肺血栓栓塞症患者蛋白C活性相关的研究
摘要
目的:通过对本院确诊的肺血栓栓塞症(Pulmonary thromboembolism, PTE;)患者蛋白C活性(activity protein C, APC)分析,了解蛋白C活性与年龄的关系,探讨其随着年龄的增加蛋白C活性的变化,及其在不同性别、民族之间的差异。方法:采用回顾性分析的方法对2006年1月至2009年12月的临床确诊的110例肺栓塞患者的临床资料进行分析,了解蛋白C活性与年龄的相关性,随着年龄增加的变化。按年龄大于60岁和年龄小于60岁及不同性别、民族分组,了解两组之间蛋白C活性水平、蛋白C活性降低发生率的差异。结果:1.110例PTE患者中男性72例、女性38例,年龄呈正偏态分布,整体中位数为61岁;最小年龄21岁,最大年龄82岁;男性年龄中位数65岁,最小年龄21岁,最大年龄82岁;女性年龄中位数61岁,最小年龄28岁,最大年龄72岁,秩和检验两组发病年龄比较无差异(P>0.05)。2.PTE患者PC缺乏的发生率为26.4%,随着年龄的增加蛋白C活性平均水平呈逐渐下降趋势,相关系数为-0.041,P=0.668,无线性相关性。年龄大于60岁的蛋白C活性降低的发生率明显高于年龄小于60岁的PTE患者,差异具有统计学意义(P<0.05)。3.蛋白C活性水平在男、女的中位数分别为83.0%、86.0%;两组蛋白C活性比较无统计学意义(P>0.05)。蛋白C活性降低分别为:男性正常55例,降低17例;女性正常26例,降低12例;两组比较蛋白C活性降低发生率无统计学意义(P>0.05)。4.肺血栓栓塞症患者汉族69例,维族41例,蛋白C活性水平的中位数分别为:汉族84.0%;维族83.4%,两组差异无统计学意义(P>0.05)。蛋白C活性降低分别为:汉族正常48例,降低21例;维族正常33例,降低8例,维汉两民族比较蛋白C活性降低的发生率无统计学意义(P>0.05)。结论:1.蛋白C活性平均水平随着年龄的增加呈逐渐下降的趋势,但是无线性相关性。2.年龄大于60岁的患者蛋白C活性降低的发生率明显高于年龄小于60岁的PTE患者。3.蛋白C活性水平、蛋白C活性降低的发生率在男女之间无差别。4.蛋白C活性水平、蛋白C活性降低的发生率在维吾尔族、汉族之间无差别。
Objective: The analysis of activity protein C to patients with pulmonary thromboebolism (to call for short name pulmonary thromboebolism PTE) diagnosed in the hospital. The aim is to explore the change of APC with the age, and the difference between different nations, genders. Methods: Clinical data of 110 patients with PTE between January of 2006 and December of 2009 is analyzed retrospectively. The aim is to explore the relativity between APC and age, and the change of APC with the rising of age. The different level of protein C and the reduction of protein C between two groups are beyond 60 years and below 60 years. The second aim is to find the difference between the level of protein C and the reduction of protein C in different genders, nations. Results: 1. There are 72 men and 38 women among 110 cases, and their ages appear positive skewness distribution. The median is 61 years. The smallest age is 21 years old, and the oldest age is 82 years in the data. The median of age about men is 65 years, and the smallest and the oldest age is 21 years and 82 years respectively. The median of age about women is 62 years, and the smallest and the oldest age is 28 years and 72 years respectively. There is no difference between the ages of two groups. The absent incidence rate of active protein C in 60 years eld is obviously higher than the younger. 2. The incidence rate to absence of protein C in PTE patients is 26.4%. The average level of active protein C appears decreasing along with the patients’age increase, and the result shows to be no difference. The coefficient correlation is -0.041, P=0.668 which shows there is no linear correlation. 3. The median of active protein C among men and women is 83.0% and 86.0% respectively. The compared result of two groups is P>0.05 showing that there is no difference. The absent incidence rate of active protein C is the below. There are 55 men with normal level of protein C, and 17 men with low level of protein C. 26 women with normal level of protein C and 12 women with low level of protein C. The result is P>0.05, and there is on statistical significance between two groups. 4. There are 69 cases of Han nationality and 41 cases of Uygur nationality. The result compared to the ages of two groups is not significant (P>0.05). The median of active protein C is 84.0% and 83.4% respectively among the Han nationality and the Uygur nationality. Absence of active protein C is 48 cases of Han nationality with normal level of protein C, 21 cases with low level; 33 cases of Uygur nationality with normal level of protein C, and 8 cases with low level of protein C respectively. There is no evident statistical significance (P>0.05). Conclusion: 1. The average level of protein C is decreasing with the age becoming older. But there is no linear correlation. 2. The absent incidence rate of active protein C in 60 years eld is obviously higher than the younger. 3.There is no evident difference in the level of APC and absent incidence rate of active protein C between different genders. 4. The average level of protein C and absent incidence rate of active protein C has on difference in Han nationality and the Uygur nationality.
Objective: The analysis of activity protein C to patients with pulmonary thromboebolism (to call for short name pulmonary thromboebolism PTE) diagnosed in the hospital. The aim is to explore the change of APC with the age, and the difference between different nations, genders. Methods: Clinical data of 110 patients with PTE between January of 2006 and December of 2009 is analyzed retrospectively. The aim is to explore the relativity between APC and age, and the change of APC with the rising of age. The different level of protein C and the reduction of protein C between two groups are beyond 60 years and below 60 years. The second aim is to find the difference between the level of protein C and the reduction of protein C in different genders, nations. Results: 1. There are 72 men and 38 women among 110 cases, and their ages appear positive skewness distribution. The median is 61 years. The smallest age is 21 years old, and the oldest age is 82 years in the data. The median of age about men is 65 years, and the smallest and the oldest age is 21 years and 82 years respectively. The median of age about women is 62 years, and the smallest and the oldest age is 28 years and 72 years respectively. There is no difference between the ages of two groups. The absent incidence rate of active protein C in 60 years eld is obviously higher than the younger. 2. The incidence rate to absence of protein C in PTE patients is 26.4%. The average level of active protein C appears decreasing along with the patients’age increase, and the result shows to be no difference. The coefficient correlation is -0.041, P=0.668 which shows there is no linear correlation. 3. The median of active protein C among men and women is 83.0% and 86.0% respectively. The compared result of two groups is P>0.05 showing that there is no difference. The absent incidence rate of active protein C is the below. There are 55 men with normal level of protein C, and 17 men with low level of protein C. 26 women with normal level of protein C and 12 women with low level of protein C. The result is P>0.05, and there is on statistical significance between two groups. 4. There are 69 cases of Han nationality and 41 cases of Uygur nationality. The result compared to the ages of two groups is not significant (P>0.05). The median of active protein C is 84.0% and 83.4% respectively among the Han nationality and the Uygur nationality. Absence of active protein C is 48 cases of Han nationality with normal level of protein C, 21 cases with low level; 33 cases of Uygur nationality with normal level of protein C, and 8 cases with low level of protein C respectively. There is no evident statistical significance (P>0.05). Conclusion: 1. The average level of protein C is decreasing with the age becoming older. But there is no linear correlation. 2. The absent incidence rate of active protein C in 60 years eld is obviously higher than the younger. 3.There is no evident difference in the level of APC and absent incidence rate of active protein C between different genders. 4. The average level of protein C and absent incidence rate of active protein C has on difference in Han nationality and the Uygur nationality.
引文
[1]刘丽华,刘晶.肺栓塞临床分析.吉林大学学报[J].2008,1-63.
[2]张锦,杨霞,张红,等.急性肺血栓栓塞症患者凝血纤溶系统功能变化相关研究[J].宁夏医学大学学,200,31(1):41-42.
[3]李杰,辛晓敏,刘娅娜.血浆蛋白C、蛋白S在静脉血栓病人诊断及治疗中的应用[J].中国微循环,2004,8(50):317-318.
[4]赵文,门剑龙.活化蛋白C抵抗对老年人凝血、抗凝血系统指标的影响[J].中华老年医学杂志,2001,20(2).
[5]吴坎金,朱一堂,周丽荣,等.急性肺栓塞血栓塞患者血清蛋白S、血清蛋白C和D-二聚体检测的临床意义[J].中国综合临床,2006,9,22(9):800-801.
[6] Reitsma PH, Bernardi F, Doig RG, et al, Protein C deficiency: a database of mutations [J]. Thromb Haemost,1995,73(5):876-889.
[7] Miyata T, Kimura R, Kokubo Y, et al, Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K169E mutation[J].Int J Hematol,2006, 83(3):217-223.
[8] Shen MC, Lin JS, Tsay W. Protein C and Protein S deficiencies are the most important risk factor associated with thrombosis in Chinese venous thrombophilic patients in Taiwan[J].Thromb Res,2000,99(5):447-452.
[9] Liu D, Cheng T, Griffin JH, et al. Activated protein C blocks p53 mediated apoptosis in ischemic human brain endothelium and is neuroprotective[J].Nat Med,2003, 9(3):338-342.
[10]邬超,杨晓红.蛋白C活性与维汉两民族肺栓塞栓塞症患者的相关性研究[J].新疆医学,2008,38:21-23.
[11] Tsay W, Shen MC. R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese[J]. Am J Hematol, 2004,76(1):8-13.
[12] Gale AJ, Characterization of a thrombomodulin binding site on protein C and its comparison to an activated protein C binding site for factor Va[J]. Proteins, 2004, 54 (3):433-441.
[13]周荣富,王鸿利.遗传性蛋白C缺陷症的研究进展[J].国外医学输血及血液学分册,2005,28(3):227-229.
[14]贾玮,吴琦.蛋白C缺陷症的研究进展[J].国外医学呼吸系统分册,2005,25(增刊):69-71.
[15] TiongY, Alkotob ML, Ghaffari S. Protein C deficiency manifesting as an acute myo-cardial infarction and ischaemic stroke[J].Heart,2003,89(2):210.
[16] Dahlback B, Villoutreix BO. The anticoagulant protein C pathway[J]. FEBS Lett, 2005,579:3310-3316.
[17] Okajima K. Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications[J].Curr Vasc Pharmacol,2004,2 (2): 125- 133.
[18]张本平,梁庆成.蛋白C、蛋白S活性与缺血性脑血管病的相关性研究[J].哈尔滨医科大学学报,2007,41(4):365-369.
[19] Okajima K. Prevention of endiothelial cell injury by activated protein C[J].Vasc Pharmacol,2004,2(2):125-133.
[20]张本平,梁庆成.蛋白C、蛋白S活性与缺血性脑血管病的相关性研究[J].哈尔滨医科大学学报,2007,41(4):365-366.
[21] Griffin JH, Fernandez JA, Liu D, et al. Activated protein C and ischemic stroke[J].Crit Care Med,2004,32(5Suppl):S247-253.
[22] Folsom AR, Aleksic N, Wang L, et al. Protein C, antithrombin, and venous throm- boembolism incidence: aprospective population based study[J].Arterioscler Thromb Vase Biol,2002,22(6):1018-1022.
[23]靳岩,袁宏,王卫东,侯金萍.蛋白C抗凝系统在肾病综合症中的变化[J].血栓与止血学,2005,11(1):24-25.
[24]郑艳珍,周伯通,蒲小群,等.静脉及心脑血栓性疾病抗活化的蛋白C研究[J].中华血液病学杂志,1996,17(9):479-481.
[25]车琳,王乐民.深静脉血栓形成的先天性致栓性因素的研究现状[J].心血管病学进展,2005,26(增刊),54-55.
[26] Nicolases-Gerry AF, Dahlback B, Factor V and thrombotic disease: description of a Janus-faced protein[J]. Arte-rioscler Thromb Vase Biol,2002,22(4):530-538.
[27] Dahlback B,Carlsson M,Svensson PJ, et al. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: predication of a cofactor to APC[J]. Proc Natl Acad Sci USA, 1993,90:1004-1008.
[28]张雅妮,潘旭东,刑岩,等.中青年缺血性脑病与因子V Leiden突变的研究[J].中国神经精神疾病杂志,2005,31(3),220-223.
[29]韩轩茂,任景芳,郝斌,等.静脉血栓栓塞症患者活化蛋白C抗性及凝血因子V活性和基因多态性研究[J].中国实验血液学杂志,2007,15(3):612-616.
[30]王兵,张武臣,张畔,等.中国汉族人血栓性疾病与抗活化蛋白C关系的系统评价[J].中国微循环,2007,11(3):154-157.
[31] Hasstedt SJ, Scott BT, Callas PW, et al. Geno me scan of venous thrombosis in a pedigree with protein C deficiency[J].J Thromb Haemost,2004,2(6):868-873.
[32]熊立凡,倪培华,吴洁敏,等.中国人动脉血栓性疾病与活化蛋白C裂解FV和FVIII基因位点突变的相关性研究[J].微循环学杂志,2004,14(4):49-51.
[33] Zhou RF, Fu QH, Wang WB, et al. Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigrees[J].Chin Med J(Engl), 2004,117(6):813-817.
[34] LeviM, DeJonge E, van der poll T. Recom binant hum an activated protein C(Xigris) [J].Int J of Clin Pract,2002,56(7):542-545.
[35] LI SB, TANG HP, ZHANG MY, et al. Value of spiral computed tomographic pulmo- nary angiography (CTPA) and measurement of plasma D-dimer in diagnosis of pu- lmonary embolism[J].China Journal of Modern Medicine,2007,17(10):1249-1252.
[36] YANG YM, LI NJ, QIU F, et al. Study on the interrelationship between plasma D- dimer and transient ischemic attack of the aged[J].China Medical Engineering 2006, 14(5):516-520.
[37]沈芊,曾艳.重组人活化蛋白C-治疗严重感染的新型药物[J].中国药学杂志,2005,40(1):75-76.
[38] De Money W, Sanson BJ, Mac Gillavry MR, et al Embolus location affects the sensi- tivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism [J].Am J Respir Crit Care Med.2002,165(3):345-348.
[39]刘阳,谭最.治疗深静脉血栓形成过程中活性蛋白C和D-二聚体的改变[J].医学新知识杂志,2006,16(2),84-86.
[40]程显声,程芮,马秀平.心电图在急性肺栓塞诊断中的应用[J].中华心血管病杂志,2001,29(5):274-276.
[41] Starin,et al. Activated Protein Cameliorates TNF-α-induced Inflammatory Response of Endothelium Via the Endothelial Protein C Receptor[J].Journal of Biomedical Engineering,2009,625-630.
[42] Muhicenter clinical trial on the efficacy of thrombolytic therapy with urokinase and / or anticoagulati on with low molecular weight heparin (fluxum) in patients with acute pulmonary embolism. Diagnostic value of arterial blood gas analysis in acute pulmonary thromboembolism[J].Chinese Circulation Journal,2004,19(50):367-369.
[43]王建国,王辰,郭佑民,等.CT肺血管成像分析肺栓塞程度及右心功能的价值[J].中国医学影像学杂志,2009,17(2):81-83.
[1]薛汉荣,傅向春.蛋白C抗凝活性检测在慢性肺系疾病血瘀证中的应用价值探讨[J].江西中医学院学报,2000,12(3):97-98.
[2] Glueek Cj et al, Resistance to activeated protein C and legg perrthes diseas[J].Clin Orthop, 1997:139-152.
[3]靳岩,袁宏,王卫东等.蛋白C抗凝系统在肾病综合征中的变化[J].血栓与止血学,2005,11(1):24-25.
[4]贾玮,吴琦.蛋白C缺陷症的研究进展[J].国外医学呼吸系统分册,2005,25,增刊:9-70.
[5] Glueek Cj et al, Resistance to activeated protein C and legg perrthes diseas[J].Clin Orthop, 997:139-152.
[6] Zhou RF,Fu QH , Wang WB, et al. Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigree[J].Chin Med J (Engl), 2004,117(6):813-817.
[7] Tsay W, Shen MC. R147W mutation lf PROC gene is common in venous thrombotic patients in Taiwanese Chinese.Am J Hematol,2004,76(1):8-13.
[8] Hasstedt SJ, Scott BT, Callas PW, et al. Genome scan of venous thrombosis in a pedigree with protein C deficiency[J].J Thromb Haemost, 2004,2(6):868-873.
[9]梁传栋,于振海.蛋白C缺陷症研究进展[J].山东医药,2005,45(14):69-70.
[10] Goodw in TM, Gazit G, Gordon EM. Heterozygous protein C deficiency presenting as severe protein C deficiency and peripartum thrombosis: successful treatment with protein C concentrate[J].Obstet Gynecol,2004,86:662-664.
[11] Singh S, Evans TW. Organ dysfunction during sepsis[J].Intensive Care Med, 2006, 32(3):349-360.
[12] Hisamichi Y, Yukihiko A, Osamu T, et al. Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice[J].Blood,2004, 103 (6):2196-2204.
[13] Riewald M, Ruf W. Science review: role of coagulation protease cascades in sepsis [J].Crit Care,2003,7(2):123-129.
[14]王志远,秦俭.重组人活化蛋白C在脓毒症中的应用进展[J].中国误诊学杂志,2008,8(6):1282-1283.
[15] Abraham E,Laterre PF, Garg R, et al. D rotrecogin alfa(activated) for adults with severe sepsis and a low risk of death[J].N Engl J Meg, 2005,353(13):1332-1341.
[16] Gardlund B. Activated protein C (Xigris) treatment in sepsis a drug in trouble[J].Acta A naesthesiol Scand,2006,50(8):907-910.
[17]周谊辉,解勤之. DVT患者血浆蛋白C活性和D_二聚体测定及意义[J].中国现代医学杂志,2008,18(7):965-966.
[18] Okajima K. Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications [J].Curr Vasc Pharmacol, 2004,2(2):125-133.
[19] Miyata T, Kimura R, Kokubo Y, et al, Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K169E mutation[J].Int J Hematol, 2006, 83(3):217-223.
[20] Shen Ming Ching. Protein C and Protein S Deficiencies Are the Most Important Risk Factors Associated With Thrombosis in Chinese Venous Thromboembolism Patients in Taiwan[J].Thromb Res,2000,99(5):447.
[21]张锦,杨霞,张红,等.急性肺血栓栓塞症患者凝血纤溶系统功能变化相关研究[J].宁夏医科大学学报,2009,31(1):41-42.
[22] Dhainaut JF, Yan SB, Claessens YE, Protein C/activated protein C pathway: Over view of clinical trial result in severe sepsis[J].Crit Care Med,2004, 32(suppl):194-201.
[23]陈平,章永平,乔敏敏,等.活化蛋白C对重症急性胰腺炎大鼠的疗效[J].上海医药2007,30(1):40-43.
[24]李汉东.老年人下肢深静脉血栓形成患者的几项抗凝因子的观察[J].亚太传统医药,2008,4(7):48-49.
[25]刘阳,谭最.治疗深静脉血栓形成过程中活化蛋白C和D一二聚体的改变[J].中国新知识,2006,16(2):84.
[26]张本平,梁庆成.蛋白C、蛋白S和缺血性脑血管病的关系[J].哈尔滨大学学报,2007,41(4):365-369.
[27]孙爽.血浆蛋白C蛋白S与脑梗死的相关性研究[J].中风与神经疾病杂志,2007,24(5):551-553.
[28] Koppelman S J, Vant Veer C, Sixma J J, et al. Synergistic inhibition of the intrinsic factor X activation by protein S and C4b binding protein[J].Blood ,1995 ,86 (7): 2653-2660.
[29] Amaral A, Opal SM, Vincent JL, Coagulation in sepsis[J].Intensive Care Med, 2004,30(6):1032-1040.
[30] Griffin JH, Zlokovic B, Fernandez JA. Activated protein C: potential therapy for severe sepsis, thrombosis, and stroke[J].Semin Hematol, 2002,39(3):197-205.
[31]常文秀,曹书华,张会云.多器官功能障碍综合征患者血浆蛋白C水平与预后的关系[J].天津医药,2006,34(2):85-86.
[32] Mosnier LO, Grifin JH. Protein C anticoagulant activity in relation to anti- inflammatory and anti-apoptotic activities[J].Front Biosci,2006,11:2381-2399.
[33]郑延松,郑秋甫.活化蛋白C抵抗现像与血栓性疾病的关系[J].国外医学心血管疾病分册,2004,31(2):87-89.
[34] Freeman BD.A meta-analysis of controlled trials of anticoagulant therapies in patients with sepsis[J].Shock,2003,20(1):5-9.
[35] Bernard GR, Vincent JL. Efficacy and safety of recombinant human activated protein C for severe sepsis[J].N Enfl J Med ,2001,344:699-709.
[36] Okajima K. Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications[J].Curr Vase Pharmacol,2004, 2 (2):125-133.
[37]陈平,袁慧宗.活化蛋白C[J].中国急救医学,2005,25(4):277-278.
[38] Van Veen S Q,Levi M, van Vliet A K,et al. Peritoneal lavage with activated protein C alters compartmentalized coagulation and fibrinolysis and improves survival in polymicrobial peritonitis[J].Crit Care Med,2006,34(11):2799-2805.
[39] Winn RK, Harlan JM. The role of endothelial cell apoptosis in inflammatory and immune diseases[J].J Thromb Haemost,2005,3(8):1815-1824.
[40] Anti-infective Advisory Committee, FDA briefing document: drotrecogin (activated) [recombinant human activated protein C (rhAPC)] Xigris[J], Food and Drug Adminis- tration,2001,34(56):108-112.
[41] Youqin Chen, Jun Peng, Xiaoheng Liu et al. Activated Protein Cameliorates TNF-α-induced Inflammatory Response of Endothelium Via the Endothelial Protein C Receptor[J].Journal of Biomedical Engineering,2009,625-630.
[42] Ercan E, Tengiz I, Sekuri C, et al. Cardiac thrombi in a patient with protein C and S deficiencies: a case report[J].Thromb J,2004,2(1):1-4.
[43]付向春,郭德华.血浆蛋白C活性检测在呼吸疾病中的的临床意义[J].江西医学检验,2005,2(23):54-55.
[44]王兵,张武臣,张畔,等.中国汉族人血栓性疾病与抗活化蛋白C关系的系统评价[J].中国微循环,2007,11(3):154-157.
[45]沈芊,曾艳.重组人活化蛋白C[J].中国药学杂志,2005,40(1):75-76.
[2]张锦,杨霞,张红,等.急性肺血栓栓塞症患者凝血纤溶系统功能变化相关研究[J].宁夏医学大学学,200,31(1):41-42.
[3]李杰,辛晓敏,刘娅娜.血浆蛋白C、蛋白S在静脉血栓病人诊断及治疗中的应用[J].中国微循环,2004,8(50):317-318.
[4]赵文,门剑龙.活化蛋白C抵抗对老年人凝血、抗凝血系统指标的影响[J].中华老年医学杂志,2001,20(2).
[5]吴坎金,朱一堂,周丽荣,等.急性肺栓塞血栓塞患者血清蛋白S、血清蛋白C和D-二聚体检测的临床意义[J].中国综合临床,2006,9,22(9):800-801.
[6] Reitsma PH, Bernardi F, Doig RG, et al, Protein C deficiency: a database of mutations [J]. Thromb Haemost,1995,73(5):876-889.
[7] Miyata T, Kimura R, Kokubo Y, et al, Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K169E mutation[J].Int J Hematol,2006, 83(3):217-223.
[8] Shen MC, Lin JS, Tsay W. Protein C and Protein S deficiencies are the most important risk factor associated with thrombosis in Chinese venous thrombophilic patients in Taiwan[J].Thromb Res,2000,99(5):447-452.
[9] Liu D, Cheng T, Griffin JH, et al. Activated protein C blocks p53 mediated apoptosis in ischemic human brain endothelium and is neuroprotective[J].Nat Med,2003, 9(3):338-342.
[10]邬超,杨晓红.蛋白C活性与维汉两民族肺栓塞栓塞症患者的相关性研究[J].新疆医学,2008,38:21-23.
[11] Tsay W, Shen MC. R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese[J]. Am J Hematol, 2004,76(1):8-13.
[12] Gale AJ, Characterization of a thrombomodulin binding site on protein C and its comparison to an activated protein C binding site for factor Va[J]. Proteins, 2004, 54 (3):433-441.
[13]周荣富,王鸿利.遗传性蛋白C缺陷症的研究进展[J].国外医学输血及血液学分册,2005,28(3):227-229.
[14]贾玮,吴琦.蛋白C缺陷症的研究进展[J].国外医学呼吸系统分册,2005,25(增刊):69-71.
[15] TiongY, Alkotob ML, Ghaffari S. Protein C deficiency manifesting as an acute myo-cardial infarction and ischaemic stroke[J].Heart,2003,89(2):210.
[16] Dahlback B, Villoutreix BO. The anticoagulant protein C pathway[J]. FEBS Lett, 2005,579:3310-3316.
[17] Okajima K. Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications[J].Curr Vasc Pharmacol,2004,2 (2): 125- 133.
[18]张本平,梁庆成.蛋白C、蛋白S活性与缺血性脑血管病的相关性研究[J].哈尔滨医科大学学报,2007,41(4):365-369.
[19] Okajima K. Prevention of endiothelial cell injury by activated protein C[J].Vasc Pharmacol,2004,2(2):125-133.
[20]张本平,梁庆成.蛋白C、蛋白S活性与缺血性脑血管病的相关性研究[J].哈尔滨医科大学学报,2007,41(4):365-366.
[21] Griffin JH, Fernandez JA, Liu D, et al. Activated protein C and ischemic stroke[J].Crit Care Med,2004,32(5Suppl):S247-253.
[22] Folsom AR, Aleksic N, Wang L, et al. Protein C, antithrombin, and venous throm- boembolism incidence: aprospective population based study[J].Arterioscler Thromb Vase Biol,2002,22(6):1018-1022.
[23]靳岩,袁宏,王卫东,侯金萍.蛋白C抗凝系统在肾病综合症中的变化[J].血栓与止血学,2005,11(1):24-25.
[24]郑艳珍,周伯通,蒲小群,等.静脉及心脑血栓性疾病抗活化的蛋白C研究[J].中华血液病学杂志,1996,17(9):479-481.
[25]车琳,王乐民.深静脉血栓形成的先天性致栓性因素的研究现状[J].心血管病学进展,2005,26(增刊),54-55.
[26] Nicolases-Gerry AF, Dahlback B, Factor V and thrombotic disease: description of a Janus-faced protein[J]. Arte-rioscler Thromb Vase Biol,2002,22(4):530-538.
[27] Dahlback B,Carlsson M,Svensson PJ, et al. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: predication of a cofactor to APC[J]. Proc Natl Acad Sci USA, 1993,90:1004-1008.
[28]张雅妮,潘旭东,刑岩,等.中青年缺血性脑病与因子V Leiden突变的研究[J].中国神经精神疾病杂志,2005,31(3),220-223.
[29]韩轩茂,任景芳,郝斌,等.静脉血栓栓塞症患者活化蛋白C抗性及凝血因子V活性和基因多态性研究[J].中国实验血液学杂志,2007,15(3):612-616.
[30]王兵,张武臣,张畔,等.中国汉族人血栓性疾病与抗活化蛋白C关系的系统评价[J].中国微循环,2007,11(3):154-157.
[31] Hasstedt SJ, Scott BT, Callas PW, et al. Geno me scan of venous thrombosis in a pedigree with protein C deficiency[J].J Thromb Haemost,2004,2(6):868-873.
[32]熊立凡,倪培华,吴洁敏,等.中国人动脉血栓性疾病与活化蛋白C裂解FV和FVIII基因位点突变的相关性研究[J].微循环学杂志,2004,14(4):49-51.
[33] Zhou RF, Fu QH, Wang WB, et al. Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigrees[J].Chin Med J(Engl), 2004,117(6):813-817.
[34] LeviM, DeJonge E, van der poll T. Recom binant hum an activated protein C(Xigris) [J].Int J of Clin Pract,2002,56(7):542-545.
[35] LI SB, TANG HP, ZHANG MY, et al. Value of spiral computed tomographic pulmo- nary angiography (CTPA) and measurement of plasma D-dimer in diagnosis of pu- lmonary embolism[J].China Journal of Modern Medicine,2007,17(10):1249-1252.
[36] YANG YM, LI NJ, QIU F, et al. Study on the interrelationship between plasma D- dimer and transient ischemic attack of the aged[J].China Medical Engineering 2006, 14(5):516-520.
[37]沈芊,曾艳.重组人活化蛋白C-治疗严重感染的新型药物[J].中国药学杂志,2005,40(1):75-76.
[38] De Money W, Sanson BJ, Mac Gillavry MR, et al Embolus location affects the sensi- tivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism [J].Am J Respir Crit Care Med.2002,165(3):345-348.
[39]刘阳,谭最.治疗深静脉血栓形成过程中活性蛋白C和D-二聚体的改变[J].医学新知识杂志,2006,16(2),84-86.
[40]程显声,程芮,马秀平.心电图在急性肺栓塞诊断中的应用[J].中华心血管病杂志,2001,29(5):274-276.
[41] Starin,et al. Activated Protein Cameliorates TNF-α-induced Inflammatory Response of Endothelium Via the Endothelial Protein C Receptor[J].Journal of Biomedical Engineering,2009,625-630.
[42] Muhicenter clinical trial on the efficacy of thrombolytic therapy with urokinase and / or anticoagulati on with low molecular weight heparin (fluxum) in patients with acute pulmonary embolism. Diagnostic value of arterial blood gas analysis in acute pulmonary thromboembolism[J].Chinese Circulation Journal,2004,19(50):367-369.
[43]王建国,王辰,郭佑民,等.CT肺血管成像分析肺栓塞程度及右心功能的价值[J].中国医学影像学杂志,2009,17(2):81-83.
[1]薛汉荣,傅向春.蛋白C抗凝活性检测在慢性肺系疾病血瘀证中的应用价值探讨[J].江西中医学院学报,2000,12(3):97-98.
[2] Glueek Cj et al, Resistance to activeated protein C and legg perrthes diseas[J].Clin Orthop, 1997:139-152.
[3]靳岩,袁宏,王卫东等.蛋白C抗凝系统在肾病综合征中的变化[J].血栓与止血学,2005,11(1):24-25.
[4]贾玮,吴琦.蛋白C缺陷症的研究进展[J].国外医学呼吸系统分册,2005,25,增刊:9-70.
[5] Glueek Cj et al, Resistance to activeated protein C and legg perrthes diseas[J].Clin Orthop, 997:139-152.
[6] Zhou RF,Fu QH , Wang WB, et al. Biochemical activity and gene analysis of inherited protein C and antithrombin deficiency in two Chinese pedigree[J].Chin Med J (Engl), 2004,117(6):813-817.
[7] Tsay W, Shen MC. R147W mutation lf PROC gene is common in venous thrombotic patients in Taiwanese Chinese.Am J Hematol,2004,76(1):8-13.
[8] Hasstedt SJ, Scott BT, Callas PW, et al. Genome scan of venous thrombosis in a pedigree with protein C deficiency[J].J Thromb Haemost, 2004,2(6):868-873.
[9]梁传栋,于振海.蛋白C缺陷症研究进展[J].山东医药,2005,45(14):69-70.
[10] Goodw in TM, Gazit G, Gordon EM. Heterozygous protein C deficiency presenting as severe protein C deficiency and peripartum thrombosis: successful treatment with protein C concentrate[J].Obstet Gynecol,2004,86:662-664.
[11] Singh S, Evans TW. Organ dysfunction during sepsis[J].Intensive Care Med, 2006, 32(3):349-360.
[12] Hisamichi Y, Yukihiko A, Osamu T, et al. Activated protein C inhibits bronchial hyperresponsiveness and Th2 cytokine expression in mice[J].Blood,2004, 103 (6):2196-2204.
[13] Riewald M, Ruf W. Science review: role of coagulation protease cascades in sepsis [J].Crit Care,2003,7(2):123-129.
[14]王志远,秦俭.重组人活化蛋白C在脓毒症中的应用进展[J].中国误诊学杂志,2008,8(6):1282-1283.
[15] Abraham E,Laterre PF, Garg R, et al. D rotrecogin alfa(activated) for adults with severe sepsis and a low risk of death[J].N Engl J Meg, 2005,353(13):1332-1341.
[16] Gardlund B. Activated protein C (Xigris) treatment in sepsis a drug in trouble[J].Acta A naesthesiol Scand,2006,50(8):907-910.
[17]周谊辉,解勤之. DVT患者血浆蛋白C活性和D_二聚体测定及意义[J].中国现代医学杂志,2008,18(7):965-966.
[18] Okajima K. Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications [J].Curr Vasc Pharmacol, 2004,2(2):125-133.
[19] Miyata T, Kimura R, Kokubo Y, et al, Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K169E mutation[J].Int J Hematol, 2006, 83(3):217-223.
[20] Shen Ming Ching. Protein C and Protein S Deficiencies Are the Most Important Risk Factors Associated With Thrombosis in Chinese Venous Thromboembolism Patients in Taiwan[J].Thromb Res,2000,99(5):447.
[21]张锦,杨霞,张红,等.急性肺血栓栓塞症患者凝血纤溶系统功能变化相关研究[J].宁夏医科大学学报,2009,31(1):41-42.
[22] Dhainaut JF, Yan SB, Claessens YE, Protein C/activated protein C pathway: Over view of clinical trial result in severe sepsis[J].Crit Care Med,2004, 32(suppl):194-201.
[23]陈平,章永平,乔敏敏,等.活化蛋白C对重症急性胰腺炎大鼠的疗效[J].上海医药2007,30(1):40-43.
[24]李汉东.老年人下肢深静脉血栓形成患者的几项抗凝因子的观察[J].亚太传统医药,2008,4(7):48-49.
[25]刘阳,谭最.治疗深静脉血栓形成过程中活化蛋白C和D一二聚体的改变[J].中国新知识,2006,16(2):84.
[26]张本平,梁庆成.蛋白C、蛋白S和缺血性脑血管病的关系[J].哈尔滨大学学报,2007,41(4):365-369.
[27]孙爽.血浆蛋白C蛋白S与脑梗死的相关性研究[J].中风与神经疾病杂志,2007,24(5):551-553.
[28] Koppelman S J, Vant Veer C, Sixma J J, et al. Synergistic inhibition of the intrinsic factor X activation by protein S and C4b binding protein[J].Blood ,1995 ,86 (7): 2653-2660.
[29] Amaral A, Opal SM, Vincent JL, Coagulation in sepsis[J].Intensive Care Med, 2004,30(6):1032-1040.
[30] Griffin JH, Zlokovic B, Fernandez JA. Activated protein C: potential therapy for severe sepsis, thrombosis, and stroke[J].Semin Hematol, 2002,39(3):197-205.
[31]常文秀,曹书华,张会云.多器官功能障碍综合征患者血浆蛋白C水平与预后的关系[J].天津医药,2006,34(2):85-86.
[32] Mosnier LO, Grifin JH. Protein C anticoagulant activity in relation to anti- inflammatory and anti-apoptotic activities[J].Front Biosci,2006,11:2381-2399.
[33]郑延松,郑秋甫.活化蛋白C抵抗现像与血栓性疾病的关系[J].国外医学心血管疾病分册,2004,31(2):87-89.
[34] Freeman BD.A meta-analysis of controlled trials of anticoagulant therapies in patients with sepsis[J].Shock,2003,20(1):5-9.
[35] Bernard GR, Vincent JL. Efficacy and safety of recombinant human activated protein C for severe sepsis[J].N Enfl J Med ,2001,344:699-709.
[36] Okajima K. Prevention of endothelial cell injury by activated protein C: the molecular mechanism(s) and therapeutic implications[J].Curr Vase Pharmacol,2004, 2 (2):125-133.
[37]陈平,袁慧宗.活化蛋白C[J].中国急救医学,2005,25(4):277-278.
[38] Van Veen S Q,Levi M, van Vliet A K,et al. Peritoneal lavage with activated protein C alters compartmentalized coagulation and fibrinolysis and improves survival in polymicrobial peritonitis[J].Crit Care Med,2006,34(11):2799-2805.
[39] Winn RK, Harlan JM. The role of endothelial cell apoptosis in inflammatory and immune diseases[J].J Thromb Haemost,2005,3(8):1815-1824.
[40] Anti-infective Advisory Committee, FDA briefing document: drotrecogin (activated) [recombinant human activated protein C (rhAPC)] Xigris[J], Food and Drug Adminis- tration,2001,34(56):108-112.
[41] Youqin Chen, Jun Peng, Xiaoheng Liu et al. Activated Protein Cameliorates TNF-α-induced Inflammatory Response of Endothelium Via the Endothelial Protein C Receptor[J].Journal of Biomedical Engineering,2009,625-630.
[42] Ercan E, Tengiz I, Sekuri C, et al. Cardiac thrombi in a patient with protein C and S deficiencies: a case report[J].Thromb J,2004,2(1):1-4.
[43]付向春,郭德华.血浆蛋白C活性检测在呼吸疾病中的的临床意义[J].江西医学检验,2005,2(23):54-55.
[44]王兵,张武臣,张畔,等.中国汉族人血栓性疾病与抗活化蛋白C关系的系统评价[J].中国微循环,2007,11(3):154-157.
[45]沈芊,曾艳.重组人活化蛋白C[J].中国药学杂志,2005,40(1):75-76.