血栓前体蛋白在诊断血栓形成性疾病中的应用

血栓前体蛋白(TpP)是血栓形成过程中的一个重要产物,是血栓形成性疾病诊断中的一种重要标志物,血浆TpP含量测定在诊断血栓前状态和血栓病中的重要意义已受到关注.现就TpP在急性心肌梗死、深部静脉血栓形成、弥散性血管内凝血及脑梗死等血栓形成相关性疾病中的诊断应用作一综述.     

血栓前体蛋白在诊断血栓形成性疾病中的应用

血栓前体蛋白（TpP）是血栓形成过程中的一个重要产物,是血栓形成性疾病诊断中的一种重要标志物,血浆TpP含量测定在诊断血栓前状态和血栓病中的重要意义已受到关注.现就TpP在急性心肌梗死、深部静脉血栓形成、弥散性血管内凝血及脑梗死等血栓形成相关性疾病中的诊断应用作一综述.     

血清TpP、hs-CRP、CKMB、cTnI在急性心肌梗死中的诊断意义

目的探讨血栓前体蛋白(TpP)、高敏C反应蛋白(hs-CRP)、肌酸激酶同工酶(CKMB)及心肌肌钙蛋白I(cTnI)联合检测在急性心肌梗死(AMI)中的诊断价值。方法 测定26例急性心肌梗死患者胸痛发作6小时内及24小时TpP、hs-CRP、CKMB及cTnI。结果AMI胸痛发作6小时内TpP的敏感性最高,发病6小时后hs-CRP、CKMB及cTnI显著升高,cTnI阳性持续时间长,而hs-CRP在AMI时可出现明显升高。结论TpP对于AMI具有早期诊断价值,cTnI与hs-CRP、CKMB一起相互补充,具有重要的临床诊断及判断预后的意义。     

血栓前体蛋白检测的临床意义

目的　探讨血浆中血栓前体蛋白 (TpP)浓度变化 ,在诊断DIC或前DIC状态中的意义。方法　应用酶联免疫技术测定 47例健康正常人 ,77例临床不同疾病血浆中TpP浓度 ,同时检测DIC相关指标 ,并进行统计学比较。结果　各临床病例DIC组、未发生DIC组血浆中TpP浓度 (11 2 0±5 10 )mg/L均显著较正常组高 (1 2 9± 1 0 2 )mg/L(P <0 0 0 1) ;DIC组 (13 2 0± 7 96)mg/L较未发生DIC组 (8 3 3± 6 3 0 )mg/L明显增高 (P <0 0 1) ,在DIC组TpP的异常率为 10 0 % ,比其他DIC相关指标异常率高。结论　据实验结果和相关文献表明血浆中TpP浓度测定在诊断DIC或前DIC状态中较之D二聚体、纤维蛋白原等方法具有更高的特异性和敏感性。同时在诊断DIC及其病程发展、疗效评估方面均有一定参考价值     

血栓前体蛋白和糖原磷酸化酶同工酶BB对急性心肌梗死早期诊断的价值

目的 评价血栓前体蛋白(TpP)和糖原磷酸化酶同工酶BB(GPBB)对急性心肌梗死(AMI)早期诊断的潜在价值。方法 选择168例确诊或疑似AMI的患者，以酶联免疫吸附法(ELISA)测定干预前其血浆TpP和GPBB浓度，同期常规检测肌酸激酶同工酶：MB(CK-MB)、门冬氨酸氨基转移酶(AST)牙和心脏肌钙蛋白I(CTnI)，比较这些生化指标对AMI的诊断价值。结果 这五种生化标志物中，TpP和GPBB诊断AMI优势明显，两者灵敏度分别为100％和96．5％：特异度分别为85．5％和90．9％；真实度分别为95．2％和94．1％；阳性预测值分别为93．4％和95．6％；阴性预测值分别为100％和192．6％。结论 血浆TpP和GPBB是有价值的早期诊断AMI的生化指标。     

血栓标志物vWF、GMP-140、TpP、Hey对肺癌诊断的研究

目的探讨血管性假性血友病因子（vWF）、血小板颗粒膜蛋白（GMP-140）、血栓前体蛋白（TpP）、同型半胱氨酸（Hcy）在诊断肺癌血栓前状态的临床价值。方法 1.选取30例Ⅰ～Ⅲa期手术患者作为手术组,30例体检正常者作为对照组。ELISA方法检测vWF、GMP-140、TpP,荧光生化法定量检测Hcy。2.Ⅱ期、Ⅲa期手术病人,取癌旁2cm肺组织,病理组织学检查,寻找微小血栓,比较找到微小血栓的血管根数及相应血液标志物水平变化。结果 1.手术组vWF、GMP-140、TpP、Hcy水平高于对照组（P〈0.01）,术后明显高于术前（P〈0.01）;2.Ⅱ期、Ⅲa期手术标本找到微小血栓的血管根数有统计学差异（P〈0.01）,相应血液标志物水平有统计学差异（P〈0.05）。结论肺癌患者存在血栓前状态,随着肺癌TNM分期,血液指标逐渐升高,肺内存在的微小血栓数目逐渐增多。2.vWF、GMP-140、TpP、Hcy均可作为早期诊断血栓前状态的血液标志物,其中TpP、Hcy具有较高的敏感性与特异性。     

TpP、Fg与CHD患者冠状动脉病变严重程度相关性研究

目的探讨血栓前体蛋白(thrombosome precursor protein,TpP)、血纤维蛋白原(fFibrinogen,Fg)与冠心病(coronary heart disease,CHD)患者冠状动脉病变严重程度的相关性。方法选择120例CHD患者作为观察组,根据SYNTAX积分将患者分为三组,低危组(SYNTAX积分为1～22分)54例、中危组(SYNTAX积分为23～32分)40例、高危组(SYNTAX积分≥33分)26例。选取同期在我院体检中心行常规体检的健康志愿者40例作为对照组。分析四组临床资料及TpP、Fg水平,并分析TpP、Fg与SYNTAX积分、Gensini得分相关性。结果四组年龄、性别、体质量指数、吸烟史、合并高血压、合并糖尿病、高密度脂蛋白胆固醇、总胆固醇、甘油三酯差异无统计学意义(P> 0.05),CHD患者低密度脂蛋白胆固醇高于对照组(t=24.27,P <0.05)。四组Fg、TpP水平差异有统计学意义(P <0.05)。且高危组Fg及TpP水平>中危组>低危组>对照组(F=15.97、20.50,P <0.05)。相关性分析显示,低密度脂蛋白胆固醇、Fg水平、TpP水平与Gensini得分、SYNTAX积分呈正相关(r=0.26～0.47,P <0.05)。结论 TpP和Fg水平与CHD冠状动脉病变严重程度密切相关,冠状动脉病变程度随TpP和Fg水平升高而增加。     

血栓前体蛋白在血栓类疾病中的研究现状

<正> 在纤维蛋白形成过程中,凝血酶从纤维蛋白原上切割掉纤维蛋白肽A,余下的部分称为纤维蛋白单体单位。纤维蛋白单体单位有聚合位点,可以彼此聚合。在聚合过程中,凝血酶从其上再切掉一个纤维蛋白肽B,剩下部分被称为desAABB纤维蛋白。这些可溶性纤维蛋白是不溶性纤维蛋白的直接前体,称之为血栓前体蛋白(TpP)。TpP在血浆中的出现仅见于血管内凝血,是循环中凝血酶的一个标志,目     

血栓前体蛋白和抗凝血酶Ⅲ在糖尿病微血管病变患者中的变化及与脑梗死的相关性研究

目的 探讨糖尿病微血管病变患者体内血栓前体蛋白（TpP）浓度和抗凝血酶Ⅲ（AT-Ⅲ）活性改变及其与糖尿病合并脑梗死的关系. 方法 选取糖尿病微血管病变患者101例和正常对照（NC）者31名,观察各组TpP浓度、AT-Ⅲ活性变化及脑梗死发生的风险指标. 结果 与NC组相比,糖尿病微血管病变组TpP浓度高[（5.53±3.16）vs（3.86±1.37）μg/ml,P＜0.05]、AT-Ⅲ活性低[（92.26±13.97）％vs（102.24±10.45）％,P＜0.05].糖尿病微血管病变合并脑梗死亚组、糖尿病微血管病变未合并脑梗死亚组和NC组TpP浓度、AT-Ⅲ活性比较差异有统计学意义[（6.82±4.12）vs（4.88±2.32）vs（3.86±1.37）μg/ml,P＜0.05;（86.21±13.47）％vs（95.33±13.30）％vs（102.24±10.45）％,P＜0.05].Logistic多元回归分析显示,年龄、SBP、TpP、AT-Ⅲ与脑梗死发生独立相关. 结论 糖尿病微血管病变组TpP浓度升高,AT-Ⅲ活性降低,糖尿病患者机体处于血栓前状态,存在血栓形成风险.糖尿病患者联合检测血浆TpP浓度和AT-Ⅲ活性,有助于血栓性疾病的早期发现及治疗.     

急性冠脉综合征病人血栓前体蛋白、P选择素与血小板聚集率水平变化及临床意义

目的观察急性冠脉综合征(ACS)病人血栓前体蛋白(TpP)、P选择素(Ps)及血小板最大聚集率(MAR)水平并探讨其临床意义。方法选择我院心血管内科住院的ACS病人122例作为ACS组,其中ST段抬高心肌梗死(STEMI)32例,非ST段抬高心肌梗死(NSTEMI)41例,不稳定型心绞痛(UA)49例,所有入选病人均在胸痛等症状发作12 h~24 h入院,未进行抗血小板药物治疗。另入选65例稳定型心绞痛(SAP)病人作为对照组,所有病人于入院时抽取空腹静脉血检测TpP及Ps,并采用SPCM法检测血小板聚集功能。结果与对照组比较,ACS组病人TpP、Ps水平及MAR显著高于SAP病人(P0.05)。与UA病人比较,STEMI病人TpP、Ps、MAR水平均显著增高(P0.05)。结论 ACS病人TpP、Ps水平显著高于SAP病人,发病早期,ACS病人MAR明显升高,提示血小板呈聚集、活化状态。     

Measurement of thrombus precursor protein in septic patients with disseminated intravascular coagulation and liver disease

BACKGROUND AND OBJECTIVES: Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to the widespread deposition of fibrin in the circulation. Therefore, the determination of soluble fibrin is crucial for the diagnosis of DIC. Thrombus precursor protein (TpP) levels can be determined as a measure of soluble polymers, which are the immediate precursors of insoluble fibrin. In this study, the potential diagnostic usefulness of this TpP test was investigated in septic patients with DIC and liver diseases. DESIGN AND METHODS: TpP analysis was performed on 155 plasma samples from 95 septic patients, including 72 patients without liver disease and 23 patients with liver diseases, and on 42 plasma samples from normal healthy subjects. The study population was subdivided according to three phases of DIC described as compensated, decompensated and full-blown DIC. Plasma TpP level was determined using a new assay, the TpPTM (American Biogenetic Sciences, USA), which is based on an ELISA method. RESULTS. Septic patients with decompensated (16.1 9.1 mg/mL) or full- blown (20.9 12.4 mg/mL) phases of DIC had significantly higher TpP levels than those with the compensated (5.6 6.2 mg/mL) phase of DIC or healthy controls (2.9 1.6 mg/mL). In septic patients with liver disease, a significant difference was found between the TpP levels of patients with full- blown DIC (21.6 10.6 mg/mL) and those of patients with the decompensated phase (13.4 6.5 mg/mL). Plasma TpP levels correlated significantly with other DIC parameters including platelet count, fibrinogen, antithrombin and TAT, and correlated weakly with D-dimer. INTERPRETATION AND CONCLUSIONS: Our findings indicate that septic patients who developed decompensated or full-blown DIC or organ dysfunction have significantly higher plasma levels of TpP, and suggest the potential usefulness of the TpP assay as an aid to the diagnosis of DIC in cases of sepsis and liver disease complicated by sepsis.     

Comparison of plasma D-dimer and thrombus precursor protein in patients with operable breast cancer as a potential predictor of lymph node metastasis.

Fibrin formation and removal is continuous during the development of malignancy. Plasma D-dimer is indicative of ongoing fibrinolysis, and circulating soluble fibrin polymer [thrombus precursor protein (TpP)] represents thrombogenic activity. We evaluated the relationship between plasma D-dimer and TpP levels with tumor extent and examined the use of these markers as possible predictors of lymph node metastasis in breast cancer. Preoperative plasma levels of D-dimer and TpP were measured in these 120 patients (93 breast cancer, 27 benign breast disease) and 29 healthy controls. Plasma levels of D-dimer in patients with breast cancer were significantly higher than in healthy controls and in those with benign breast disease. Plasma D-dimer levels in patients with breast cancer were found to be significantly increased according to tumor stage. We also observed that plasma levels of D-dimer were higher in patients with lymph node metastasis than in patients without metastasis. In contrast, TpP levels were not significantly different by the tumor stages and lymph node metastasis. In conclusion, increased D-dimer levels in breast cancer may suggest that an ongoing fibrinolysis within breast cancer tissue occurs during tumor progression. Positive D-dimer levels might be useful for identifying metastatic lymph node in patients with operable breast cancer. However, plasma TpP was not found to be a sensitive marker for detecting tumor-associated subclinical coagulopathy.     

Failure of soluble fibrin polymers in the diagnosis of clinically suspected deep venous thrombosis.

A new diagnostic test has recently become available which is highly specific for plasma soluble fibrin polymers, the thrombus precursor protein (TpP) enzyme immunoassay. In order to evaluate the diagnostic accuracy of this test and that of a new rapid and automated test for the determination of D-dimers, the BC D-dimer test, in patients with clinically suspected deep vein thrombosis (DVT), 70 consecutive symptomatic patients underwent laboratory analysis with both tests and with the classic enzyme-linked immunosorbent assay (ELISA) D-dimer test, followed by the execution of a compression ultrasound (CUS) test of the affected limb. Patients with a positive CUS test were considered to have DVT (20 of 70), whereas those with a serially negative test and an uneventful 3-month follow-up test were regarded as not having DVT (50 of 70). The sensitivity of the TpP test (45.0%) was significantly lower than that of both the BC D-dimer test (80.0%; P = 0.02) and the classic ELISA test (90.0%; P = 0.002). The specificity of the TpP test (66.0%) did not differ from that of either D-dimer test (60.0 and 64.0%, respectively). The negative predictive value of the TpP test (75.0%) was significantly lower than that of the classic ELISA D-dimer test (94.1%; P = 0.02), which in turn did not differ from that of the BC D-dimer test (88.2%). The positive predictive value was similarly low for each investigated test (34.6, 44.4, and 50.0%, respectively). In conclusion, the TpP test can neither be used to detect a DVT nor to exclude its development in patients with the clinical suspicion of this disease. By contrast, the BC D-dimer might safely replace the classic ELISA test for excluding DVT in symptomatic patients.     

The use of thrombus precursor protein, D-dimer, prothrombin fragment 1.2, and thrombin antithrombin in the exclusion of proximal deep vein thrombosis and pulmonary embolism.

We examined various nonSTAT commercially available coagulation activation markers in an attempt to help diagnose or exclude the often subtle clinical presentations of proximal deep vein thrombosis (PDVT) and pulmonary embolism (PE). Fifty-five patients presenting to the Emergency Department were completely assessed. Eleven patients were diagnosed with PDVT, six patients were diagnosed with PE, and three patients were diagnosed with both PDVT and PE. Thrombus precursor protein (TpP) excluded the diagnosis in 19 of the 35 patients negative for PDVT and/or PE, D-Dimer in 15 patients, prothrombin fragment 1.2 in 17 patients, and thrombin-antithrombin (TAT) in 14 patients. Both the TpP and TAT enzyme-linked immunosorbent assay (ELISA) tests had 100% sensitivity and negative predictive value for evaluating PDVT and/or PE. The TpP ELISA had the highest specificity (54%) of all four markers studied.     

The use of coagulation activation markers (soluble fibrin polymer, TpP, prothrombin fragment 1.2, thrombin-antithrombin, and D-dimer) in the assessment of hypercoagulability in patients with inherited and acquired prothrombotic disorders.

A total of 260 consecutive patients, referred for hypercoagulable assessment, was included in this study. Four coagulation activation markers were utilized to assess these patients [enzyme-linked immunosorbent assays for soluble fibrin polymer (TpP), prothrombin fragment 1.2, thrombin-antithrombin complex, and D-dimer]. The mean levels of the activation markers directly correlated with the number of hypercoagulable abnormalities. The percentage of patients with increased TpP levels for each group was lower than the other activation markers. The findings indicate that activation markers reflect the number of underlying thrombophilic abnormalities. Our data suggest that there is a utility in performing a panel of coagulation activation markers to assess the thrombotic risk. The measurement of soluble fibrin polymer may be more reflective of an impending vascular event.     

Coagulation indicators in chronic stable effort angina and unstable angina: relationship with acute phase reactants and clinical outcome.

The aim of the study was to evaluate which pattern of coagulation indicators characterizes unstable angina and, particularly, its relationship with short-term prognosis. Forty patients with unstable angina (UA Group) at admission in the intensive care unit, 40 patients with chronic stable effort angina (SEA Group), and 20 age- and sex-matched healthy controls were studied. Blood coagulation indicators were fibrinogen, prothrombin fragment F1 + 2 (F1 + 2), thrombus precursor protein (TpP), and D-dimer. C reactive protein (CRP) and cardiac Troponin I (cTnI) have also been determined and compared. Patients in the UA Group were followed for in-hospital adverse events (sudden death, acute myocardial infarction and angina refractory to medical therapy). CRP, D-dimer and cTnI plasma levels were significantly lower in the SEA Group than in the UA Group; the same trend was found for fibrinogen and F1 + 2 plasma levels, although not statistically significant. The TpP was similar in all groups. The control group showed the lowest levels for all indicators. Within the UA Group, 17 patients developed adverse events during hospitalization; F1 + 2, D-dimer, cTnI and CRP plasma levels were higher in these patients than in those with good outcome. Relative risks for adverse events associated with the highest tertile of D-dimer, cTnI, and CRP plasma levels were 8.4 (95% confidence interval, 1.5-48.9), 6.7 (95% confidence interval, 1.1-38.6) and 5.2 (95% confidence interval, 1.1-25.2), respectively. D-Dimer is significantly increased in patients with unstable angina and, in particular, in those who develop an adverse event.