von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction

Background—Haemostasis plays a major part in the process initiating a myocardial infarction. The impact of haemostatic variables on long term prognosis is unknown.
Objective—To evaluate von Willebrand factor (vWF), tissue plasminogen activator antigen (t-PA) and its activity before and after venous occlusion, plasminogen activator inhibitor (PAI-1), dehydroepiandrosterone sulphate (DHEAS), and established clinical risk factors as long term predictors for reinfarction and mortality.
Patients—123 consecutive survivors of myocardial infarction followed up for 10 years.
Design—Study entry took place between 1982 and 1983. Fifty seven patients died (54 of cardiovascular disease) during the mean observation time of 10 years.
Results—Cox's univariate regression analysis showed that cardiovascular mortality was significantly associated with age, hypertension, previous history of angina pectoris, DHEAS, mass concentration of t-PA, and vWF. These associations were significant for vWF and mass concentration of t-PA after adjusting for age and hypertension.
Conclusions—A low concentration of DHEAS and high levels of the endothelially derived haemostatic variables vWF and mass concentration of t-PA are predictors of cardiovascular mortality in survivors of myocardial infarction. This association is independent of established clinical risk factors for mass concentration of t-PA and vWF.

Keywords: myocardial infarction;  risk factors;  fibrinolysis;  tissue plasminogen activator;  plasminogen activator inhibitor;  von Willebrand factor;  dehydroepiandrosterone sulphate     

Pre-Hospital Fibrinolysis Followed by Angioplasty or Primary Angioplasty in Acute Myocardial Infarction: The Long-Term Clinical Outcome

BACKGROUND: Randomized trials comparing primary angioplasty and in-hospital fibrinolysis in acute myocardial infarction (AMI) have shown an advantage for primary angioplasty. The long-term follow-up of pre-hospital fibrinolysis followed by elective or rescue coronary angioplasty versus primary angioplasty is not well established after acute myocardial infarction. This study sought to assess the long-term clinical outcome of patients with AMI having either received pre-hospital fibrinolysis optimized by coronary angioplasty or primary angioplasty. METHODS: We conducted a retrospective analysis involving 318 patients who either underwent primary angioplasty ( n = 157) or received pre-hospital fibrinolysis followed by an angioplasty (rescue or elective) ( n = 161) within 6 hours of the onset of chest pain. RESULTS: The groups were similar regarding their baseline characteristics except for the ages. No difference was noted for in-hospital mortality (primary PTCA group: 2.48%, combined group: 2.54%; p = ns) with no increased risk of hemorrhage. The 3-year mortality was not significantly different in the two groups (9.7% vs. 4.9%; p = 0.15). Regarding major adverse cardiac events (29.5% vs. 37.5%; p = 0.23), reintervention (22.5% vs. 23.2%; p = 0.99) or target lesion revascularization (16.1% vs. 14.7%; p = 0.68), the groups were statistically similar. CONCLUSION: These data from real-life practice emphasize the safety and similar benefits on the long-term clinical outcome of AMI patients having undergone either pre-hospital fibrinolysis followed by angioplasty or primary angioplasty.     

On-demand but not prophylactic treatment with FVIII concentrate increase thrombin activatable fibrinolysis inhibitor activation in severe haemophilia A patients

Introduction: Thrombin activatable fibrinolysis inhibitor (TAFI) down‐regulates fibrinolysis after activation by thrombin/thrombomodulin. We investigated the effect of treatment with FVIII concentrate on plasma levels of pro‐TAFI and activated TAFI in haemophilia A patients. Methods: Samples were collected pre and posttreatment from patients treated prophylactically or on‐demand. Pro‐TAFI, TAFI/TAFIi and FVIII levels were measured in all samples. Results: Treatment had no effect on pro‐TAFI levels. Pro‐TAFI was similar in both patient groups but higher than in controls. Patients from the prophylactic treatment group had measurable FVIII levels pretreatment while in the treatment‐on‐demand group FVIII levels were ≤0.01 IU/mL. In the prophylactic treatment group, the levels of TAFI/TAFIi were significantly lower pre‐ and posttreatment (4.31 ± 3.14 and 3.48 ± 2.65 ng/mL respectively) than in the on‐demand group (13.02 ± 3.47 and 14.87 ± 3.47 ng/mL respectively). This difference may be due to release of tissue factor at the injury site in the on‐demand group. This could induce thrombin and TAFI activation within the clot counterbalancing fibrinolysis in these patients. In the prophylactic group, no injury existed, thus there was insufficient thrombin generation within the clot to activate TAFI. Conclusion: These findings suggest that in patients to whom FVIII is administered on demand the fibrinolysis activity is more down regulated than in patients following a prophylactic treatment regime.     

凝血酶激活的纤溶抑制物编码区基因多态性与心肌梗死相关性探讨

目的：探讨TAFI编码区基因单核苷酸多态性与心肌梗死（MI）的关系。方法：应用聚合酶链反应-限制性内切酶片段长度多态性分析技术（PCR-RFLP）检测100例MI患者和90例正常对照者的CPB2基因2个位点G505A和C1040T的多态性。结果：CPB2基因G505A位点的3种基因型（G505G、G505A、A505A）频率在MI组和对照组分别为35（35%）、54（54%）、11（11%）和32（35.6%）、46（51.1%）、22（24.4%）,等位基因G、A频率在MI组和对照组分别为124（62.0%）、76（38.0%）和110（61.1%）、70（38.9%）;C1040T位点的3种基因型（C1040C、C1040T、T1040T）频率在MI组和对照组分别为32（32%）、53（53%）、15（15%）和31（31.4%）、49（54.4%）、10（11.2%）,等位基因C、T频率在MI组和对照组分别为117（58.5%）、83（41.5%）和111（61.7%）、69（38.3%）,2组之间基因型及等位基因频率分布差异无统计学意义（G505A位点：χ^2=1.6757,P=0.8524;χ^2=0.7881,P=0.6973;C1040T位点：χ^2=0.6482,P=0.3958;χ^2=0.7231,P=0.5291）。结论：编码TAFI的CPB2基因2个位点G505A和C1040T的基因多态性与MI没有明显关系。     

动态监测D-二聚体及凝血-纤溶参数对深静脉血栓的意义

目的：观察D-二聚体（DD）动态变化及凝血-纤溶参数对开胸术后深静脉血栓（DVT）的意义．方法：选择40例开胸手术（食管癌根治术和肺叶切除术）患者,于术前、关胸时、术后1d、术后3d行血浆DD、纤维蛋白原（FIB）、凝血酶原时间（PT）、部分凝血活酶时间（APTT）、凝血酶时间（TT）及凝固启动时间（CST）、最大凝固程度（MCE）、凝血达峰值时间（MCT）、平衡时间（BLT）和全反应时间（WFT）等凝血-纤溶图参数进行检测．术前所有患者下肢深静脉彩超检测均阴性．根据术后4—7d下肢彩超检测结果将患者分为血栓（T）组（n=13）和非血栓（NT）组（n=27）．结果：与NT组比较,T组DD关胸及术后各时点均明显升高（P〈0．01～0．05）,FIB术后3d明显增加（P〈0．05）;与基础值比较,两组DD,FIB,MCE,BLT,WFT、术后各时点均明显升高（P〈0．01—0．05）,而PT,APTT均于术后1d明显缩短（P〈0．01—0．05）,TT于术后3d明显缩短（P〈0．01）．结论：血浆DD动态监测对开胸术后并发DVT具有早期诊断价值,而凝血-纤溶参数对预测DVT的形成无指导意义;且所有参数均提示术后血液呈高凝状态．     

严重创伤失血性休克患者复苏前凝血纤溶功能的变化及其意义

目的探讨严重创伤失血性休克患者复苏前凝血纤溶功能的变化及其意义。方法108例严重创伤失血性休克患者按照简明损伤标准与损伤严重度评分（AIS-ISS）分为S1组（ISS〈25分）69例和S2组（ISS≥25分）39例;根据创伤后至开始有效复苏时间分为5组：A组（≤30min）35例、B组（30min〈t≤2h）28例、C组（2h〈t≤4h）20例、D组（4h〈t〈8h）15例、E组（t≥8h）10例。分别检测各组凝血酶原时间（PT）、部分活化凝血酶原时间（APTT）、纤维蛋白原浓度（FB）、D-二聚体（D-D）浓度、抗凝血酶活性（AT：A）和纤溶酶原活性（PLG：A）;并与对照组（健康体检者）进行对照。结果A、D、E3组PT、APTT、FB、D-D、AT：A、PLG：A值与对照组比较差异均有统计学意义（P〈0．05或P〈0．01）;B组D-D、AT：A、PLG：A值与对照组比较差异均有统计学意义（P〈0．05或P〈0．01）,而PT、APTT、FB值与对照组比较差异均无统计学意义（均P〉0．05）;C组PT、D-D、AT：A、PLG：A值与对照组比较差异均有统计学意义（P〈0．05或P〈0．01）,而APTT、FB值与对照组比较差异均无统计学意义（均P〉0．05）;S1、S2组PT、APTT、FB、D-D、AT：A、PLG：A值与对照组比较差异均有统计学意义（P〈0．05或P〈0．01）,S2组PT、FB、D-D、AT：A、PLG：A值与S2组比较差异均有统计学意义（均P〈0．01）。结论严重创伤失血性休克后凝血纤溶系统出现明显异常,并随休克时间的长短而有不同的改变;凝血纤溶系统的异常可能与创伤严重程度有关。     

Depression of factor XII-dependent fibrinolytic activity in survivors of acute myocardial infarction at risk of reinfarction

Defective fibrinolysis may constitute a risk for the developmentof myocardial infarction in patients with ischaemic heart disease.We studied prospectively the factor XII-dependent plasminogenproactivator system in 49 survivors of an acute myocardial infarction.Blood samples were collected 8 weeks after hospital discharge.The factor XII-dependent fibrinolytic activity in the specimenswas determined on fibrin plates after complete immuno-inhibitionof the urokinase-like and the t-PA related fibrinolytic systems.During the subsequent follow-up period of 2.4 years, 10 patientsdeveloped recurrent myocardial infarction, whereas the remaining39 patients did not. The reinfarction group of patients hada signficantly lower median factor XII-dependent fibrinolyticactivity (24.9 blood activating units (BAU) . ml^–1) thanthe patients without a relapse (41.9 BAU . ml^–1, P <0.02). Plasma concentrations of factor XII did not deviate significantlybetween the groups (P > 0.05), whereas the median plasmaconcentrations of prekallikrein was slightly lower in the reinfarctiongroup (90%) than in the non-reinfarction group of patients (105%,P < 0.02). These observations point to an association betweena depressed factor XII-dependent fibrinolytic activity and anenhanced risk of reinfarction in patients with a previous episodeof acute myocardial infarction.     

高血压患者胰岛素抵抗与纤溶系统的关系

目的　研究高血压病 (EH)患者胰岛素抵抗 (IR)与纤溶系统的关系。方法　EH病人 71例 ,采用 75g葡萄糖口服负荷法 (OGTT) ,将EH患者分为糖耐量正常组 (NGT) 44例和糖耐量异常组 (IGT) 2 7例 ,正常对照组 3 1例。测定血浆组织型纤溶酶原激活物活性 (t PA)、纤溶酶原激活物抑制物 -1活性 (PAI 1)、纤溶酶原活性 (PLG) ,在OGTT测定的同时作血胰岛素 (INS)测定 ,并根据Cederholm公式计算出胰岛素敏感指数 (ISIc)。结果　NGT组和IGI组相比t PA无明显差别 (P >0 0 5) ,但两组均较正常对照组降低 (P <0 0 5)。NGT组和IGT组PAI -1与正常对照组比较均无明显差别 (P >0 0 5)。IGT与NGT相比PLG增高 (P <0 0 5) ,与正常对照比较PLG明显增高 (P <0 0 1)。ISIc在NGT组和IGT组较正常对照组明显降低 (P <0 0 5,P <0 0 1) ,且IGT组较NGT组更低 (P <0 0 1)。ISIc与t PA ,PAI 1不相关。结论　高血压病人存在胰岛素抵抗 ,当高血压病合并IGT时 ,胰岛素抵抗更明显。EH病人存在纤溶活性的下降 ,当合并IGT时 ,纤溶活性的降低更为明显。t PA和PAI 1与ISIc无明显相关性     

Out-of-hospital treatment of acute myocardial infarction in Andalusia, Spain

INTRODUCTION AND OBJECTIVES: Clinical trials and meta-analyses have shown that out-of-hospital thrombolysis is effective. Our objectives were to investigate out-of-hospital emergency management of acute myocardial infarction by paramedical teams and to identify factors associated with out-of-hospital use of fibrinolytic therapy. PATIENTS AND METHOD: The study made use of a registry of all patients with ST-segment elevation acute coronary syndrome who were diagnosed and treated out of hospital by emergency paramedical teams in Andalusia, Spain in the 2-year period: 2001-2002. Follow-up was carried out during hospital admission and after one month. RESULTS: The study included 981 patients, mean age 65 [13] years, 777 male (79.2%). In total, 152 (15.5%) received out-of-hospital thrombolysis; 18% within the first hour, and 68% within the first 2 hours following symptom onset. No hemorrhagic stroke was observed following thrombolysis. During hospitalization, 206 (21%) patients died, eight (0.8%) of whom had received out-of-hospital thrombolysis. Factors associated with the administration of out-of-hospital thrombolysis included: age under 55 years (P<.0001), normal systolic blood pressure (odds ratio = 6.825; 95% confidence interval, 2.442-19.069), and an in-hospital diagnosis of anterior acute myocardial infarction (P<.022). CONCLUSIONS: The administration of out-of-hospital thrombolysis by emergency paramedical teams enables treatment to be administered within the optimum time interval. Mortality during hospital admission is lower in this subgroup of patients than in those who did not receive out-of-hospital thrombolysis. Moreover, the low complication rate observed indicates that the procedure is safe. However, the patients who received out-of-hospital thrombolysis appeared to be those at a lower risk.     

Fibrinolytic inhibitor levels and polymorphisms in Behçet disease and their association with thrombosis

This study aimed to assess the fibrinolytic inhibitors and their association with thrombosis in Behçet disease. Thrombin activatable fibrinolysis inhibitor (TAFI) (P < 0·001) and plasminogen activator inhibitor‐1 (PAI‐1) levels (P = 0·022) were significantly higher in 79 patients than in 84 controls. No significant differences were observed in CPB2 (TAFI) Thr325Ile and SERPINE1 (PAI1) 4G/5G polymorphism distribution between patients and controls. TAFI activity levels were significantly higher in patients with thrombosis than in those without thrombosis (P = 0·024). In conclusion, the increased TAFI levels in Behçet disease could contribute to the increased risk of thrombosis observed in these patients.