血栓病患者凝血、抗凝和纤溶活性改变的研究

目的 观察血栓病患者凝血、抗凝和纤溶指标的变化,以探讨出凝血系统机能紊乱与血栓病发生的关系,并在此基础之上为以后临床筛查、确诊血栓病提供依据。方法 应用ACL Futrua全自动凝血仪对50例静脉血栓、51例动脉血栓病患者及36例正常人进行凝血、抗凝及纤溶系统蛋白分子检测,包括凝血因子Ⅱ、Ⅶ、Ⅷ活性测定,蛋白C（PC）、蛋白S（PS）、抗凝血酶（AT）、纤溶酶原（PLG）、α2-抗纤溶酶（α2-PI）活性测定,D-二聚体、纤维蛋白原含量测定及狼疮抗凝物（LA）、活化蛋白C抵抗（APCR）的检测。结果 LA阳性者,正常组中有4例,静脉组中有总16例,动脉组中有13例。PC系统缺陷在静脉血栓病组织中,共有14例,分别为PC缺陷8例（19.0%）、PS缺陷5例（11.5%）、APCR1例;动脉血栓组中,PC系统缺陷共11例,PC缺陷2例,PS缺陷7例、APCR2例。结论 获得性因素LA阳性和PC系统缺陷是引起血栓病的主要原因,建议对于血栓患者选这两项实验进行筛查,以提高检出率。     

人工髋关节置换术围手术期凝血、抗凝活性变化

目的:检测人工髋关节置换术围手术期凝血、抗凝活性,探讨手术方式本身对凝血、纤溶活性的影响规律,为评估人工关节置换后的血栓性疾病并发症提供理论依据。方法:选择人工髋关节置换患者50例,分别于术前、术后即刻、术后24 h、术后3 d检测凝血指标(凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原),抗凝指标(抗凝血酶Ⅲ、抗Ⅱ因子活性),纤溶指标(D-二聚体),并进行分析比较。结果:术前、术后凝血酶原时间、活化部分凝血活酶时间比较差异无统计学意义(P>0.05),纤维蛋白原术后即刻减低(P<0.05),术后24 h,3 d增高(P<0.05);术后抗凝血酶Ⅲ、抗Ⅱ因子活性较术前降低(P>0.05);D-二聚体术后即刻、术后24 h增高(P<0.05),术后3 d恢复正常(P>0.05)。结论:人工髋关节置换术围手术期存在凝血活性增强,抗凝活性变化不明显、纤溶活性增强的失动态平衡状态,血栓性疾病的发生倾向明显增强。     

巴曲酶对突发性耳聋患者凝血及纤维蛋白溶解功能的影响

目的探讨巴曲酶对突发性耳聋患者凝血及纤维蛋白溶解功能的影响。方法选择突发性耳聋患者87例,在巴曲酶治疗前及治疗3、6d后检测患者凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（Fib）、D-二聚体及纤维蛋白（原）降解产物（FDP）。结果与治疗前比较,经巴曲霉治疗后,患者PT、TT延长（P〈0.05）,Fib降低（P〈0.01）,FDP升高（P〈0.01）,而APTT、D-二聚体的差异无统计学意义（P〉0.05）。结论 PT、TT、Fib、FDP可用于巴曲酶治疗突发性耳聋患者凝血及纤维蛋白溶解功能的监测。     

肿瘤患者凝血及纤溶状态的改变

目的 探讨恶性肿瘤患者凝血、抗凝及纤溶指标的变化及其临床意义。方法 用Culter ACL-200全自动血凝仪对35例正常对照,25例子宫肌瘤,98例恶性肿瘤(胃癌20例,结直肠癌21例,食道癌18例,肺癌19例,宫颈癌20例)的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fbg)、凝血酶凝固时间(TT)、抗凝血酶Ⅲ(AT-Ⅲ)、纤溶酶原(PLG)及α2-纤溶抑制物(α2-PI)进行检测。结果 恶性肿瘤组PT、APTT、TT水平较正常对照组增高,但无显著性差异;Fbg含量增高,AT-Ⅲ活性降低,PLC及2-PI活性增高,有显著性差异(p<0.05或p<0.01);恶性肿瘤有转移组与无转移组比较Fbg舍量增加、TT缩短、AT-Ⅲ、PLG及α2-PI活性均有显著性改变(p<0.05或p<0.01)。子宫肌瘤的上述指标与正常对照组之间无统计学差异。结论 恶性肿瘤凝血功能增强,抗凝及纤溶活性降低,机体处于高凝状态,有血栓形成倾向;恶性肿瘤有转移组纤溶活性增高则有助于恶性肿瘤转移。     

D-二聚体在膀胱肿瘤诊断中的应用及手术影响

目的探讨D-二聚体含量在膀胱肿瘤诊断中的应用及手术创伤对其含量的影响。方法通过定量酶联免疫吸附试验对43例膀胱移行细胞癌患者行D-二聚体测定。结果肿瘤患者血浆D-二聚体含量较非肿瘤患者及正常组明显增高（P＜0.01）,水后膀胱肿瘤患者及非肿瘤患者血浆D-二聚体含量较术前明显增高（P＜0.01）,肿瘤患者高于非肿瘤患者（P＜0.01）。结论膀胱肿瘤患者体内处于继发性纤溶活性增高状态。手术创伤可增强肿瘤患者和非肿瘤患者血浆纤溶活性增高状态。     

Plasminogen activator inhibitor 1: Molecular aspects and clinical importance

Plasminogen activator inhibitor-1 (PAI-1) is the major physiologic inhibitor of plasminogen activation in plasma and in the blood vessel wall. PAI-1 exhibits distinctive structural and functional properties that have been extensively studied over the past decade. Aside from the physiological role of PAI-1, there is accumulating evidence that increased production of PAI-1 may contribute to the development of ischemic cardiovascular disease. Efforts are now underway to develop and test specific inhibitors of PAI-1.     

慢性阻塞性肺疾病急性期凝血纤溶系统功能变化的临床研究

目的探讨慢性阻塞性肺疾病(COPD)凝血纤溶功能异常的可能机制。方法选择北京朝阳医院2006—2007年慢性阻塞性肺疾病急性期(AECOPD)住院患者38例,并选择同期47名健康体检者做对照,入选者采用酶联免疫吸附试验(ELISA)测定血浆血管性血友病因子(vWF)、组织因子(TF)、组织因子途径抑制物(TFPI)、凝血因子X、血栓调节蛋白(TM)、蛋白C、组织型纤溶酶原激活物(tPA)、纤溶酶原激活剂抑制物-1(PAI-1)及D-二聚体(D-dimer),发色底物法测定抗凝血酶Ⅲ(AT-Ⅲ)。测定AECOPD患者血气分析、血常规、血脂、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)及血浆纤维蛋白原(FBG)等指标。结果与对照组比较,AECOPD患者vWF、TF、凝血因子Ⅹ、D-dimer及tPA显著升高(P<0.01);TM及蛋白C显著下降(P<0.01)。而两组的AT-Ⅲ、TFPI及PAI-1比较,差异无统计学意义。结论AECOPD患者存在显著凝血纤溶功能失衡状态,在诊治AECOPD患者时,要充分考虑到患者存在的凝血纤溶功能异常,要注意监测相关凝血纤溶指标,对防治AECOPD有重要意义。     

Do determinants of platelet function co-segregate with genetic markers of type 1 diabetes mellitus?: Analysis of platelet and fibrinolytic parameters in families with type 1 diabetes mellitus

This study examined the significance of selected parameters of primary haemostasis to discriminate between relatives of children with insulin-dependent diabetes mellitus (IDDM). Platelet function, including markers of spontaneous and agonist-induced platelet activation (CD62), platelet consumption (microparticles) and clumping (aggregates), as well as selected parameters of the fibrinolytic system (t-PA and PAI-1), were studied in IDDM children (n = 45), their parents (n = 65), siblings (n = 17) and unrelated healthy controls (n = 51). The fraction of activated platelets circulating in whole blood amounted to 4.3±2.1% in IDDM children, and significantly exceeded the level found in parents (1.3±0.7%, P < 0.002), siblings (1.2±1.0%, P < 0.002), and controls (1.2±0.6%, P < 0.002). Furthermore, an enhanced formation of platelet microparticles was observed in the IDDM group, both in resting platelets and also when platelets were stimulated with thrombin. Significantly decreased total PAI-1 occurred in IDDM children (P < 0.02 versus parents); also slightly lowered active PAI-1 and t-PA antigen were noticed in IDDM subjects compared to other groups, however, the differences were not statistically significant. To assess dissimilarities between the groups of subjects we applied the forward stepwise model of discriminant function analysis, which included platelet flow cytometry parameters. The best separation and the highest discrepancy (expressed as the so called squared Mahalanobis distances, d_M) was revealed between controls and IDDM patients (P ? 0.0001) and between controls and parents (P ? 0.0001). The values of d_M found between IDDM children and their siblings (P < 0.001), as well as parents (P < 0.01), were of much lower significance. The finding that the control group, representing unrelated subjects, remains particularly well separated from the other groups, more or less clustered together, implies the possible involvement of genetic factor(s) which might potentially affect platelet activation and reactivity. In addition, the distinguished distribution of HLA DQAI⁵² and HLA DQBI⁵⁷ genotypes in the groups further validates the suspicion that the altered platelet function and response in diabetes might be associated with some independent genetic factor(s), and is not likely to result from HLA DQAI⁵² and HLA DQBI⁵⁷ impact.     

Enhanced Streptokinase-Induced Thrombolysis Using Heparin in a Rabbit Model

Heparin potentiation of clot lysis by streptokinase was studied in a rabbit model. Clot was initiated in the rabbit aorta with stasis and thrombin and allowed to naturally propagate proximally until stasis met flow. The clot was allowed to age for 1 h before assigning treatment. Fifteen rabbits (group I) were given streptokinase (10,000 IU/h) and 11 rabbits (group II) were given streptokinase (10,000 IU/h) plus sodium-heparin (120 IU/h). Thrombolytic therapy was continued for 5 h. Clot lysis averaged 30% in group I and 70% in group II. Ten of 11 rabbits in group II had more than 50% clot lysis, whereas only 4 of 15 in group I had this degree of lysis. One group II rabbit and four group I rabbits died prematurely; each was noted to have clot propagation at the time of death. While a trend for amelioration of hypofibrinogenemia was observed in the group receiving both streptokinase and heparin, this difference was not statistically significant. We conclude, in the animal model, that thrombolysis by a combination of heparin und streptokinase is more effective than streptokinase alone. Systemic effects are apparently no worse with the combination.     

The impact of fibrinolytic therapy for ST-segment-elevation acute myocardial infarction

Summary.  As privileged witnesses of the initiation and widespread use of reperfusion therapy the authors review the history of fibrinolytic therapy and of tissue-plasminogen activator (t-PA) more particularly and the current indications for its use in the era of mechanical reperfusion.