Antithrombin after cardiac surgery: implications on short and mid-term outcome

Backgrounds Antithrombin (AT) drop during cardiac surgery has been described. The causes and the effects of this phenomenon are not clear. The objective of the study is to evaluate the relationship of AT postoperative values on short and mid-term outcome after cardiac surgery. Methods Between January and June 2005, 405 patients, who underwent cardiac operations at our Institution had AT values available preoperatively and postoperatively. Using Receiver Operating Characteristic curves, a cut-off equal to 63.7% for ICU-arrival AT was chosen in order to divide the entire population in two groups (117 patients with ICU-arrival AT < 63.7%, Low AT group, and 288 patients with ICU-arrival AT ≥ 63.7%, High AT group). Objective of the study was to evaluate the predictive role of ICU-arrival AT < 63.7% on in-hospital mortality and morbidity and on 18 months follow-up after cardiac surgery. Results ICU-arrival AT was significantly lower than preoperative AT (90.7 ± 16.3% vs. 71.2 ± 15.1%, P < 0.0001). Patients in the Low AT group were older, more often female, had a worse Euroscore and required longer CPB duration and cross clamp time. They had significantly higher preoperative and postoperative d-dimer levels. ICU arrival AT < 63.7% was not associated with increased in-hospital mortality but it was an independent risk factor for longer mechanical ventilation, need of inotropic support, excessive bleeding and blood products transfusion. ICU arrival-AT < 63.7% was associated with worse survival during 18 months follow up (92.3% vs. 85.4% in the High AT and Low AT group, respectively, P = 0.05). Conclusions Low AT after cardiac surgery is associated with higher incidences of peri-operative complications and worse survival in the mid-term. Future studies should clarify the pathophysiologic mechanism of this findings and possible therapeutic directions.     

急性心肌梗死患者血浆凝血因子Ⅶ和抗凝血酶Ⅲ的变化及其意义

目的 探讨急性心肌梗死（AMI）患者血浆凝血因子/Ⅶ、抗凝血酶Ⅲ（AT-Ⅲ）活性的变化及其意义.方法 对40例AMI患者血浆FVIIag含量、FVIIa水平、FVII;C及AT-Ⅲ水平进行检测,并与20名健康人进行比较,分析其变化,并探讨其在急性心血管事件中的意义.结果 AMI患者血浆FVIIag含量、FVIIa水平及FVII：C高于（P〈0.05或P〈0.01）,且FVIIa水平升高更显著,而血浆AT-Ⅲ活性显著低于健康对照组（P〈0.01）.结论 血浆凝血因子Ⅶ和AT-Ⅲ参与AMI时的凝血过程,血浆活化凝血因子Ⅶ增高及AT-Ⅲ活性降低可能是急性心血管事件敏感预测指标.     

Antithrombin replacement in neonates: is there any indication?

INTRODUCTION: Activation of the coagulation system and severe acquired antithrombin (AT) deficiency are common and prognostically important findings in sick and preterm neonates. It has been hypothesised that treatment of the acquired AT deficiency with AT concentrate may improve the outcome of conditions such as the neonatal respiratory distress syndrome (RDS), intracranial hemorrhage (ICH) and sepsis. MATERIALS AND METHODS: We performed a systematic review of randomised controlled trials (RCTs) of AT replacement therapy in newborn infants. RESULTS: Two full-length trial reports were found. Both were placebo-controlled. The first RCT examined the effects of AT therapy in 122 preterm infants with RDS. Administration of AT prolonged rather than shortened the duration of mechanical ventilation and oxygen therapy. The second RCT determined whether AT replacement decreased the incidence of ICH in 60 preterm infants who were born before 30 weeks of gestation. No beneficial effect on ICH was found. CONCLUSIONS: Preterm infants with RDS do not benefit from therapy with AT concentrate and may be harmed. There is also little evidence that the administration of AT reduces the risk of ICH. The role of AT replacement during neonatal sepsis remains uncertain.     

D-二聚体纤维蛋白原抗凝血酶Ⅲ在早期冠心病诊疗中的价值

目的探讨D-二聚体、纤维蛋白原、抗凝血酶Ⅲ在早期冠心病诊疗中的临床价值。方法选择2011年1月-2012年7月我院收治的早期冠心病患者128例为观察组,选择本院同期健康体检人员130例为对照组,分别检测两组人员的血脂水平、凝血系统指标、血浆指标。结果血脂检测中,观察组总胆固醇、三酰甘油、低密度脂蛋白均明显高于对照组,观察组高密度脂蛋白明显低于对照组,差异均有统计学意义（均P〈0．05）。凝血系统指标检测中,观察组凝血酶原时间、活化部分凝血活酶时间均明显小于对照组,差异均有统计学意义（均P〈0．05）。血浆指标检测中,观察组D-二聚体、纤维蛋白原均明显高于对照组．观察组抗凝血酶Ⅲ明显低于对照组．差异均有统计学意义（均P〈0．05）。结论早期冠心病患者存在血脂、D-二聚体、纤维蛋白原、抗凝血酶Ⅲ的异常表达,及早检测有助于早期冠心病的诊断和病情判断,值得临床推广使用。     

遗传性易栓症相关抗凝因子的研究进展

易栓症可定义为血栓形成的倾向性增高,主要由于凝血系统和抗凝血系统两方面因素造成。易栓症分为遗传性易栓症与获得性易栓症。现就遗传性易栓症的相关抗凝因子进行研究,从分子生物学水平上对抗凝血酶Ⅲ(AT-Ⅲ)、蛋白C(PC)、蛋白S(PS)缺陷的病理机制、疾病的诊断及其相应的实验室检查予以综述。同时,结合近年来相关国内外研究报道提出两个观点:①遗传性AT-Ⅲ、PC、PS缺陷在东西方人群的分布可能存在较大差异;②遗传性易栓症患者中存在联合缺陷。     

3个遗传性抗凝血酶缺陷症家系的表型和基因型关系的研究

目的探讨遗传性抗凝血酶缺陷症家系表型和和基因型的关系。方法对3个遗传性抗凝血酶缺陷症家系(家系1~3)作表型和基因型诊断:常规检测活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、纤维蛋白原(Fg)、凝血酶时间(TT)以筛查凝血功能,发色底物法检测蛋白C、蛋白S和抗凝血酶活性(PC∶A,PS∶A及AT∶A),免疫比浊法检测抗凝血酶抗原(AT∶Ag),Western blot检测血浆中抗凝血酶的分子量和含量;PCR扩增AT基因所有外显子及侧翼序列,DNA测序并进行基因分析。针对新基因突变,在100例正常人中检测相应突变以排除多态性,用TA克隆PCR产物测序鉴定杂合碱基缺失突变。结果 3名先证者均为反复发作的静脉血栓患者,凝血指标及PC∶A和PS∶A都正常,AT∶A分别为正常人(100%)的60%、52%和60%,AT∶Ag分别为16.9、14.1和11.4 mg/dl,Western blot显示3位先证者的血浆AT蛋白分子量正常(58 kD)而含量低于正常;基因分析发现3名先证者各携带1个杂合突变,分别为g.8263 C>T(Leu340Phe)、g.5894-6 del TTC(Phe122del)和g.5898 T>G(Phe123Cys)。3个家系中与先证者表型相似的成员,则携带有相同的AT基因突变;但除家系2先证者的父亲有静脉血栓外,家系1和3中含有相应AT基因突变的家庭成员均无血栓发生。结论 3名先证者遗传性抗凝血酶缺陷症分别由Leu340Phe、Phe122del和Phe123Cys突变所致,其中Leu340Phe和Phe123Cys突变为国际上首次报道。     

血浆抗凝血酶Ⅲ、纤维蛋白原浓度与冠状动脉病变严重程度的关系

目的探讨血浆抗凝血酶Ⅲ、纤维蛋白原（fibrinogen，Fbg）浓度与冠状动脉病变严重程度的关系。方法冠心病患者137例，按Gensini评分分为三组，A组（〈20分组）、B组（20．40分组）、C组（〉40分组），另对照组患者131例。分别比较各组间外周血血浆抗凝血酶Ⅲ、纤维蛋白原浓度。结果冠心病患者的血浆抗凝血酶Ⅲ浓度明显低于对照组（P〈0．01），纤维蛋白原的浓度明显高于对照组（P〈0．01），且不同Gensini积分组血浆抗凝血酶Ⅲ、纤维蛋白浓度之间差异有统计学意义（P〈0．01）。结论血浆抗凝血酶Ⅲ、纤维蛋白原浓度与冠脉病变严重程度有密切关系，且可以预测患者冠状动脉病变的严重程度。     

凝固时间法测定血浆AT-Ⅲ活性

目的介绍凝固时间法测定血浆AT-Ⅲ活性的实验方法。方法将校正血浆用含肝素缓冲液稀释成不同浓度(即不同活性AT-Ⅲ),加入纯品纤维蛋白原共同孵育后,测定其凝固时间;根据不同AT-Ⅲ活性与相应凝固时间制作标准曲线;测定待检血浆凝固时间,查标准曲线即可得到待检血浆AT-Ⅲ活性。结果该法AT-Ⅲ活性在25%～125%范围内线性良好;日内变异系数为3.2%,日间变异系数为4.9%;凝固时间法与发色底物法比较相关性良好(r=0.999,P<0.05);检测178例健康人血浆AT-Ⅲ活性为105.4%±18.8%。结论该方法重复性好,结果可靠,简便实用,可用于常规检验。     

类肝素聚乙烯醇复合材料抗凝血性能的研究

本文报道了聚乙烯醇羧甲醚（ＰＣ）、聚乙烯醇硫酸酯（ＰＳ）及聚乙烯醇接枝甲基丙烯酸β羟乙酯、丙烯腈（ＰＶＡｇＨＥＭＡＡＮ）的合成制备方法。通过红外光谱和元素分析定性、定量证实了合成方法的可行性。研究了将ＰＣ、ＰＳ以不同重量比加入ＰＶＡｇＨＥＭＡＡＮ后形成的聚乙烯醇衍生物复合材料（ＣＤＰＶＡ）对抗凝血性能的影响。（ＣＤＰＶＡ）对人血的溶血度仅为３２％,人血复钙时间比空白对照延长２０２ｓ,凝血时间延长１８５７ｓ。ＳＥＭ观察表明ＣＤＰＶＡ接触血液一定时间后表面没有形成血液蛋白纤维网络,具有微相分离结构。