throm Res,1994,75(2):219-222
    7 Prisco D,De Gaudio AR,Carla R.Videolaparoscopic cholecystectomy induces a hemostasis activation of lower grade than does open surgery.Surg Endosc, 2000, (14) 2:170~174
    8 Milic DJ,Pejcic VD,Zivic SS.Coagulation status and the presence of postoperative deep vein thrombosis in patients undergoing laparoscopic cholecystectomy.Surg Endosc, 2007,21(9):1588~1592
    9 Papaziogas B,Koutelidakis I,Kabaroudis A. Modifications of coagulation and fibrinolysis mechanism in laparoscopic vs open cholecystectomy.Hepatogastroenterology,2007,54 (77): 1335~1338
    10 Nguyen NT,Luketich JD,Shurin MR.Coagulation modifications after laparoscopic and open cholecystectomy in a swine model.Surg Endosc,1998,12(7):973~978
    11 Larsen JF,Ejstrud P,Svendsen F.Randomized study of coagulation and fibrinolysis during and after gasless and conventional laparoscopic cholecystectomy.Br J Surg, 2001, 88(7):1001~1005
    12 Brokelman WJ,Holmdahl L,Bergstrom M.Peritoneal fibrinolytic response to various aspects of laparoscopic surgery: a randomized trial.J Surg Res, 2006, 136 (2): 309~313
    13 Dexter SP,Griffith JP,Grant PJ.Activation of coagulation and fibrinolysis in open and laparoscopic cholecystectomy.Surg Endosc,1996,10 (11):1069~1074
    14 Varughese GI,Patel JV,Tomson J.Prognostic value of plasma soluble P-selectin and von Willebrand factor as indices of platelet activation and endothelial damage/dysfunction in high-risk patients with hypertension: a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial.J Intern Med,2007,261(4):384~391
    15 Blann AD,Lip GY.Hypothesis: is soluble P-selectin a new marker of platele activation? Atherosclerosis, 1997, 128 (2): 135~138
    16 Linden MD,Furman MI,Frelinger AL.Indices of platelet activation and the stability of coronary artery disease.J Thromb Haemost, 2007,5(4):761~765
    17 Softeland E,Framstad T,Nordvik A.Evaluation of a porcine model to study in vivo platelet activation.Thromb Res, 2006, 118(3):341~352
    18 Blann AD,Noteboom WM,Rosendaal FR.Increased soluble P-selectin levels following deep venous thrombosis: cause or effect?Br J Haematol, 2000, 108(1):191~193
    19 Sartori MT,Serena A,Saggiorato G.Variations in fibrinolytic parameters and inhibin-A in pregnancy: related hypertensive disorders.J Thromb Haemost,2008,6(2):352~358
    20 Lu A,Sipehia R.Antithrombotic and fibrinolytic system of human endothelial cells seeded on PTFE: the effects of surface modification of PTFE by ammonia plasma treatment and ECM protein coatings. Biomaterials, 2001,22(11): 1439~1446
    21 Rupin A,Martin F,Vallez MO.Inactivation of plasminogen activator inhibitor-1 accelerates thrombolysis of a platelet-rich thrombus in rat mesenteric arterioles.Thromb Haemost,2001,86(6):1528~1531
    22 Kawasaki T,Dewerchin M,Lijnen HR.Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice.Blood,2000,96(1):153~160
    23 Hakki SI,Fareed J,Hoppensteadt DA.Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.Clin Appl Thromb Hemost,2001,7(1):65~71
    24 Onishi H,Kaniyu K,Iwashita M.Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy.Ann Clin Biochem,2007,44(5):449~454
    25 Peetz D,Hafner G,Hansen M.Dose-adjusted thrombosis prophylaxis in trauma surgery according to levels of D-Dimer.Thromb Res,2000,98(6):473~483
    26 Hinterhuber G,Bohler K,Kittler H.Extended monitoring of hemostatic activation after varicose vein surgery under general anesthesia.Dermatol Surg,2006,32(5):632~639
    27 Meissner MH,Zierler BK,Bergelin RO.Coagulation, fibrinolysis, and recanalization after acute deep venous thrombosis.J Vasc Surg,2002,35(2):278~285
    28 Ishikura K,Wada H,Kamikura Y.High prevalence of anti-prothrombin antibody in patients with deep vein thrombosis.Am J Hematol,2004,76(4):338~342
    29 Sakata T,Kario K,Katayama Y.Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state.Thromb Res,1996,82(3):235~244
    30 Atwal OS,McDonell W. In vivo interaction of pulmonary intravascular macrophages with activated platelets in microvessels of equine lung after multiple exposures to halothane, isoflurane, and thiamylal: a comparative ultrastructural and cytochemical study.Anat Rec A Discov Mol Cell Evol Biol, 2005,284(2):574~584
    31 De Rossi LW,Horn NA,Hecker KE.Effect of halothane and isoflurane on binding of ADP-and TRAP-6-activatedplatelets to leukocytes in Whole blood.Anesthesiology, 2002, 96(1):117~124
    32 Almagor M,Mintz A,Sibirsky O.Preoperative and postoperative levels of interleukin-6 in patients with acute appendicitis: comparison between open and laparoscopic appendectomy.Surg Endosc,2005,19 (3):331-333
    33 Caine GJ,Harris AL,Christodoulos K.Analysis of combination anti-angiogenesis therapy on markers of coagulation, platelet activation and angiogenesis in patients with advanced cancer.Cancer Lett, 2005,219(2):163~167
    34 Blobner M,Bogdanski R,Kochs E.Effects of intraabdominally insufflated carbon dioxide and elevated intraabdominal pressure on splanchnic circulation: an experimental study in pigs. Anesthesiology, 1998,89(2):475~482
    35 Tan M,Xu FF,Peng JS,et al.Changes in the level of serum liver enzymes after laparoscopic surgery[J].World J Gastroenterol,2003,9(2):364
    36 Molinas CR,Tjwa M,Vanacker B.Role of CO2 pneumoperitoneum-induced acidosis in CO2 pneumoperitoneum-enhanced adhesion formation in mice. Fertil Steril,2004,81(3):708~711
    37 Hanly EJ,Aurora AR,Fuentes JM.Abdominal insufflation with CO2 causes peritoneal acidosis independent of systemic pH.J Gastrointest Surg,2005,9(9):1245~1251
    38 Wagner CT,Kroll MH,Chow TW.Epinephrine and shearstress synergistically induce platelet aggregation via a mechanism that partially bypasses VWF-GP IB interactions. Biorheology,1996, 33(3):209~229
    39 Freyburger G,Dubreuil M,Audebert A.Changes in haemostasis after laparoscopic surgery in gynaecology: contribution of the thrombin generation test. Haemostasis, 2001(31)1:32~41
    40 Fang SD,Lin CZ,Zhong LC,et al.Discussion of applying continuous TCI of isopropyl hydroxybenzene in compound epidural anesthesia to epigastric operation[J].Zhongguo Yixue Gongcheng,2002,10(6):59~64
    41 Michelsn LG, Salmenper AM, Hug CC, et al.Anesthetic potency of remifentanil in dogs[ J]. Anesthesiology,1996, 84: 865~872
    42 刘仁玉.阿片类药新进展[J].国外医学,麻醉学与复苏分册, 1997, 18: 265~267
    43 Romic P, Ignjatovic D, Rankovic, et al.Total intravenous anesthesia using remifentanil and propofol with midazolam co-induction in laporoscopic surgery of the gallbladder[J]. Acta Chir Iugos, 2001, 48: 48~51
    44 Catheline JM,Capelluto E,Gaillard JL,et al. Thromboembolism prophylaxis and incidence of thromboembolic complications after laparoscopic surgery[J]. Int J Surg Investing, 2000,2:41~47
    45 Okuda Y,Kitajima T,Egawa H.A combination of heparin and an intermittent pneumatic compression device may be moreeffective to prevent deep-vein thrombosis in the lower extremities after laparoscopic cholecystectomy.Surg Endosc,2002(16)5:781~784
    46 Ido K,Suiuki T,Kimura K,et al.Lower-extremity enous stasis during laparoscopic cholecystetomy asassessed using color Doppler ultrasound.Surg Endosc,1995,9:310
    47 Freyburger G,Dubreuil M,Audebert A,et al.Changes in haemostasis after laparoscopic surgery in gynaecology: contribution of the thrombin generation test.Haemostasis, 2001,31(1):32~41
    48 Kotake Y,Takeda J,Matsumoto M,et al.Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy[J].Br J Anaesth,2001,87(5):774~777
    49 Sefr R,Puszkailer K,Frana J,et al.Effect of carbon dioxide pneumoperitoneum on selected parameters of the acid-base equilibrium in laparoscopic cholecystectomy[J].Rozhl Chir,2001,80(4):206~212
    50 Myre K,Rostrup M,Buanes T.Plasma catecholamines and haemodynamic changes during pneumoperitoneum.Acta Anaesthesiol Scand,1998,42(3):343~347
    1 Holzheimer RG.Laparoscopic procedures as a risk factor of deep venous thrombosis, superficial ascending thrombophlebitis and pulmonary embolism-case report and review of the literature.Eur J Med Res,2004,9(9):417~422
    2 Gulec B,Oner K,Yigitler C.Lower extremity venous changes in pneumoperitoneum during laparoscopic surgery.Anz J Surg,2006,76(10):904~906
    3 Weiler Guettler H,Christie PD,Beeler DL.A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state.J Clin Invest, 1998,101(9):1983~1991
    4 De Groot CJ,Taylor RN.New insights into the etiology of pre–eclampsia[J].Ann Med,1998,25(3) :243~249
    5 Softeland E,Framstad T,Nordvik A.Evaluation of a porcine model to study in vivo platelet activation.Thromb Res,2006,118(3):341~352
    6 Grabowski EF,Lam FP.Endothelial cell function,including tissue factor expressing,under flow conditions.Thromb Haeost,1995,74(1):123
    7 Kenneth Ouciel,MD,Richard Mreen,et al.The anatomy of deep venous thrombosis of the lower extremity.Journal of Vascular Surgery,2003,31(5):895
    8 Gonzalez QH,Tishler DS,Plata Munoz JJ.Incidence of clinically evident deep venous thrombosis after laparoscopic Roux-en-Y gastric bypass.Surg Endosc,2004,18(7): 1082~1084
    9 Delis KT,Knaggs AL,Mason P,et al.Effects of epidural-and-general anesthesia combined versus general anesthesia alone on the venous hemodynamics of the lower limb.A randomized study.Thromb Haemost,2004, 92(5): 1003~1011
    10 Zuckerman R,Gold M,Jenkins P,et al.The effects of pneumoperitoneum and patient position on hemodynamics during laparoscopic cholecystectomy.Surg Endosc,2001, 15(6):562~565
    11 Atwal OS,McDonell W. In vivo interaction of pulmonary intravascular macrophages with activated platelets in microvessels of equine lung after multiple exposures to halothane, isoflurane, and thiamylal: a comparative ultrastructural and cytochemical study.Anat Rec A Discov Mol Cell Evol Biol, 2005,284(2):574~584
    12 De Rossi LW,Horn NA,Hecker KE.Effect of halothane and isoflurane on binding of ADP-and TRAP-6-activated platelets to leukocytes in Whole blood. Anesthesiology, 2002,96(1):117~124
    13 Molinas CR,Tjwa M,Vanacker B.Role of CO2pneumoperitoneum-induced acidosis in CO2 pneumoperitoneum-enhanced adhesion formation in mice. Fertil Steril,2004,81(3):708~711
    14 Hanly EJ,Aurora AR,Fuentes JM. Abdominal insufflation with CO2causes peritoneal acidosis independent of systemic pH.J Gastrointest Surg, 2005,9(9):1245~1251
    15 Linden MD,Furman MI,Frelinger AL 3rd.Indices of platelet activation and the stability of coronary artery disease.J Thromb Haemost,2007,5(4):761~765
    16 Pirttikangas CO,Salo M, Peltola. Propofol influsion anaesthesia and the immune response in elderly patients undergoing ophthalmic surgery.Anaesthesia,1996,51(4):318
    17 Brian A,Rosenfeld MD,Nauder F,et al.Hemostatic effects of stress hormone infusion[J].Anesthesiology,1994, 81: 1116~ 1126.
    18 Fang SD,Lin CZ,Zhong LC,et al.Discussion of applying continuous TCI of isopropyl hydroxybenzene in compound epidural anesthesia to epigastric operation[J].Zhongguo Yixue Gongcheng,2002,10(6):59~64.chinese
    19 Christen Y,reymond MA,Vogel JJ,et al. Hemodynamic effects of intermittent pneumatic compression of the lower limbs during laparoscopic cholecystectomy[J].Am J Surg,1995,170(4):395~398
    20 Maillo CL,Martin E,lopez J,et al.Effect of pneumoperitoneum on venous hemodynamics during laparoscopic cholecystectomy.Influence of patients'age and tine of surgery.Med Clin(Barc),2003,120(9):330~334
    21 Ido K,suzukit,kimura K,et al. Lower-extremity venous stasis during laparoscopic cholecystectomy as assessed using color Doppler ultrasound[J].endosc Surg,1995,9:310~313
    22 Nguyen NT,Owings JT,Gosselin R,et al.Systemic Coagulation and Fibrinolysis After Laparoscopic and Open Gastric Bypass.Archives of Surgery[J].Pacific Coast Surgical Association,2001,136(8):909~916
    23 Gulec B,Oner K,Yigitler C.Lower extremity venous changes in pneumoperitoneum during laparoscopic surgery.Anz J Surg,2006,76(10):904~906
    24 Kotake Y,Takeda J,Matsumoto M,et al.Subclinical hepatic dysfunction in laparoscopic cholecystectomy and laparoscopic colectomy[J].Br J Anaesth,2001,87(5):774~777
    25 Wagner CT,Kroll MH,Chow TW.Epinephrine and shearstress synergistically induce platelet aggregation via a mechanism that partially bypasses VWF-GP IB interactions.Biorheology, 1996,33(3):209~229
    26 Sefr R,Puszkailer K,Frana J,et al.Effect of carbon dioxide pneumoperitoneum on selected parameters of the acid-base equilibrium in laparoscopic cholecystectomy[J].Rozhl Chir,2001,80(4):206~212
    27 Weiss N,Bemstein-PS.Rush factor scoring for predicting venous thromboembolish in obstetric patient. Am-J-Obstet-Gynecol,2000,182(5):1073~1075
    28 Blann AD,Lip GYH.Is soluble P-selectin a new marker of platelet activation?Atheroselerosis,1997,128:135~138
    29 Sakata T,Kario K,Katayama Y.Clinical significance of activated protein C resistance as a potential marker for hypercoagulable state.Thromb Res,1996,82(3):235~244
    30 Ishikura K,Wada H,Kamikura Y.High prevalence of anti-prothrombin antibody in patients with deep vein thrombosis.Am J Hematol,2004,76(4):338~342
    31 王虹,张京岚.慢性肺心病急性期血栓前状态相关指标的临床观测.中国实用内科杂志,1999,19(5)286~288
    32 Simpson EL,Lawrenson RA,Nightingale AL E,et al.Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database, 2001,108 (1):56~60
    33 Franco RF,Reitsma PH.Genetic risk factors of venous thrombosis.Hum Genet,2001,109(4):369~384

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