甲状腺功能紊乱患者止凝血功能异常的研究

目的 观察甲状腺功能紊乱患者止凝血各系统功能异常的特征并探讨其变化机制.方法 选择自2008年1月至12月于本院住院和门诊就诊的甲状腺功能紊乱患者122例,其中弥漫性毒性甲状腺肿(甲亢患者组)47例,男9例、女38例,年龄27～53岁,平均37.1岁;原发性成年型甲状腺功能减退症患者组(甲减组)75例,男18例、女57例,年龄31～58岁,平均36.5岁.体检健康者50名为对照组,男10名、女40名,年龄26～54岁,平均39.1岁.采用IL ACL-9000型血液凝固仪测定PC:A、FPS;A、AT:A、Vwf、t-PA:A、PAI-1 A、D-二聚体(D-dimer).采用Sysmex CA-7000型血液凝固仪测定FIB、凝血因子Ⅴ、Ⅷ活性(FⅤ:A、FⅧ:A)、PT及Aptt.采用ADVIA Centaur化学发光免疫分析仪测定FT_3、FT_4、TSH.结果 与对照组比较PAI-1:A(0.50±0.38)Ku/L、Vwf:Ag(105.1±40.7)%、FⅧ:A(103.4±29.2)%、Aptt(32±8)s],甲亢组PAI-1:A(2.89±2.15)Ku/L]、Vwf:Ag(265.8±81.1)%]、FⅧ:A(158.6±37.0)%]显著增高,Aptt(42±12)s]显著延长(q=7.660、q=13.677、q=10.228、q=5.714,P<0.01).甲亢组t-PA:A(0.49±0.22)Ku/L、D-Dimer(0.21±0.13)ms/L、PT(12.1±1.8)s]和甲减组t-PA:A(0.41±0.25)Ku/L、D-Dimer(0.20±0.11)mg/L、PT(12.2±2.5)s]分别与对照组比较t-PA:A(0.46±0.17)Ku/L、D-Dimer(0.19±0.12)mg/L、PT(12.5±1.5)s],甲亢组和甲减组各指标差异均无统计学意义(q=1.508、q=1.171、q=1.521,P>0.05;g=1.730、g=0.952、q=1.038,P>0.05).与对照组比较PAI-1:A、FⅤ:A(112.2±36.4)%、FIB(3.1±0.9)g/L、Aptt],甲亢组FⅤ:A(120.8±27.3)%水平差异无统计学意义(q=2.160,P>0.05);甲减组PAI-1:A(0.51±0.30)Ku/L]、FIB(3.03±1.04)g/L、Aptt(34±12)s]水平差异无统计学意义(q=0.286,q=0.327,q=1.433,P>0.05).与对照组比较AT:A(97.1±16.6)%、FPS:A(115.2±30.3)%、PC:A(107.5±20.4)%、Vwf:Ag、FⅤ:A(112.2±36.4)%、FⅧ:A],甲减组AT:A(74.5±15.8)%]、FPS:A(95.1±30.2)%]、PC:A(28.3±12.7)%]、Vwf:Ag(68.5±24.6)%]、FⅤ:A(72.8±23.6)%]和FⅧ:A(84.5±29.7)%]显著降低(q=12.384、q=5.764、q=53.988、q=12.883、q=14.459、q=5.510,P<0.01).与对照组比较,甲亢组AT:A(88.6±14.2)%]、PC:A(26.7±9.5)%]和FIB(2.3±0.8)g/L]显著降低(q=4.104、q=58.297、q=6.856,P<0.01).甲减组AT:A和FPS:A显著低于甲亢组AT:A(88.6±14.2)%、FPS:A(111.8±19.5)%,q=7.726、q=4.789,P<0.01].甲亢组FT_3(19.1±10.4)pmol/L、FT_4(47.0±19.5)pmol/L和TSH(0.03±0.02)Μiu/m1]与甲减组比较n(2.5±1.1)pmol/L、FT_4(9.5±2.9)pmol/L和TSH(56.9±38.7)Μiu/ml],甲亢组FT_3和FT_4显著增高(q=10.993、q=16.985,P<0.01),TSH显著减低(q=18 956.667,P<0.01).甲亢组Vwf:Ag、PAI-1均与FT_3呈显著正相关(r=0.616 9、r=0.644 7,P<0.01),甲减组的Vwf:Ag、PAI-1均与FT_3呈显著正相关(r=0.603 7,r=0.635 2,P<0.01).甲亢组和甲减组其他各项止凝血指标与FT_3、FT_4和TSH之间无显著性相关(P>0.05).将甲亢组和甲减组合并后进行相关分析,FT_3与Vwf:Ag、PAI-1呈显著正相关(r=0.757 3、r=0.7260,P<0.01),其他指标与FT_3、FT_4和TSH之间均无显著性相关(P>0.05).结论 甲状腺功能紊乱患者的止凝血各系统存在功能失调的状态,其病理生理机制可能与甲状腺激素过剩或不足导致血管内皮功能失调有关.

The haemostasis and coagulation system dysfunction in patients of thyroid dysfunction

Objective To investigate the dysfunction of haemostasis and coagulation system in patients of the thyroid dysfunction and study its mechanism.Methods Totally 122 patients were selected from in-and outpatients at our hospital from Jan 2008 to Dec 2008.The hyperthyroidism group included 47Graves disease patients,9 males and 38 females,age 27-53 years,mean age 37.1 years.The hypothyroidism group consisted of 75 patients,18 males and 57 females,age 31-58 years,mean age 36.5years.Then we used the IL ACL-9000 blood coagulation instrument to assay the PC:A,FPS:A,AT:A,Vwf:AS,t-PA:A,PAI-1:A and D-Dimer,SYSMEX CA-7000 blood coagulation instrument to assay the FIB,FⅤ:A,FⅧ:A,PT,Aptt and ADVIA Centaur chemiluminesent immunoassay analyzer to assay the FT_3,FT_4 and TSH.Results Compared with the control groupPAI-1:A(0.50±0.38)Ku/L,Vwf:Ag(105.1±40.7)%,FⅧ:A(103.4±29.2)%,Aptt(32±8)s],the levels of PAI-1:A(2.89±2.15)Ku/L],Vwf:Ag(265.8±81.1)%],FⅧ:A(158.6 ±37.0)%]of the hyperthyroidism group were increased and Aptt(42±12)s]was prolonged significantly(q=7.660,q=13.677,q=10.228,q=5.714,P<0.01).When comparing the hyperthyroidism groupt-PA:A(0.49±0.22)Ku/L,D-Dimer(0.21 ±0.13)ms/L,PT(12.1 ±1.8)s]and the hypothyroidism groupt-PA:A(0.41±0.25)Ku/L,D-Dimer(0.20±0.11)ms/L,PT(12.2 ±2.5)s]with the controlt-PA:A(0.46±0.17)Ku/L,D-Dimer(0.19 ±0.12)mg/L,PT(12.5±1.5)s]respectively,there were no significant change(q=1.508,q=1.171,q=1.521,P>0.05;q=1.730,q=0.952,q=1.038,P>0.05)in the hyperthyroidism group and the hypothyroidism group.when comparing with the control groupPAI-1:A,FⅤ:A(112.2±36.4)%,FIB(3.1±0.9)g/L,Aptt],the levels of FⅤ:A(120.8±27.3)%of the hyperthyroidism group were no significant change(q=2.160,P>0.05),the levels of PAI-1:A(0.51 ±0.30)Ku/L],FIB(3.03±1.04)s/L,Aptt(34±12)s]of the hypothyroidism group had no obvious change(q=0.286,q=0.327,q=1.433,P>0.05).When comparing the hypothyroidism group with the controlAT:A(97.1±16.6)%,FPS:A(115.2±30.3)%,PC:A(107.5±20.4)%,Vwf:Ag,FⅤ:A(112.2±36.4)%,FⅧ:A],the level of AT:A(74.5±15.8)%],FPS:A(95.1 ±30.2)%],PC:A(28.3 ±12.7)%],Vwf:Ag(68.5 ±24.6)%],FⅤ:A(72.8±23.6)%]and FⅧ:A(84.5 ±29.7)%]were decreased significantly in the hypothyroidism group(q=12.384,q=5.764,q=53.988,q=12.883,q=14.459,q=5.510,P<0.01).When comparing the hyperthyroidism group with the control group,the AT:A(88.6 ±14.2)%],PC:A(26.7±9.5)%]and FIB(2.3 ±0.8)g/L]were decreased obviously in the hyperthyroidism group(q=4.104,q=58.297,q=6.856,P<0.01).The levels of the AT:A and FPS:A of the hypothyroidism group were lower than the hyperthyroidism groupAT:A(88.6 ±14.2)%,FPS:A(111.8±19.5)%,q=7.726,q=4.789,P<0.01].Compared the hyperthyroidism groupFF3(19.1±10.4)pmol/L,FT_4(47.0 ±19.5)pmoL/L and TSH(0.03±O.02)Μiu/ml]with the hypothyroidism groupFT_3(2.5±1.1)pmol/L,FF_4(9.5 ±2.9)pmol/L and TSH(56.9±38.7)Μiu/ml],the level of FT_3and FT_4 of the hyperthyroidism group were increased significantly(q=10.993,q=16.985,P<0.01),and the TSH of the hyperthyroidism group was decreased significantly(q=18 956.667,P<0.01),There were strong positive relationships between the Vwf:Ag,PAI-1 and the FT_3 in the hyperthyroidism group(r=0.6169,r=0.644 7,P<0.01)and the hypothyroidism group(r=0.603 7,r=0.635 2,P<0.01).There was no strong relationship between the other coagulation parameters and the FT_3,FT_4,TSH in the hyperthyroidism group and the hypothyroidism group(P>0.05).Combining the hyperthyroidism group and the hypothyroidism group,there were strong positive relationships between FT_3 and Vwf:Ag,PAI-1(r=0.757 3,r=0.726 0,P<0.01),and no strong relationships between the other parameters and FT_3,FT_4,TSH(P>0.05).Conclusion The function of haemostasis and coagulation system was disorganized in patients with thyroid dysfunction,and the main pathophysiological mechanism maybe associated with the endothelium cell dysfunction caused by thyroid hormone excess or shortage.