Lattová V, Procházka M, Procházková J, Ulehlová J, Slavík L, Lubušký M, Brychtová P
Ceska Gynekol. 2013 Nov;78(5):466-72.
Acquiring new information to allow prediction of the development of diseases associated with impaired coagulation. Design effective preventive measures most serious diseases (TEN) in the fields of gynecology and obstetrics. For pregnant women with preeclampsia, hypertension compared with women with normal pregnancies could lead to increased thrombin generation due to the synergistic effect of thrombotic risk factors. Based on the results and found statistically significant differences between the groups among pregnant can select for a higher risk of developing deep vein thrombosis. This risk group could then greatly benefit from more stringent follow-up and possible preventive treatment prophylactic doses of LMWH in reducing maternal and perinatal morbidity and mortality.
Prospective study.
Department of Obstetrics and Gynecology, University Hospital Olomouc.
In early pregnancy - during pregnancy standard samples (up to the end of the first trimester) patients venous blood was sampled and they completed information questionnaire. A second sampling was carried out between 24 to 28 week, the third sample and between 36th to 40th week. Obtained blood samples were subsequently processed in the coagulation laboratory Hemato-Oncology Clinic and Olomouc. The blood samples were investigated protein C and S, antithrombin, FVIII level, FII, Leiden, and plasma endothelial microparticles, and lupus anticoagulant and APC resistance standardized methodologies. Thrombin generation was determined thrombin generation test. Thrombin generation was measured fully automatically using a kit (Technothrombin TGA, Technoclone, Vienna, Austria) and analyzer Ceveron Alpha (Technoclone, Vienna, Austria) with fully automatic analysis software. As the main parameter is evaluated by the maximum thrombin generation, at the same time, however, was also detected in the total amount of thrombin and the time until the beginning of the formation of thrombin.
In the period 2008-2011 were analyzed blood samples of 303 healthy pregnant women. 215 women, ie 71% were nuliparas, 60 women, ie 19.8% were primiparas, 28 women, 9,2% were secundiparas. The average age of pregnant women was 28.6 years(± 3.8 years). The average maternal weight at the beginning of pregnancy was 63.6 kg (± 7.8 kg). Of the 303 women in 18 (6%) developed slight to moderate degree of preeclampsia or HELLP syndrome with varying severity of clinical manifestations. 20 mothers (6.6%) gave birth prematurely terminated before 37 week of pregnancy. 3 pregnancies (0.9%) were discontinued due to genetic indication for fetal birth defect. The complete study protocol (sampling in all three trimesters) thus completed 280 pregnancies. Of the three evaluated, parameter Lag time, ETP and peak we observed significant differences when comparing physiological pregnancies and pregnancies with preeclampsia (Table 3 and Figure 5-7), the statistical level of p < 0.01. In pregnancies with chronic hypertension, these differences were not significant. Comparison of 18 pregnancies, in which the III. trimester developed preeclampsia with other pregnant with physiological pregnancy did not show statistically significant differences in I. and II. trimester. The results suggest the activation of coagulation through the late stages of pregnancy. Results are influenced by strong clinical variability of disease. In severe and early preeclampsia this activation and significant differences begin much earlier.
We demonstrated significantly higher activation of thrombin generation in women with preeclampsia [10]. Changes in preeclampsia are characterized by increased generation of thrombin in plasma. This fact may explain the partial success of the clinical use of aspirin in preeclampsia. In the third trimester, during the manifestation of the disease, patients with preeclampsia have significantly higher ETP compared to patients with a normal pregnancies. Pregnant women with chronic hypertension also show a slight increase in the activation of thrombin. However, these results are not statistically significant. Examination of coagulation in the first and second trimester in women who later developed preeclampsia, showed no statistically significant differences and thus can not be used in this case as predictive, but only as a diagnostic test.
获取新信息以预测与凝血功能受损相关疾病的发展。设计有效的预防措施，针对妇产科领域最严重的疾病（中毒性表皮坏死松解症）。对于患有先兆子痫的孕妇，与正常妊娠的女性相比，高血压由于血栓形成风险因素的协同作用可能导致凝血酶生成增加。基于结果并发现孕妇组间存在统计学显著差异，可选择出深静脉血栓形成风险较高的人群。然后，这一风险组可能会从更严格的随访以及可能的预防性治疗（低分子量肝素的预防剂量）中大大受益，从而降低孕产妇和围产期发病率及死亡率。
前瞻性研究。
奥洛穆茨大学医院妇产科。
在孕早期——孕期标准样本采集（至孕早期末）时，采集患者静脉血并让他们完成信息问卷。第二次采样在孕24至28周进行，第三次采样在孕36至40周进行。随后，采集到的血样在血液肿瘤学诊所和奥洛穆茨的凝血实验室进行处理。血样采用标准化方法检测蛋白C和S、抗凝血酶、FVIII水平、FII、莱顿因子以及血浆内皮微粒、狼疮抗凝物和活化蛋白C抵抗。采用凝血酶生成试验测定凝血酶生成。使用试剂盒（Technothrombin TGA，Technoclone，维也纳，奥地利）和Ceveron Alpha分析仪（Technoclone，维也纳，奥地利）以及全自动分析软件全自动测量凝血酶生成。作为主要参数，通过最大凝血酶生成进行评估，然而，同时也检测凝血酶总量以及直至凝血酶形成开始的时间。
在2008 - 2011年期间，分析了303名健康孕妇的血样。215名女性，即71%为初产妇，60名女性，即19.8%为经产妇，28名女性，9.2%为二次经产妇。孕妇的平均年龄为28.6岁（±3.8岁）。妊娠开始时孕妇的平均体重为63.6千克（±7.8千克）。在303名女性中，18名（6%）发生了轻度至中度先兆子痫或HELLP综合征，临床表现严重程度各异。20名母亲（6.6%）在妊娠37周前早产终止妊娠。3例妊娠（0.9%）因胎儿出生缺陷的遗传指征而终止。因此，完整的研究方案（三个孕期均采样）完成了280例妊娠。在比较生理性妊娠和先兆子痫妊娠的三个评估参数（滞后时间、内源性凝血酶生成量和峰值）时，我们观察到显著差异（表3和图5 - 7），统计学水平为p < 0.01。在慢性高血压妊娠中，这些差异不显著。将18例在孕晚期发生先兆子痫的妊娠与其他生理性妊娠的孕妇进行比较，在孕早期和孕中期未显示出统计学显著差异。结果表明在妊娠后期凝血被激活。结果受该疾病强烈的临床变异性影响。在重度和早期先兆子痫中，这种激活和显著差异更早开始。
我们证明了先兆子痫女性的凝血酶生成激活显著更高[10]。先兆子痫的变化特征是血浆中凝血酶生成增加。这一事实可能解释了阿司匹林在先兆子痫临床应用中的部分成功。在孕晚期，疾病表现期间，先兆子痫患者的内源性凝血酶生成量相比正常妊娠患者显著更高。患有慢性高血压的孕妇也显示出凝血酶激活略有增加。然而，这些结果无统计学显著意义。对后来发生先兆子痫的女性在孕早期和孕中期进行凝血检查，未显示出统计学显著差异，因此在这种情况下不能用作预测指标，而仅作为诊断试验。
