Development of the human coagulation system in the healthy premature infant

This study was designed to determine the postnatal development of the human coagulation system in the healthy premature infant. Consecutive mothers of healthy premature infants born at either St Joseph's Hospital or McMaster University Medical Centre in Hamilton were asked for consent. One hundred thirty-seven premature infants (30 to 36 weeks of gestational age) entered the study. The premature infants did not have any major health problems and did not require ventilation or supplemental oxygen. Demographic information and a 20-mL blood sample were obtained in the postnatal period on days 1, 5, 30, 90, and 180. Between 40 and 96 premature infants were studied on each day for each of the following tests: prothrombin time, activated partial thromboplastin time, thrombin clotting time, plasminogen; 13 factor assays [fibrinogen, II, V, VII, VIII, IX, X, XI, XII, XIII, high-mol-wt kininogen (HMWK), prekallikrein (PK), von Willebrand factor (vWF)] and eight inhibitors [antithrombin III (AT-III), heparin cofactor II, alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, C1 esterase inhibitor, protein C (PC), and protein S (PS)]. A combination of biologic and immunologic assays were used. Between 30 to 36 weeks there was a minimal effect of gestational age for levels of AT-III, PC, and factors II and X only; therefore, the entire data set was used to generate reference ranges for these components of the coagulation system for premature infants. Next, the results for the premature infants were compared with those of a previously published study in 118 fullterm infants and with those for adults. An effect of gestational age was shown for plasminogen, fibrinogen, factors II, V, VIII, IX, XI, XII, HMWK, and all eight inhibitors. In general, the postnatal maturation towards adult levels was accelerated in premature infants as compared with the fullterm infants. By 6 months of age, most components of the coagulation system in premature infants had achieved near adult values.     

Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit

Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor (PAI), D-dimer, euglobulin-clot-lysis-time (ECLT), plasminogen, alpha 2-antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II-score). An increase in D-dimer and t-PA-antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t-PA-activity was not detectable, PAI-function was elevated, the ECLT was prolonged and alpha 2-antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t-PA-antigen, PAI-function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II-score of the patients. We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, alpha 2-antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.     

Hemostatic and fibrinolytic effects of systemic prostaglandin E1 therapy in patients with peripheral arterial disease

BACKGROUND: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). PATIENTS AND METHODS: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global, plasminogen, plasminogen activator inhibitor activity (PAI), alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). RESULTS: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global, plasminogen, PAI, alpha 2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. CONCLUSION: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.     

A bleeding disorder due to deficiency of alpha 2-antiplasmin

A deficiency of alpha 2-antiplasmin has been identified in a female patient with severe and frequent bleeding episodes. Routine coagulation and platelet assays of the patient's plasma were within normal limits. However, abnormally rapid whole blood or dilute plasma clot lysis times and an abnormal FXIII test in which clots were lysed in the presence of urea or saline suggested an abnormal fibrinolytic system. Analysis of alpha 2-antiplasmin levels by radioimmunoassay revealed less than 1.0 microgram/ml alpha 2-antiplasmin. Functional assays indicated an alpha 2-antiplasmin level less than or equal to 10% of normal. Addition of purified alpha 2-antiplasmin to the patient's plasma restored its ability to inhibit plasmin in in vitro assays, and mixtures of patient plasma with normal plasma did not interfere with the antiplasmin activity of the normal plasma. Whereas normal platelets contain 68 ng alpha 2-antiplasmin/10(9) platelets, platelets from the patient contained 30% of the normal level of antigen. Analysis of alpha 2- antiplasmin functional and antigenic levels in the plasma of both parents and four siblings of the propositus provided evidence consistent with an autosomal mechanism of inheritance of alpha 2- antiplasmin deficiency. One sibling appeared to be homozygous and three siblings and the parents were heterozygous for the deficiency. Two heterozygotes had positive bleeding histories. The association of a bleeding disorder with a deficiency of alpha 2-antiplasmin emphasizes that lack of regulation of the fibrinolytic system can result in a hemostatic dysfunction.     

Components of the fibrinolytic system are differently altered in moderate and severe hypothyroidism

T(4) levels are determinant of several components of the fibrinolytic system. However, relationships between hypothyroidism and alteration of fibrinolytic capacity are not well established, and published data remain conflicting. As the impact of hypothyroidism on both degradation and synthesis of proteins may vary according to the severity of the disease, we measured fibrinolytic activity across varying states of hypothyroidism. We measured fibrinogen, D-dimers (DDI), alpha(2)-antiplasmin activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen, plasminogen activator inhibitor antigen (PAI-1 Ag), and factor XII (FXII) of the coagulation. We prospectively included 76 middle-aged female subjects: 25 controls, 24 patients displaying moderate hypothyroidism (TSH, 10--50 mU/L), and 27 patients with severe hypothyroidism (TSH, >50 mU/L). Blood pressure, body mass index, smoking habits, total cholesterol as well as high and low density lipoprotein subfractions, triglyceride, fasting glycemia, and insulinemia were recorded. We found a different pattern of fibrinolytic abnormalities according to the severity of hypothyroidism. Compared with controls, patients with moderate hypothyroidism displayed a decreased fibrinolytic activity, as reflected by lower DDI levels, higher alpha(2)-antiplasmin activities, and higher levels of t-PA and PAI-1 Ag. In sharp contrast, patients with severe hypothyroidism exhibited higher DDI levels, lower alpha(2)-antiplasmin activities, and lower t-PA and PAI-1 Ag levels. These results were not accounted for by confounding factors such as age, smoking, and components of the insulin resistance syndrome. Free T(4) was significantly associated with fibrinogen, alpha(2)-antiplasmin, PAI-1 Ag, total cholesterol, and triglyceride and was negatively associated with DDI. The main hypotheses underlying the mechanisms by which thyroid status may affect the fibrinolytic system remain to be established. In conclusion, patients with moderate hypothyroidism, who were consistently shown to be at high risk for cardiovascular disease, have decreased fibrinolytic activity. Subjects with severe hypothyroidism have a tendency toward increased fibrinolytic activity, and these modifications may participate to the bleeding tendency observed in such patients.     

Study of fibrinolytic parameters in different types of polycythemia

Polycythemia vera (PV) is a myeloproliferative disorder characterized by thrombotic and, less often, bleeding complications. Many mechanisms have been advanced to explain the occurrence of these complications, none of them satisfactory. We examined a cohort of 27 patients with PV, secondary erythrocytosis, and essential thrombocythemia for coagulation and fibrinolytic parameters, including euglobulin lysis test, D-dimer, and alpha2 antiplasmin. Ten of the 27 patients developed one or more thrombotic complications during the study. We found no clinical correlation between the studied parameters and the complications. Three patients, one of each group, with elevated serum alpha2 antiplasmin levels, developed severe arterial or venous thromboses.     

Effects of pulsatile and nonpulsatile perfusion mode during extracorporeal circulation--a comparative clinical study.

In a prospective randomized study with 80 male patients scheduled for aorto-coronary bypass grafting we investigated the influence of pulsatile and nonpulsatile perfusion mode on cell count (leukocytes, platelets, hematocrit), concentrations of thromboxane (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), plasma hemoglobin, PMN-elastase, complement C3a, clotting factor XII, lactate, plasmatic inhibitors (C1-INH, AT-III, alpha 2-antiplasmin), arterio-venous oxygen difference (AVDO2) and hemodynamic parameters. Changes in hematocrit were similar in both groups, whereas plasma hemoglobin concentration was significantly higher with pulsatile perfusion. Platelet count paralleled changes in hematocrit and was not influenced by the perfusion mode. Leukocyte count as well as concentrations of PMN-elastase and C3a showed a strong increase during cardiopulmonary bypass, but there were no significant differences between the two groups. Similar changes of the concentrations of TXB2 and 6-keto-PGF1 alpha were noted irrespective of the perfusion mode applied. The observed alterations in the concentrations of clotting factor XII, alpha 2-antiplasmin, AT-III and C1-INH largely paralleled hematocrit changes in either flow mode. Significant differences between the two groups were found with lactate: with nonpulsatile perfusion there was a slight but continuous increase, while with pulsatile flow lactate levels remained unchanged. There was no evidence for a better oxygen uptake (AVDO2) with pulsatile perfusion. Pulsatile perfusion seems to be advantageous to tissue perfusion, however, at the cost of a higher rate of hemolysis. We cannot confirm further salutary effects of the pulsatile perfusion mode with the 1-pump-system on cellular and humoral blood constituents.(ABSTRACT TRUNCATED AT 250 WORDS)     

肝硬化患者凝血、抗凝及纤溶指标的变化与Child-Pugh分级的关系

目的 探讨肝硬化患者凝血、抗凝及纤溶指标的变化及其与Child-Pugh分级的关系。 方法肝硬化患者43例,Child-Pugh分级A级13例,B级15例,C级15例。正常对照组16例,男11例,女5例。均检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)、凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、血管性假性血友病因子(vWF)、抗凝血酶-Ⅲ(AT-Ⅲ)、蛋白-C(PC)、D-二聚体(D-d)、组织纤溶酶原激活物(t-PA)抗原和组织纤溶酶原激活物抑制剂(PAI)。 结果 PT、APTT随病情加重而显著延长,F值分别为32.828和18.743,P值均<0.01;Fib随病情加重逐渐降低,F=4.747,P<0.01。凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅸ、Ⅹ随病情加重活性逐渐降低,F值分别为43.129、12.677、36.405、9.380和21.988,P值均<0.01。Ⅷ、vWF因子随病情加重活性逐渐增高,F值分别为16.672和14.657,P值均<0.01。AT-Ⅲ、PC随病情加重活性逐渐降低,F值分别为22.602和15.430,P值均<0.01。D-d、t-PA抗原随病情加重逐渐增高,F=5.957,P<0.05。PAI活性正常对照组和3组患者检测结果近似,差异无统计学意义。 结论 肝硬化患者存在明显的凝血、抗凝血以及纤溶机制的异常,且与肝硬化程度密切相关。在防治肝硬化患者出血时,不仅要纠正患者的凝血因子异常,还要给予一定的抗纤溶治疗。     

不稳定心绞痛血凝/纤溶系统变化临床研究

目的 探讨对强化药物治疗反应不同的两组不稳定性心绞痛病人血凝及纤溶指标变化规律，及其在不稳定性心绞痛危险度分层中的意义。方法 不稳定心绞痛病人共163例作为治疗组（UA组），依强化治疗72小时病情是否得到良好控制分为UAA、UAB两个亚组，另20例稳定性心绞痛为对照组SA组，所有病例均进行凝血酶原时间（PT）、分凝血活酶时间（APTT）、纤维蛋白原（FG）、D－二聚体（DD）测定，并于第3天、5天、7天、10天UA再重复测定上述指标。随访90天内被迫采取心脏介入治疗、发生心肌梗死及死亡情况。结果 临床首次检测结果均提示PT、APTT在UAA、UAB与SA间无差异、也无预后意义（P＞0.05)，UAA组FG血液浓度水平于病程经五天达高峰后迅速下降，而DD血液浓度水平于第三天后开始逐步下降；UAB组则FG、DD血液浓度水平至病程第十天则仍然保持它们在第5天及第3天的高峰水平，UAA、UAB两组病人的短期预后亦有明显差异（P＜0.05)。结论 DD、FG血液浓度水平在起病后前十天保持高水平是难治性不稳定性心绞痛的血液学标志，同时也是提示病人近期预后较差的预报因子。     

冠心病患者抗凝与纤溶功能的改变及其临床意义

目的：探讨冠心病患者凝血、抗凝与纤溶功能的改变及临床意义。方法：应用发色底物法及胶乳增强的免疫比浊法分别测定不同类型的冠心病患者160例及健康对照者80例血浆抗凝血酶（AT）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活抑制物-1（PAI-1）及D-二聚体（D-dimer）的活性或含量水平,并进行比较分析。结果：与对照组比较,冠心病患者AT、t-PA的活性显著降低,PAI-1、D-dimer的活性或含量水平显著增高（P〈0.05或P〈0.01）;与稳定性心绞痛患者组比较,不稳定性心绞痛组及心肌梗死组AT、t-PA、PAI-1、D-dimer的活性或含量水平亦有显著性改变（P〈0.05或P〈0.01）。结论：冠心病患者特别是不稳定性心绞痛及心肌梗死患者存在高凝状态及纤溶活性亢进。     

凝血纤溶指标的变化与缺血性心脏病的关系

目的：探讨缺血性心脏病患者的凝血、纤溶变化及其临床意义，并对部分患者跟踪观察。方法：用高效液相色谱仪测定２６例急性心肌梗死患者，２６例不稳定性心绞痛患者，以及２０例正常人的尿纤维蛋白肽Ａ（ＦＰＡ）；并用相应方法同步测定了血浆Ｄ－二聚体（Ｄ－ｄｉｍｅｒ）含量、组织型纤溶酶原激活物（ｔＰＡ）及其抑制剂（ＰＡＩ）活性。结果：急性心肌梗死、不稳定性心绞痛患者较正常对照组尿纤维蛋白肽Ａ值增高，血浆Ｄ－二聚体水平、ＰＡＩ活性升高，ｔＰＡ活性降低。且急性心肌梗死与不稳定性心绞痛患者之间上述指标也存在显著性差异。结论：研究结果提示凝血纤溶系统的变化在缺血性心脏病的发生、发展中起着重要作用，研究凝血、纤溶指标对探讨其发病机制及判断预后可能有一定帮助。     

Thrombin formation and fibrinolytic activity in patients with acute myocardial infarction or unstable angina: in-hospital course and relationship with recurrent angina at rest

OBJECTIVES

The goal of this study was to investigate possible differences in thrombin generation or fibrinolytic capacity in patients with unstable angina (UA) or acute myocardial infarction (AMI) with or without recurrent angina at rest.

BACKGROUND

Angina at rest in patients with AMI or UA is generally produced by a reduction in coronary flow, but it is unclear whether patients with or without this event differ in their thrombin generation or in their fibrinolytic capacities, which might influence the course of the culprit lesion.

METHODS

Thrombin-antithrombin complex (TAT), D-dimer, fibrinogen and plasminogen activator inhibitor (PAI-1) antigen plasma levels were determined in 40 patients with AMI and in 23 with UA on admission, at 10 days and at three months.

RESULTS

First day values for TAT, fibrinogen and D-dimer were comparable in patients with AMI and in those with UA. At 10 days they increased significantly in each group, and at 3 months they decreased to a similar extent. First day PAI-1 levels, however, were highest in both groups and declined in AMI patients at 10 days and at three months, whereas they also decreased at 10 days in UA patients but not any further at three months. Ten patients with AMI (25%) and 12 with UA (52%) developed in-hospital angina at rest. First day values for TAT, fibrinogen and D-dimer were similar in patients with or without angina, but PAI-1 levels were higher in the former subset (p < 0.008). At 10 days, however, TAT (p < 0.013) and D-dimer (p < 0.013) were higher in patients who developed angina than in those who did not.

CONCLUSIONS

The higher inhibition of fibrinolytic activity in the first day in patients with AMI or UA who will develop recurrent angina suggests that maintenance of a prothrombotic status may contribute to its mechanisms, perhaps by preventing passivation of the culprit thrombus/plaque. This is consistent with greater thrombin generation and greater levels of fibrynolitic products at 10 days observed in these patients compared with those who attain early stability.     

Activation of clotting factors XI and IX in patients with acute myocardial infarction

In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.     

The effects of perioperatively administered crystalloids and colloids on concentrations of molecular markers of activated coagulation and fibrinolysis.

To explore whether intravenous administration of routinely used crystalloid or colloid solutions differently affects the coagulation system, we investigated orthopaedic patients. Since crystalloid solutions might cause hypercoagulability, we here present our results on molecular markers of coagulation and fibrinolysis. Patients undergoing knee replacement surgery randomly received isovolemic amounts of lactated Ringer's solution, 6% hydroxyethyl starch 200/0.5 or 4% modified gelatine. Arterial blood samples for determination of specific molecular markers of activated coagulation (thrombin/antithrombin complex, D-dimer, prothrombin fragment F1 + 2), fibrinolysis (plasmin/alpha 2-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1), and concentrations of coagulation factor XIII were obtained at baseline, before tourniquet release, at the end of surgery and 2 h after operation. During the observation period, thrombin/antithrombin complex increased from 4.8 to 54.7 microg/l, D-dimer increased from 0.3 to 6.0 mg/ml, prothrombin fragment F1 + 2 increased from 1.7 to 5.9 nmol/l, tissue plasminogen activator decreased from 7.3 to 6.7 ng/ml, plasminogen activator inhibitor-1 increased from 68.4 to 71.0 ng/ml, plasmin/alpha 2-antiplasmin complex increased from 281.5 to 884 microg/l and factor XIII decreased from 89.0 to 58.5%. All parameters changed significantly but without any detectable difference in the response profile between the groups receiving different intravenous fluids. During knee replacement surgery a pronounced activation of the coagulation/fibrinolytic system was observed, regardless of whether patients received crystalloid or colloid fluids. Thus, these results cannot confirm the hypothesis that crystalloid fluids per se cause hypercoagulability in vivo.     

Coagulation and fibrinolysis in thyroid disease.

The levels of components of the coagulation mechanism and fibrinolytic system in 20 hyperthyroid patients and 9 hypothyroid patients were compared with those of 20 euthyroid control subjects. The mean levels of fibrinolytic activity and plasminogen were significantly reduced in the hyperthyroid patients while mean levels of alpha1-antitrypsin and C1 inactivator were increased. Patients with hypothyroidism had significantly increased levels of fibrinolytic activity and alpha2-macroglobulin, a prolonged partial thromboplastin time, and reduced levels of factor XII and antithrombin III.     

卡托普利对冠心病患者内源性纤溶系统活性的影响

目的探讨卡托普利对不稳定性心绞痛（ＵＡＰ）和急性心肌梗死（ＡＭＩ）患者内源性纤溶系统的影响及其临床意义。方法４０例ＡＭＩ和ＵＡＰ患者随机分为卡托普利组和对照组。采用发光底物显色方法,检测两组治疗前和治疗后第３、７、１４、２１天血浆组织型纤溶酶原激活剂（ｔＰＡ）及其抑制物（ＰＡＩ）的活性。结果治疗前血浆ｔＰＡ活性呈现正常人＞ＵＡＰ＞ＡＭＩ患者,ＰＡＩ活性则相反,而且ＡＭＩ与ＵＡＰ,ＵＡＰ和正常人同项比较均有显著性差异（Ｐ＜０．０１）。卡托普利组血浆ＰＡＩ活性降低,ｔＰＡ活性增强,与治疗前和对照组同期比较差异显著（Ｐ＜０．０５,０．０１）。结论卡托普利增强冠心病患者内源性纤溶系统活性。     

Regional left atrial coagulation and fibrinolytic activities in patients with mitral stenosis

Systemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05). The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation.     

Intra- and postoperative fibrinolysis in patients undergoing cardiopulmonary bypass surgery

The influence of cardiopulmonary bypass (CPB) on fibrinolytic activity was assessed in 100 patients with valvular heart disease or atrial septal defects. Euglobulin fibrinolytic activity (EFA), tissue type plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 2-antiplasmin (alpha 2-AP), fibrinogen degradation products (FDP), and D-dimer were measured pre-, intra-, and postoperatively. There were significant increases in EFA and t-PA activity (p less than 0.002), and decreases in plasminogen and alpha 2-AP (p less than 0.0001) intraoperatively with respect to baseline values. t-PA activity decreased significantly after surgery (p less than 0.002), whereas PAI-1 activity showed a marked increase shortly after operation and on postoperative day 1 (p less than 0.0001). FDP and D-dimer levels were significantly increased both intra- and postoperatively, the latter showing higher values (p less than 0.01 and p less than 0.0001, respectively). This study shows that there is an activation of the fibrinolytic system, as a result of the increased activation of plasminogen and decreased levels of plasmin inhibitors, during CPB surgery followed by a postoperative fibrinolytic shutdown.     

纤溶指标的变化与急性冠状动脉事件的关系

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Severity of coronary artery disease and basal fibrinolysis

Basal venous blood levels of several components of the fibrinolytic enzyme system (plasminogen activator, plasminogen, fibrin degradation products, alpha 2-antiplasmin, and alpha 2-macroglobulin) were measured in 100 white men with angiographically defined coronary artery disease. The tests of fibrinolysis were not related to the severity of coronary artery disease, as indicated either by the number of vessels involved or by a coronary score system. Fibrinogen levels, however, did show a modest association with the extent of coronary atheroma (r = 0.21, p less than 0.05). Triglyceride levels were associated with the inhibitors of fibrinolysis: positively with alpha 2-antiplasmin (r = 0.31, p less than 0.005) and negatively with alpha 2-macroglobulin (r = -0.25, p less than 0.05). The alpha 2-antiplasmin levels were significantly elevated in patients with hypertriglyceridaemia. Neither smoking nor beta-blockade had any effect on the tests of fibrinolysis. This study adds support to the association of plasma fibrinogen with ischaemic heart disease.