血浆蛋白C活性、活化蛋白C抵抗与急性脑梗死的相关性研究

目的探讨血浆蛋白C(PC)活性、活化蛋白C抵抗(APCR)与急性脑梗死(C I)间的相关性。方法检测69例急性C I患者(急性期36例、恢复期33例)和39例非脑血管病患者(对照组)的血浆PC活性、APCR阳性率,并对检测结果进行分析。结果 C I组患者血浆PC活性(98.27±37.35)%明显低于对照组(124.58±26.14)%,差异具有统计学意义(p<0.05);C I组患者APCR的阳性率(21.74%),与对照组(5.13%)比较具有显著性差异(p<0.001)。C I急性期组与恢复期组APCR阳性率无明显差异(p>0.05);C I急性期组患者血浆PC活性(91.62±34.52)%明显低于恢复期组(105.53±23.18)%,差异有统计学意义(p<0.01)。结论血浆蛋白C活性、APCR与急性脑梗死的发生直接相关。     

餐后不同时间抗凝蛋白活性测定结果的差异研究

目的研究餐后不同时间抗凝血酶Ⅲ(ATⅢ)、蛋白C(PC)、蛋白S(PS)活性测定结果的差异。方法选择30名健康志愿者,分别检测其空腹、餐后2 h、餐后4 h ATⅢ、PC、PS水平,对测得的结果分别进行比较。结果与空腹相比,餐后2 h、餐后4 h血浆ATⅢ、PC、PS水平均降低,差异有统计学意义(P<0.05);而餐后4 h三种抗凝蛋白的活性比餐后2 h有所升高,但其差异不显著(P>0.05)。结论进食是ATⅢ、PC、PS活性水平的重要影响因素,为保证检测结果的准确性,应严格要求空腹采集标本。     

深静脉血栓患者血浆蛋白Z水平的研究

目的研究深静脉血栓(DVT)患者的血浆蛋白Z(PZ)水平,探讨DVT和PZ的相关性。方法采用酶联免疫吸附检测(ELISA)法测定68例DVT患者和55名健康人的蛋白Z水平;采用发色法测定蛋白C(PC),抗凝血酶(AT);采用凝固法测定蛋白S(PS)活性。结果DVT组PZ、PC、PS、AT水平分别为:PZ(1.31±0.60)mg/L,PC(123±25)%,PS(54±23)%,AT(114±17)%;健康对照组PZ、PC、PS、AT水平分别为:PZ(1.11±0.51)mg/L,PC(135±26)%,PS(68±17)%,AT(130±8)%。两组PZ水平无显著性差异(P>0.05);两组PC,PS,AT活性有显著性差异(P<0.05)。DVT组男性和女性PZ水平分别为(1.34±0.61)mg/L和(1.27±0.60)mg/L,健康对照组男性和女性PZ水平分别为(1.09±0.55)mg/L和(1.12±0.49)mg/L,不同性别之间PZ水平无显著性差异(P>0.05)。结论DVT患者和健康人的PC,PS和AT水平有显著性差异,DVT和PC,PS和AT水平具有相关性。DVT患者和健康人的PZ水平无显...     

妊娠晚期孕妇抗凝与纤溶活性检测的临床意义

目的:探讨妊娠晚期孕妇血浆中D-二聚体(DD)含量、抗凝血酶(AT)、蛋白C(PC)、蛋白S(PS)活性的变化。方法:分别测定94例妊娠晚期孕妇和27例正常未妊娠妇女血浆中AT、PC、PS的活性以及DD的含量并进行对比分析。结果:妊娠晚期孕妇血浆中DD含量比对照组明显增高,AT、PC、PS活性显著减低。结论:正常妊娠晚期孕妇血浆中抗凝成分AT、PC、PS活性减低、纤溶活性增强,妊娠期检测AT、PC、PS活性、DD含量的变化,对预防出血、降低DIC的发生率具有指导意义,临床应用中各实验室应建立孕妇AT、PC、PS活性及DD含量的参考范围,而不能套用一般健康人的参考范围。     

失血性休克大鼠活化蛋白C抵抗相关因素在休克后凝血紊乱发展中作用的研究

目的观察失血性休克SD大鼠蛋白C系统变化及活化蛋白C抵抗发生率,探讨失血性休克活化蛋白C抵抗相关因素及对失血性休克凝血紊乱的影响。方法制作失血性休克大鼠模型。30只SD大鼠随机分为休克组和对照组,每组15只。观察2组大鼠休克后1 h、2 h、4 h、6 h、8 h血浆蛋白C活性（PC：A）、血浆总蛋白S（TPS）、血浆游离蛋白S（FPS）、血栓调节蛋白（TM）、活化蛋白C抑制剂（PCI）水平及活化蛋白C抵抗（APCR）阳性率。结果大鼠失血性休克组血浆蛋白C活性、血浆总蛋白S、血浆游离蛋白S、活化蛋白C抑制剂水平明显低于对照组（P〈0.05）。血浆血栓调节蛋白水平明显高于对照组（P〈0.05）。APCR阳性组血浆蛋白C活性、血浆总蛋白S、血浆游离蛋白S水平明显低于APCR正常组,二者血浆血栓调节蛋白水平差异无统计学意义（P〉0.05）。休克组APCR阳性率明显高于对照组,2组的APCR阳性率为分别为33.3%、6.7%（P〈0.01）。休克2 h、8 h后,APCR发生率明显增加。结论PC、PS、PCI消耗、TM异常及活化蛋白C抵抗共同导致失血性休克大鼠血液高凝状态,活化蛋白抵抗与血浆PC、游离PS下降、PCI与PC比例失调、血栓调节蛋白作用下调等多种因素有关。PCI对失血性休克过程中产生APCR影响较小,APCR的形成主要与PC、PS下降有关。     

围手术期凝血系统活化指标的研究

目的探讨手术患者围手术期血栓状态的影响因素。方法采用SLTSPECTRA酶标仪以ELISA法测定纤维蛋白肽A(FPA)、凝血酶原片段1 2(F1 2)、可溶性纤维蛋白单体复合物(SFMC),蛋白C抗原(PC:Ag)。采用CA-530凝血仪测定活化蛋白C抵抗性(APCR)、蛋白C活性(PC:A)。结果APCR阳性的患者组手术前及手术后凝血系统的活化程度均显著高于APCR正常的患者组的同期水平。结论手术患者术前测定凝血系统活化指标对判断术后血栓形成倾向,具有重要价值。     

肺血栓栓塞症患者血浆蛋白S、蛋白C和抗凝血酶Ⅲ活性变化及其临床价值分析

目的探讨血浆蛋白S(PS)、蛋白C(PC)和抗凝血酶Ⅲ(AT-Ⅲ)活性在肺血栓栓塞症(PTE)病情评估中的价值。方法选取47例PTE患者为研究组、同期47例健康体检者为对照组,测定其PS、PC和AT-Ⅲ活性。统计研究组与对照组患者血浆PS、PC和AT-Ⅲ活性,并分析血浆PS、PC和AT-Ⅲ活性与PTE病情相关性。结果研究组PS活性(83.20±13.17)%、PC活性(82.43±10.41)%及AT-Ⅲ活性(79.71±11.40)%均低于对照组(P0.05);不同病情程度PTE患者PS、PC或AT-Ⅲ活性均存在明显差异,差异均有统计学意义(P0.05);随病情加重,血浆PS、PC和AT-Ⅲ活性均逐渐降低,PS、PC或AT-Ⅲ活性与PTE病情程度呈负相关(P0.05)。结论通过检测血浆PS、PC和AT-Ⅲ活性,可评估PTE病情程度,并且各指标与其呈负相关。     

遗传性抗凝血酶缺陷症凝血指标筛查在疾病早期快速诊断的分析研究

目的：探讨检测血浆抗凝血酶（AT）活性（A）、血浆抗凝血酶（AT）抗原（Ag）、蛋白S（PS）、血浆蛋白C（PC）以及D-二聚体等凝血易栓指标对诊断遗传性抗凝血酶缺陷症的临床价值。方法：选择42例抗凝血酶缺陷症患者作为疾病组,再根据PS、PC水平将疾病组进一步分为单纯AT缺乏组、AT联合PS缺乏组、AT联合PC缺乏组和AT、PS、PC全缺乏组;同时选择60名健康查体人员作为健康对照组。用发色底物法检测两组AT∶A、PC及PS活性;用免疫比浊法检测两组AT∶Ag及血浆D-二聚体浓度水平。采用独立样本的t检验比较各组间差异。结果：AT缺陷症组AT∶A和AT∶Ag水平明显减低,与健康对照组比较差异有统计学意义（t=-11.68,t=-6.118;P〈0.01）;AT联合PS、PC缺乏患者的PS、PC水平明显减低,与健康对照组比较差异有统计学意义（t=-9.397,t=-3.065;P〈0.01）;AT缺陷症组患者血浆D-二聚体水平明显增高,与健康对照组比较差异有统计学意义（t=4.358,P〈0.01）。结论：AT缺陷是静脉血栓栓塞性疾病的主要遗传性危险因素,检测其相关凝血指标有助于疾病的早期诊断,为临床提供诊疗依据,对预防静脉血栓栓塞症（VTE）的发生起到预警作用。     

健康妇女孕期抗凝指标的变化

目的研究正常妊娠妇女血浆抗凝血酶Ⅲ(AT-Ⅲ)、蛋白C(PC)、蛋白S(PS)的活性在不同孕期的变化及临床意义。方法收集正常非孕妇(对照组90例)和正常妊娠妇女(552例),其中正常妊娠妇女组分为3个亚组,早孕组(150例)、中孕组(153例)和晚孕组(249例)。应用发色底物法检测AT-Ⅲ、PC活性,凝固法检测PS活性并对结果进行分析。结果与对照组比较,早孕组、中孕组、晚孕组妇女AT-Ⅲ活性差异有统计学意义(P0.01),各孕组间差异无统计学意义(P0.05)。与对照组相比,早孕组的PC活性降低(P0.001),在孕中期和孕晚期升高(P0.001);PS活性显著低于正常对照(P0.01),各孕组之间差异有统计学意义(P0.01)。进一步线性相关分析发现,PC活性与孕周数呈显著正相关(r=0.531,P0.001),而PS活性与孕周数呈显著负相关(r=-0.393,P0.001)。结论与正常妇女相比,妊娠妇女PC、PS活性指标发生显著变化,且整个孕期呈现动态变化,为产科医生对孕妇孕期的血栓风险的评估提供了一定的依据。     

关于糖尿病患者抗凝血因子检测与分析

目的:探讨糖尿病患者血管病变及抗凝血因子改变在其发病机制中的意义。方法:采用酶联免疫法检测血浆血管性血友病因子(vWF),发色底物法检测蛋白C、蛋白S活性(PC:A、PS:A),对健康对照组、糖尿病无血管病变和伴发血管病变患者进行检测和分析。结果:血管病变组vWF、PC:A、PS:A与对照组比较差异有统计学意义(P<0.01),无血管病变组PC:A、PS:A与对照组比较差异有统计学意义(P<0.01)。血管病变组vWF、PC:A、PS:A异常分布率分别为91.4%、85.0%、45.5%,vWF含量与PC:A含量相比呈负相关(r=-0.741,P<0.05),而与PS:A含量呈正关(r=0.765,P<0.05),PC:A含量与PS:A含量亦呈正相关关系(r=0.844,P<0.01)。结论:血浆vWF、PC:A、PS:A检测在糖尿病发病及病程发展的监测中具有一定的临床价值。     

Protein C,S and antithrombin III levels in patients with acute mechanical valve thrombosis

BACKGROUND: Mechanical prosthetic heart valve thrombosis is a serious complication with an incidence of 1-6%. The reduction in active vitamin-K dependent protein C and S levels caused by warfarin treatment also results in a prothrombotic state. This study was conducted to investigate the connection between protein C (PC), protein S (PS), antithrombin III (ATIII) deficiency and prosthetic mechanical valve thrombosis. METHODS: Twenty-nine of the 283 patients who underwent valve replacement with St. Jude medical prosthesis had mechanical valve thrombosis (group 2). The rest were considered as group 1. Twelve of the 29 patients (41.4%) had isolated aortic valve replacement, 12 had isolated mitral valve replacement (41.4%) and 5 patients had double valve replacement (17.2%). Most of the patients had rheumatic valve disease at their 1st operation. The mean time of occurrence for mechanical valve occlusion was 4.1+/-1.0 years following surgery. RESULTS: The values of PC, PS and ATIII were obtained when the mechanical valves stuck or at routine follow-up. PC, PS and ATIII levels were significantly lower in the mechanical valve thrombosis group. PC levels were 75.4+/-37.6% and 49.9+/-32.2% in group 1 and 2, respectively (p=0.001). PC, PS and ATIII values were mostly lower in the 2nd group but this difference only became significant after at least 2 years of warfarin usage. CONCLUSIONS: Natural anticoagulant levels can be low during the use of warfarin. In which case the dose can be increased in order to hold the international normalized ratio (INR) at 3-3.5. However, more frequent follow-up is required and patients should be investigated for hypercoagulation states or deficiency in anticoagulant proteins. Patients referred to hospital with any mechanical valve thrombosis or recurrent thromboembolism should be evaluated for hypercoagulant proteins.     

National evaluation of the diagnosis of activated protein C resistance

Thrombophilia or prothrombotic state appears when activation of blood hemostatic mechanisms overcomes the physiological anticoagulant capacity allowing a thrombotic event. Thrombosis is the leading worldwide mortality cause and due to its high associated morbidity and mortality, it should be insisted in the opportune identification of a thrombophilic state. The study of thrombophilia identifies individuals at high risk for thrombosis. This meeting was conceived first to analyze the current status of the diagnosis of thrombophilia in Mexico and second to create the base for a national consensus for thrombophilia screening and for the establishment of a national center for laboratory reference and quality control for thrombophilia. Since searching of activated protein C resistance (APCR) and FV Leiden seem to have priority either in the clinical setting and in public health services, it was decided to start with these two abnormalities as a model to analyze the current status of thrombophilia diagnosis in the clinical laboratory. At this time, several thrombophilic abnormalities have been described however, APCR remains the most important cause of thrombophilia, accounting for as much as 20% to 60% of all venous thrombosis. APCR is a consequence of the resistance of activated FV to be inactivated by activated protein C. Procoagulant activity of activated FV increases the risk of thrombosis. Hereditary APCR is almost always due to a point mutation at the nucleotide 1691 of the FV gen inducing an Arg506Glu substitution in FV molecule. This mutation is better known as FV Leiden. Heterocygous carriers of FV Leiden have a thrombotic risk 5 to 10 times higher than general population while the risk for the homocygote state is increased 50 to 100-fold. When activated PC is added to plasma from patients with FV Leiden, this last resists the anticoagulant effect of activated PC. Therefore, thrombin production is not inhibited. This phenomenon is called APCR. The functional test evaluates the partially activated thromboplastin time (aPTT) in a plasma sample before and after adding activated PC. The result is reported as a standardized sensibility index: aPTT post-activated PC/aPTT pre-activated PC. The conclusions of this national reunion pretend to optimize the available resources in our country in order to allow a wide and less-expensive diagnosis of patients with thrombosis.     

活化蛋白C抵抗与胎儿生长受限的相关性研究

目的:探讨活化蛋白C抵抗(APCR)与胎儿生长受限(FGR)发生的关系,为FGR的早期诊断和预防提供新的思路。方法:对2004年6月~2005年2月该院产科门诊、住院的FGR患者20例(研究组),非孕期健康育龄妇女20例(对照组1),孕期健康妇女20例(对照组2)进行研究,应用APTT-APC法检测APCR现象。结果:对照组1APCR阳性率为5·0%(1/20),APC-SR(APC敏感比值)为2·41±0·158;对照组2阳性率为30·0%(6/20),APC-SR为2·15±0·166;研究组阳性率为65·0%(13/20),APC-SR为1·97±0·117。研究组APCR阳性率显著高于对照组1和对照组2,差别有统计学意义(P<0·01,P<0·05),APC-SR显著低于对照组1和对照组2,差别有统计学意义(P<0·01),但对照组1和对照组2之间APCR阳性率比较无统计学差异(P>0·05)。结论:FGR孕妇血浆APCR现象的阳性率明显升高,提示FGR的发生与APCR现象有关。     

肿瘤患者并发下肢深静脉血栓形成行抗凝治疗18例临床分析

目的探讨抗凝治疗肿瘤患者并发下肢深静脉血栓形成的临床效果。方法对18例恶性肿瘤并发下肢深静脉血栓形成的患者抗凝治疗结果进行进行回顾性分析。结果本组病例中痊愈7例(38.9%),有效11例(61.1%),总有效率为100%,均治疗有效出院。结论抗凝治疗合并下肢深静脉血栓形成的肿瘤患者是安全、有效、方便。     

活化蛋白C抵抗与反复妊娠丢失相关性

目的:探讨凝血因子V Leiden(FVL)突变、活化蛋白C抵抗(APCR)和抗磷脂抗体(APL)与不明原因反复妊娠丢失的相关性及反复妊娠丢失的高危因素。方法:选择不明原因的妊娠丢失患者71例,正常健康有生育史者60例作为对照组,除外有血栓病史和口服避孕药者。研究组及对照组均检测FVL突变、APCR和抗磷脂抗体。结果:①反复妊娠丢失患者及正常对照组均未见FVL突变;②妊娠丢失患者中APCR发生率为22.5%,正常对照妇女的发生率是8.3%,P<0.05;③研究组抗磷脂抗体(APL)阳性率21.1%,对照组APL阳性率6.7%,两组比较差异有统计学意义,P<0.05;胎死宫内与对照组比较P<0.001;④获得性APCR使妊娠丢失的风险增加4.2倍,而且抗磷脂抗体阳性患者中APCR发生率明显高于阴性者。结论:非FVL获得性APCR和APL是妊娠丢失的高危因素,而且APL可能是获得性APCR的原因之一。故不明原因的RPL妇女应常规筛查APL和APCR。     

胎儿生长受限孕妇血浆活化蛋白c抵抗与抗心磷脂抗体检测结果分析

目的:研究活化蛋白c抵抗(APCR)、抗心磷脂抗体(ACA)与胎儿生长受限(FGR)的相关性,并进一步探讨FGR患者APCR与ACA的关系。方法:采用APTT±APC法检测20例原因不明FGR患者(实验组)、35例正常待产妇(对照组)的APCsr;Elisa方法检测ACA-IgG、IgM滴度水平。结果:①实验组APCR阳性率60.0%,明显高于对照组(31.4%),P(0.05;②实验组ACA阳性率20.0%,对照组2.9%,差异有显著性;③APCR阳性组ACA阳性3例,阴性组ACA阳性2例,无显著差异。结论:APCR和ACA均是FGR的危险因素,但获得性APCR的发生并非ACA抑制蛋白c通路导致凝血异常及导致FGR形成的唯一通路。     

Screening for activated protein C resistance before oral contraceptive treatment: a pilot study.

The feasibility and cost-effectiveness of screening women for congenital thrombophilic alterations before oral contraceptive (OC) treatment was investigated. A total of 525 women (mean age 21.9 years, 73% aged < 25 years) were examined before their first OC course. At first screening, completely normal results were recorded in 485 (92.4%) women, the remaining showing single (n = 34) or multiple (n = 6) alterations. At second examination (possible in 37 of 40), activated protein C resistance (APCR) was confirmed in 21 cases (4.0%, 18 with factor V Leiden), protein C, or protein S reduction in 8 (1.5%) and 2 (0.4%) cases, respectively. No cases with antithrombin III deficiency were detected. The global estimated cost ($US) to detect one altered case was: $7795 for protein S, $2696 for antithrombin III (no case found), $1374 for protein C and $433 for APCR. The present study confirms that extensive thrombophilic screening before OC treatment is not currently advisable. APCR assessment, however, seems to have a favorable cost-effectiveness ratio: the alteration is frequent and has a synergistic effect with OC; sensibility and specificity of some methods are good; family history is unreliable to single out possible carriers; finally, carriers can be fully informed of their increased thrombotic risk if treated with OC and can receive thromboprophylaxis during life situations associated with high thrombotic risk (e.g., pregnancy and puerperium).