老年不稳定型心绞痛患者纤维蛋白、纤维蛋白原及其降解产物的变化

目的探讨凝血系统在老年人不稳定型心绞痛（ＵＡ）发生和发展中的作用。方法采用一组抗纤维蛋白单克隆抗体（ＳＺ－５８、６４、６５）酶免疫分析法测定２６例老年ＵＡ患者、２４例稳定型心绞痛（ＳＡ）患者和２０例健康老年人（对照组）血浆纤维蛋白原（Ｆｇ）、可溶性纤维蛋白复合物（ＳＦＣ）及血清纤维蛋白降解产物（ＦＤＰ）的浓度。结果ＵＡ患者心绞痛发作时血浆Ｆｇ、ＳＦＣ及血清ＦＤＰ浓度（分别为３．７±０．６ｇ／Ｌ、４９．６±１９．３ｍｇ／Ｌ、３２５．６±７９．４μｇ／Ｌ）显著高于ＳＡ患者心绞痛发作时（分别为３．２±０．６ｇ／Ｌ、２０．９±１０．４ｍｇ／Ｌ、２２４．４±４７．４μｇ／Ｌ）和健康对照组（均为Ｐ＜０．０１），后两者间差异无显著性。ＵＡ发作终止后血浆Ｆｇ和血清ＦＤＰ浓度高于健康对照组，但差异无显著性。结论血栓形成是老年人ＵＡ发生和发展的重要因素之一。     

纤维蛋白(原)、纤维蛋白(原)降解产物及其基序拮抗剂与动脉粥样硬化

动脉粥样硬化是缺血性脑血管病最主要的病理学基础。作为动脉粥样硬化的独立危险因素,纤维蛋白(原)及其降解产物参与了动脉粥样硬化的形成和发展过程。文章综述了纤维蛋白(原)及其降解产物与动脉粥样硬化的关系,并对纤维蛋白(原)某些特定基序拮抗剂在治疗动脉粥样硬化和缺血性脑血管病方面的开发和应用前景做了介绍。     

不稳定性心绞痛患者内皮素和纤维蛋白(原)及其降解产物的变化

目的：探讨内皮素（ＥＴ）和凝血系统在不稳定性心绞痛发生和发展中的作用。方法：采用酶联免疫吸附双抗体夹心法测定不稳定性心绞痛组（ｎ＝３０）、稳定性心绞痛组（ｎ＝２５）和正常人组（ｎ＝２０）血浆纤维蛋白原、可溶性纤维蛋白复合物及血清纤维蛋白降解产物，同时用放射免疫法测定血浆ＥＴ的浓度。结果：不稳定性心绞痛组患者心绞痛发作时血浆ＥＴ、纤维蛋白原、可溶性纤维蛋白复合物及血清纤维蛋白降解产物浓度显著高于稳定性心绞痛组患者心绞痛发作时和正常人组（Ｐ＜０．０１），后两者间无显著差异。不稳定性心绞痛组患者心绞痛终止后血浆纤维蛋白原和血清纤维蛋白降解产物与正常人组无显著差异。血浆ＥＴ、可溶性纤维蛋白复合物也趋下降，仍显著高于正常人组（Ｐ＜０．０５）。结论：提示冠状动脉痉挛和血栓形成在部分不稳定性心绞痛的发病中可能具有重要意义     

老年不稳定型心绞痛患者纤维蛋白,纤维蛋白原及其降解产物？…

目的 探讨凝血系统在老年人不稳定型心绞痛（ＵＡ）发生和发展中的作用。方法 采用一组抗纤维蛋白单克隆抗体（ＳＺ－５８、６４、６５）酶免疫分析法测定２６例老年ＵＡ患者、２４例稳定型心绞痛（ＳＡ）患者和２０例健康老年人（对照组）血浆纤维蛋白原（Ｆｇ）、可溶性纤维蛋白复合物（ＳＦＣ）及血清纤维蛋白降解产物（ＦＤＰ）的浓度。结果 ＵＡ患者民心绞痛发作时血浆Ｆｇ、ＳＦＣ及血清ＦＤＰ浓度（分别为３．７±０．６ｇ     

急性白血病血管内皮细胞活性功能的研究

应用放射免疫法、Ｌａｕｒｅｌｌ＇ｓ５火箭免疫电泳法、交叉免疫电泳法和发色底物法对急性白血病（急白）患者中由血管内皮细胞产生释放的一些重要活性因子如ｖｏｎＷｉｌｌｅｂｒａｎｄ因子相关抗原（ｖＷＦ：Ａｇ）、前列环素、血浆纤维结合蛋白（Ｆｎ）、血浆纤溶酶原激活物（ｔ－ＰＡ）和抑制物的水平和活性变化进行研究，并探讨这些活性因子与急白病情变化及疗效转归的关系，揭示血管内皮细胞在急白中的地位。结果发现急白患者血浆中ｖＷＦ：Ａｇ、血浆６－酮－前列腺素Ｆ＿（１α）和ｔ－ＰＡ显著高于正常水平，在有出血倾向患者中有特征性变化，病情好转后逐渐趋向正常。急白在发生感染、出血或慢性粒细胞白血病急变时其血浆Ｆｎ明显低于正常水平。急白患者ｖＷＦ和Ｆｎ质量也有变化。     

类风湿关节炎患者血浆纤维蛋白原/纤维蛋白降解产物和D-二聚体水平与病情活动性的相关性研究

目的 分析类风湿关节炎(RA)患者血浆纤维蛋白原/纤维蛋白降解产物(FDP)、D-二聚体(DD)和纤维蛋白原(Fg)水平,探讨纤溶活性增强与RA病情活动性的关系.方法 活动性RA组50例,病情缓解RA组50例.应用血凝仪、特定蛋白仪等,采用免疫散射比浊法测FDP、DD和C反应蛋白(CRP),Clauss法测定Fg水平;光学毛细管法测红细胞沉降率(ESR);免疫透射比浊法测类风湿因子(RF)IgG.采用两样本t检验、x2检验、直线相关进行统计学分析.结果 活动性RA组FDP,DD和Fg升高(12.0±8.2)μg/ml,(3.1±3.1)μg/ml,(4.6±1.4)g/L],与RA缓解组[(2.1±1.1)μg/ml,(0.4±0.4)μg/ml,(3.0±0.6)g/L]比较差异有统计学意义(F＞1.60,P＜0.05;t’＞2.69,P＜0.01).FDP,DD性别差异无统计学意义(t＜2.00,P＞0.05);活动组与缓解组男性Fg均高于女性(t=2.19,2.38;P＜0.05).FDP与疾病活动指数(DAS28)呈直线正相关(r=048,P＜0.01),与ESR呈直线正相关(r=0.28,P＜0.05).DD与DAS28,ESR呈直线正相关(r=0.69,0.52,P均＜0.01).Fg与DAS28,ESR,CRP呈直线正相关(r=0.57,0.64,0.68,P均＜0.01).FDP,DD,Fg与RF水平无直线相关(r=-0.07,0.06,-0.01,P均＞0.05).FDP对活动性RA诊断的灵敏度94％、特异性100％、Kappa值0.94;DD为90％,86％,0.76;Fg为60％,88％,0.48.结论 活动性RA患者FDP与DD升高,纤溶活性增强与病情活动性密切相关,FDP、DD升高可作为RA活动的判断依据.诊断活动性RA的准确性FDP＞CRP＞DD＞ESR＞Fg＞RF;RF对FDP和DD测定结果无影响.     

三参通脉合剂对冠心病病人纤溶酶、纤维蛋白原影响的临床研究

目的：探讨三参通脉合剂对冠心病病人纤溶酶、纤维蛋白原的影响。方法：选择128例冠心病病人，其中治疗组82例，对照组46例，治疗组服三参通脉合剂，对照组服长效心痛定，测定治疗前后纤溶酶、纤维蛋白原，并观察临床疗效。结果：治疗组病人纤维蛋白原治疗后较治疗前降低，纤溶酶较治疗前升高。心绞痛疗效比较，治疗组总有效率为92．68％，高于对照组。各组病人心电图疗效比较，治疗组总有效率为69．51％高于对照组。结论：三参通脉合剂可改善冠心病病人血液高凝状态，改善心肌缺血，缓解心绞痛。     

纤维蛋白(原)降解产物检测在血栓性疾病中的研究

【】目的：探讨纤维蛋白(原)降解产物(FDP)检测在血栓性疾病中的研究。方法：选取2015年4月~2017年2月我院收治的急性脑梗死(ACI)患者82例、深静脉血栓(DVT)患者59例、急性心肌梗死(AMI)76例,分别设为ACI组、DVT组、AMI组,分别于治疗前和溶栓治疗后采用胶体免疫比浊法定量检测血浆FDP含量,另选取同期健康志愿者64名为对照组,评价FDP在血栓性疾病诊断的效能。结果：溶栓治疗前,ACI组、DVT组、AMI组血浆FDP含量及阳性率均明显高于对照组(P＜0.05);血浆FDP对DVT的诊断效能最高,其灵敏性、特异性、阳性预测值、阴性预测值分别为83.05%、100.00%、100.00%、86.49%;溶栓治疗2h后,ACI组、DVT组、AMI组有效亚组患者血浆FDP含量均明显高于无效亚组,而在溶栓治疗24h、48h后,有效亚组患者在溶栓治疗24h、48h后血浆FDP含量均明显低于治疗无效亚组(P＜0.05)。结论：血浆FDP含量测定对ACI、DVT、AMI等血栓性疾病的早期诊断具有一定的作用,溶栓治疗期间监测血浆FDP含量有助于评估溶栓效果。     

New strategies in the determination of fibrin and fibrin(ogen) derivatives by monoclonal antibodies

Summary Until recently only tests with a limited specificity were available for the assessment of the products of activated coagulation and/or fibrinolysis. Those assays were based on polyclonal antibodies, which crossreact with fibrinogen, and as a consequence they were performed on serum samples i.e. after removal of fibrinogen by clotting. Serum preparation, however, is a notorious source of artefactually high or low levels of fibrin(ogen) degradation products, and is not suitable for the determination of coagulation products. Recently, highly specific monoclonal antibodies (MoAb's) have been developed, the majority of which do not crossreact with fibrinogen. This has enabled new strategies to be developed, i.e. assays using these MoAb's on plasma samples. Furthermore, the new assays can discriminate between (individual) fibrin and fibrinogen degradation products, and coagulation products can be assessed in the same plasma samples.     

Association between plasma levels of D-dimer and fibrinogen/fibrin degradation products (FDP) for exclusion of thromboembolic disorders

Background: D-dimer and fibrinogen/fibrin degradation products (FDP) levels are elevated in subjects with thromboembolic disorders, and the assays for detection of D-dimer and FDP are used in many laboratories for the investigation of these disorders. The aim of this study was to evaluate the association between the plasma levels of D-dimer and FDP in the investigation of thromboembolic disorders. Methods: D-dimer and FDP immunoassays were performed in 217 consecutive blood samples from subjects with suspected of thromboembolic disorders by use of Liatest D-dimer and Plasma FDP. Results: FDP results were classified in: <5, 5–20, >20 μg/mL, and D-dimer levels obtained in these groups ranged to 350–1210 ng/mL, 420–1960 ng/mL, and 1190–51170 ng/mL, respectively. A significant association between D-dimer levels and the reaction times necessary to occur agglutination in latex agglutination test for FDP was observed. Conclusions: There was an association between plasma levels of D-dimer and FDP. The preliminary determination of FDP levels could be useful because it allows estimating the D-dimer levels before of the automated systems analysis, reducing costs associated to dilutions of plasma samples.     

Estimation of the levels of D-dimer by use of an alternative method based in the reaction time of fibrinogen/fibrin degradation products assay

Background D-dimer and fibrinogen/fibrin degradation products (FDP) levels are elevated in thromboembolic disorders, and its assays are used in many laboratories for the investigation of these disorders. The aim of this study was to propose a cost saving alternative method for determination of D-dimer levels based in the reaction time of FDP assay. Methods D-dimer and FDP immunoassays were performed in 100 blood samples from subjects by use of Liatest D-dimer and Plasma FDP. The results of D-dimer obtained by the Liatest D-dimer were compared with the results obtained by the estimation method. Results A significant association between D-dimer levels and the reaction times necessary to occur agglutination in latex agglutination test for FDP was observed. A close agreement between D-dimer results obtained by the Liatest D-dimer and by the estimation method (D-dimer = 82829 FDPt^−0.8683) was observed. Conclusions The estimation method described in this study could be useful for clinical laboratories because it allows estimating the D-dimer levels before of the automated systems analysis, reducing costs associated to dilutions of plasma samples and reagents.     

Specific identification of fibrin(ogen) degradation products in plasma and serum using blotting and peroxidase labeled antiserum

We describe a method for identifying fibrinogen and fibrin split products using electrophoresis on agarose gel with sodium dodecyl sulfate (SDS) followed by blotting in nitrocellulose paper. Detection of these derivatives after blotting is accomplished with peroxidase-conjugated rather than by isotopically labeled antibodies. This technique can detect diverse fibrinogen derivatives produced in vivo or in vitro by the combined action of thrombin, plasmin, and factor XIII. This methodology is applicable to plasma, serum, and other body fluids including urine and ascitic fluid. This sensitive and specific assay, distinguishing the products of cross-linked fibrin from those of fibrinogen and detecting fibrin polymers in plasma, can be achieved without the use of radioactivity.     

Unique secretory dynamics of tissue plasminogen activator and its modulation by plasminogen activator inhibitor-1 in vascular endothelial cells

We analyzed the secretory dynamics of tissue plasminogen activator (tPA) in EA.hy926 cells, an established vascular endothelial cell (VEC) line producing GFP-tagged tPA, using total internal reflection-fluorescence (TIR-F) microscopy. tPA-GFP was detected in small granules in EA.hy926 cells, the distribution of which was indistinguishable from intrinsically expressed tPA. Its secretory dynamics were unique, with prolonged (> 5 minutes) retention of the tPA-GFP on the cell surface, appearing as fluorescent spots in two-thirds of the exocytosis events. The rapid disappearance (mostly by 250 ms) of a domain-deletion mutant of tPA-GFP possessing only the signal peptide and catalytic domain indicates that the amino-terminal heavy chain of tPA-GFP is essential for binding to the membrane surface. The addition of PAI-1 dose-dependently facilitated the dissociation of membrane-retained tPA and increased the amounts of tPA-PAI-1 high-molecular-weight complexes in the medium. Accordingly, suppression of PAI-1 synthesis in EA.hy926 cells by siRNA prolonged the dissociation of tPA-GFP, whereas a catalytically inactive mutant of tPA-GFP not forming complexes with PAI-1 remained on the membrane even after PAI-1 treatment. Our results provide new insights into the relationship between exocytosed, membrane-retained tPA and PAI-1, which would modulate cell surface-associated fibrinolytic potential.     

Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products.

Several investigators have reported that tumor necrosis factor (TNF) can alter the production of plasminogen activator type-1 (PAI-1) and plasminogen activators (PAs) by endothelial cells in vitro. We have examined the in vivo effects of recombinant human TNF administration on fibrinolysis as assessed by parameters in plasma during a 24-hour period of continuous TNF infusion to 17 cancer patients with active disease. The plasma levels of PAI activity increased sevenfold after 3 and 24 hours of TNF infusion. This was the result of an increase of PAI-1 antigen; PAI-2 antigen was not detectable. Plasma concentrations of tissue-type PA (t-PA) antigen increased twofold to fivefold after 3 and 24 hours of TNF infusion, whereas urokinase-type PA antigen levels in plasma remained unaltered. After 3 hours of TNF infusion the plasma levels of alpha 2-antiplasmin were slightly decreased, 5% on average, suggesting that fibrinolysis continued. After 24 hours of TNF infusion a highly significant increase in fibrin- plus fibrinogen-degradation products, and separately of fibrin degradation products and fibrinogen degradation products, was found. This indicates that fibrinolysis persisted, at least partly, in the presence of high levels of PAI activity. Whereas PAI-1 production increased, t-PA production by human endothelial cells in vitro remains unaltered or even decreases on TNF addition. It has been shown previously that TNF infusion in our patients results in thrombin and fibrin generation. Therefore, it is possible that thrombin, not TNF, is the actual stimulus for t-PA production in our patients. We speculate that fibrin is formed during TNF infusions and that plasmin is generated by t-PA action immediately on the initial formation of (soluble) fibrin molecules. Such a process may explain the generation of degradation products of both fibrin and fibrinogen during infusion of TNF in patients.