Thrombosis during pregnancy: Risks,prevention, and treatment for mother and fetus—harvesting the power of omic technology,biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta‐mediated complications including the pre‐eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. “Omic” technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non‐invasive imaging technologies of the utero‐placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non‐cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases. Birth Defects Research (Part C) 105:209–225, 2015. © 2015 Wiley Periodicals, Inc.     

Thrombosis in pregnancy and maternal outcomes

Pregnancy increases the risk of thrombosis four‐ to five‐fold. Seventy‐five to eighty percent of pregnancy‐related thrombotic events are venous and twenty to –twenty‐five percent are arterial. The main reason for the increased risk is hypercoagulability. Women are hypercoagulable because they have evolved so that they are protected against the bleeding challenges of pregnancy, miscarriage, or childbirth. Both genetic and acquired risk factors can further increase the risk of thrombosis. The maternal consequences of thrombosis of pregnancy include permanent vascular damage, disability, and death. While the maternal outcomes of thrombosis can be modified by anticoagulation therapy, management of thrombosis during pregnancy is the subject of another paper in this issue (see paper by B. Konkle). This review will focus on the epidemiology, pathophysiology, risk factors, and maternal consequences of thrombosis in pregnancy. Birth Defects Research (Part C) 105:159–166, 2015. © 2015 Wiley Periodicals, Inc.     

脊柱骨折患者术后下肢深静脉血栓形成的干预措施

目的:分析综合护理干预对脊柱骨折患者术后下肢深静脉血栓形成的预防效果。方法:将120例脊柱骨折患者分为观察组和对照组,每组各60例。对照组给予常规护理干预,观察组进行综合护理干预,比较不同干预措施对患者下肢深静脉血栓形成的预防效果。结果:观察组DVT发生率为3.33%,对照组为18.33%,观察组干预效果明显优于对照组,差异有统计学意义(P0.05)。结论:综合护理干预可有效降低脊柱骨折患者术后DVT的形成,对临床具有指导意义。     

综合护理对脑卒中患者下肢深静脉血栓形成的预防效果

目的:分析综合护理干预在脑卒中偏瘫患者下肢深静脉血栓形成中的预防效果及临床效应。方法:将120例经颅部CT或MRI确诊的脑卒中患者分为观察组和对照组,每组各60例。对照组给予常规护理干预,观察组进行综合护理干预,比较不同干预措施患者下肢深静脉血栓形成情况。结果:观察组DVT发生率为3.33%,对照组为18.33%,观察组干预效果明显优于对照组,差异有统计学意义(P0.05)。结论:综合护理干预可有效降低脑卒中偏瘫患者DVT的形成,在脑卒中偏瘫患者DVT方面具有显著的预防作用与临床效应,值得借鉴。     

应用手持激光器建立光化学法脑梗死动物模型

目的应用手持激光器作为光源建立光化学法局灶性脑梗死动物模型。方法将36只SD大鼠随机分为4组,即A组：开骨窗至硬脑膜,不注射玫瑰红,手持激光器照射5rain;B组：开骨窗至硬脑膜,注射玫瑰红,手持激光器照射5min;C组：保留颅骨内板,注射玫瑰红,手持激光器照射5min;D组：开骨窗至硬脑膜,注射玫瑰红,冷光源照射40rain。于术后24、48h对各组大鼠进行神经功能的行为学评分,进行MR扫描,术后48h处死动物,TTC染色测量梗死体积,光镜下观察病理改变,比较各组的模型制作成功率。结果不同方法进行动物模型制作时,24h神经功能的行为学评分有显著性差异,48h后差异消失。头部MR扫描显示,A组未见脑梗死形成,B组、c组全部有脑梗死灶形成,D组仅部分大鼠形成梗死灶,但体积明显较B、C组小,另外C组有2例合并硬膜外血肿。TTC染色A组未见梗死灶形成,B组、C组可见恒定的梗死灶,D组仅部分形成梗死灶。B、C、D组模型制作成功率分别为100％、80％、50％,将B组、C组合并为手持激光器组,与冷光源组（D组）比较,两种方法间有显著性差异（P=0．026）。结论应用手持激光器作为照射光源与冷光源相比,有更高的模型制作成功率。     

恶性肿瘤并发急性下肢深静脉血栓形成的病因分析与治疗

目的：探讨恶性肿瘤患者并发急性下肢深静脉血栓（deep vein thrombosis of the lower extremity,DVT）的形成原因、诊断要点与治疗、护理及预防措施,为相关治疗提供参考。方法：回顾性分析了我院22例恶性肿瘤并发下肢深静脉血栓患者的临床病理表现,诊断方式及采取的治疗与护理措施,所有患者采用小-中等剂量尿激酶溶栓、同时予以低分子肝素钠抗凝、低分子右旋糖酐及丹参川芎嗪注射液辅助治疗,部分患者采取切除根治手术,分析比较患者的疗效。结果：采取上述治疗后21例患者取得了满意的效果,其中1例患者经治疗半月后效果不明显,进一步检查确诊为恶性淋巴瘤,还有1例患者经治疗好转出院3个月后再次出现对侧下肢深静脉血栓,进一步检查确诊为胆管癌。结论：DVT患者经联合抗凝、溶栓、祛聚、扩血管等综合治疗效果明显,以DVT为首发表现的患者治疗效果不佳或再发应及早考虑恶性肿瘤,以免漏诊,耽误原发病的治疗。     

Effects of platelets on the protein expression in aortic segments: A proteomic approach

It is well known the effects of the vascular wall on platelet activity but little is known about the effects of platelets on the proteins expression in the vascular wall. We analyzed whether platelets may modify the protein expression in the vascular wall. We used an in vitro model coincubating human platelet rich plasma (PRP) with control and 10 ng/ml tumor necrosis factor‐α (TNF‐α)‐preincubated bovine aortic segments. 2DE, mass spectrometry and Western blot analysis were used to determine changes in the expression of proteins associated with the cytoskeleton and energetic metabolism in the aortic segments. In control healthy vascular wall, only the cytoskeleton‐related proteins expression was modified by PRP. However, when PRP was coincubated with TNF‐α pre‐stimulated aortic segments lesser number of cytoskeleton‐related proteins were modified. With respect to energetic metabolism, in control segments, PRP failed to modify any of the analyzed energetic‐related proteins. However, in TNF‐α‐preincubated segments the presence of PRP upexpressed glyceraldehyde‐3‐phosphate dehydrogenase. Moreover, by western blot experiments it was observed that in TNF‐α‐preincubated segments the expression of fructose 1,6‐bisphosphate aldolase was downregulated by platelets. However, no differences were found in the expression of triosephosphate isomerase and ATP synthase α‐chain. In addition, the activity of fructose 1,6‐bisphosphate aldolase and piruvate content was significantly reduced without modification on triosephosphate isomerase activity. In conclusion, the crosstalk between platelets and vascular wall is bidirectional and platelets regulated in the vascular wall the expression of proteins associated with the cytoskeleton and energetic metabolism, particularly in the healthy vascular wall. J. Cell. Biochem. 111: 889–898, 2010. © 2010 Wiley‐Liss, Inc.     

Analysis of a potential trigger of an acute illness

Sometimes certain short-term risk exposures are postulated to act as a trigger for the onset of a specific acute illness. When the incidence of the illness is low it is desirable to investigate this possible association using only data on cases detected during a specific observation period. Here we propose an analysis for such a study based on a model expressed in terms of the probability that the exposure triggers the illness and a random delay from a triggered illness until its diagnosis. Both the natural hazard rate for the illness and the probability that the exposure triggers the illness are assumed to be small and possibly dependent on age and covariates such as sex and duration or severity of the exposure. The method of analysis is illustrated with a study of the association between long flights and hospitalization for venous thromboembolism.     

Experimental indication for the existence of multiple Trp rotamers in von Willebrand Factor A3 domain

The first step in both normal haemostasis and arterial thrombosis is the interaction between collagen, von Willebrand factor (vWF), and glycoprotein Ib. The A3 domain of vWF forms the principal binding site for collagen type I and type III. Inhibition of the vWF-collagen interaction by an anti-human vWF monoclonal antibody (MoAb) 82D6A3 can be a potential way to prevent arterial thrombosis. Identification of the epitope of MoAb 82D6A3 showed recently that the consensus sequence SPWR obtained by phage display could adopt the conformation of the discontinuous epitope. Modelling showed that Trp982 in the vWF had to obtain a more solvent accessible conformation. We performed a detailed fluorescence study of Trp982 in the vWF A3. Using the method described by Hellings et al. (Biophys J 2003;85:1894-1902), we were able to identify two different low-energy Trp982 rotamers and to link them with their experimentally derived fluorescence lifetimes. Fluorescence anisotropy showed no interconversion in the nanosecond timescale between the two different rotameric states. With these experiments, we gather strong indications for the existence of an exposed rotamer conformation and a rotamer that corresponds to the one observed in the X-ray structure. These results strongly support the modeling work (Vanhoorelbeke et al., J Biol Chem 2003;278:37815-37821).