急性乙型肝炎纤维蛋白原水平及其功能的研究

目的了解急性乙型肝炎血浆中纤维蛋白原的浓度与其纤维蛋白单体的聚合功能.方法以蕲蛇毒水解纤维蛋白原,用计算机自动检测系统测定.结果40例急性乙型肝炎纤维蛋白单体聚合反应速率(FMPS)为0.380±0.100,最大吸光度(Amax)为0.199±0.032,凝固性纤维蛋白原浓度(FC)为1.99±0.46g/L,功能指数(FI)(FMPS/Amax)1910.反应延滞时间(DT)0±1s,均低于正常,除FI外P值均＜0.05.结论急性乙型肝炎因肝功能受损常影响凝血功能.本研究发现病人呈低凝状态,可能导致出血倾向.     

脂肪肝患者血浆纤维蛋白原与纤维蛋白单体聚合功能的测定及临床意义

目的测定脂肪肝患者血浆中纤维蛋白原的浓度与纤维蛋白单体聚合功能,以了解其凝血功能.方法以蕲蛇酶水解纤维蛋白原,用计算机测定其相关数值.结果 20名脂肪肝患者,其纤维蛋白聚合反应速率为0.393±0.07g/min;最大吸光度为0.201±0.045OD;纤维蛋白原浓度为1.943±0.44(g/L);反应延滞时间为22±3.5sec.结论脂肪肝患者除纤维蛋白原水平降低外,其功能反应也减弱,但尚无出血之虞.     

乙型肝炎患者血浆纤维蛋白原的变化及临床意义

目的：探讨乙型肝炎病毒所致各类型肝病患者血浆中纤维蛋白原（Fbg）水平与功能变化的临床意义。方法：将连续收治的乙型肝炎患者96例根据疾病类型分为4组：急性乙型肝炎组（40例）；亚急性重症乙型肝炎组（12例）；慢性乙型肝炎组（30例）；乙型肝炎病毒致肝硬化失代偿期（14例）；对照组（30名）为健康查体者。采用微电脑自动测定系统对其血浆Fbg水平与功能进行系列测定。结果：与对照组比较，除急性乙肝组Fbg功能指数差异无显著性意义外（P〉0．05），其余各组Fbg的各项指标：包括纤维蛋白单体聚合反应速率、最大吸光度、凝固性纤维蛋白原含量、反应迟滞时间、功能指数，差异均有显著性意义（P〈0．05～0．001）。结论：在乙型肝炎病毒所致的各类型肝病中进行纤维蛋白原系列检测，能反映患者肝功能受损时所涉及的凝血功能变化，对判断预后有帮助。     

肝硬化患者纤维蛋白原结合唾液酸水平的研究

应用饱和硫酸铵制备纯化纤维蛋原,硫代巴妥酸法测定了肝硬化患者纤维蛋白原结合唾液酸(FSA)的水平,结果显示病人的纤维蛋白原结合唾液酸水平23.6±2.6nmul/mg,显著高于正常对照组18.4±3.7mol/mg(P＜0.01),并且凝血酶时间的延长与FSA的升高呈高度正相关(P＜0.01);纤维蛋白单体聚合的速度与纤维蛋白原结合唾液酸成反比.表明纤维蛋白原结合唾液酸的水平可作为诊断肝硬化获得性异常纤维蛋白血症拘理想指标.     

冠心病及健康者男女βHae多态性与血浆纤维蛋白原浓度比较

目的 :分析比较冠心病 (CHD)及健康者男女β纤维蛋白原基因启动子区 Hae (β Hae )多态性和血浆纤维蛋白原浓度的差异。方法 :经冠状动脉造影确诊的 CHD患者 94例 (男 82例 ,女 12例 ) ,健康对照组 6 8例(男 31例 ,女 37例 ) ,采用酚 /氯仿抽提方法从白细胞中提取人基因组 DNA,经多聚酶链式反应 (PCR)加 Hae 内切酶技术检测目的基因片段 ;Follin酚法测定血浆纤维蛋白原浓度。结果 :在 CHD患者和健康者中 ,男女性别间 βHae 多态性分布频率明显不同 ,女性 H1H2杂合基因型比例高于男性 (男比女 :CHD组为 0 .31比 0 .5 0 ,对照组为0 .13比 0 .32 ,P <0 .0 5 ) ,男性表现为 H2 H2纯合基因型 (CHD组比对照组为 0 .0 5比 0 .0 3) ,女性未发现 H2 H2基因型 (P <0 .0 5 )。男性血浆纤维蛋白原浓度较女性高 ,CHD组分别为 (5 .4± 0 .9) g/ L ,(4.7± 1.1) g/ L ,P <0 .0 5 ;对照组为 (4.5± 0 .9) g/ L ,(4.4± 0 .8) g/ L ,P >0 .0 5。结论 :无论是 CHD患者还是健康人群 ,男女性别间βHae 多态性分布频率和血浆纤维蛋白原浓度存在明显差异     

肾小球疾病患者凝血和纤溶功能的改变与血清脂蛋白(a)变化的关系

目的:研究肾小球疾病患者纤维蛋白单体聚合功能(FMPF)、D-二聚体(D-D)的改变与血清脂蛋白(a)[(Lp(a)]变化的关系。方法:用纤维蛋白单体聚合功能动力学法、免疫比浊法、酶联免疫吸附法(ELISA法)和酶动力学法分别测定健康人和肾小球疾病患者的纤维蛋白单体聚合速率(FMPV)、纤维蛋白原(Fbg)、D-D及LP(a)。结果:患者血清FMPV、Fbg、D-D及LP(a)水平均显著或极显著增高(P<0．05或P<0．01),LP(a)的增高与FMPV、Fbg、D-D的增高呈正相关(r=0．453)。结论:Fbg的质与量显著增高,提示凝血激活的持续存在;反映肾小球内凝血和纤溶的关系D-D明显增加;具有抗纤溶作用的Lp(a)显著增加,且与FMPV和D-D的增高呈正相关。因此本研究认为上述指标为肾脏疾病的血栓形成及预后判断提供了可靠的实验依据。     

血尿酸与纤维蛋白原Bβ链7个位点基因多态性及其功能表达的关系

目的研究尿酸与纤维蛋白原(fibrinogen,Fib)Bβ链-1420G/A、-993C/T、1689T/G、BsmAIG/C、I6I/D、345C/T和HinfIA/C位点的基因多态性及其血浆Fib和聚合功能表达的关系。方法选取开滦集团离退休职工940例,均抽取清晨空腹静脉血测定血生化、尿酸、血浆Fib,以及纤维蛋白单体聚合速率(FMPV)、最大吸光度(Amax)和FMPV/Amax等反映Fib聚合功能的指标,并检测Fib Bβ链7个位点的基因多态性。依据尿酸值将人群分为高尿酸血症组111例和正常尿酸组829例,分析尿酸异常与血浆Fib相关指标的关系。结果高尿酸血症组-1420GG型、-993CC型、1689TT型、BsmAIGG型、HinfIAC+CC型人群FMPV/Amax明显低于正常尿酸组,I6II型、345CC型人群Fib、FMPV、Amax、FMPV/Amax明显低于正常尿酸组(P<0.05);以尿酸为因变量的多元逐步回归分析,依次筛选出男性、VLDL-C、肌酐、体质量指数、尿素、血糖、高血压及FMPV/Amax等指标(P<0.05,P<0.01)。结论高尿酸作为缺血性脑血管病的重要危险因素,并非仅通过影响血浆Fib系统发挥作用,而可能还与高脂血症、血糖异常以及引发的特殊类型慢性炎性反应共同参与其发病的结果。     

脑梗死与血浆D-二聚体/纤维蛋白原比值的关系

目的:探讨脑梗死与血浆D-二聚体(D-dimer)、纤维蛋白原(Fbg)及2者比值(D／F值)的关系。方法:全自动凝血分析仪检测47例脑梗死患者及34例健康人血浆D-dimer及Fbg水平,并分别计算出2组D／F值。结果:脑梗死组血浆D-dimer、Fbg及D／F值明显高于健康对照组,差异均有统计学意义(P<0．05);脑梗死组D-dimer与Fbg之间存在正相关性(r=0．295,P<0．05)。结论:D／F值可作为支持脑梗死诊断的指标之一。     

碱性电解水对大鼠抗氧化及抗纤维蛋白原作用的实验研究

目的　探讨碱性电解水抗氧化及抗纤维蛋白原的作用。方法　W istar雄性大鼠 36只 ,分三组 ,每组 1 2只。A组 :空白对照 ,B组 :高脂模型组。 C组 :高脂 +碱性电解水组。实验结束后 ( 30 d) ,乙醚麻醉 ,腹主动脉取血 ,采用硫代巴比妥酸比色法在日本岛津 UV— 36 0分光光度计上测定丙二醛 ( MDA) ;上海斯隆纤维蛋白原测定仪测定纤维蛋白原。结果　 A、B、C三组 M DA分别为 3.39± 0 .50 ( nmol/ m1 )、4 .1 0± 0 .37及 3.6 8±0 .4 6 ;纤维蛋白原分别为 1 94 .6 3± 2 3.6 3( mg/ d1 )、2 0 1 .2 2± 2 4 .32及 1 6 9.50± 1 1 .1 7。 C组比 B组显著下降 ( P<0 .0 5)。结论　碱性电解水具有一定抗氧化及降低纤维蛋白原的功能。     

不稳定型心绞痛危险分层中血纤维蛋白原浓度的临床意义

目的　本文旨在探讨血纤维蛋白原浓度在不稳定型心绞痛不同危险分层中的变化。方法　将 162例入选的不稳定型心绞痛患者 ,分成高危组 ( n=3 4)、中危组 ( n=5 8)及低危组 ( n=70 ) ,同时测定三组血浆纤维蛋白原及心脏肌钙蛋白 T( c Tn T)浓度。结果　三组血纤维蛋白原浓度有显著性差异 ,随危险分层的增高 ,血纤维蛋白原浓度有增加的趋势 [( 3 98.3 6± 12 6.3 2 ) m g/ dl( 42 5 .75± 14 3 .5 2 ) m g/ dl及 ( 473 .15± 160 .61) mg/ dl,P<0 .0 1]。结论　血纤维蛋白原浓度有助于不稳定型心绞痛的危险分层 ;血纤维蛋白原升高提示 ,不稳定型心绞痛患者危险分层高 ,有较强的血栓形成趋势。     

纤维蛋白原Bβ—249C／T和Bcl-1G／A基因多态性与脑梗死的相关性研究

目的研究纤维蛋白原（Fg）Bβ-249C／T和Bcl-1G／A基因多态性与血浆Fg浓度、分子聚合活性等指标和脑梗死（CI）的关系。方法选取160例急性CI患者、114例陈旧CI患者和160例正常对照者,应用PCR方法进行Bβ—249C／T和Bcl-1G／A位点的基因多态性分析;采用微机辅助血浆如功能自动监测系统测定血浆Fg浓度、Fg单体聚合反应速率（FMPV）、最大光密度（Amax）、FMPV／Amax等。结果急性CI组Bβ—249C／T的CT＋TT型FMPV／Amax低于CC型,Bcl-1G／A的GA＋AA型Fg浓度、FMPV均高于GG型,陈旧cI组Bcl-1G／A的GA＋AA型FMPV／Amax高于GG型,正常组Bcl-1G／A的GA＋AA型Fg浓度高于GG型（P均〈0．05）。结论FgBβBcl-1G／A变异基因型可调控血浆Fg含量,吸烟、血糖升高等因素可通过Bcl-1G／A变异基因型使血浆赡浓度和FMPV的表达增强,Bcl-1G／A变异基因型是CI发病或复发的高危人群。     

Intraperitoneal coagulation in chronic liver disease ascites

Twenty patients with the ascites of chronic liver disease were investigated for in vivo evidence of active coagulation within ascites by detection of fibrin monomer. Increased levels of fibrin monomer, increased fibrin/fibrinogen degradation products, and absent or low levels of fibrinogen in the ascites of all patients tested confirmed the presence of intraperitoneal coagulation when ascites is present.Portions of this data have been published in abstract form (Gastroenterology 76(5), part 2:1155, May 1979) and presented to the American Association for the Study of Liver Diseases, New Orleans, May 22, 1979.     

Detection of soluble intermediates of the fibrinogen-fibrin conversion using erythrocytes coated with fibrin monomers

The presence of minimal amounts of fibrinogen-fibrin intermediates in human plasma was visualized by an agglutination reaction of glutaraldehyde-treated human erythrocytes coated with purified fibrin monomers. A degree of monomer coating was established which produced erythrocytes not agglutinated by normal plasma but by plasma containing minimal amounts of soluble complexes of fibrinogen with fibrin monomers. Under standardized conditions of coating, erythrocyte concentration, temperature, pH, and incubation time, the agglutination time varied with the ratio of soluble fibrin to fibrinogen in plasma. The test was sensitive down to a soluble fibrin concentration of 0.675% of the plasma fibrinogen concentration. Early fibrinogen and fibrin degradation products (FDP) in the plasma led to a prolongation of the agglutination time at a concentration of more than 16 mg/100 ml. Late FDP in a concentration of 100 mg/100 ml did not convert a positive test to negative. The test was not affected by heparin and protamine at concentrations of up to 12.5 and 50 NIH units/ml, respectively.     

Effects of divalent cations on the conversion of fibrinogen to fibrin and fibrin polymerization

Effects of divalent cations on fibrinogen and its reaction with thrombin were re-examined and correlated to improve definition of mechanisms underlying the acceleration of clot formation by the ions. The rate of release of fibrinopeptides from fibrinogen was not affected by any of the specific ions studied, but increased rates of fibrin monomer polymerization were obtained with all but magnesium ions. Maximal acceleration of monomer polymerization was observed with the divalent ions at concentration of 2.5–5 mM, and no added specific ion effects were observed with much higher levels. The acceleratory ions were found to have a corresponding effect on the solubility of fibrinogen, as judged from acceleration of its precipitation at low temperature. Although magnesium ions had no effect on fibrin monomer polymerization, they did have a low ranking effect on cryoprecipitation. These data confirm that the principal effect of divalent cations in the fibrinogen-fibrin transformation is to accelerate fibrin monomer polymerization, and suggest that the acceleration is associated with effects on the solubility of fibrinogen.     

Analysis of fibrin formation and proteolysis during intravenous administration of ancrod

Ancrod is a purified fraction of venom from the Malayan pit viper, Calloselasma rhodostoma, currently under investigation for treatment of acute ischemic stroke. Treatment with ancrod leads to fibrinogen depletion. The present study investigated the mechanisms leading to the reduction of plasma fibrinogen concentration. Twelve healthy volunteers received an intravenous infusion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were drawn and analyzed before and at various time points until 72 hours after start of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading to the formation of desAA-fibrin monomer. In addition, a considerable proportion of desA-profibrin is formed. Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod. Both desA-profibrin and desAA-fibrin monomers form fibrin complexes. A certain proportion of complexes carries exposed fibrin polymerization sites E(A), indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Soluble fibrin complexes potentiate tissue-type plasminogen activator-induced plasminogen activation. Significant amounts of plasmin are formed when soluble fibrin in plasma reaches a threshold concentration, leading to the proteolytic degradation of fibrinogen and fibrin. In the present setting, high concentrations of soluble fibrin are detected after 1 hour of ancrod infusion, whereas a rise in fibrinogen and fibrin degradation products, and plasmin-alpha(2)-plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cross-inked fibrin degradation product D-dimer in plasma. (Blood. 2000;96:2793-2802)     

活化蛋白C抵抗对老年人凝血、抗凝血系统指标的影响

目的探讨活化蛋白C抵抗（APCR）对老年血栓性疾病患者凝血、抗凝血系统功能状态的影响。方法采用酶联免疫分析法测定凝血酶原片段1+2（F1+2）、纤维蛋白肽A（FPA）、可溶性纤维蛋白单体复合物（SFMC）;使用CA-530血液凝固仪测定纤维蛋白原（FIB）、抗凝血酶-Ⅲ抗原（AT-ⅢAg)及活性(AT-ⅢA）、蛋白C抗原（PCAg)及活性(PCA）及APCR。结果老年血栓性疾病患者中APCR正常者血F1+2、FPA、SFMC和FIB分别为(5.4±0.6)nmol/L、(6.9±1.9)μg/L、(72.4±8.7)g/L和(5.18±0.68)g/L,与健康老年人〔(2.6±1.3)nmol/L、(4.8±2.3)μg/L、(56.3±11.7)g/L和(3.82±0.74)g/L〕比较显著增高（P＜0.01）;血AT-ⅢAg和PCAg分别为(212±19)mg/L和(63.5±9.2)mg/L,较健康老年人〔(255±26)mg/L和(82.7±20.1)mg/L〕显著降低（P＜0.01）,APCR阳性者上述改变更为显著。结论APCR可导致老年血栓性疾病患者凝血途径活化加速,凝血系统功能显著增强,抗凝血系统功能显著降低,这可能是APCR阳性者血栓形成危险性高于APCR正常者的原因之一。     

Fibrin monomer induces binding of endogenous platelet von Willebrand factor to the glycocalicin portion of platelet glycoprotein IB

This study demonstrates that when platelets are stimulated by thrombin in the presence of low concentrations of purified human fibrinogen (10 to 20 micrograms/mL, final concentration) binding of released platelet von Willebrand factor (plt-vWF) to the platelet membrane is enhanced. This effect appears to be mediated by fibrin monomer produced by the action of thrombin on the fibrinogen in the incubation suspension. When fibrin polymerization is inhibited, the binding of released plt-vWF to the platelets is markedly increased. This enhanced binding is dependent on platelet glycoprotein Ib (GPIb) as shown by a decreased response with Bernard-Soulier platelets and inhibition by both monoclonal and polyclonal antibodies against glycocalicin. The binding of fibrin to thrombin-activated platelets preincubated with monoclonal antibody against GPIIb/IIIa is increased when the predominant form of fibrin is fibrin monomer. The fibrin binding is also decreased in the presence of antibody against glycocalicin. Our data demonstrate that fibrin monomer facilitates plt-vWF binding to the glycocalicin portion of platelet GPIb on thrombin-stimulated platelets and that binding of fibrin monomer to glycocalicin is necessary for this response to occur.     

Platelet and fibrin modification by radiographic contrast media.

The effect of the radiographic contrast agents, iopamidol and diatrizoate, on fibrin assembly and structure as well as platelet surface charge was studied. Increasing the iopamidol concentration from 0 to 4.5 mM prolongs the fibrin gelation time from 20 to 105 seconds (an anticoagulant effect) and reduces the fibrin fiber mass/length ratio from 3.2 x 10(12) to 0.5 x 10(12) Da/cm (i.e., produces very thin fibrin fibers). Ultraviolet difference spectroscopy of fibrinogen showed both a 15-nm shift in the ultraviolet difference maximum for iopamidol (suggesting binding) and a perturbation of the aromatic amino acid side chain region for fibrinogen (suggesting a conformational change in fibrinogen) as the concentration of iopamidol was increased from 0 to 9 mg/ml. Binding of iopamidol to fibrinogen was also shown by affinity chromatography using a Sepharose-fibrinogen column. Electrophoretic quasi elastic light scattering was used to show platelet interaction with iopamidol as reflected in a reduction in the platelet electrophoretic mobility from 2.0 to 0.5 (microns-cm)/(V-sec) as the concentration of iopamidol was increased from 0 to 4.5 mM. In addition, the ionic radiopaque contrast agent, Renografin, was also studied and found to inhibit fibrin monomer assembly. Although iopamidol is not shown to be thrombogenic, iopamidol does appear to reduce platelet surface charge, bind fibrinogen, and modify fibrin clot structure.     

Fibrin formation: effect of calcium ions

Using laser fluctuation spectroscopy, a technique that measures particle size change in solution, the kinetics of fibrin clot formation from fibrinogen can be studied. With this technique the effect of calcium on the three distinguishable phases of clot formation, (1) proteolysis of fibrinogen, (2) fibrinogen-fibrin monomer complex formation, and (3) fibrin monomer polymerization, were investigated. Only a small change in the length of the induction period that results from the fibrinogen-fibrin monomer interactions was observed. However, there was a marked increase in the rate of fibrin monomer polymerization in the presence of calcium ions. These data show that calcium decreases the time required for fibrin formation from fibrinogen by markedly accelerating the phase of fibrin monomer polymerization.     

Soluble fibrin monomer complexes demonstrated by agarose gel filtration and by adsorption on insolubilized fibrinogen: a comparative study.

Incubation of fibrinogen with small amounts of thrombin resulted in the occurrence of soluble fibrin monomer complexes. These complexes consisted predominantly of a derivative with a higher molecular weight than that of fibrinogen. It was characterized by its relative electrophoretic mobility in 5% PAA gel (0.28 X 10(-5) cm2/V X sec) and its elution position prior to the fibrinogen peak following gel filtration. Using adsorption chromatography on insolubilized fibrinogen the derivative dissociated at a ratio of almost 1 : 1 into one part which was adsorbed and into fibrinogen which was not adsorbed. The part which was adsorbed seemed to be the thrombin mediated fibrin monomer. This study confirms the concept that dissociable dimeric fibrinogen-fibrin monomer complexes occur after limited action of thrombin on fibrinogen.