下肢深静脉血栓形成患者抗凝蛋白缺陷的临床研究

目的：研究中国人群下肢深静脉血栓形成（IDVT）患者抗凝蛋白缺陷的发生率，探讨中国人群LDVT的主要发病机制。方法：应用ACLPutLlm型全自动血凝仪检测1幔）例LDVT患者（73例初发，27例复发）和100例健康人的抗凝血酶（AT）、蛋白S（PS）、蛋白C（PC）活性及活化蛋白C抵抗性（APCR）。结果：LDVT组与正常对照组相比、LDVT复发组与初发组相比，AT、PS、PC活性明显降低，APCR阳性率明显升高，均有极显著差异（P〈0．01）；本组100例LDVT患者中共有25例患者存在有抗凝蛋白缺陷，以PS缺陷的总发生率最高，为13％（13例），其次是PC缺陷，为8％（8例）；AT缺陷占5％（5例），APCR缺陷的总发生率最小，为4％（4例）。结论：先天性或获得性抗凝蛋白缺陷是中国人LDVT发病和复发的重要机制之一，因此有必要对LDVT患者进行抗凝蛋白水平的筛选。     

六例遗传性易栓症的血栓发生与实验表型及基因型关联分析

易栓症包括遗传性和获得性.获得性易栓症继发于手术创伤、制动、口服避孕药、母体免疫性疾病、恶性肿瘤等,遗传性易栓症主要是由蛋白C(PC)、蛋白S(PS)和抗凝血酶(AT)缺陷导致.AT缺陷的发病率为1/5000～1/500,病情较为严重.遗传性PC缺陷为常染色体显性遗传病,杂合子型PC缺陷症患者多在30～40岁发病,有很大一部分杂合子型不发病,纯合子和复合杂合较罕见.PS缺陷为常染色体显性遗传,杂合子型60％ ～ 80％患有深静脉血栓(VTE),发病年龄多在40～45岁[1].本研究对我院2010至2012年收治的6例AT、PC和PS缺陷的患者及其家系进行血栓发生及相关研究.     

遗传性抗凝蛋白缺陷症与静脉血栓关系的研究进展

抗凝蛋白缺陷症是静脉血栓栓塞症发病的主要危险因素之一。抗凝蛋白缺陷症分为遗传性和获得性两种，其中遗传性抗凝蛋白缺陷症主要是由蛋白C（PC）、蛋白S（PS）和抗凝血酶（AT）缺陷症导致。PC、PS和AT缺陷症在静脉血栓发病中所占的比率分别为2．0％～8．0％、7．3％和1．0％～8．0％；不同抗凝蛋白缺陷所导致的临床症状差别不大，但AT缺陷症的临床表现最为严重。     

抗凝蛋白缺陷与反复自然流产的相关性研究

目的 探讨抗凝蛋白缺陷与不明原因的反复自然流产(RSA)的相关性.方法 采用血液凝固法、发色底物法检测102例RSA患者和36例经产健康体检妇女血浆中蛋白S(PS)、蛋白C(PC)及抗凝血酶Ⅲ(AT-Ⅲ)的活性水平.结果 RSA组PS、PC及AT-Ⅲ缺陷的发生率分别为28.4%、1.9%及21.2%,PS缺陷及AT-Ⅲ缺陷与健康对照组相比差异有统计学意义(P<0.05),PC缺陷与健康对照组间差异无统计学意义(P>0.05);RSA晚期流产组(孕周大于或等于12周)的PS和AT-Ⅲ缺陷发生率分别为48.9%和35.6%,与健康对照组比较均有统计学差异(P<0.01),RSA早期流产组(孕周小于12周)的PS和AT-Ⅲ缺陷发生率与健康对照组比较,差异均无统计学意义(P>0.05).结论 抗凝蛋白缺陷可能与RSA的发生,特别是晚期流产的发生有关.     

蛋白C和蛋白S活性、活化蛋白C抵抗与急性缺血性脑血管病的相关性研究

目的研究PC和PS活性、APCR与急性缺血性脑血管病间的关系。方法对804例急性脑血管病人及168例健康对照组行PC、PS,APCR检测。结果在缺血性中风组,PC、PS活性分别为115.8%±125%和112.6%±138%明显低于出血性中风组的119.2%±13.3%和112.1%±16.5%,对照组的120.2%±12.8%和122.4%±15.8%,P<0.01。进一步比较发现,<45岁的缺血性中风组的PC、PS分别为54.67%±8.9%,40.49%±9.1%明显低于其他各组,PS在45岁以上的缺血性中风组为119.2%±15.6%±明显低于对照组的122.4%±45 8%,p<0.01,其余各组间无显著差异。APCR总发生率66%(64/972),其中缺血性中风组为7.14%(46/644),出血性中风组为625%(10/160),p>0.05,45岁以下缺血性中风组APCR的发生串46.3%(25/54),明显高于其他各组。结论PC、PS活性降低,APCR是缺血性脑血管病发生的重要因素,特别与45岁以下的缺血性中风的发生密切相关。     

溶血和脂血对血浆中抗凝蛋白及纤溶系统的影响

目的探讨标本溶血和脂血对血浆中抗凝蛋白和纤溶系统的影响。方法用真空采血管抽取50例住院患者空腹静脉血各两管,无黄疸、脂血、溶血,即刻以3 000r/min离心10min,立即测定抗凝血酶Ⅲ(ATⅢ)、蛋白C(PC)、蛋白S(PS)、D-二聚体(D-Dimer)、纤维蛋白降解产物(FDP)水平,作为对照组。然后每管分装3份,同时制备不同水平溶血和脂血标本,分别测定上述抗凝和纤溶指标,与对照组结果进行比较。结果不同程度溶血标本与对照组相比,轻、中度溶血患者5种指标水平差异无统计学意义(P0.05);重度溶血组ATⅢ活性显著升高(P0.05),PC活性显著降低(P0.05),而PS活性、D-Dimer、FDP水平差异无统计学意义(P0.05)。不同程度脂血标本与对照组相比,轻、中度脂血患者5种指标水平差异无统计学意义(P0.05);重度脂血组ATⅢ活性显著降低(P0.05),PC和PS活性、D-Dimer、FDP水平显著升高(P0.05)。结论为保证抗凝蛋白活性和纤溶系统水平,应严格控制分析前质量控制。     

三种抗凝蛋白和D-二聚体含量检测及临床意义

目的检测不同病因引起弥漫性血管内凝血(DIC)患者血浆中D-二聚体(D-D)含量,及抗凝血酶Ⅲ(AT)、蛋白C(PC)、蛋白S(PS)活性,探讨其临床意义。方法采用法国STAGO公司的全自动血凝分析仪,检测由不同疾病引起DIC的72例患者血浆中D-D含量(免疫比浊法)及AT(发色底物法)、PC(凝固法)、PS(凝固法)活性。结果不同病因引起的DIC患者血浆D-D均明显升高,多数病例组为正常对照组的10~30倍,恶性肿瘤组为正常对照组的近百倍;除白血病组血浆AT与正常对照组无明显差别(P>0.05)外,其余所有DIC病例组的血浆AT、PC、PS均明显降低(P<0.05)。结论血浆D-D升高是诊断DIC的敏感指标。在多数病因造成的DIC中,抗凝系统功能降低是病理生理过程的重要环节。     

672例静脉血栓栓塞症相关危险因素分析

目的 分析静脉血栓栓塞症（VrrE）住院患者的患病情况、临床特征和危险因素。方法 回顾性分析北京协和医院1994年至2004年住院VTE病例的患病趋势、人口学特点、获得性及遗传性危险因素。结果 共收集VTE患者672例，男：女=1．2：1，中位年龄53（14—92）岁。初发患者580例（86．3％），发病高峰年龄男性患者为40～50岁，女性为50-60岁。主要获得性危险因素有抗磷脂抗体阳性（32．0％）、外伤和（或）手术（31．1％）、肿瘤（17．1％）。其中具有多种获得性危险因素者占35．7％。94例患者在抗凝治疗前取外周血检测了蛋白C（PC）、蛋白S（PS）和抗凝血酶（AT）活性。抗凝蛋白总缺陷率为44．7％，以PC缺乏以及PC与AT联合缺乏为主，分别占13．8％和10．6％。同时具有遗传和获得性危险因素者占31．6％。结论 研究结果显示综合医院的住院VTE病例数呈逐年上升趋势，男性VTE患者的初发年龄较女性提早约10年。主要获得性危险因素为抗磷脂抗体阳性、外伤或手术和肿瘤，而遗传性危险因素则以PC缺乏和PC与AT联合缺乏为主。多种危险因素并存是促发VTE的重要原因。     

慢性肾小球疾病患者血浆中部分抗凝和纤溶指标变化的探讨

目的研究慢性肾小球疾病患者血浆中部分抗凝和纤溶物质与其止凝血障碍的关系。方法在STAGO-STA全自动血凝仪上检测79例慢性肾小球疾病患者和60名正常对照的血浆蛋白C(PC)、蛋白S(PS)、抗凝血酶(AT-)、纤溶酶原(PLG)和抗纤溶酶(AP)活性。结果与正常对照比较肾病综合征患者PC、PLG活性升高,有显著性差异(P<0.01);PS和AT活性降低(P<0.01),有显著性差异;AP升高,与正常对照无显著性差异。慢性肾炎患者PC升高(P<0.05),PLG升高(P<0.01),与正常组比较有显著性差异;PS和AT降低(P>0.05)与正常组比较无显著性差异,AP无变化。结论慢性肾小球疾病患者存在不同程度的凝血亢进和纤溶亢进,测定抗凝和纤溶系统的一些项目可帮助了解疾病的进展及指导治疗。     

创伤患者血液组织因子抗凝血酶Ⅲ血液蛋白C活化率水平变化及其与前弥散性血管内凝血的关系研究

目的 探讨创伤患者早期血液蛋白C(PC)活化率、组织因子(TF)、抗凝血酶Ⅲ(ATⅢ)的变化及其与前弥散性血管内凝血(前DIC)的相关性.方法 将44例患者分为重伤组(ISS≥16分,29例)和轻伤组(ISS<16分,15例),另10例健康人为正常对照组.44例患者又分为前DIC组(16例)和非前DIC组(28例).所有研究对象于伤后1、3、6 d空腹采外周静脉血,对照组采集空腹外周血3次,检测血液TF、PC活化率及ATⅢ水平变化.结果 重伤组和轻伤组PC活化率、TF水平在伤后明显升高,显著高于对照组(P<0.01),且重伤组又高于轻伤组(P<0.05或P<0.01);ATⅢ水平在伤后明显降低,显著低于对照组(P<0.01),且重伤组又低于轻伤组(P<0.05).前DIC组TF、PC活化率水平高于非前DIC组(P<0.01),而ATⅢ水平在伤后明显低于非前DIC组(P<0.01).相关分析表明,严重创伤患者血液TF、ATⅢ、PC活化率水平的变化与前DIC发生密切相关.结论 创伤后急性期TF、ATⅢ、PC活化率水平变化不仅与创伤严重程度有关,且与前DIC的发生显著相关,检测严重创伤患者急性期外周血TF、ATⅢ、PC活化率的水平变化对早期预测DIC具有较重要价值.     

复发性流产患者易栓症指标筛检的意义

目的探讨易栓症相关指标与不明原因复发性流产(URSA)的相关性,为URSA患者的病因排查和治疗提供参考。方法选取2016年11月—2018年3月上海交通大学医学院附属国际和平妇幼保健院104例流产次数≥2次的URSA患者作为URSA组,以45例健康经产妇作为对照组,检测所有研究对象血浆狼疮抗凝物(LA)阳性率、抗心磷脂抗体(ACA)阳性率、蛋白C(PC)活性、蛋白S(PS)活性、抗凝血酶(AT)活性、凝血因子Ⅻ(FⅫ)活性和D-二聚体(DD)水平。结果URSA组LA阳性率、PC活性、PS活性、AT活性、FⅫ活性、DD水平与对照组比较差异均有显著统计学意义(P<0.05)。结论LA阳性、PS缺陷、FⅫ缺陷和DD增高与URSA密切相关。LA、PS、FⅫ、DD是URSA患者体内高凝状态较好的筛查指标,联合检测AT、PC,对预测URSA血栓形成有临床指导意义。     

纤溶系统标志物的变化在不同临床类型冠心病诊疗中的应用

目的 通过检测不同临床类型冠心病（CHD）患者血浆中D-二聚体（D-D）、纤维蛋白原（Fg）、纤维蛋白原降解产物（FDP）含量和抗凝血酶Ⅲ（AT-Ⅲ）、蛋白C（PC）、蛋白S（PS）活性的动态变化,探讨其在冠心病诊疗中的临床意义.方法 回顾性分析126例临床确诊的冠心病（CHD）患者,其中稳定型心绞痛（SAP）42例,不稳定型心绞痛（UAP）45例,急性心肌梗死（AMI）39例,并选40例健康体检者为对照组.用STA-R全自动凝血仪分别测定上述项目的血浆含量和活性,并进行比较分析.结果 AMI组较UAP组、SAP组及对照组,血浆AT-Ⅲ、PC 、PS活性明显降低,有显著性差异（P＜0.01）,血浆Fg、FDP、D-D含量明显升高,有显著性差异（P〈0.01）;UAP组较SAP组及对照组,血浆AT-Ⅲ、PC 、PS活性明显降低,有显著性差异（P＜0.01）,血浆Fg、FDP、D-D含量明显升高,有显著性差异（P＜0.01）;SAP组与正常对照组比较,血浆AT-Ⅲ、PC 、PS活性和Fg、FDP、D-D含量均无显著性差异（p0.05）.结论 不同临床类型冠心病（CHD）患者血浆纤溶系统失衡,其中AMI和UAP患者存在异常激活的高凝状态.其发病机制可能有血栓因素的参与,联合测定上述标志物,有利于冠心病的早期诊断、临床分型及疗效观察.     

血栓疾病患者血浆肝素辅因子Ⅱ活性和抗原水平检测及意义

目的　了解肝素辅因子Ⅱ (HCⅡ )活性及抗原水平在动、静脉血栓性疾病中的变化及其与动、静脉血栓性疾病之间的关系。方法　用发色底物法测定 5 0名正常人 ,75例脑梗死、5 0例心肌梗死及 36例深静脉血栓患者血浆HCⅡ活性 ;发色底物法检测深静脉血栓患者中HCⅡ缺乏者血浆抗凝血酶 (AT)活性 ;Westernblot检测部分样品 (每组 36例 )血浆HCⅡ抗原含量。结果　血浆HCⅡ活性与其抗原呈平行变化 ;正常对照组血浆HCⅡ活性及抗原水平分别为 (96 .80± 2 0 .11) % ,0 .93± 0 .19与脑梗死组 [(99.97± 2 1.14 ) % ,0 .96± 0 .2 4 ]、心肌梗死组 [(98.18± 2 9.35 ) % ,0 .95± 0 .2 0 ]及深静脉血栓形成组 [(89.5 7± 17.12 ) % ,0 .87± 0 .18]比较 ,差异无显著性 ,但深静脉血栓形成组HCⅡ活性和抗原均呈降低趋势 ;HCⅡ明显减低者在正常人及患者之间的分布频度无显著差异 ;深静脉血栓中HCⅡ缺乏者血浆抗凝血酶活性及纤维蛋白原浓度正常。结论　血浆HCⅡ变化可能不是中国湖南汉族人心、脑血栓病的危险因子 ;是否与静脉血栓形成相关有待进一步证实。     

Combined antithrombin and protein C supplementation in meningococcal purpura fulminans: a pharmacokinetic study

PURPOSE: To document in patients with meningococcal purpura fulminans (PF), the effects of a combined supplementation with antithrombin (AT) and protein C (PC) plasma concentrates and to estimate the pharmacokinetics and dose requirements of each inhibitor. DESIGN: Retrospective study of 15 patients. SETTING. One paediatric and one adult ICU in a university hospital. INTERVENTIONS: In addition to standard intensive care, all patients received a 100 IU/kg loading dose of AT and PC concentrates, followed by a continuous infusion (AT: 100-150 IU.kg.day; PC: 100 IU.kg.day in adults, and 400 IU/kg in infants). MEASUREMENTS: Clinical data, coagulation, and fibrinolysis parameters, AT and PC activities, and free protein S (PS) levels were sequentially measured. Restitution ratio, median increment after supplementation, and half-life of clearance from plasma were calculated for the two plasma substitutes. RESULTS. At admission, all patients had a severe decrease in AT, PC, and PS levels. The supplementation regimen induced a substantial increase in AT and PC activities, peaking at H18 and H48, respectively. The supplementation procedure did not modify free PS levels. The median values of AT and PC restitution ratio, increment in plasma activity observed after 100 IU/kg concentrate, and apparent half-life of clearance from plasma were 0.85 U.ml.U.kg and 0.59 U.ml.U.kg, 23% and 21%, 16 h and 6 h, respectively. CONCLUSION: If AT and PC concentrates are to be given in fulminant meningococcemia, the doses of supplementation should be at least 150 IU/kg AT and 250 IU/kg PC as loading dose and 150 IU/kg AT and 200 IU/kg PC as daily maintenance therapy. Taking into account the individual variability in inhibitor deficiency and restitution ratio, repeated measurements of plasma levels are mandatory to obtain a patient-based adjustment of the supplementation.     

Low borderline plasma levels of antithrombin,protein C and protein S are risk factors for venous thromboembolism

Summary. Background: Inherited deficiencies of antithrombin (AT), protein C (PC) and protein S (PS) are risk factors for venous thromboembolism (VTE). They are usually defined by laboratory cut‐offs (in our setting 81, 70 and 63 IU dL^?1, respectively), which give only a rough idea of the VTE risk associated with plasma levels of these proteins. Objectives: We investigated whether the risk of VTE associated with the plasma deficiencies of AT, PC or PS has a dose–response effect, and whether low borderline levels of these proteins are associated with an increased risk of VTE, both in the whole study population and separately in carriers of either factor V Leiden or G20210A prothrombin gene mutation. Patients/Methods: A case–control study of 1401 patients with a first objectively‐documented VTE and 1847 healthy controls has been carried out. Results: A dose–response effect on the VTE risk was observed for all the three anticoagulant proteins. Compared with individuals with AT, PC or PS levels > 100 IU/dL, the adjusted odds ratio (95%CI) of VTE was 2.00 (1.44–2.78) for AT levels between 76 and 85 IUdL^?1, 2.21 (1.54–3.18) and 1.84 (1.31–2.59) for PC and PS levels between 61 and 75 IUdL^?1. The risk of unprovoked VTE in factor V Leiden or prothrombin G20210A carriers appears 2 to 3‐fold increased when levels of AT or PS are low borderline. Conclusions: Low borderline plasma levels of AT, PC and PS are associated with a 2‐fold increased risk of VTE and should be considered in the assessment of the individual VTE risk.     

Clinical and biological aspects of juvenile thrombophilia

Summary The clinical status of 418 consecutive thrombotic patients was assessed and they were investigated for deficiencies of the proteins involved in the modulation of blood coagulation and fibrinolysis. The whole cohort was divided into two groups according to the age at which the first thrombotic event occurred: group 1 younger than 45 years and group 2 older than 45 years. Deficiencies were significantly more frequent in the juvenile thrombotic population; in this subset of patients the prevalences of single deficiencies were: protein S (6.9%), protein C (4.9%), antithrombin III (3%), plasminogen (0.5%) and dysfibrinogenemia (0.3%). It was possible to diagnose 41 additional deficiencies in the relatives of the probands. The clinical picture and the presence, absence and type of predisposing factors were not statistically different in deficient and non-deficient patients. However, deficient patients experienced their first episode significantly earlier than non-deficient patients and had a significantly higher number of recurrences and pulmonary embolism episodes. From the analysis of the thrombosis-free survival curves, there is no doubt that age represents a strong cofactor in thrombotic risk-related deficiency.     

Clinical and biological aspects of juvenile thrombophilia.

The clinical status of 418 consecutive thrombotic patients was assessed and they were investigated for deficiencies of the proteins involved in the modulation of blood coagulation and fibrinolysis. The whole cohort was divided into two groups according to the age at which the first thrombotic event occurred: group 1 younger than 45 years and group 2 older than 45 years. Deficiencies were significantly more frequent in the juvenile thrombotic population; in this subset of patients the prevalences of single deficiencies were: protein S (6.9%), protein C (4.9%), antithrombin III (3%), plasminogen (0.5%) and dysfibrinogenemia (0.3%). It was possible to diagnose 41 additional deficiencies in the relatives of the probands. The clinical picture and the presence, absence and type of predisposing factors were not statistically different in deficient and non-deficient patients. However, deficient patients experienced their first episode significantly earlier than non-deficient patients and had a significantly higher number of recurrences and pulmonary embolism episodes. From the analysis of the thrombosis-free survival curves, there is no doubt that age represents a strong cofactor in thrombotic risk-related deficiency.     

抗凝血酶Ⅲ、蛋白C、蛋白S活性与脑梗死的相关性研究

目的：研究血浆抗凝血酶Ⅲ（AT-Ⅲ）、蛋白 C（PC）和蛋白 S（PS）活性动态变化与脑梗死发病的关系。方法对126例脑梗死患者按年龄、发病时间和梗死范围分组,同时选择健康体检30例作为健康对照组,检测血浆中 AT-Ⅲ、PC 和 PS 的活性,并分析其活性变化与脑梗死年龄、发病时间及梗死范围之间的关系。结果急性期青年组的 AT-Ⅲ、PC、PS 活性低于急性期中老年组、差异有统计学意义（P ＜0．05）;急性期 AT-Ⅲ、PC、PS 活性低于恢复期和对照组,差异有统计学意义（P ＜0．05）;恢复期AT-Ⅲ和 PS 活性低于对照组,差异有统计学意义（P ＜0．05）,而恢复期 PC 活性与对照组比较,差异无统计学意义（P ＞0．05）;进一步研究发现,AT-Ⅲ、PC、PS 活性在小梗死组、中梗死组、大梗死组间呈逐渐降低的趋势,差异均有统计学意义（P ＜0．05）。结论AT-Ⅲ、PC、PS 活性降低是脑梗死发生的重要因素,特别与45岁以下青年人脑梗死的发生密切相关。观察其活性变化对判断脑梗死病情的发展有重要的临床意义。