The medical management of acute coronary syndromes and potential roles for new antithrombotic agents

Antithrombic therapy is recommended to prevent ischemic complications in patients with high-risk non-ST-segment elevation acute coronary syndromes, including patients with unstable angina/non-ST-segment elevation myocardial infarction and patients with ST-segment elevation myocardial infarction undergoing fibrinolysis with fibrin-specific agents. Ischemic benefit from these agents must be balanced against an increased risk of bleeding, which may itself carry adverse long-term consequences. Recent trials suggest that the low-molecular-weight heparin enoxaparin may be superior to unfractionated heparin for preventing ischemic complications, although it also may be associated with an increase in bleeding risk. In two other contemporary trials, the Factor Xa inhibitor fondaparinux improved mortality and morbidity in patients with unstable angina/non-ST-segment elevation myocardial infarction and in patients with ST-segment elevation myocardial infarction undergoing fibrinolytic reperfusion, without increasing bleeding risk. These data underscore the promise of new antithrombotic agents to improve outcomes in acute coronary syndrome (ACS) patients being medically managed.     

Enhanced fibrinolytic activity during cardiopulmonary bypass in open-heart surgery in man is caused by extrinsic (tissue-type) plasminogen activator

The nature of the enhanced blood fibrinolytic activity which is known to occur during cardiopulmonary bypass is not understood. We show here that the cause is an increase in extrinsic (tissue-type) plasminogen activator. In six patients, the nature of the enhanced blood fibrinolytic activity that evolved during cardiopulmonary bypass was characterized by differential inhibition using the fibrin plate method and was shown to be C1-inactivator-resistant (extrinsic-activator activity). The C1-inactivator-resistant-activator activity was completely quenched by an antibody against extrinsic (tissue-type) plasminogen activator but not by antiurokinase, proving that the activity was due to the presence of extrinsic (tissue-type) plasminogen activator. The concentration of extrinsic (tissue-type) plasminogen activator increased during cardiopulmonary bypass and disappeared rapidly thereafter. Fibrinogen, plasminogen and alpha 2-antiplasmin were not consumed during cardiopulmonary bypass, while no increase or occasionally a moderate one in fibrinogen degradation products occurred. This is in accord with the property of extrinsic (tissue-type) plasminogen activator which activates plasminogen predominantly at sites where fibrin is present and not in the free circulation.     

凝血及纤溶指标检测与产后出血的关系研究

目的探讨常规凝血及纤溶指标的变化与产后出血的关系。方法对82例产后出血患者根据产后出血量的不同分为三组:少量出血组26例,出血量500～1 000 ml;大量出血组32例,出血量>1 000 ml;对照组24例,为正常孕产妇,出血量<500 ml。定量检测三组产时及产后48 h常规凝血指标血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)及D-二聚体(D-D)、血小板(PLT)、血红蛋白(HGB)。结果与对照组比较,少量出血组PT、APTT、TT、D-D均明显升高(P<0.05或P<0.01),而FIB、HGB、PLT均明显降低(P<0.05或P<0.01);与少量出血组比较,大量出血组PT、APTT、TT、D-D均明显升高(P<0.01),而FIB、HGB、PLT则明显降低(P<0.01)。结论产后及时监测常规凝血及纤溶指标的变化对于了解产妇机体凝血功能以及产后出血的发生从而降低孕产妇病死率具有重要意义。     

TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction

Thrombin-activatable fibrinolysis inhibitor (TAFI) was reported as an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). Its level in plasma appears to influence vascular disease. In addition, TAFI activity is strongly influenced by genetic polymorphism, especially at amino acids 147 and 325. We investigated whether these TAFI polymorphisms would act as a risk factor for cerebral infarction (CI) by examining 253 samples in which the diagnosis was cliniconeuropathologically confirmed. We found little that was statistically significant in terms of these polymorphisms among patients with no vascular problems or in a population-based control group. In the present study of an elderly Japanese group, our samples revealed a lower percentage of the Ile allele at Thr/Ile-325 compared with western counterparts. Although patients with severe infarcts had a lower percentage of the Ile allele (10%) at amino acid position 325 compared with the slightly and moderately affected patients and the population-based control group (15-18%), no statistical significance was found. None of our results showed any statistical correlation between TAFI polymorphisms and CI.     

Predictive Value of Inflammatory and Coagulation Parameters in the Course of Severe Ulcerative Colitis

Alterations in markers of coagulation have been found in patients with inflammatory bowel disease. Our aim was to study the predictive value of coagulation and inflammatory parameters in the course of severe ulcerative colitis. Twenty-seven patients were included. The disease course was followed for one year. Sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratio, as well as the clinical predictive value of laboratory variables were calculated. Inflammatory variables, such as ESR, CRP, and leukocyte and platelet count showed poor diagnostic accuracy. Several coagulation parameters, such as fibrinogen and fibrin(ogen) degradation products, were increased in patients with active ulcerative colitis, whereas coagulation factor XIII was decreased. No significant relationship between clinical course and coagulation parameters was demonstrated, though both inflammatory and coagulation parameters were useful in the assessment of disease activity in patients with active ulcerative colitis.     

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

Summary Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 β -estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA_1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA_1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL₂-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary. [Diabetologia (1997) 40: 843–849] Received: 12 November 1996 and in revised form: 21 March 1997     

MiR-340经组织型纤溶酶原激活剂调控施万细胞的纤溶能力

目的:探讨microRNA-340(miR-340)对施万细胞纤溶能力的调控作用及作用的靶基因。方法:采用溶圈实验来检测miR-340对施万细胞纤溶能力的影响,用荧光素酶双报告基因系统确定miR-340与组织型纤溶酶原激活剂的靶向关系,用实时定量聚合酶链反应检测坐骨神经夹伤后组织型纤溶酶原激活剂mRNA和miR-340的表达变化。结果:miR-340能够抑制施万细胞的纤溶能力,并直接靶向作用于组织型纤溶酶原激活剂的3’UTR,坐骨神经夹伤后组织型纤溶酶原激活剂mRNA与miR-340的表达呈负相关性。结论:miR-340通过直接靶向组织型纤溶酶原激活剂的3’UTR,从而下调靶基因组织型纤溶酶原激活剂的表达抑制施万细胞的纤溶能力。     

益气活血片对人工寒潮诱发脑卒中大鼠凝血和纤溶系统的影响

【目的】探讨益气活血片对人工寒潮促发脑卒中大鼠凝血和纤溶系统的影响。【方法】选用SD大鼠,随机分为4组,按照双肾双夹法复制易卒中型肾血管性高血压大鼠模型,中药组给予益气活血片（剂量为1.89 g·kg－1·d－1）,阳性对照组给予阿司匹林（剂量为80 mg·kg－1·d－1）,模型组及空白对照组给予等容积蒸馏水,从高血压模型复制术后14 d开始,每天1次,直到112 d后置于人工寒潮箱中3 d诱发卒中,取血检测血浆凝血酶激活的纤溶抑制物（TAFI）、蛋白C （PC）、凝血酶—抗凝血酶复合物（TAT）及纤溶酶（PAP）水平。【结果】与模型组比较,益气活血片组可显著降低血浆TAFI、 PC、 TAT、 PAP水平,差异均有统计学意义（P＜0.05）。【结论】益气活血片对脑卒中的防治作用与其能改善凝血和纤溶系统的平衡状态有关。