Ⅱ型糖尿病患者血浆可溶性凝血酶调节蛋白的变化及临床意义

目的 评价血浆可溶性凝血酶调节蛋白与Ⅱ型糖尿病患者凝血和纤溶系统之间的关系。方法 我们检测了50例Ⅱ型糖尿病患者血浆中可溶性凝血酶调节蛋白、蛋白C(PC)(由凝血酶-TM复合物诱导产生的抗凝物质)、凝血酶原片段F1+2(一种凝血酶生成的直接标志物)、纤溶酶-α2-抗纤溶酶复合物(PAP)和D二聚体(DD)。结果 患者血浆中的sTM(P<0.01)、PAP(P<0.01)、PC(P<0.05)和F1+2(P<0.05)较50例正常对照组明显增高,糖尿病肾病患者的sTM和PAP升高更加显著。在糖尿病患者中,sTM与PC呈负相关(r=-0.50,P<0.001),而与PAP呈正相关(r=0.47,P=0.01)。结论 结果表明糖尿病患者的凝血和纤溶系统均是活化的,血浆中的可溶性凝血酶调节蛋白升高与糖尿病患者凝血和纤溶系统活化相关。     

妇科肿瘤手术凝血及纤溶水平变化的分析

凝血系统、纤溶系统与妇科恶性肿瘤有密切相关,为明确妇科肿瘤手术前后机体凝血和纤溶系统变化,本文动态监测56例妇科恶性肿瘤患者和48例妇科良性肿瘤患者血浆中血管性血友病因子（vWF）、血小板α颗粒膜蛋白（GMP140）、凝血酶-抗凝血酶复合物（TAT）、抗凝血酶（ATⅢ）,纤溶系统敏感特异性分子标志物有纤溶酶原（PLG）、     

2型糖尿病合并冠心病患者血栓分子标志物水平分析

目的:分析2型糖尿病(T2DM)合并冠心病(CHD)患者血栓分子标志物水平变化。方法:2018-01—2018-12本院收治的166例CHD患者,按照是否合并T2DM将其分为单纯CHD组(CHD组,n=101)和CHD合并T2DM组(CHD+T2DM组,n=65),另选同期体检健康者作为对照组(n=82)。采用化学发光免疫分析两步法检测各组受检者血浆血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2抗纤溶酶复合物(PIC)和组织型纤溶酶原激活剂抑制剂复合物(tPAI-C)水平并比较组间差异。结果:各组TM、TAT、PIC和tPAI-C水平比较差异均有统计学意义,且均呈对照组CHD组CHD+T2DM组趋势,差异均有统计学意义(P0.05或P0.01,CHD组与CHD+T2DM组PIC水平除外)。结论:CHD和T2DM患者均存在凝血和纤溶系统异常,监测血浆TM、TAT、PIC和tPAI-C水平对评估患者出凝血状态有重要临床意义。     

应用抗凝-纤溶标志物联合检测对髋关节置换术后静脉血栓进行诊断及疗效评估研究

目的探讨TAT、PIC、TM及tPAI-C四个抗凝-纤溶标志物联合检测在髋关节置换术后静脉血栓的诊断效能及对疗效的评估价值。方法选取2017年10月至2018年3月于我院完成髋关节置换术的84例患者作为研究对象,根据是否并发静脉血栓分为实验组(并发)和对照组(未并发),分别为48例和36例。采用高敏化学发光法检测两组患者手术前后凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶抑制物复合物(PIC)、血栓调节蛋白(TM)及组织型纤溶酶原激活物抑制剂复合物(tPAI-C);绘制各单项和联合标志物对髋关节置换术后静脉血栓ROC曲线;统计实验组疗效,并分析抗凝-纤溶标志物与疗效之间的相关性。结果术前,两组患者各项抗凝-纤溶标志物差异无统计学意义(P>0. 05);术后,实验组各项抗凝-纤溶标志物均明显高于对照组,差异具有统计学意义(均P<0.001)。ROC曲线显示,各抗凝-纤溶单项标志物对髋关节置换术后静脉血栓均有一定的诊断价值,以t-PAI-C诊断效能最佳,余下依次为PIC、TAT及TM;与各单项检测比较,四组抗凝-纤溶标志物联合检测诊断效能明显提高。治疗后,经评估示实验组总有效者为45例,有效率为93.75%;经Pearson相关分析示,抗凝-纤溶标志物四组联合检测结果与术后静脉血栓疗效呈正相关(r=0. 715,P=0.006)。结论 TAT、PIC、TM及tPAI-C四个新型抗凝-纤溶标志物联合检测可明显提高髋关节置换术后静脉血栓的诊断效能,且与其疗效呈正相关,值得推广运用。     

几种凝血/纤溶标志物在部分血栓性疾病中的应用

机体凝血增强、纤溶降低,可能预警血栓形成。相关标志物凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶抑制剂复合物(PIC)、血栓调节蛋白(TM)、组织纤溶酶原激活物-纤溶酶原激活物抑制剂-1复合物(tPAI-C)、纤维蛋白(原)降解产物(FDP)和D-二聚体(DD)水平异常成为临床上分析血栓性病变的重要参考指标,并在深静脉血栓、心血管疾病、弥散性血管内凝血(DIC)等的应用中获益。这些指标能反映血管内皮受损、血液高凝、纤溶状态,相较于常规指标:凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)等的变化,出现更早、更灵敏,因而对血栓形成的警示更及时,遗漏更少。     

凝血、纤溶状态与糖尿病肾病

目的观察2型糖尿病（Diabetes mellitus，DM）患者的凝血、纤溶状态指标在糖尿病肾病（Diabetic nephropathy，DN）各期的水平，探讨其在DN发生、发展中的作用。方法检测30例正常人和90例2型DM患者凝血、纤溶状态指标：抗凝血酶-Ⅲ（AT-Ⅲ）、凝血酶-抗凝血酶复合物（TAT），组织型纤溶酶原激活剂（t-PA），纤溶酶原激活抑制物-1（PAI-1）。结果①DM各组血浆TAT水平高于正常对照组，t-PA水平、AT活性低于正常对照组，在DM无并发症时即出现上述改变（P〈0．01）。②血浆PAI-1水平在DN正常白蛋白尿组出现有统计学意义的升高（P分别〈0．05）。结论①DM在无并发症时，即存在凝血活性亢进、纤溶系统活性抑制。②PAJ-1是早期诊断DN较敏感的指标，并能反映DN的发生和发展，与尿白蛋白排泄量（Urinary Albumin Excretion，UAE）指标联合检测有助于早期诊断DN。     

凝血纤溶异常与早期糖尿病肾病的关系

目的:分析凝血纤溶异常在糖尿病肾病(DN)发生、发展中的作用,为早期诊断DN提供检测指标。方法:将90例2型糖尿病(DM)病人分为:无并发症组、正常白蛋白尿组(DMa组)、微量白蛋白尿组(DMb组)和临床蛋白尿组(DMc组)。测定其抗凝血酶-Ⅲ(AT-Ⅲ)、蛋白C(PC)、凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物(t-PA)、纤溶酶原激活抑制物(PAI)等指标水平。结果:①无并发症组PAI、TAT、PC水平升高,AT-Ⅲ、t-PA活性降低,并随UAE增加而加重。②TAT、AT-Ⅲ水平在DMa、DMb、DMc组与无并发症组间,呈显著性差异(P<0.01),且DMc组TAT水平依次高于DMb组、DMa组(P<0.01);AT-Ⅲ水平DMc组依次低于DMb组、DMa组(P<0.01)。③PC、TAT、PAI与DM病程呈正相关。结论:DN患者早期即存在凝血功能亢进、纤溶活性低下,并随DN的进展而逐渐加重。     

紫杉醇联合卡铂化疗对卵巢癌凝血/纤溶及CA125/HE4水平的调控及临床意义

目的：探讨紫杉醇联合卡铂联合化疗对卵巢癌（OC）凝血/纤溶及肿瘤标志物的影响及临床意义。方法：研究分为OC联合化疗（CC）和良性卵巢肿瘤对照（control）组，各组50例。借助苏木精-伊红（HE）染色和透射电镜（TEM）观察卵巢病理学改变；采用全自动凝血分析仪及凝固法检测凝血酶原时间（PT-SEC）、凝血酶原国际标准比值（PT-INR）、凝血酶原时间比值（PT-RATIO）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）及抗凝血酶-Ⅲ（AT-Ⅲ）水平；免疫比浊法测定纤维蛋白（原）降解产物（FDP）和D-二聚体（D-D）含量；采用电化学发光法检测糖类抗原125(CA125)和人附睾蛋白4(HE4)水平；并绘制受试者工作特征（ROC）曲线，以分析凝血/纤溶产物与肿瘤标志物的相关性。结果：光镜显示卵巢浆液性癌（SC）细胞坏死和腺腔样结构，超微结构显示线粒体显著肿胀和嵴溶解，联合化疗后卵巢SC呈现正常线粒体与“脂质空泡”并存的现象。凝血与纤溶指标检测显示，OC患者化疗前TT和AT-Ⅲ水平显著降低（P<0.01）,APTT、FIB、FDP、D-D、CA125和...     

血浆GMP-140测定在慢性喘息型支气管炎患者中的临床意义

应用双抗体夹心、固相免疫放射分析法(IRMA)对46例慢性喘息型支气管炎(慢喘支)患者血浆α-颗粒膜蛋白(GMP-140)进行检测,以探讨粘附分子在慢喘支患者血浆中的变化及意义。结果显示慢喘支患者血浆GMP-140含量显著高于正常对照组(p<0.01),其中急性加重期患者明显高于缓解期患者(p<0.01),综合治疗可使慢喘支患者血浆GMP-140含量降低,治疗前后相比较有显著性差异(p<0.01)。提示P-选择素粘附分子在慢喘支加重期表达增高,是参与慢喘支发病的重要粘附分子,其血浆GMP-140水平与病情变化有一定的相关性,可作为判断病情及预后的参考指标。     

纤溶酶-α2抗纤溶酶复合物单克隆抗体的制备及鉴定

目的 :制备纤溶酶 α2 抗纤溶酶复合物 (PAP)的单克隆抗体(mAb)。方法 :以从血浆中纯化的PAP免疫BALB/c小鼠。按常规方法融合 ,以固相等分子浓度的纤溶酶原、α2 抗纤溶酶(α2 AP)及PAP为抗原 ,建立间接ELISA筛选杂交瘤细胞培养上清 ,并对杂交瘤细胞分泌的mAb的特异性和亲和力进行鉴定。结果 :共获得 2 4株可稳定分泌特异性mAb的杂交瘤细胞。其中 ,针对PAP分子中纤溶酶结构的mAb 16株 ,针对α2 AP结构的mAb 1株 ,针对新抗原 (PAP分子中新出现的不同于前体分子纤溶酶原及α2 AP的抗原决定簇 )结构的mAb 7株。这些腹水中抗PAPmAb的滴度为 2× 10 -4～ 1× 10 -8,其中 4株mAb的亲和常数为 5 .6 2× 10 -9～ 3.5 8× 10 -11mol/L之间。结论 :成功地制备针对PAP新抗原的具有高亲和力的mAb ,为建立不受其前体分子干扰的PAP特异性检测方法 ,研究纤溶系统的激活状态提供了工具。     

Effect of iodinated low-osmolar contrast media on the hemostatic system after intraarterial and intravenous contrast administration

PurposeSome of the adverse clinical effects of intravascular radiological contrast agents include the interference of these contrast media with normal hemostatic processes. The aim of this report was to investigate in vivo whether a non-ionic iodinated contrast agent possess prothrombotic or anticoagulant properties.Material and methodsHemostatic parameters: vWF (von Willebrand factor), F1+2 (prothrombin fragments 1+2), TAT (thrombin-antithrombin complexes), D-Dimer, β-TG (beta-thromboglobulin) were measured in a group of 35 patients. Blood samples for laboratory investigations were collected before and 30 min after the administration of a iodine contrast agent.ResultsThere was observed statistically highly significant contrast-induced increase in TAT and F1+2 (p = 0.005 and p = 0.008, respectively). D-Dimer increase and decrease of β-TG and vWF after contrast medium administration were non significant. The volume of contrast medium has no influence on the assessed hemostatic parameters, while the type of contrast medium and/or the route of the contrast administration may significantly affect hemostatic parameters.ConclusionWe found significant effects of non-ionic agents on hemostatic activation. These effects may be important for adverse reactions and for thromboembolic complications.     

急性淋巴细胞白血病患者CD4+CD25+调节性T细胞水平变化

目的 观察急性淋巴细胞白血病(ALL)患者外周血中CD4+ CD25+调节性T细胞(Treg)的变化,探讨其临床意义.方法 收集47例ALL初诊患者组、13例经化疗完全缓解组、9例未缓解组及20例健康对照组抗凝血,采用流式细胞仪检测CD4+ CD25+ Treg的水平.结果 CD4+ CD25+ Treg比例在ALL初...     

A complete remission can be achieved despite persistence of abnormal bone marrow promyelocytes in acute promyelocytic leukemia--experience in 2 patients.

Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) and is distinguished from other subsets of AML by its distinctive morphology, specific chromosomal abnormality, associated consumptive coagulopathy, and response to treatment. Interestingly, patients with APL frequently enter complete remission without undergoing a characteristic period of bone marrow hypoplasia. In two cases in this report, complete remission was achieved without bone marrow hypoplasia without further additional course of chemotherapy despite the appearance of persistent malignant cells in the bone marrow after first induction chemotherapy. During the period of treatment, severe coagulopathy occurred in both cases but resolved as the patients entered into remission. Remission in patients with APL may occur even when induction therapy fails to cause marrow hypoplasia or to eradicate replicative cells. To avoid unnecessary exposure to toxic therapy, caution should be exercised in assessing the adequacy of remission induction treatment.     

卡托普利对家兔急性心肌梗塞早期血小板活化及纤溶活性的影响

本研究观察了家兔急性心肌梗塞（ＡＭＩ）早期血浆血小板α－颗粒膜蛋白（ＧＭＰ－１４０）、血栓素Ｂ２（ＴＸＢ２）、组织型纤溶酶酶原激活剂（Ｔ－ＰＡ）及其抑制物（ＰＡＩ－１）水平的变化及卡托利干预的ＰＡ活性显著降低；相关分析表明，血浆ＧＭＰ－１４０浓度与ＰＡＩ－１活性显著正相关。卡托普利干预后，血浆ＧＭＰ－１４０浓度、ＴＹＸＢ２浓度、Ｔ－ＰＡ浓度、ｔ－ＰＡ含量、ＰＡＩ－１活性均明显降低，而ｔ－ＰＡ活性显     

Hyperfibrinolysis in hepatosplenic schistosomiasis.

AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. METHODS: The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. RESULTS: The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.     

Coagulation and fibrinolysis parameters in disseminated intravascular coagulation (DIC)]

Eighty six plasma samples from 41 patients with suspected disseminated intravascular coagulation (DIC) were divided into 3 groups as follows: Group A, 53 samples from established DIC; Group B, 19 samples from possible DIC; and Group C, 14 samples from probable DIC. The following parameters of coagulation and fibrinolysis were evaluated: thrombin/antithrombin III complex (TAT), plasmin/alpha 2 plasmin inhibitor complex (PIC), D-dimer (D-D) and fibrin monomer (FM). In Group A, TAT and PIC were significantly elevated, being 29.5 +/- 20.7 micrograms/l and 7.2 +/- 6.1 mg/l respectively, suggesting marked hypercoagulability and accelerated fibrinolysis. There were no correlations between antithrombin III (ATIII) and TAT, between alpha 2 plasmin inhibitor (alpha 2PI) and PIC, or between TAT and PIC, showing the clinical diversity of patients with DIC. In all groups abnormal TAT, PIC and D-D findings were observed in many samples (86-100%), and FM was present in 83%, 63%, and 29% of samples in Groups A, B, and C respectively. In Groups B and C, abnormal findings for TAT, PIC, D-D, FM and alpha 2PI apparently indicated hypercoagulability and accelerated fibrinolysis, even though fibrinogen and platelet count were within normal limits.     

Plasma level of IL-6 and its relationship to procoagulant and fibrinolytic markers in acute ischemic stroke

Procoagulant or impaired fibrinolytic states as well as inflammatory reactions mediated by cytokines are likely involved in the pathogenesis of acute ischemic stroke. We examined the potential relationship between interleukin 6 (IL-6) and hemostatic markers. The procoagulant and fibrinolytic states were assessed in 46 patients with acute stroke by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and plasminogen-antiplasmin complex (PAP). Circulating IL-6 levels were measured using ELISA (Quantikine, R and D systems, MN, USA). Circulating IL-6 (mean, 26.5 pg/mL) and PAI-1 (mean, 19.9 ng/mL) levels were higher in patients with acute stroke than in healthy subjects (mean, 3.0 pg/mL, 10.4 ng/mL, respectively). TAT levels were statistically different according to the etiologic subtypes of stroke (atherogenic, 2.5 ng/mL; lacunar 3.2 ng/mL; cardiogenic 9.9 ng/mL, p = 0.021). Neither procoagulant levels nor fibrinolytic markers significantly correlated with circulating IL-6 levels. Our findings suggest that elevated proinflammatory cytokines during the initial hours of ischemic stroke may be an independent pathogenic factor or a consequence of the thrombotic event with no relationship to the procoagulant or fibrinolytic states.     

Clinical trial of low dose cytosine arabinoside in the treatment of acute promyelocytic leukemia.

The purpose of this study is to determine the efficacy of low dose cytosine arabinoside (LD Ara-C) as an alternative treatment to conventional cytotoxic induction chemotherapy in childhood acute promyelocytic leukemia (APL). Four children with APL in poor medical condition prior to chemotherapy were treated with LD Ara-C (10 mg/m2/12 h) for 3 weeks. In three patients, the second course was administered after a resting period of two weeks. Subsequent conventional cytotoxic induction chemotherapy was applied in patients who did not enter complete remission (CR). After induction of CR, maintenance chemotherapy with a conventional monthly multi-drug regimen was applied. CR in one patient and partial remission (PR) in two patients were obtained after two courses of LD Ara-C. Patients who did not enter CR after LD Ara-C entered on subsequent conventional chemotherapy. There were no major complications such as intracranial hemorrhage and sepsis; myelosuppression was not as severe as in conventional chemotherapy; there was clinical and laboratory improvement in coagulopathy. We concluded that LD Ara-C may be an alternative treatment to the conventional chemotherapy in children with APL, especially in whom conventional cytotoxic induction chemotherapy is thought to increase the risk of serious complications and early fatality during induction chemotherapy.     

Fluorescence in situ hybridization: a highly efficient technique of molecular diagnosis and predication for disease course in patients with myeloid leukemias.

The accuracy of cytogenetic diagnosis in the management of hematological malignancies has improved significantly over the past 10 years. Fluorescence in situ hybridization (FISH), a technique of molecular cytogenetics, has played a pivotal role in the detection of unique sub-microscopic chromosomal rearrangements that helped in the identification of chromosomal loci, which contain genes involved in leukemogenesis. We studied the feasibility and sensitivity of the FISH technique for molecular analysis of translocations markers, t(9;22) and t(15;17) for accurate molecular diagnosis and for monitoring the disease in 21 patients with chronic myeloid leukemia (CML) who received interferon-alpha and/or chemotherapy (7 patients), bone marrow transplantation (14 patients), and 14 patients with acute promyelocytic leukemia (APL) who received all-trans-retinoic acid (ATRA) and/or chemotherapy. We also applied conventional karyotyping (CK) for identification of t(9;22) and t(15;17) at diagnosis. All CML cases had a Ph; t(9;22) and except for two cases all APL had t(15;17). The FISH studies on CML marrows in complete cytogenetic remission (CCR) (100% Ph- by CK) achieved by IFN-alpha, showed 0-2.5% of cells with BCR-ABL fusion in first cytogenetic remission (Controls, range 0.5-1.5%). Repeat follow-up FISH studies could be done in two cases in remission, which demonstrated 0-10% of cells with BCR-ABL fusion. Evaluation of Ph positive status of CML marrow at diagnosis by CK (100% Ph+ cells) and FISH (80-92% BCR-ABL fusion) pointed the existence of dormant clone of normal residual hematopoietic cells along with actively proliferating clones of Ph positive cells. Fluorescence in situ hybridization analysis of post-BMT CML marrows in CCR (0% Ph+ mitoses) could detect MRD with range of 1-6%. Among 14 patients, 9 who showed percentage of BCR-ABL positive cells (0.0-1.5%) almost similar to normal controls, 6 patients had comparatively good prognosis (disease-free survival 7-14 months). Of five patients with residual leukemic cells in the range of 2-6%, 4 relapsed within a period of 3-24 months. Fourteen APL patients in CCR [100% t(15;17) negative cells by CK] were evaluated by FISH to check the presence of residual leukemic cells. In these patients FISH could efficiently detect 1-14.5% of residual cells with PML-RARA (patients mean MRD 5%, controls mean MRD 3.5%, P=.02). Since the time of FISH analysis, 5 to 7 patients with higher fraction of leukemic cells (5-11%) relapsed within a short period (1-7 months). On the contrary, 5 of 7 patients with either absence or low percentage of PML-RARA positive cells remained in complete remission for 11-24 months. Our data show that FISH has a potential to detect and measure the fraction of aberrant malignant cells in remission marrows, induced by BMT in CML and chemotherapy in APL. These findings encourage the investigations on a large scale to merit its potential for identification of patients at high risk. In the present studies, FISH on interphase cells also demonstrated its efficiency in the molecular diagnosis by its ability to detect BCR-ABL and PML-RARA fusion in CML with masked/variant Ph and t(15;17) negative APL, respectively. The efficiency of technique in molecular diagnosis was also proved in one of the CML patients who progressed to myeloid blastic phase where interphase FISH could identify an extra BCR-ABL fusion on both chromosomes 9 indicating insertion of BCR into ABL and its duplication.