Antithrombotic effects of bromophenol,an alga-derived thrombin inhibitor

Thrombin,the ultimate proteinase of the coagulation cascade,is an attractive target for the treatment of a variety of cardiovascular diseases.A bromophenol derivative named (+)-3-(2,3-dibromo-4,5-dihydroxy-phenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroiso-benzofuran 1,isolated from the brown alga Leathesia nana exhibited significant thrombin inhibitory activity.In this study,we investigated the inhibition of human thrombin in vitro with this bromophenol derivative,and its antithrombotic efficacy in vivo using the arteriovenous shunt model and the ferric chloride-induced arterial thrombosis model in rats.The results show that the bromophenol derivative is a potential inhibitor of thrombin (IC50=1.03 nmol/L).In antithrombotic experiments in vivo,the bromophenol derivative also shows good effect comparing with the control group.These data indicate that the bromophenol derivative is a potential drug for prophylaxis and the treatment of thrombotic diseases.

Partial Characterization of Thrombin Inhibitor(s) Derived from Salivary Glands of the Tick, <i>Hyalomma dromedarii</i>, and Related Anti-Cancer Potential

A long-term blood feeder, like the Hyalomma dromedarii tick, requires extended control over all hemostatic defense mechanisms generated by the host during feeding, including blood coagulation. To overcome this, ticks have evolved numerous molecules that target proteases in the blood coagulation cascade. New insights into the role of clotting factors in the development and progression of cancer have identified anticoagulant treatment as a potential therapeutic approach. In this context, the present work assessed the anticoagulation activities of crude and fractionated salivary gland extract (SGE) prepared from semi-fed H. dromedarii females. Additionally, the antitumor effects of the potent anti-thrombin fractions were determined against colon cancer (Caco-2) and normal skin (HFB4) cells. Crude SGE significantly prolonged clotting time in prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT) assays and inhibited thrombin in FII-activity assay. Using anion-exchange chromatography, the fractions that strongly inhibited thrombin (3.A4 and 3.A5) were eluted. Both fractions prolonged the aPTT and TT clotting times and reduced the activity of FII significantly. The protein profiles of both fractions indicated the presence of a single polypeptide band of about 99 kDa. Regarding anti-cancer potential of the tested fractions, Caco-2 cells showed reduced viability with obvious morphological changes, induced apoptosis and a reduced level of vascular endothelial growth factor (VEGF). G2/M cell cycle arrest was observed only in 3.A5-treated cells. No cytotoxic effects were observed in HFB4 cells. These results demonstrated the potential of tick-derived anticoagulants, specifically thrombin inhibitors, as effective tools in colorectal cancer treatment. Further purification of the effector molecule(s) is required to fully characterize their structures and mechanisms of action.

THE EFFECT OF RT-PA ALONE AND IN COMBINATION WITH THROMBIN INHIBITORS IN A MODEL OF CEREBROVASCULAR THROMBOSIS IN THE RABBIT

Sustained accumulatin of 111 indium-labelled platelets is induced in the cerebral vascuiature or rabbits by bolus intracarotid (i. c. ) administration or thrombin (90 U/kg). Bolus i. c. injection of the fibrinolytic, recombiuant tissue plasminogen activator (rt-PA), 1 miu after thrombin,produced significant inbibition of the. platelet accumulation, albeit substantially less than that produced by 1 min Pretreatment. Hirulogm, PPACK and rt-PA alone had no direct effect on the hasalcirculating levels of 111 In-labedlled platelets in the pulmonary or cranial vasculature at the doses used.Hirulongm and PPACK did not enhance the ability or inrusion or a threshold dose of rt-PA to decrease an established cerebrovascular thromhosis, whereas Defibrotide plus rt-PA produced a significant reduction on accumulated plateiets. These results suggest that fiibrin deposition .plays the impor tant role in the induction and maintenance of the. sustained cerebral platelet accumulation induced bythrombin in this model and Defibrotide can .enhance the pro-fibrinolytic effect of rt-PA although thisProperty is not shared by direct thrombin inhibitors. The sustained platelet accumulation in the cranial vasculature in this model does not appear to be a result or continued generation or endogenousthrombin.

Clinical and pharmacological properties of new oral anticoagulants for the prevention of cerebral thromboembolism: Factor Xa and thrombin inhibitors

Vitamin K antagonists, such as warfarin and phen-procoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embo-lism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The ad-vantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110mg bid, a better efficacy with dabigatran 150mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise mea-surements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on throm-bin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacol-ogical and clinical properties and provide the most recent updates on their clinical trials.

Functional and binding studies of gallic acid showing platelet aggregation inhibitory effect as a thrombin inhibitor

Objective:This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine(TCM)and evaluating its biological activity in vitro and binding characteristics.Methods:A combination strategy containing molecular docking,thrombin inhibition assay,surface plasmon resonance(SPR)and molecular dynamics simulation were applied to verify the study result.Results:Gallic acid was confirmed as a direct thrombin inhibitor with IC;of 9.07μmol/L and showed a significant inhibitory effect on thrombin induced platelet aggregation.SPR-based binding studies demonstrated that gallic acid interacted with thrombin with a KDvalue of 8.29μmol/L.Molecular dynamics and binding free energy analysis revealed that thrombin-gallic acid system attained equilibrium rapidly with very low fluctuations,the calculated binding free energies was-14.61 kcal/mol.Ala230,Glu232,Ser235,Gly258 and Gly260 were the main amino acid residues responsible for thrombin inhibition by gallic acid,providing a mechanistic basis for further optimization.Conclusion:This study proved that gallic acid is a direct thrombin inhibitor with platelet aggregation inhibitory effect,which could provide a basis for the follow-up research and development for novel thrombin inhibitors.

Thrombin Activatable Fibrinolysis Inhibitor in Preeclmapsia and Gestational Hypertension throughout the Gestation

To clarify the role of TAFI in hypertensive disorders in pregnancy, 22 subjects, including 10 with pre-eclampsia （PE） and 12 with gestational hypertension were examined for the levels of TAFI and thrombin-antithrombin （TAT） complex. Thirty normal pregnant women served as controls. ELISA was employed for the detection. The results showed that the TAFI antigen levels in normal pregnancy group, gestational hypertension group and PE group were （85.35±24.69）%, （99.65±18.27）%, （110.12±23.36）%; （97.06±21.40）%, （114.08±27.76）%, （125.49±24.70）%; （106.6±19.21）%, （129.2±25.07）%, （139.1±30.12）%, in the 1st, 2nd and 3rd trimester respectively. No significant differences were found between the normal pregnancy group and gestational hypertension group but significant difference existed between normal pregnancy group and PE group in each trimester （P〈0.05）. TAT complexes were significantly higher in patients with PE than that in controls （P〈0.05）, but no correlation was found between TAT and TAFI. It is concluded that TAFI may contributed to the impairment of fibrinolysis in the patients with PE and may serves as a sensitive indicator for PE, but it may not help in the diagnosis of the gestational hypertension.

大鼠脑出血后水肿组织中的PN-1、thrombin、PAR-1表达及其作用分析

目的探讨脑出血(intracerebral hemorrhage,ICH)实验大鼠水肿周围脑组织中蛋白酶连接素-1(protease nexin-1,PN-1)、凝血酶(thrombin)、蛋白酶激活受体-1(protease activated receptor-1,PAR-1)的表达变化及其作用分析。方法选取成年健康雄性SD大鼠80只,编号后随机分为假手术组、ICH组,各40只。ICH组于右侧尾状核部注射自体动脉血方法制作ICH实验大鼠模型,分别于术后第12、24、120 h对2组大鼠的神经功能障碍程度进行评价;HE染色观察脑组织细胞中形态;Western blot分别于造模后第3、6、10、12、24、48及120 h检测2组大鼠脑组织中PN-1、thrombin、PAR-1实验指标的变化情况。结果 ICH组大鼠的神经功能障碍评分在造模后第12、48、120 h均显著的低于假手术组(P<0.05);ICH组大鼠在造模后第3、6、10、12、24、48及120 h的脑组织中PN-1、thrombin、PAR-1较假手术组均显著的增高(P<0.05);ICH组大鼠的脑组织中PN-1、thrombin、PAR-1在造模后12 h或24 h出现逐渐下降的趋势较造模后10 h或12 h(P<0.05)。结论 ICH实验大鼠血肿周围脑组织中PN-1有抑制thrombin及PAR-1过表达,引起神经损伤的作用。

血清TAFI和GDF-15在上消化道出血患者诊断及预后评估中的价值

目的 探讨上消化道出血患者的血清纤溶抑制物(TAFI)、生长分化因子-15(GDF-15)表达水平及其在诊断及预后评估中的价值。方法 选择2020年5月至2023年6月保定市第二中心医院收治的94例上消化道出血患者设为研究组,根据AIMS65评分系统对患者预后的评估结果,将患者分为预后良好组(n=65)和预后不良组(n=29),另选择80名同期健康体检者设为对照组。收集入组患者的一般资料,采用ELISA法检测各组的血清TAFI、GDF-15水平,采用Spearman等级相关分析探讨上消化道出血患者的血清TAFI、GDF-15水平与AIMS65评分的相关性,采用ROC曲线分析血清TAFI、GDF-15对上消化道出血患者诊断和预后评估的价值。结果 研究组与对照组中有消化道出血史的患者占比差异有统计学意义(P<0.05);研究组的血清TAFI水平显著低于对照组,而血清GDF-15水平显著高于对照组(P均<0.05)。预后不良组的血清TAFI水平显著低于预后良好组,而血清GDF-15水平显著高于预后良好组(P均<0.05)。Spearman等级相关分析结果显示,上消化道出血患者的血清TAFI水平与AIMS65评分呈显著负相关,而血清GDF-15水平与AIMS65评分呈显著正相关(r=-0.493,r=0.537,P均<0.001)。ROC曲线分析结果显示,血清TAFI、GDF-15诊断上消化道出血的曲线下面积(AUC)分别为0.734和0.776,两者联合诊断的AUC为0.842,两者联合诊断上消化道出血的效能优于单独诊断(P均<0.05)。血清TAFI、GDF-15水平预测上消化道出血患者预后不良的AUC分别为0.658和0.712,两者联合预测上消化道出血患者预后不良的AUC为0.820,两者联合预测预后的效能优于单独预测(P均<0.05)。结论 TAFI在上消化道出血患者血清中呈低表达,而GDF-15呈高表达,两者与AIMS65评分均有相关性,两者联合检测对上消化道出血患者具有一定的诊断和预后预测价值。

凝血酶激活的纤溶抑制物在肺部疾病中的研究进展

凝血酶激活的纤溶抑制物(TAFI)是一种血液凝块形成和纤溶过程中的重要调节因子,也是一种参与炎症调节的急性反应蛋白。TAFI在炎性应答过程和凝血、纤溶反应中起调控作用,并在肺部疾病(肺栓塞、急性肺损伤、肺癌等)发生、发展中发挥重要作用,这为凝血和纤溶瀑布之间的联系及炎症反应网络提供了重要线索。TAFI在肺部疾病中的发病机制涉及炎症反应、氧化应激以及纤维化等,但具体发病机制目前尚未明确。因此,未来深入研究TAFI在肺部疾病中的具体作用信号通路机制等具有重要的临床诊断及治疗价值,有助于改善患者预后。

TAT、TM、PIC、t-PAIC与重型血液毒毒蛇咬伤中毒患者DIC的相关性及预测价值

目的评估凝血酶抗凝酶复合物(TAT)、血栓调节蛋白(TM)、纤溶酶-抗纤溶酶复合物(PIC)和组织型纤溶酶原激活抑制复合物(t-PAIC)与重型血液毒毒蛇咬伤中毒后弥散性血管内凝血(DIC)的临床相关性及预测价值。方法连续纳入2019年4月至2023年4月收治的重型血液毒毒蛇咬伤中毒患者作为研究对象,共132例。依据住院期间是否出现DIC分为观察组(发生DIC,n=37)及对照组(未发生DIC,n=95)。检测2组血浆TAT、TM、PIC、t-PAIC浓度。应用二元、无分类协变量的非条件Logistic回归分析TAT、TM、PIC、t-PAIC浓度与重型血液毒毒蛇咬伤中毒后DIC的临床相关性,建立受试者工作特征(ROC)曲线分析TAT、TM、PIC、t-PAIC对重型血液毒毒蛇咬伤中毒后DIC的预测能力。结果观察组TAT、TM、PIC、t-PAIC显著高于对照组(P<0.05)。二元、无分类协变量的非条件Logistic回归分析显示,TAT[OR=1.517(95%CI:1.155,1.879)]、TM[OR=1.647(95%CI:1.108,2.186)]、PIC[OR=3.989(95%CI:2.986,4.992)]、t-PAIC[OR=1.111(95%CI:0.854,1.368)]是重型血液毒毒蛇咬伤中毒患者发生DIC的危险因素(P<0.05)。ROC曲线分析显示,TAT、TM、PIC、t-PAIC是预测重型血液毒毒蛇咬伤中毒患者DIC的有效指标(P<0.05),其曲线下面积(AUC)分别为0.865(95%CI:0.790,0.939)、0.771(95%CI:0.673,0.870)、0.847(95%CI:0.804,0.889)、0.680(95%CI:0.573,0.787),联合预测效能更优异(P<0.001),AUC为0.904(95%CI:0.875,0.933)。结论TAT、TM、PIC和t-PAIC检测对判断重型血液毒毒蛇咬伤中毒患者是否发生DIC有重要参考价值,可以较好地评估患者凝血功能状态,4个指标联合预测DIC的效能更优。

直接凝血酶抑制剂在体外循环期间抗凝治疗的研究进展

肝素是目前心脏外科体外循环期间抗凝治疗标准药物,但肝素过敏或肝素诱导性血小板减少症等不良反应逐渐受人关注。直接凝血酶抑制剂(DTIs)可直接与凝血酶结合,不出现上述不良反应,因此被推荐应用在可能出现肝素/鱼精蛋白不良反应且需要紧急手术患者的体外循环期间抗凝管理。近年来DTIs的临床病例报道较多,本文将简要综述DTIs的抗凝机制及几种药物的临床应用进展,为体外循环期间抗凝治疗提供新思路。

凝血酶激活的纤溶抑制物检测临床应用进展

凝血酶激活的纤溶抑制物(TAFI)是一种主要由肝脏合成分泌的,具有血浆羧肽酶样活性的单链糖蛋白,在血浆中以酶原的形式存在。传统的TAFI检测方法为酶联免疫吸附试验(ELISA)、酶学测定和功能学检测。近年来,免疫比浊法和同位素稀释质谱法等新的检测方法被开发并普及,推动了TAFI在深静脉血栓、心脑血管疾病、出血性疾病和炎症性疾病中的临床应用。文章对TAFI的生理功能进行介绍,并总结TAFI检测技术及其检测原理,梳理TAFI的临床应用价值,旨在更深入地了解TAFI,为血栓性疾病的防治提供参考。

凝血酶在脑出血继发性损伤中的研究进展

脑出血是出血性卒中的一种亚型,具有较高的发病率和病死率。脑出血后引起的继发性损伤,如氧化应激(OS)、炎症反应、血液内容物(Fe、凝血酶)引起毒性反应,最终导致神经细胞功能缺损,严重影响患者生存及预后。凝血酶在高血压脑出血患者的脑组织中以中度和高度阳性表达为主。脑出血后大量凝血酶通过多种机制发挥作用,使凝血酶成为脑出血治疗的潜在靶点。本文就凝血酶参与脑出血后继发性脑损伤的相关作用机制进行综述。

凝血酶联合质子泵抑制剂治疗上消化道出血的疗效观察

目的观察凝血酶联合质子泵抑制剂治疗上消化道出血的疗效。方法将2020年1月—2023年1月固原市原州区人民医院收治的320例上消化道出血患者作为研究对象,按照随机数表法分为对照组和观察组,每组160例。对照组采取质子泵抑制剂(奥美拉唑注射液)治疗,观察组在此基础上增加凝血酶治疗。比较两组止血情况(止血时间、输血量、再出血率、住院时间)、格拉斯哥-布拉奇福德出血评分(GBS)情况,治疗有效率及不良反应发生率。结果观察组止血时间、输血量、再出血率及住院时间均少于对照组,差异有统计学意义(P<0.05)。治疗前,两组GBS评分比较,差异无统计学意义(P>0.05);治疗后,两组GBS评分均下降,观察组评分低于对照组,差异有统计学意义(P<0.05)。观察组治疗有效率高于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论凝血酶联合质子泵抑制剂治疗上消化道出血疗效显著,能够提高止血效率,缓解出血危急程度,并且不会增加不良反应,值得临床使用。

基于TAT、PIC联合Padua评分在早期筛查慢性呼吸系统疾病合并VTE患者中的价值

目的:探究基于凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2纤溶酶抑制剂复合物(PIC)联合Padua评分在早期筛查慢性呼吸系统疾病合并静脉血栓栓塞症(VTE)患者中的价值。方法:收集2022年10月—2023年9月时间段内在我院呼吸与危重症医学科接受住院诊疗的慢性呼吸系统疾病患者100例,按照是否发生VTE分组,分为VTE组(n=43)与非VTE组(n=57)。接受血清TAT、PIC检测分析以及Padua评分评估。比较两组血清TAT、PIC水平以及Padua评分。采用ROC曲线分析血清TAT、PIC与Padua评分单一或联合对慢性呼吸系统疾病合并VTE的诊断效能。结果:VTE组患者的血清TAT、PIC水平以及Padua评分均较非VTE组患者高(P<0.05),且VTE组患者VTE高风险(Padua评分≥4分)占比高于非VTE组(P<0.05)。经分析,当血清TAT≥16.18ng/mL时,其诊断灵敏度为71.43%、特异度为77.59%;当血清PIC≥3.10μg/mL时,其诊断灵敏度为76.60%、特异度为86.79%;当Padua评分≥4分时,其诊断灵敏度为80.85%、特异度为90.57%。经血清TAT、PIC与Padua评分联合诊断的AUC为0.959,其诊断灵敏度为93.48%、特异度为100.00%。结论:慢性呼吸系统疾病合并VTE患者血清TAT、PIC水平及Padua评分明显较高,通过TAT、PIC联合Padua评分可早期筛查慢性呼吸系统疾病合并VTE,且诊断效能较高。

凝血相关指标在评估危重症患者静脉血栓栓塞风险中的应用

目的探讨血栓调节素(TM)、凝血酶-抗凝血酶复合物(TAT)、α2-纤溶酶抑制剂-纤溶酶复合物(PIC)和组织纤溶酶原激活物-抑制剂复合物(t-PAIC)在评估危重症患者静脉血栓栓塞(VTE)风险和预后中的价值。方法纳入2020年10月—2022年11月本院ICU收治的254例危重症患者资料行回顾性分析。根据有无VTE分为VTE组(106例)和无VTE组(148)。使用高灵敏度化学发光酶免疫测定法测量患者空腹静脉血中TAT、PIC、TM和t-PAIC水平。使用二元逻辑回归分析TAT、PIC、TM、t-PAIC和VTE之间的关系。采用受试者工作特征(ROC)曲线评价它们在区分VTE中的诊断效率。使用Kaplan-Meier方法估计患者的28 d存活率。结果在纳入患者中,VTE发生率41.7%,包括16.5%肺血栓栓塞(PE),20.5%深静脉血栓(DVT)和4.7%其他(静脉导管或浅静脉)血栓形成。与无VTE组相比,VTE组入院时血管加压药使用比例、机械通气比例、CRP水平、TAT、PIC、TM、t-PAIC、D-二聚体、纤维蛋白降解产物水平显著升高(均P<0.05)。多变量分析显示TAT、PIC、TM、t-PAIC与危重症患者VTE密切相关(P<0.05)。在4个凝血标志物中,tPAIC的最低曲线下面积(AUC)为0.615,TAT的最高AUC为0.711。当应用TAT、PIC、TM、t-PAIC的组合时,AUC增加到0.814,敏感性增加到74.1%。在4种凝血标志物中,TAT、PIC和TM高水平患者的28 d存活率显著低于低水平患者(P<0.05)。结论TAT、PIC、TM、t-PAIC联合在评估危重症患者VTE中表现出良好的诊断性能,并优于单一标志物。

Lp-PLA2、HDAC3、TAFI水平对大面积半球脑梗死患者预后的评估价值

目的探究脂蛋白相关磷脂酶A2(Lp-PLA2)、组蛋白脱乙酰酶(HDAC)3、凝血酶活化纤维蛋白溶解抑制物(TAFI)在大面积半球脑梗死患者预后评估中的价值。方法选取2020年3月—2023年3月河南科技大学附属黄河医院120例大面积半球脑梗死患者(大面积半球脑梗死组),另选取同期120名体检健康者(正常对照组)。采用酶联免疫吸附试验检测所有研究对象Lp-PLA2、HDAC3、TAFI水平。对所有大面积半球脑梗死患者进行90 d的随访,其中预后不良组45例、预后良好组75例。采用Spearman相关分析评价Lp-PLA2、HDAC3、TAFI水平与美国国立卫生研究院卒中量表(NIHSS)评分的关系。采用受试者工作特征(ROC)曲线评估Lp-PLA2、HDAC3、TAFI判断大面积半球脑梗死患者预后的效能。采用多因素Logistic回归分析评估大面积半球脑梗死患者预后不良的影响因素。结果与正常对照组比较,大面积半球脑梗死组Lp-PLA2、HDAC3、TAFI水平显著升高(P<0.001)。大面积半球脑梗死患者Lp-PLA2、HDAC3、TAFI水平与NIHSS评分呈正相关(r_(s)值分别为0.542、0.620、0.597,P<0.05)。与预后良好组比较,预后不良组NIHSS评分、Lp-PLA2、HDAC3、TAFI水平显著升高(P<0.001)。NIHSS评分、Lp-PLA2、HDAC3、TAFI是大面积半球脑梗死患者预后不良的危险因素(P<0.01)。Lp-PLA2、HDAC3、TAFI和NIHSS评分单项检测和联合检测判断大面积半球脑梗死患者预后不良的曲线下面积(AUC)分别为0.790、0.795、0.780、0.908和0.964。结论大面积半球脑梗死患者Lp-PLA2、HDAC3、TAFI水平显著升高,Lp-PLA2、HDAC3、TAFI和NIHSS评分联合检测对大面积半球脑梗死患者预后评估有较高的价值。

血浆凝块收缩功能实验方法学研究

目的:探讨影响血浆凝块收缩功能的关键因素,优化血浆凝块收缩功能实验方法,以用于研究血小板功能调控和评价药物对血浆凝块收缩功能的调节作用。方法:依次研究不同浓度的凝血酶、Ca^(2+)以及血小板对血浆凝块收缩率的影响,优化血浆凝块收缩检测体系。通过检测多种血小板信号通路抑制剂对血浆凝块收缩的调节作用验证该检测体系的有效性。结果:通过对凝血酶浓度、Ca^(2+)浓度和血小板浓度的优化研究,利用0.2 U/ml凝血酶处理含0.5 mmol/L Ca^(2+)以及40×10^(9)/L血小板的富血小板血浆(PRP)进行血浆凝块收缩分析。在此条件下,凝血酶处理15 min能够显著诱导血浆凝块收缩反应,处理30 min诱导的血浆凝块收缩率大于50%。利用此检测条件研究抑制剂对血浆凝块收缩的调节作用,PKC抑制剂Go 6983能够强烈抑制血浆凝块收缩反应,PI3K抑制剂Ly294002和p38 MAPK抑制剂SB203580能够轻度抑制血浆凝块收缩反应。结论:利用0.2 U/ml凝血酶处理含0.5 mmol/L Ca^(2+)和40×10^(9)/L血小板的PRP进行血浆凝块收缩检测,可以用于研究血小板功能调控和评价药物对血浆凝块收缩的调节作用。

凝血酶-抗凝血酶复合物、纤溶酶-α2-纤溶酶抑制剂复合物和血栓弹力图评估肿瘤患者凝血功能的价值

目的 分析凝血酶-抗凝血酶复合物(TAT)、纤溶酶-α2-纤溶酶抑制剂复合物(PIC)和血栓弹力图(TEG)评估肿瘤患者凝血功能的价值。方法 选取2022年1月—2023年8月中国医学科学院肿瘤医院深圳医院120例肿瘤患者(病例组),以同期体检健康者30名作为对照组。比较2组TAT、PIC、TEG各参数的差异。基于Caprini评分将肿瘤患者细分为不同血栓风险组,比较各组TAT、PIC、TEG各参数的差异。比较不同肿瘤类型患者3项指标的差异。采用受试者工作特征(ROC)曲线分析TAT、PIC、TEG各参数诊断肿瘤患者凝血功能的效能。结果 病例组TAT、PIC高于对照组(P<0.05)。血栓极高风险组TAT、PIC高于中/低风险组(P<0.05);肝癌、肺癌、肠癌、胃癌患者TAT、PIC水平均升高,但差异无统计学意义(P>0.05);TAT、PIC、TEG评价肿瘤患者血液高凝状态的敏感性分别为85.0%、55.0%、56.70%,特异性分别为93.3%、81.7%、70.0%,ROC曲线下面积分别为0.94、0.72、0.63。结论 TAT、PIC可早于TEG提示肿瘤患者凝血功能异常,能更好地提示肿瘤患者血液高凝状态。

血清TAT、t-PAIC、TM水平与颅内动脉粥样硬化性狭窄程度的相关性分析

[目的]探讨凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物-抑制剂复合物(t-PAIC)、血栓调节蛋白(TM)在颅内动脉粥样硬化性狭窄(ICAS)患者血清中的水平,以及它们与狭窄程度的相关性。[方法]收集沧州市人民医院2021年1月—2023年2月期间进行治疗的196例ICAS患者(ICAS组)作为研究对象,根据血管的狭窄程度,将其分为轻度组(n=78)、中度组(n=64)和重度组(n=54);另选取196例与ICAS患者临床基本资料一致的同期门诊健康体检者作为对照组。比较各组血清TAT、t-PAIC、TM水平;Spearman法分析ICAS患者血清TAT、t-PAIC、TM水平与狭窄程度的相关性;多因素Logistic回归分析ICAS患者重度狭窄的影响因素;ROC曲线分析血清TAT、t-PAIC、TM、总胆固醇(TC)水平对ICAS患者发生重度狭窄的预测价值。[结果]与对照组相比,ICAS组血清TAT、t-PAIC、TM水平显著升高(P<0.05);ICAS轻度组、中度组、重度组血清TAT、t-PAIC、TM、TC水平依次升高,差异有统计学意义(P<0.05)。Spearman分析显示,ICAS患者血清TAT、t-PAIC、TM水平分别与狭窄程度呈正相关(r=0.574,0.695,0.628;均P<0.05)。多因素Logistic回归分析结果显示,TAT、t-PAIC、TM、TC是ICAS患者发生重度狭窄的独立危险因素(P<0.05)。ROC曲线显示,TAT、t-PAIC、TM、TC联合检测预测ICAS患者发生重度狭窄的AUC为0.927,灵敏度为83.33%,特异度为86.62%,优于各自单独预测(Z_(联合检测-TAT)=4.617、Z_(联合检测-t-PAIC)=4.024、Z_(联合检测-TM)=4.004、Z_(联合检测-TC)=7.078,均P=0.000)。[结论]ICAS患者血清TAT、t-PAIC、TM水平显著升高,且与狭窄严重程度呈正相关,这三者和TC联合检测对ICAS患者发生重度狭窄具有较高的预测价值。