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.     

Coagulation, fibrinolytic, and inhibitory proteins in acute myocardial infarction and angina pectoris.

BACKGROUND AND METHOD: The role of thrombus formation in the pathogenesis of acute myocardial infarction (AMI) and unstable angina pectoris has been well established. However, comprehensive and systematic studies of the blood coagulation, fibrinolytic, and inhibitory proteins are not available in patients with these conditions. Fourteen patients with AMI, 10 patients with angina pectoris, and 32 normal volunteers were studied. Plasma antigen concentrations and/or activities of high-molecular-weight kininogen (HMWK), fibrinogen, fibronectin, plasminogen, D-dimer, tissue plasminogen activator (t-PA), alpha 2-antiplasmin, alpha 2-macroglobulin, alpha 1-antitrypsin, protein C, total and free protein S, antithrombin III (AT-III), von Willebrand factor (vWF), factors (F) XII, XI, IX, VIII, VII, X, V, II, and XIII, and plasma antiplasmin activity were measured using appropriate functional or immunologic assays. RESULTS: The AMI group showed a significant reduction in F XII activity, F XII activity-to-concentration ratio, and HMWK concentration. In addition, the AMI patients exhibited a significant elevation of plasma F XI activity, F IX concentration, and F IX activity, and vWF, fibrinogen, D-dimer, and t-PA concentrations. This was associated with significant reductions in F V, F II, and AT-III activity-to-concentration ratio. Many of the changes observed in AMI patients were also present in patients with angina pectoris. Furthermore, the latter group exhibited an elevation of F VIII activity, alpha 2-macroglobulin activity, and alpha 1-antitrypsin concentration and a significant reduction of antiplasmin activity despite a normal alpha 2-antiplasmin concentration. CONCLUSIONS: The observed reduction of the plasma F XII activity-to-antigen concentration ratio combined with a reduced HMWK concentration suggests intrinsic pathway activation, while the elevation of the D-dimer concentration indicates thrombin generation and fibrin formation and degradation in the AMI group. The latter changes were also present in patients with angina pectoris. Both AMI and angina groups showed several other abnormalities of the coagulation, fibrinolytic, and inhibitory systems. The results suggest the presence of a prothrombotic state associated with the activation of coagulation and fibrinolytic systems in patients with acute myocardial ischemia or infarction.     

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.     

老年前列腺癌患者去势后性激素水平变化及对凝血和纤溶系统的影响

目的探讨老年前列腺癌患者去势后性激素水平变化及对血液凝血和纤溶系统活性的影响。方法27例早期前列腺癌经手术去势的患者作为研究组,39例非前列腺癌老年患者作为正常对照组。分别测定黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(TT)、游离睾酮(FT)、雌激素(E2)、部分凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、纤维蛋白原(Fib)、凝血酶原活动度(PA)、纤溶酶原(PLG)活性、α2-抗纤溶酶(α2-PI)活性、抗凝血酶-Ⅲ(AT-Ⅲ)活性、二磷酸腺苷(ADP)活性、D-二聚体(DD)含量、血小板聚集率和黏附率、组织型纤溶酶原激活剂(t-PA)及组织型纤溶酶原激活剂抑制物(PAI-1)抗原浓度。结果研究组中患者TT、FT、E2水平显著降低,E2降低幅度小于TT,LH、FSH、FT/TT、E2/TT显著升高;PT、APTT显著缩短,Fib及DD含量显著增加,血小板聚集率、黏附率及ADP活性均显著升高,PLG、α2-PI活性显著增强,t-PA抗原含量及t-PA/PAI-1显著下降,PAI-1含量显著增加。AT-Ⅲ活性无显著变化。结论前列腺癌患者去势后性激素比例严重失调;血小板活性及血液凝血活性显著增强,纤溶活性显著抑制,提示去势患者存在发生动脉硬化的高度危险性。     

链激酶,尿激酶静脉溶栓对凝血和纤溶系统的影响

尿激酶（ＵＫ）和链激酶（ＳＫ）同属第一代溶栓剂，二者均无“纤维蛋白选择性”，本研究目的在于比较ＳＫ和ＵＫ对凝血和纤溶系统的影响及其与临床的关系。静脉溶栓治疗急性心肌梗塞１１１例，其中５５例使用ＳＫ（１５０万单位／例），５６例使用ＵＫ（１．７－２．３万单位／ｋｇ体重，平均１５３．２５万单位／例），于溶栓前、溶栓后２、６、１２、２４小时、第３天、第７天分别测定血浆纤溶酶原激活物（ＰＡ）、纤溶酶原激活物抑制物（ＰＡＩ）、及纤溶酶原（ＰＬＧ）活性，并测定纤维蛋白原（ＦＧ）浓度、激活的试管法凝血时间（ＡＣＴ）。结果显示：ＳＫ引起的凝血和纤溶系统变化均比ＵＫ明显，特征为：在溶栓后２～６小时有较高的ＰＡ活性和较低的ＰＡＩ活性；溶栓后２小时较长的凝血时间；较低的纤维蛋白原浓度从２小时持续到第７天，上述差异均有极显著意义。本文结果提示ＳＫ对凝血和纤溶系统的影响比ＵＫ强烈而持久，二者在血液学特征上的差异与临床疗效及使用抗凝剂等问题可能有一定的关系。     

Tissue plasminogen activator, plasminogen activator inhibitor, and other parameters of fibrinolysis in the early stages of taurocholate acute pancreatitis in rats.

It is well known that fibrinolytic activity in the early stages of acute experimental pancreatitis (AEP) as assessed by euglobulin lysis time (ELT) is depressed. The aim of this study was to evaluate changes in the fibrinolytic system in the early stages of taurocholate AEP in rats. Tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor 1 (PAI-1) activity, plasminogen, alpha 1 proteinase inhibitor (alpha 1 PI), alpha 2 antiplasmin (alpha 2 AP), antithrombin III (AT III), fibrinogen, and ELT were measured 0.5, 1, 3, and 6 h after the induction of taurocholate AEP in rats, as well as in sham-operated animals and the control group, which was not submitted to any operation. T-PA activity decreased significantly after 3 and 6 h of AEP; PAI activity had a time course reverse to t-PA and was parallel to alpha 1 PI activity. ELT was slightly prolonged after 0.5, 1, and 3 h, whereas alpha 2 AP activity and plasminogen levels increased significantly; AT III activity was increased after 1 h in comparison to control group. Sham operation caused nonsignificant changes in fibrinolysis. Increase of PAI activity and decrease of t-PA could be a reasonable explanation for inhibited plasma euglobulin fibrinolytic activity noted in the early period of AEP.     

健康急进高原者纤溶系统变化的研究

目的：探讨健康急进高原者纤溶系统的变化。方法：总共50名青年男性入选本试验，均为从四川省（海拔400m）招募的新兵。在乘飞机从四川进入拉萨（海拔3658m）之前及之后3d，测定血凝血酶原时间（PT）、凝血酶时间（TT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（Fg）、纤溶酶原（Plg）、纤溶酶抑制物、D-二聚体（DD）含量。结果：进入高原后，PT、TT、APTT、DD比在平原时增高，FIB、Plg、纤溶酶抑制物降低（P〈0．05）。结论：健康人急进高原后纤溶系统变化显著。     

Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with the rate (100%) for the vehicle control. Additionally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E significantly and dose-dependently ameliorated coagulation-related parameters, including the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet function, coagulation/fibrinolysis factors, plasma immunoreactive insulin secretion, and plasma glucose/insulin resistance.     

Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism

OBJECTIVE: We previously demonstrated that patients suffering from moderate hypothyroidism were at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism. The latter state is associated with hemostatic anomalies including von Willebrand type 1 disease and increased fibrinolytic capacity. With the exception of von Willebrand type 1 disease, reversibility of hemostatic changes is not established after levothyroxine replacement therapy. Therefore our objective was to analyze the reversibility of these anomalies. MATERIALS AND METHODS: We analyzed the impact of levothyroxine treatment on lipid parameters, fibrinogen, platelet count, D-dimers, alpha2 antiplasmin activity, plasminogen activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and coagulation factors (factor VIII coagulant, von Willebrand factor antigen, von Willebrand factor and factor IX) in 23 patients with severe hypothyroidism (TSH level > 50 mU/ I). RESULTS: Mean fibrinogen levels increased by 14.2% while t-PA Ag and PAI-1 Ag increased by 42.6 and 69%, respectively, after correction of hypothyroidism. Interestingly, post-treatment PAI-1 Ag levels tended to be higher in patients with normal-high final TSH levels than in patients with normal-low final TSH levels. Our results suggest that normalization of fibrinolysis is obtained after a transient decrease of fibrinolytic activity. We also confirmed the correction of coagulation factor abnormalities upon levothyroxine replacement therapy. CONCLUSIONS: We demonstrated that the coagulation disorders and the hyperfibrinolytic status of severe hypothyroid patients were corrected upon levothyroxine therapy. However, the clinical consequences of the transient decrease of the fibrinolytic activity during the course of TSH normalization need further studies.     

The pathogenesis of accelerated fibrinolysis in hepatosplenic schistosomiasis.

Seventy patients with different stages of hepatosplenic schistosomiasis and 18 non-bilharzial normal controls were studied. Plasminogen, plasminogen activators (PA), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), alpha 2-antiplasmin (alpha 2-AP), plasminogen activator inhibitor (PAI), fibrinogen/fibrin degradation products (FDP) and D-dimer were determined to elucidate the role of plasminogen activators and inhibitors in the pathogenesis of accelerated fibrinolysis in schistosomiasis. There was a progressive increase in the levels of PA, t-PA, u-PA, FDP and D-dimer indicating enhanced fibrinolytic activity with advancing disease. In addition, there was progressive decrease of plasminogen, alpha 2-AP and PAI levels which might be due to decreased hepatic synthesis and/or increased peripheral consumption. These findings suggest that the pathogenesis of accelerated fibrinolysis in schistosomiasis is multifactorial, but may be due to the progressive increase in the levels of plasminogen activators. In addition, the increase of FDP and D-dimer levels are evidence of secondary fibrinolysis following thrombin generation.     

Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin.

To delineate the role of plasmin inhibitors, especially the two molecular forms of alpha 2-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase. At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding alpha 2-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogen-binding alpha 2-antiplasmin became exhausted (less than 20%) and other plasmin inhibitors (that is, nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding alpha 2-antiplasmin consumption was complete and nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C1-inactivator consumption occurred, even at extreme degrees of plasminogen activation. Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogen-binding alpha 2-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding alpha 2-antiplasmin was decreased to less than 20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies. It is concluded that plasminogen-binding alpha 2-antiplasmin is the most important inhibitor of plasmin in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

脑梗死患者凝血、抗凝、纤溶指标改变及低分子肝素治疗研究

目的　观察脑梗死患者血浆凝血、抗凝、纤溶指标凝血酶元时间 (PT)、白陶土部分凝血活酶时间 (KPTT)、抗凝血酶Ⅲ (ATⅢ )、组织型纤溶酶元激活物 (tPA)及其抑制物 (PAI)变化和低分子肝素 (LMWH)对其影响及疗效评定。方法　将 80例脑梗死患者随机分为两组 ,分别给予LMWH和常规药物治疗 ,检测治疗前后上述指标改变并评定LMWH疗效。结果　脑梗死患者较正常对照KPTT缩短 (P <0 .0 5 ) ,ATⅢ、tPA显著下降 (P <0 .0 1) ,PAI显著升高 (P <0 .0 1) ;LMWH治疗后tPA较治疗前显著升高 (P <0 .0 5 ) ,ATⅢ升高及PAI下降较常规治疗组有显著差异(P <0 .0 5及P <0 .0 1) ;LMWH治疗组显效率明显高于常规治疗组 (P<0 .0 1) ,未发现明显副作用。结论　脑梗死急性期存在血浆凝血、抗凝、纤溶功能异常 ;LMWH可影响血浆KPTT、ATⅢ、tPA、PAI水平 ,调节凝血、抗凝及纤溶系统平衡 ;应用LMWH治疗脑梗死有效、安全     

Hyperfibrinolytic activity in hospitalized cirrhotic patients in a referral liver unit

OBJECTIVE: Increased frequency of hyperfibrinolytic activity was reported in patients with cirrhosis. However, the incidence, clinical presentation, and the parameters related to hyperfibrinolysis remain largely unknown in these patients. By utilizing euglobulin lysis time (ELT) and other clinical coagulation tests, the present study investigated the incidence of and clinical parameters related to hyperfibrinolytic activity, and assessed predicting factors to epsilon-aminocaproic acid (EACA) treatment in cirrhotic patients with hyperfibrinolysis in a liver unit. METHODS: The study included 86 consecutive patients who were referred and admitted to a referral liver unit for various liver diseases. The mean age was 50.0 yr, with a male: female ratio of 60:26. Sixty-six patients (76.7%) were Hispanic and 75 (87.2%) were cirrhotic. The etiologies of liver diseases included alcoholic liver disease (n = 68, 79.1%), hepatitis B (n = 2, 2.3%), hepatitis C (n = 6, 7.0%), autoimmune hepatitis (n = 3, 3.5%), cryptogenic liver disease (n = 4, 4.7%), and hepatocellular carcinoma (n = 3, 3.5%). Coagulation studies included ELT, PT, PTT, fibrinogen, D-dimer, and fibrin degradation product levels. RESULTS: Hyperfibrinolytic activity as reflected by shortened ELT was present in 27/75 cirrhotic (31.3%) but 0/11 noncirrhotic patients, which was significantly correlated with higher Child-Pugh (C-P) class, abnormal levels of PT, PTT, fibrinogen, platelet count, and total bilirubin. Shortened ELT was more frequently seen in patients with hepatic decompensation and mucocutaneous bleeding, although these relationships were not statistically significant. In 27 patients with hyperfibrinolysis, five (18.5%) required EACA treatment for progressive mucocutaneous bleeding and/or hematoma. EACA treatment was significantly associated with higher C-P scores; greatly shortened ELT (< or =50% of normal value); and abnormal levels of fibrinogen, total bilirubin, and PT, indicating that these factors may serve as predictors for EACA treatment. CONCLUSION: Hyperfibrinolytic activity was seen in 31.3% of patients with cirrhosis, which is correlated with higher C-P scores; abnormal PT, PTT, fibrinogen level, and platelet count; and hyperbilirubinemia. Patients who received EACA treatment usually have a more severe hyperfibrinolytic activity as indicated by shortened ELT and low level of fibrinogen, and more severe liver disease as indicated by higher C-P scores and hyperbilirubinemia.     

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。     

Blood coagulation shifts in patients with myocardial infarction treated with streptokinase

Variation in major coagulation parameters was assessed in 87 patients with acute myocardial infarction, treated with streptokinase and/or heparin under angiographic control. Streptokinase treatment was associated with a drop in plasma fibrinogen, plasminogen and alpha 2-antiplasmin, and an increase in serum fibrin/fibrinogen degradation products. The magnitude of coagulation shifts was greater in case of intravenous streptokinase infusion (1,000,000 units over 60 min), as compared to intracoronary streptokinase administration in lower doses (120,000-180,000 units over 60-90 min). In all patients with regained coronary flow, fibrinogen, plasminogen and alpha 2-antiplasmin levels began to decline significantly earlier and/or became normal significantly later, as compared to patients with persisting coronary occlusion. The rates and severity of hemorrhagic complications were basically similar in intravenous and intracoronary routes of administration, in spite of different doses and magnitude of coagulation shifts.     

Intrapleural instillation of streptokinase. Effects on systemic fibrinolysis

Ten consecutive patients aged 25 to 75 with postoperative empyema or hemothorax conventionally treated with drainage without sufficient effect were given intrapleural instillations of streptokinase (Kabikinase, 250,000 IE) for 4 hours). The effects on systemic fibrinolysis were studied. Venous blood samples for determination of fibrinolytic activity on fibrin plates, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrinogen, fibrin(ogen) degradation products (FDP) and thrombin time were taken before instillation, after instillation and then after 24 hours. Preinstillation values were compared to the values 4 and 24 hours after instillation with Student's paired t-test. There were no differences in fibrinolytic activity, alpha 2-macroglobulin and thrombin time. There was a slight increase in plasminogen, alpha 2-antiplasmin and fibrinogen, probably due to an acute phase reaction. Fibrin degradation products showed an increase with border line significance. These changes are not consistent with generalized fibrinolysis, and it is concluded that intrapleural instillations of streptokinase can be given safely in the early posttraumatic or postoperative period.     

Modifications of coagulation and fibrinolysis mechanism in laparoscopic vs. open cholecystectomy

BACKGROUND/AIMS: The incidence of thromboembolic complications following laparoscopic cholecystectomy as well as the indication for prophylactic thrombophylaxis is still controversially discussed. The aim of this study is to evaluate the alterations of the coagulation and fibrinolytic mechanism after laparoscopic vs. open cholecystectomy. METHODOLOGY: Forty-five patients, who were submitted to laparoscopic (LC-group, n=30) or open cholecystectomy (OC-group, n=15) were included in the study. The following parameters were measured preoperatively and 24h and 48h postoperatively: platelet count (PLT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FG), d-dimers (DD) and antithrombin III (AT-III). RESULTS: The preoperative values were within the normal range and did not differ between the two groups. No significant alterations were noted concerning PT and PTT. FG and PLT were significantly increased in both groups at 24h and 48h compared to the baseline values, with no statistical significant difference between them at all time points. D-dimers were significantly elevated at 24h and 48h postoperatively in both groups. The LC-group showed significantly higher AT-III levels at 24h, and significantly lower DD levels at 24h and 48h compared to the OC-group (p < 0.05). CONCLUSIONS: Laparoscopic cholecystectomy seems to induce a lower activation of the hemostatic mechanism compared to open cholecystectomy.     

The hemostatic defect of chronic liver disease. Kinetic studies using 75Se-selenomethionine.

With the use of cohort labeling with 75Se-selenomethionine, simultaneous platelet, fibrinogen, and plasminogen survival studies were carried out in 8 patients with chronic alcoholic liver disease and in 5 normal subjects. Clinical features, liver function tests, coagulation and fibrinolytic system activities, and platelet function were also assessed. On the basis of platelet survival, the patients could be divided into two groups. Three patients had shortened platelet survival; they were all thrombocytopenic and had greater prolongation of the prothrombin time (PT) and activated partial thromboplastin time (PTT) than the other 5 patients. However, platelet turnover was decreased in all the patients, and there was no difference between the two groups with regard to fibrinogen or plasminogen survival nor in the in vitro evidence of disseminated intravascular coagulation (DIC). Fibrinogen survival was increased in 5 of the 8 patients. Plasminogen survival was normal in 6 patients and prolonged in 2 patients with very low plasminogen levels. The absence of increased fibrinogen turnover in the patients studied indicates that the abnormalities in coagulation tests were not due to consumption coagulopathy. The authors' studies suggest that, at least for patients with chronic stable alcoholic liver disease, the concept that the coagulopathy of liver disease is due to increased utilization of clotting factors should be revised with caution.     

Effects of porcine plasmin on the coagulation and fibrinolytic systems in humans.

Pig plasmin (Lysofibrin) was given to 11 patients with phlebographically verified venous thrombosis, 2 of whom were treated two and three times, respectively. The effect on coagulation and fibrinolytic parameters was studied. The platelet count, Owren's P&P (prothrombin plus factors VII and X), plasminogen, factor XIII, and antithrombin III did not change during the treatment. All patients developed a proteolytic activity demonstrable on both unheated and heated fibrin plates. The fibrinogen decreased successively to very low levels, and parallel to this an increase in fibrin/fibrinogen degradation products was found. The factor VIII and factor V activities decreased immediately after each Lysofibrin infusion but normalized rapidly again. The factor VIII molecule, however, retained its reactivity to rabbit antiserum against factor VIII. Immediately after the plasmin infusion a decrease of both alpha2-macroglobulin (alpha2-M) and the rapidly reacting alpha2-antiplasmin was observed. alpha2-M decreased successively and in several of the patients values were unmeasurable for a period of some days. A complex formation between pig plasmin and the alpha2-antiplasmin was demonstrated in crossed immunoelectrophoresis. The complexes were rapidly cleared from the circulation. No interaction between the pig plasmin and the inhibitor of the plasminogen activation, alpha1-antitrypsin or inter-alpha-inhibitor, was found.     

Changes in coagulation and fibrinolytic parameters caused by extracorporeal circulation

Summary During cardiopulmonary bypass (CPB) mechanical stress and the contact of blood with artificial surfaces lead to the activation of pro- and anticoagulant systems and the complement cascade, and to changes in cellular components. This phenomenon causes the postperfusion-syndrome, with leukocytosis, increased capillary permeability, accumulation of interstitial fluid, and organ dysfunction. In this study, we focused on the influence of the extracorporeal circulation, sternotomy, and heparin administration on the activation of coagulation and fibrinolysis. In 15 patients we investigated coagulation parameters before, during and post CPB, i.e., fibrinogen, antithrombin (AT) III, thrombin-antithrombin complex (TAT), prothrombin fragments F1 + 2 (F1 + 2), factor (F) XIIa, tissue factor (TF), and parameters of the fibrinolytic system, i.e., plasmin-antiplasmin-complex (PAP), D-dimer, tissueplasminogen-activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen-activator inhibitor type 1 (PAI 1). The results demonstrate distinct alterations in the above mentioned parameters. Despite administration of a high dose of heparin (activated clotting time [ACT] > 450s) combined with a low dose of aprotinin, activation of the coagulation and fibrinolytic pathways was observed. We found this activation was mainly caused by CPB and not by sternotomy. The activation of coagulation was due to foreign surface contact (F XII F XIIa) as well as to an effect of tissue factor release in the late phase of CPB. The enhanced fibrinolytic activity during CPB was, at least in part, caused by tPA and was followed by PAI 1 release.