Coagulation and Fibrinolytic Systems in Pre-eclampsia and Eclampsia

The coagulation and fibrinolytic mechanisms were investigated in a group of patients with severe pre-eclampsia and eclampsia and the findings were compared with those of healthy women in late pregnancy. In patients with pre-eclampsia the following significant differences were found: (1) greater depression of plasma fibrinolytic activity (euglobulin lysis time) than in normal pregnancy, (2) a higher level of inhibitor to urokinaseinduced lysis, (3) increased levels of serum fibrin degradation products, and (4) reduced platelet counts.In patients with eclampsia a progressive increase of the level of serum fibrin degradation products was found over the three days following eclamptic seizures. No such increase occurred after grand mal seizures in late pregnancy. The findings in this study support the view that intravascular clotting is taking place in pre-eclampsia and that this disturbance of the balance between coagulation and fibrinolysis may be localized to certain areas of the vascular compartment, particularly the placental and renal circulations. Fibrin deposition in the maternal vessels supplying the placenta would impair the placental blood flow, which may explain the placental insufficiency which occurs in pre-eclampsia. Likewise fibrin deposition in the renal vasculature will result in glomerular damage and proteinuria. Hypertension may be related to the renal ischaemic changes or a compensatory response to the presence of fibrin deposition in the vascular compartment. This evidence of intravascular fibrin deposition raises the question of the possible therapeutic value of antithrombotic agents to inhibit the clotting process. On a theoretical basis such treatment might be expected to improve blood flow to the placenta and thereby fetal growth.     

不同化疗方案对非小细胞肺癌患者凝血纤溶功能及血小板参数的影响及其临床意义

目的:探讨不同化疗方案对非小细胞肺癌患者凝血纤溶功能及血小板参数的影响及临床意义。方法:回顾性分析2013年2月至2016年2月于我院进行治疗的96非小细胞肺癌患者的临床资料,按照化疗方案的不同分为TP组(50例)及GP组(46例),TP组患者给予多西他赛联合卡铂方案(TP方案)进行化疗,GP组患者给予吉西他滨联合卡铂方案(GP方案)进行化疗,另选择45例健康体检者作为对照组。比较三组治疗前者血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血浆凝血酶时间(TT)、血浆纤维蛋白原含量(FIB)以及D-二聚体(D-dimer)、血小板数(PLT)、血小板比积(PCT)、血小板平均体积(MPV)、血小板体积分布宽度(PDW)以及大体积血小板比率(P-LCR)及TP组和GP组治疗后以上指标的差异。结果:TP组和GP组患者化疗前PT、APTT、TT、FIB、D-dimer、PLT、PCT、MPV、PDW以及P-LCR水平均明显高于对照组(P0.05),而TP组与GP组以上指标比较无显著差异(P0.05)。治疗后,TP组和GP组患者PT、APTT、TT、FIB、D-dimer、PLT、PCT、MPV、PDW以及P-LCR水平均较治疗前有所下降,且GP组TT明显长于TP组(P0.05),PLT、PCT明显低于TP组(P0.05)。结论:凝血纤溶功能及血小板参数对于评价不同化疗方案治疗非小细胞肺癌患者预后具有积极的临床价值,不同化疗方案选择对于患者凝血系统均具有一定的影响。     

Liver Transplantation in Man—IV,Haemorrhage and Thrombosis

Blood coagulation and fibrinolytic factors have been measured in 13 patients treated by liver transplantation. During operation intravascular coagulation and fibrinolysis were increased, but seldom to a degree which would cause abnormal bleeding. Measurement of the catabolism of radioactive fibrinogen showed that increased intravascular coagulation continued for long periods after the operation. Despite secondarily increased fibrinolysis, there was a high incidence of thrombosis. Treatment with anticoagulants or with fibrinolysis inhibitors may be valuable in these patients.     

Effects of prolonged poisoning by Russell's viper venom on blood coagulation, platelets and fibrinolysis

The effects of Russell's viper venom on blood coagulation, platelets and the fibrinolytic enzyme system were studied in rabbits after injecting repeated doses of 0.05 MLD of the venom. Thrombocytopenia was the earliest change to appear. It was followed by rise in serum fibrinogen degradation products and prolongation of prothrombin time, activated partial thromboplastin time and thrombin time indicating a progressive consumption coagulopathy and activation of fibrinolysis. Red blood cell morphology was unchanged during the first three weeks; whereas the fragmentation appeared after the fourth week and it increased in severity with further envenomations, i.e. when chronic DIC was established.     

Antithrombotic effects of odorless garlic powder both in vitro and in vivo

Antithrombotic activities of odorless garlic powder were demonstrated in blood fibrinolytic and coagulation systems. Though the odorless garlic preparation did not influence tissue-type plasminogen activator (t-PA) or its inhibitor secretions from human umbilical vein endothelial cells, it enhanced plasmin generation by t-PA on fibrin film and in chromogenic assays by 1.8-fold and 8.7-fold respectively. The coagulation system was considerably reduced after the administration of the garlic in a rat in situ loop model, indicating that increased levels of thrombin-antithrombin III (TAT) complex in the control group were significantly reduced to normal (sham) in the garlic group (p<0.05), which was associated with decreasing tendencies towards prolonged or increased values of coagulation parameters in the control group. These findings suggest that odorless garlic not only activates fibrinolytic activity by accelerating t-PA-mediated plasminogen activation, but also suppresses the coagulation system by downregulating thrombin formation, suggesting a beneficial role in preventing pathological thrombus formation in such cardiovascular disorders.     

The effect of three variables on adsorption of rabbit IgG to colloidal gold

The purpose of this investigation was to (a) begin to evaluate the coagulation curve as a means of selecting the minimal quantity of IgG required to stabilize colloidal gold (Au); (b) determine the effect of the quantity of IgG added, the pH of adsorption, and the isoelectric point (pI) range of the IgG on the quantity of IgG bound and the stability of the IgG-Au complex with respect to desorption; and (c) discuss these results with respect to current theory on the effect of pH on adsorption of IgG to surfaces. No absolute minimal value required to prevent coagulation could be determined despite the high reproducibility of the values obtained; approximate values were selected. Each variable had an effect on the quantity of IgG bound: as the quantity of IgG added increased, the quantity bound increased; as the pH of adsorption became more alkaline, the quantity bound decreased; and as the pI range of the IgG became more alkaline, the quantity bound increased. IgG-Au complexes with a variable number of bound IgG molecules, depending on the three variables selected, can be produced. Production of IgG-Au composed of uniform numbers of IgG is discussed. A modification of the current theory on the effect of pH on adsorption of IgG is proposed.     

急、慢性缺氧对大鼠凝血机能的影响

本文讨论了实验性缺氧对大鼠凝血机能产生的影响。实验结果表明,大鼠在模拟8000米高度两小时后,血小板凝聚性、血小板因子3活性明显增加,纤溶活性下降,同时,纤维蛋白原含量和因子X也明显下降。大鼠在模拟7000米经36天间歇性慢性缺氧,血小板计数、血小板凝聚性,血小板因子3活性、纤维蛋白原含量、因子X活性均显著增加,部分凝血活酶时间缩短、纤溶活性下降,明显地出现凝血增强的趋势。本文还讨论了抗缺氧药物复方党参、异叶青兰对人鼠急性缺氧时凝血机能的影响。     

Effects of preeclampsia and eclampsia on cord blood coagulation tests

Blood coagulation tests were determined in fifty-three paired umbilical cord blood and maternal venous blood samples originating from term singleton vaginal cephalic deliveries. The index group comprised seventeen deliveries complicated by preeclampsia or eclampsia, and the control group comprised thirty-six healthy women with uneventful pregnancies and deliveries. Mean values obtained from the coagulation and fibrinolytic assays did not significantly differ between study groups, except for antithrombin III levels in index group of neonates, which were significantly lower. Comparison of coagulation and fibrinolytic characteristics between mothers and their neonates produced expected level of difference due to immaturity of their haemostatic mechanisms. We found alterations in maternal blood coagulation and fibrinolysis and evidence of increased intravascular coagulation with severe preeclampsia and IUGR.     

Isolation and characterization of <Emphasis Type="Italic">Bacillus</Emphasis><Emphasis Type="Italic">polyfermenticus</Emphasis> isolated from <Emphasis Type="Italic">Meju,</Emphasis> Korean soybean fermentation starter

Bacteria of the Bacillus species have been reported as an important microorganism in fermented soybean products. In the present study, thirty Bacillus isolates were screened from Meju, a Korean soybean fermentation starter. The comparative analysis of 16S rDNA sequences, 16S-23S internal transcribed spacer sequences, phenotypic, and biochemical characterizations revealed three phylogenetically distinct groups namely Bacillus atrophaeus, Bacillus polyfermenticus and Bacillus subtilis. The isolates were assayed for poly-γ-glutamate production and fibrinolytic activity. Among the isolates, B. polyfermenticus exhibited maximum poly-γ-glutamate production and fibrinolytic activity. Moreover, the soybean products fermented by B. polyfermenticus have increased the time taken for coagulation and hemorrhage in mice. The results of the present study clearly indicate the functional role of B. polyfermenticus in fermented soybean products.     

Hemostasis and fibrinolysis in patients with intermittent claudication: effects of prostaglandin E1

There is evidence that the coagulation system is activated in patients with peripheral arterial occlusive disease (PAOD). The beneficial effects of the vasoactive drug prostaglandin E1 (PGE1) may rely in part on the modulation of the coagulation system. The study was designed to evaluate the effects of PGE1 on hemostatic and fibrinolytic variables in patients with intermittent claudication. Therefore molecular markers of thrombin (prothrombin fragment 1+2, PTF 1+2; thrombin-antithrombin III complexes, TAT) and fibrin formation (fibrinopeptide A, FPA) and markers of the fibrinolytic activity (fibrin degradation products, D-dimers) were determined before and immediately after the first PGE1 dose (60 microg in 100 ml NaCl over 2 h i.v.) as well as after 4 weeks of daily infusion therapy in 12 PAOD patients and in eight control patients before and after a single placebo infusion. Plasma levels of PTF1+2, TAT, FPA and D-dimers tended to decrease after the initial dose of PGE1. Infusion therapy with PGE1 for 4 weeks led to a decrease of all hemostatic and fibrinolytic parameters with most pronounced changes for PFT1+2, D-dimers and plasminogen activator inhibitor-1 decreasing by 11% (P<0.05), 20% (P<0.05), and 7% (P<0.05), respectively. These variables remained unchanged in controls with placebo infusion.In summary, infusion therapy with PGE1 in patients with PAOD reduces thrombin formation and results in a decrease of fibrin degradation. PGE1 may thus reduce fibrin deposition involved in the pathogenesis of atherosclerosis.     

Fibrin monomer complexes (SFMC) after substitution of antithrombin III (AT III) in consumption coagulopathy

The report refers to substitution therapy of 33 patients who suffered consumption coagulopathy. Various blood coagulation and fibrinolytic variables were measured. After successful AT III donation to patients suffering DIC, soluble fibrin monomer complexes (SFMC) disappeared within 0.5-12 hours. If AT III decreases SFMC proves positive again. In addition to analysis of AT III we recommend to analyse SFMC to detect thrombin induced consumption reaction (DIC). Furthermore we found the fibrin split product D-dimer was a particularly sensitive indicator of DIC in case of hyperfibrinolysis (D-dimer was analysed in six patients). The reactions of fibronectin and SFMC proved inversely proportional.     

Effect of ethyloestrenol on fibrinolysis in the vessel wall.

Forty-nine patients with decreased fibrinolytic activity in the vessel walls or a decreased release mechanism, or both, were treated with ethyloestrenol for three to 17 months. Forty-five of the patients had had recurrent, phlebographically verified, deep venous thrombosis (DVT) and four had arterial thrombosis. Ethyloestrenol 8 mg/day was given to 31 patients and 4 mg/day was given to 12. The remaining six patients had been treated with a combination of phenformin and ethloestrenol. The phenformin was withdrawn but they were kept on ethyloestrenol 8 mg/day. Another 15 patients with a normal fibrinolytic system--four with recurrent DVT and 11 with severe arteriosclerosis--were given ethyloestrenol 8 mg/day. The spontaneous fibrinolytic activity, local fibrinolytic activity during standardised venous occlusion of the arms, and fibrinolytic activity of the vessel walls increased significantly after treatment with ethyloestrenol 8 mg/day for three months. No further increase occurred after three months, and ethyloestrenol 4 mg/day had no effect. No values rose significantly in the patients with a normal fibrinolytic system. One patient suffered a recurrence within three months of treatment, before the fibrinolytic system became normal. In one patient the fibrinolytic defect reappeared after 10 months in spite of continued treatment. Two of the three women of fertile age developed irregular cycles and intermenstrual bleeding, which disappeared when the treatment was withdrawn. No other side effects were observed.     

Pathophysiological changes of gram-negative bacterial infection can be reproduced by a synthetic peptide mimicking loop L7 sequence of Haemophilus influenzae porin

Several in vivo models have been used to dissect the molecular mechanisms that contribute to activate the coagulation and fibrinolytic systems by bacteria and bacterial products but many aspects remain poorly understood. In this study we examined the in vivo effect of the synthetic peptide corresponding to loop L7 from Haemophilus influenzae type b (Hib) porin to evaluate its role on the coagulative/fibrinolytic cascade and the circulating markers of endothelial injury. Plasma was obtained from rats injected intravenously with loop L7, Hib porin or a scrambled peptide and tested for fragment 1+2 (F1+2), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type I (PAI-1) antigen, von Willebrand factor (vWF) and soluble E-selectin (sE-selectin). The coagulative/fibrinolytic cascade was impaired as shown by PAI-1 level increased. Concomitantly, E-selectin, a marker of endothelial injury, was also significantly elevated. In addition either loop L7 or Hib porin injection induced hyperglycaemia and inflammatory cytokine production. The data were correlated with hemodynamic functions. The results indicate that loop L7 plays an essential role in the pathophysiologic events observed during gram-negative infection. These findings may have implications for the development of alternative therapies to counteract excessive inflammatory responses during septic shock.     

Role of intermediate products of prothrombin proteolysis by thrombin in the stimulation of the anticoagulation system of blood]

Two components - the intermediate product 1 (P-1) converting under certain conditions into thrombin, and product 2 (P-2) which possesses no such properties were isolated from the products of prothrombin proteolysis by thrombin. The intravenous injection of the P-1 to rats lengthened the blood coagulation time and plasma recalcification. The sum total fibrinolytic activity proved to increase and the fibrinogen concentration - to decrease. A sharp 5-fold rise of the nonfermentative fibrinolysis was observed. It seems that this effect of the anticoagulating and fibrinolytic potential mobilization was stimulated by the response of the second anticoagulating blood system.     

Prevention of intravascular blood coagulation in rats by DIP-alpha-thrombin administration

The possibility of prevention of intravascular blood coagulation in rats by DIP-alpha-thrombin devoid of proteolytic activity and capable of stimulating the reaction of anticoagulation system was studied. The injection of lethal thromboplastin dose was shown to produce a sharp increase in soluble fibrin blood content, total disappearance of fibrinolytic activity and intravascular blood coagulation. The animals died of thrombosis in 90% of cases. It was established that the injection of lethal thromboplastin dose 5 min after DIP-alpha-thrombin injection caused a 13% lethality from thrombosis. No reliable changes in fibrinolytic activity and soluble fibrin content were observed. A significant increase in thrombin and recalcification time was recorded. It is suggested that DIP-alpha-thrombin prevents intravascular blood coagulation induced by lethal thromboplastin dose due to mobilization of the reserve capacities of neuro-humoral anticoagulation system.     

大剂量氨甲环酸对全膝关节置换患者术后纤溶活性与炎症因子的影响

目的:探讨大剂量氨甲环酸对全膝关节置换患者术后纤溶活性与炎症因子的影响。方法:回顾性分析在我院行初次全膝关节置换术的180例患者,按照给药方式分为对照组、常规组、大剂量组,每组各60例。对照组患者直接给予生理盐水,常规组给予10 mg/kg氨甲环酸,大剂量组给予15 mg/kg氨甲环酸。比较三组术后总失血量、隐形失血量、术前与术后3天三组凝血功能(纤维蛋白原、凝血酶原时间、活化部分凝血活酶时间)、纤溶活性[纤维蛋白(原)降解产物(FDP)、D-二聚体]以及炎性因子[C-反应蛋白(CRP)、白介素-6(IL-6)]水平变化及术后2周血栓事件的发生情况。结果:大剂量组与常规组的总失血量与隐形失血量均明显低于对照组,大剂量组总失血量与隐形失血量均低于常规组(P0.05);三组患者纤维蛋白原、凝血酶原时间以及活化部分凝血活酶时间相比差异均无统计学意义(P0.05);术后3天,大剂量组和常规组FDP与D-二聚体、CRP、IL-6水平均显著低于对照组,且与常规组相比,大剂量组水平较低(P0.05);术后2周,三组肌间静脉血栓发生率比较均无显著差异(P0.05)。结论:在全膝关节置换术后使用氨甲环酸可进一步减少术后隐形失血量,且不会增加血栓事件的风险,且随着药物剂量的增加,其止血效果越强,同时具有更为显著的抗纤溶作用与抗炎效果。     

Effect of physical exercise on fibrinolytic properties of erythrocytes

The fibrinolytic properties of blood and erythrocytes were studied before and after physical exercise in male volunteers. Their fibrinolytic responses were of two distinct types. In type 1 response, fibrinolytic activities of blood and erythrocytes increased; the plasminogen activator and active plasmin contents in erythrocytes also increased, whereas the profibrinolysin content correspondingly decreased. In addition, physical exercise increased the erythrocyte adsorption properties for plasma activators of fibrinolysis. Type 2 response was characterized by a decrease in the fibrinolytic activity of blood; neither fibrinolytic activity nor adsorption properties of erythrocytes increased. The type of blood and erythrocyte response to muscular activity was determined by the pre-exercise level of red blood cell fibrinolytic activity. It was low in type 1 response due to a lesser content of plasmin activators and greater content of antiplasmin. In type 2 response, the initially high lytic capacity is connected with a greater reserve of activators and lesser reserve of inhibitors of the fibrinolytic system. A conclusion was made that individual differences in fibrinolytic responses to physical exercise were largely accounted for by the properties of erythrocytes.     

The effects of a transcontinental flight on markers of coagulation and fibrinolysis in healthy men after vigorous physical activity

Purpose: Athletes and military service members are known to undergo strenuous exercise and sometimes have to take long haul flights soon afterwards; however, its combined effect on many physiological functions is relatively unknown. Therefore, we examined the combined effects of a full-body muscle-damaging workout and transcontinental flight on coagulation and fibrinolysis in healthy, resistance trained men. We also determined the efficacy of a full-body compression garment in limiting their coagulation responses. Materials and Methods: Nineteen healthy, resistance trained men flew from Connecticut (CT) to California (CA), performed a full-body muscle-damaging workout and then flew back to CT. Ten participants wore full-body compression garments (FCG) for the duration of both flights and during all other portions of the study except during workouts and blood draws, when they wore loose clothing. Nine controls wore loose clothing (CON) throughout the study. Blood samples were collected at 16 h and 3 h before the initial flight from CT, immediately after landing in CA, immediately before and immediately after the full-body workout in CA, immediately after landing in CT, and at 29 h after landing in CT. Plasma markers of coagulation included activated partial thromboplastin time (aPTT), prothrombin fragment 1+2 (PTF 1+2) and thrombin ant-thrombin (TAT). Markers of the fibrinolytic system included the tissue plasmigen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and D-Dimer. Results: Both FCG and CON groups exhibited a faster aPTT after the full-body workout compared to all other time points. Thrombin generation markers, TAT and PTF 1+2, increased significantly after the full-body workout and immediately after landing in CT. Additionally, tPA increased after the full-body workout, while PAI-1 increased before the flight to CA, after the full-body workout, and just after landing in CT. The D-Dimer significantly increased after the full-body workout and at 29 h post-flight in both groups. Between groups, aPTT was significantly faster and TAT elevated with the CON group at 29 h post-flight. Also, PAI-1 demonstrated higher concentrations immediately after landing in CT for the CON group. Conclusion: A full-body muscle-damaging workout in conjunction with a trans-continental flight activated the coagulation and fibrinolytic systems. Additionally, wearing a full-body compression garment may limit coagulation following a workout through the recovery period.     

炭疽灭活和裂解芽胞抗原免疫家兔后血清中的IgG抗体应答

炭疽杆菌芽胞在炭疽免疫中发挥基本作用。实验中以炭疽活芽胞疫苗为原形,建立了制备灭活和裂解炭疽芽胞的方法,研究了各种灭活和裂解炭疽芽胞疫苗不同浓度、不同剂次免疫家兔的抗芽胞和毒素IgG应答,总结分析了各种灭活和裂解炭疽芽胞疫苗用于新疫苗成分之一的可能性。甲醛灭活炭疽芽胞疫苗设芽胞浓度2.5×108剂量组、5×108剂量组、1×109剂量组,于0、4、8周时3次免疫。在3剂免疫后血清抗炭疽芽胞IgG水平持续升高,首次免疫后4、8、12周时家兔血清中抗芽胞IgG几何平均滴度可达到600～16000。裂解炭疽芽胞疫苗的制备和动物免疫中,只采取了2.5×108芽胞浓度,两剂免疫,免疫时间为0、4周。在首次免疫后4、8、12周时家兔血清中抗芽胞IgG几何平均滴度分别为362、776和388。各时间点采集的家兔血清未能测出或只测出极微量的抗炭疽毒素IgG。通过上述研究认为,以裂解炭疽芽胞抗原作为炭疽疫苗成分之一,其抗原性和免疫原性是适宜的;免疫剂量可以设定为2.5×108芽胞浓度上下;免疫次数可定为2剂间隔1个月。     

Surface plasmon resonance and free oscillation rheometry in combination: a useful approach for studies on haemostasis and interactions between whole blood and artificial surfaces

In haemostatic and biomaterial research biological processes at surfaces and in the bulk phase of the surface-contacting medium are important. The present work demonstrates the usefulness of the combination of surface plasmon resonance (SPR), sensitive to changes in refractive index at surfaces, and free oscillation rheometry (FOR), sensitive to rheological properties of the bulk, for simultaneous real-time measurements on coagulation and fibrinolysis of blood plasma and coagulation of whole blood. SFLLRN stimulated coagulation of native whole blood presented a higher SPR signal with different appearance than plasma coagulation, while the FOR signals corresponding to plasma and whole blood coagulation were similar. This indicated that the SPR technique was more sensitive to cell-surface interactions than to fibrin formation in whole blood during coagulation, while the FOR technique were equally sensitive to coagulation in whole blood and plasma. Spontaneous coagulation of native whole blood in contact with methyl- and hydroxyl-terminated self-assembled monolayers (SAM) on gold and gold surfaces regenerated after coagulation were also studied. The regenerated gold surfaces displayed the shortest coagulation times, although the contact-activation of blood coagulation for these surfaces was low. The methylated and hydroxylated surfaces were comparable in terms of coagulation activation, while the hydroxylated surfaces presented FOR signals that indicated detaching of the coagulum from the surface. The combination of SPR and FOR is well suited for studies of cell- and protein-surface interactions and simultaneous bulk processes. Possible applications are investigations of blood cell defects in patients and monitoring of native whole blood interactions with artificial surfaces.