新型血管内液体栓塞剂中有效组分的体外促凝血作用研究

目的研究用于颅内动脉瘤治疗的新型血管内液体栓塞剂中有效栓塞成分（白芨多糖与二醋酸纤维素聚合物）的体外促凝血作用。方法将有效栓塞成分按质量比不同分为4组，观察各组样品对凝血酶原时间（PT）与活化部分凝血活酶时间（am）的影响。结果新型血管内液体栓塞剂能显著缩短PT，且缩短程度与主要栓塞成分白芨多糖所占比例成正相关；同时此栓塞剂也可缩短aPTT。结论新型血管内液体栓塞剂在体外实验中明显促进凝血，并偏重于影响外源性凝血途径；此外，主要栓塞成分白芨多糖在促进凝血过程中起关键作用。     

4项凝血相关指标的检测在临产孕妇中的临床应用

目的通过对凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib)和D-二聚体(D-Dimer)含量的检测,掌握临产孕妇的高凝状态,预防分娩过量中出现产后大出血、弥散性血管内凝血(DIC)和血栓栓塞的发生。方法回顾性分析200例正常临产孕妇(产后无大出血、无DIC)血浆中PT、APTT、Fib和D-Dimer含量和50例妇科一般炎症非妊娠妇女作对照。结果临产孕妇的PT、APTT明显低于非妊娠妇女对照组(P<0.05),Fib和D-Dimer的含量明显高于对照组(P<0.05)。结论对临产孕妇监测PT、APTT、Fib和D-Dimer,了解其凝血状态,预防产后大出血、DIC和血栓栓塞的发生起着重要的作用。     

血浆PT、APTT在女性妊娠期的变化

目的探讨女性妊娠期血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）的变化及临床意义。方法PT、APTT的测定均为凝固法，用德国TECO CoatronM4半自动血凝仪检测，孕妇20．0例为测定组。结果测定组中妇女与对照组或早期妊娠妇女比较，PT、APTT的时间均明显缩短，差异具有显著性（P〈0．05）。结论 女性妊娠这一特殊生理期内血液成分及血流动力学的改变是PT、APTT测定时间缩短的生理基础，其对预防、诊断妊娠合并血栓栓塞性疾病有着重要的意义。     

400例孕晚期产妇凝血4项检测的临床意义

目的探讨孕晚期产妇凝血4项检测的临床意义,为临床预防和治疗孕晚期产妇弥散性血管内凝血等并发症提供参考。方法检测400例孕晚期产妇与150例健康妇女活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB),分析结果与研究对象凝血状态的关系。结果孕晚期产妇组血浆APTT、PT、TT明显低于健康对照组,FIB水平明显高于健康对照组。结论孕晚期产妇凝血4项检测可以有效监测血液高凝状态,指导临床采取针对性的预防和治疗措施。     

子痫前期凝血功能检测及临床价值

目的 探讨凝血功能的变化在子痫前期发病中的作用.方法 采用凝固法检测68例子痫前期患者血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)及纤维蛋白原(Fib)的含量,与65例正常妊娠妇女及60例育龄非孕妇女对照分析.结果 子痫前期组与对照组比较,PT、APTT缩短,Fib升高,差异有统计学意义(P＜0.01);子痫前期组与正常妊娠组比较,PT、APTT缩短,Fib升高,差异有统计学意义(P＜0.01).子痫前期组随着病情的恶化,PT、APTT逐渐缩短,Fib逐渐升高,且与病情的严重程度呈正相关.结论 子痫前期患者存在高凝状态,产前进行凝血功能动态监测,对预测子痫前期的发展,及时治疗血栓前状态,有效预防弥散性血管内凝血的发生具有一定的临床意义.     

148例待产孕妇凝血筛选结果分析

目的对产科待产孕妇的凝血酶原时间(PT)、部分凝血活酶时间(APTT)、凝血活酶时间(TT)、纤维蛋白原(FIB)的检测结果进行分析总结。方法用凝固、光散射等方法对148例待产孕妇和健康体检者的PT、APTT、FIB以及TT。结果 148例待产孕妇的PT为(9.59±1.32)s、APTT为(26.18±5.56)s、FIB为(5.40±0.83)g/L、TT为(11.92±2.83)s;健康对照组PT为(12.91±1.43)s、APTT为(33.40±3.87)s、FIB为(2.75±0.98)g/L、TT为(13.52±2.87)s,孕妇组的PT、APTT、TT比健康对照组明显缩短;FIB明显增高,两组结果比较差异有统计学意义(P<0.05)。结论临产孕妇和健康对照组的凝血筛选差异有统计学意义,随时监测待产孕妇的PT、APTT、TT、FIB是非常必要的,可以防止产妇异常出血和弥散性血管内凝血的发生,确保母婴平安具有非常重要的作用。     

对比试验分析凝血四项检测的影响因素

目的 通过对比试验分析探讨影响凝血四项检测的因素.方法 对本院检验科进行凝血四项检测的标本采集和处理、血凝仪及试剂、操作人员等资料进行统计分析,按标本放置时间(1、2、4 h)、离心时间(5、10、15 min)及是否溶血(溶血和未溶血)随机抽取各100份抗凝血分别就标本存放时间、离心时间和是否溶血等方面进行对比试验.结果 血液标本放置时间过长可以使凝血酶时间(TT)缩短、活化部分凝血活酶时间(APTT)延长;标本以3 000 r/min速度离心5 min时,血浆凝血酶原时间(PT)、APTT明显缩短,与离心10 min作对照有统计学差异;溶血标本PT、APTT结果缩短,TT延长.结论 凝血四项检测易受多种因素影响,试验时应规范操作,才能确保结果准确可靠.     

正常孕产妇常规凝血指标变化规律的序贯研究

目的观察正常孕产妇在不同妊娠阶段和产褥期常规凝血指标的变化规律,探讨动态监测凝血四项变化的临床意义。方法选择2013年10月至2015年03月期间在我院产科进行常规产检和分娩,妊娠期、产褥期和新生儿均无异常的139例首孕单胎孕产妇做为观察对象,分别于妊娠早、中、晚期和临产前及产后进行凝血四项检测,并对结果进行统计学分析。结果孕产妇在妊娠早期和产后凝血四项检测结果与对照组比较均无显著性差异(P0.05)。凝血酶原时间(PT)在孕妇妊娠早、中、晚期呈现进行性缩短趋势(P0.05),妊娠晚期与临产前的PT变化无统计学差异(P0.05);活化部分凝血活酶时间(APTT)在整个妊娠过程中呈现逐渐缩短的趋势,妊娠早期至中期明显缩短(P0.01),妊娠中期与晚期无显著性差异(P0.05),妊娠晚期至临产前明显缩短(P0.05);凝血酶时间(TT)在孕妇的整个妊娠过程中均无显著变化(P0.05);纤维蛋白原含量(Fib)在妊娠早期至中期明显增高(P0.01),妊娠中期至晚期无显著变化(P0.05),妊娠晚期至临产前呈现急剧升高(P0.01)。结论对孕妇妊娠过程中凝血四项指标的变化进行动态监测,有助于预防分娩过程中和产后的异常出血,弥漫性血管内凝血以及动静脉血栓疾病等分娩并发症,有重要的临床指导意义。     

2型糖尿病与凝血功能障碍

目的　探讨2型糖尿病(2DM)患者凝血功能指标的变化,及其与血管并发症的关系。方法　分别检测糖尿病组(n=85 )和对照组(n =6 0 )血浆凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、甘油三酯(TG)、胆固醇(CH)。结果　(1) 2DM组与对照组比较:无论有无血管并发症2DM患者PT、APTT显著下降(P <0 .0 5或P <0 0 1) ,FIB显著上升(P <0 .0 5或P <0 .0 1) ,无血管病变组TT的变化没有统计意义;伴血管病变组患者TT显著下降(P <0 0 1)。(2 ) 2DM组组内比较,伴血管病变组凝血指标PT、APTT、TT均较无血管病变组显著下降(P <0 0 1) ,且FIB水平显著上升(P <0 .0 5 )。(3)DM患者血脂异常的分型比较,DM患者以高甘油三酯血症为主,有血管并发症组的高甘油三酯血症阳性率可达2 8.9% ,但两组差异不明显(P >0 .0 5 ) ;并且TG与四项凝血指标均无明显相关性。结论　2型糖尿病患者存在凝血功能的障碍,且随着血管并发症的出现,患者凝血活性增强。     

妊娠中晚期凝血功能变化分析

目的观察中晚期孕妇凝血功能的变化趋势,判断凝血功能的状态,为及时干预、防止异常高凝状态加重提供实用指标。方法采用法国STAGO-Compact全自动血凝仪检测100例孕妇于4个不同时间段:中孕期(24～28周)、中晚孕期(28～32周)及晚孕期(32～36周)(、36～40周)与30例健康非孕妇女的凝血酶原时间(PT)、部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)。结果中孕组、中晚孕组与正常对照组相比,PT、APTT及TT均缩短,Fib水平升高,但无统计学差异(P>0.05)。而晚孕组与对照组相比,PT、APTT及TT均明显缩短,Fib水平显著升高,差别均有非常显著性意义(P<0.01)。结论妊娠期妇女随着孕周的增加,凝血功能有增强趋势,机体呈现轻度高凝状态。可能有利于产后快速有效止血。但凝血活性过强就会有血栓形成趋势。     

Stability of prothrombin time and activated partial thromboplastin time tests under different storage conditions

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are common laboratory tests that are useful in the diagnosis of coagulation disorders and monitoring anticoagulant therapy. Recent expansions in the outreach laboratory services at our institution prompted us to investigate the shipping limitations for some tests, including PT and aPTT. Although we followed NCCLS guidelines for the collection of blood specimens, we observed falsely elevated PT and aPTT values due to the different storage conditions. The objective of this study is to determine the effect of conditions and duration of storage on PT and aPTT tests using plasma and whole blood samples, respectively. For this study, 36 plasma samples with normal and prolonged PT and aPTT were exposed to different storage conditions. Blood was centrifuged immediately and plasma was stored at room temperature (RT), refrigerated at 4°C, or frozen at −20°C. The samples were analyzed at 0 h and repeated at 6, 12 and 24 h under various conditions. Although statistically significant differences were observed for plasma samples for normal PT tests after 12 h at refrigerated and frozen storage conditions, the differences would not change the clinical interpretation of the results. On the other hand, samples stored refrigerated or at RT showed significant differences for aPTT at 24 h. These differences would change clinical interpretation, especially for samples with normal or near normal aPTT times. Interestingly, aPTT was significantly higher for samples stored frozen when compared to refrigerated and RT conditions at 6 h. Similar patterns were also observed on ten whole blood samples with normal PT and aPTT values. In conclusion, either plasma or whole blood samples can be accepted for PT testing up to 24 h and for aPTT testing up to 12 h only, when transported either at RT or at 4°C.     

Reference intervals for coagulation tests in adults with different ABO blood types

IntroductionCoagulation tests are affected by many factors, such as age, race, and gestation. Although coagulation test results vary by ABO blood type, reference intervals of different ABO blood groups remain to be determined. This study aims to investigate the reference ranges of coagulation tests for different ABO blood groups in the Han population in South China.MethodsA retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College. In all, 9600 individuals aged between 20 and 79 years were included. Coagulation tests, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, and fibrinogen, were performed.ResultsThere was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non‐O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups.ConclusionThe study provides reference data on coagulation tests from ABO blood groups in South China. The established reference intervals specific to ABO blood type, sex, and age may improve clinical decisions based on coagulation tests.     

The aPTT assay as a monitor of heparin anticoagulation efficacy in clinical settings

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are 2 major methods of screening patients for bleeding tendency. Heparin is an anticoagulant commonly used for various clinical conditions and will thus affect the coagulation profile. The influence of heparin on PT vs aPTT, seldom addressed in the past, should be carefully investigated. Prospective data on 35 patients who were heparinized for clinically indicated conditions were collected and analyzed for the change in PT (dPT) and aPTT (daPTT) at 3 time points after treatment, all of which were compared with baseline data checked before therapy. Age, sex, and the results of a complete blood count and liver and renal function tests were also evaluated for each patient to determine their effects on dPT and daPTT. The therapeutic goal of keeping the aPTT within a desirable range was achieved in ∼75% of patients by the last day of heparin therapy. Within this range, dPTs were not statistically significant, nor was the effect of age, sex, hemoglobin level, serum albumin level, white cell count, platelet count, or renal or hepatic function. In patients with thrombosis, dPT was not significantly influenced by heparin dose. During an overlap in the periods of coumadin and heparin administration, PT was used as a guide for adjusting the coumadin dose. The anticoagulant effect, indicated by a PT in the target range, would occur primarily secondary to coumadin administration and would make it relatively easy to decide when to discontinue heparin.     

白芨对大鼠创面愈合几个要素的影响

目的:研究白芨对大鼠创面愈合几个要素的影响,探讨其促进伤口愈合的机制。方法:大鼠麻醉后,在背部脊柱两侧1.5cm处切除两个直径约1.6cm的圆形,以随机数字表法选择其中一个创面局部涂抹白芨胶溶液;或在背部脊柱两侧1.5cm处各切开一约8cm长的全皮层切口,埋入聚乙烯醇(Polyvinylalcohol,PVA)海绵,随机数字表法选择一侧注入白芨胶溶液。结果:伤后3(或5),7,10,14,21d白芨治疗组创面残留面积百分率显著低于对照组,创面平均愈合时间提前2.5d,创面组织蛋白含量和羟脯氨酸含量也显著高于对照。伤后3,5,7d白芨组伤口巨噬细胞数量也显著提高。结论:白芨提高创面愈合的速度和愈合的质量,增加伤口巨噬细胞数量可能是其促愈合的重要机制之一。     

Non-frozen transports of whole blood samples do not cause relevant bias for global coagulation tests in clinical trials evaluating the drug safety

Sample shipments with dry ice have a large economic impact on clinical research. Therefore, the bias caused for global coagulation tests by non-frozen transports of whole blood instead of frozen plasma was investigated experimentally and by a meta-analysis of 6-year central laboratory data. In the experiment, aliquots from 14 healthy volunteers were kept as whole blood at 20+/-2 degrees C and as frozen plasma until an analysis of prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and antithrombin III (ATIII) at day 0, 1, 2, and 3 from collection. Within these 3 days only PT and aPTT demonstrated any changes: in blood samples kept at 20+/-2 degrees C these amounted about 10% for both. In frozen plasma, aPTT did not change whereas PT increased by 14%. In a meta-analysis of central laboratory data, PT and aPTT results were grouped across various phase II-IV trials by the type of sample transfer, either as frozen plasma on dry ice or non-frozen as whole blood. For the latter the mean difference to a reference group of phase I trials with same-day analysis was in line with the amount of bias found in the experiment (aPTT, 34.6+/-6.0 vs. 31.6+/-3.5 s; PT, 87.7+/-13.3 vs. 97.3+/-7.9%). The consistent bias resulted in shifted, but still normal distribution curves with a total rate of clinically relevant outliers of about 1.9% for aPTT and 2.4% for PT. Biases thus appear irrelevant for a common safety evaluation within clinical trials. Non-frozen whole blood transports for the measurement of global coagulation tests appear justified for this purpose, if protocols do not require frozen shipments for other reasons. However, transit time must not exceed 2 days and pre-analytical conditions should be consistent within the same trial.     

Preferential consumption of coagulation factors I, V, and VIII in rat endotoxemia

To ascertain the time course of prolonged coagulation time and the coagulation factors that were consumed preferentially after injection of Escherichia coli endotoxin (ETX, 3 mg/kg, intravenously) in rats, the activated partial thromboplastin time (aPTT) and prothrombin time (PT) were measured. Using aPTT and PT, the residual levels of the major coagulation factors were quantified by partial replacement of ETX-injected rat plasma with individual factor-deficient human plasma. The residual levels of prekallikrein and high molecular weight (HMW) kininogen were also measured. After ETX injection, aPTT and PT showed gradual increasing prolongation, which was marked at 3-5 h after the injection. The residual level of fibrinogen was markedly reduced between 1 and 3 h after ETX injection and dropped to the determination limit 7 h after the injection. Ratios of the consumed coagulation factors, prekallikrein, and HMW kininogen in rat plasma collected 7 h after intravenous injection of ETX were obtained as follows: prekallikrein (18.0 +/- 4.8%), HMW kininogen (36.2 +/- 1.9 %), factor XII (54.0 +/- 0.7%), factor VIII (86.1 +/- 1.8%), factor VII (35.6 +/- 7.7%), factor V (90.6 +/- 0.8%), and factor I (fibrinogen) (>89.6 +/- 0.0%). Thus, coagulation factor I (fibrinogen) and factors V and VIII (cofactors) were consumed preferentially. The extrinsic coagulation pathway was dominantly activated, whereas the intrinsic coagulation pathway, including plasma kallikrein-kinin system, played less important role in the ETX-induced consumption coagulopathy in rat.     

Dabigatran deliberate overdose: two cases and suggestions for laboratory monitoring

Context: Dabigatran etexilate (dabigatran) is a direct thrombin inhibitor anticoagulant agent. There is limited information about the changes in coagulation profile and outcomes in overdose. A monoclonal antibody has been developed to neutralize the anticoagulant effect of dabigatran. Case reports describe enhanced clearance of dabigatran by haemodialysis as an intervention to prevent haemorrhagic complications – however, the threshold for initiating haemodialysis is not well defined in an asymptomatic patient with normal renal function. Case details: Two patients presented following deliberate dabigatran overdoses. A 55-year-old woman ingested 10?×?150?mg dabigatran. A 21-year-old woman with a history of systemic lupus erythematosus and pulmonary embolus ingested 100?×?110?mg dabigatran. Both were admitted to the intensive care unit and managed expectantly. Serial coagulation tests normalized over 60 h. The half-life of dabigatran was not prolonged following overdose, being calculated between 7 and 11 h in each case. There was positive correlation between international normalized ratio (INR), prothrombin time (PT) and activated partial thromboplastin time (aPTT) with plasma dabigatran levels. Conclusion: There is limited experience with dabigatran overdoses. Normal aPTT, PT and INR assays 12 h following deliberate ingestion indicate that the drug concentration is not high. Individual risk assessment of bleeding risk needs to be formulated for each patient and expectant management is reasonable in the presence of normal renal function and absent risk factors for bleeding.     

Effects of telavancin on coagulation test results

Background: The lipoglycopeptide antibiotic, telavancin, may interfere with some laboratory coagulation tests including prothrombin time (PT) and activated partial thromboplastin time (aPTT). Objective: To evaluate the effects of telavancin on PT and aPTT assays in common use. Methods: Pooled normal human plasma was spiked with telavancin 10, 20, 100 or 200 μg/ml (equivalent to trough, 2 × trough, peak and 2 × peak clinical plasma concentrations, respectively) or diluent control (0.9% sodium chloride). Samples were analysed using 16 PT reagents and seven aPTT reagents. Results: Telavancin 200 μg/ml (corresponding to 2 × peak clinical plasma concentration), produced significant PT prolongation (> 9% difference vs. diluent control) with all the 16 PT reagents (range 12% to > 600%). At lower telavancin concentrations, PT prolongation was dose‐dependent and varied among reagents, but appeared greatest with preparations containing recombinant tissue factor. With telavancin 10 μg/ml (equivalent to trough), PT prolongation was 10% with HemosIL^® PT‐Fibrinogen Recombinant, while ranging from 5% to –1% with all other reagents. Significant (> 34% difference vs. baseline) and dose‐dependent aPTT prolongation was observed with all the seven reagents in samples spiked with telavancin 100 or 200 μg/ml (range 65–142% at 200 μg/ml). aPTT reagents containing a silica activator appeared to be more sensitive to telavancin interference. Telavancin 10 μg/ml was not associated with increased aPTT with any of the reagents tested. Conclusions: Telavancin has the potential to prolong both PT and aPTT in vitro. It is recommended that samples for PT or aPTT be obtained just prior to a telavancin dose (trough).     

Effect of lepirudin on the international normalized ratio

BACKGROUND: Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited. OBJECTIVE: To evaluate the effect of lepirudin on the INR. METHODS: Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy. RESULTS: Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean +/- SD lepirudin dose was 0.05 +/- 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45-75 seconds (1.5-2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45-75 seconds with lepirudin correlated to an INR of 1.6-3.2. CONCLUSIONS: Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.