血栓弹力图预测下肢骨折围手术期深静脉血栓的应用研究

目的:探讨血栓弹力图(TEG)预测下肢骨折围手术期深静脉血栓的临床价值。方法:选择在我院进行体检的健康志愿献血者作为对照组(Ⅰ),同时选择82例在我院进行骨科手术的下肢骨折患者作为实验组(Ⅱ)。分别在骨折后第2天、手术当天、术后第3天、术后第7天和术后第10天进行血栓弹力图检测,比较实验组(Ⅱ)与对照组(Ⅰ)TEG各参数差异,并对所有数据进行相关性分析。结果:实验组(Ⅱ)82例研究对象中有63例(76.83%)于术后一周内出现高凝状态。与对照组(Ⅰ)比较,实验组(Ⅱ)骨折第2天、手术当天、术后第3天、术后第7天和术后第10天R、K缩短,Angle角、MA、CI值均延长。与手术当日比较,实验组(Ⅱ)术后第3天、术后第7天R和K明显缩短,Angle角、MA、CI值均明显延长(P0.05),与术后第3天、术后第7天比较,术后第10天R、K延长,Angle角、MA、CI值有缩短趋势。结论:血栓弹力图能及时准确监测下肢骨折患者凝血状态变化情况,及时预测下肢深静脉血栓(LDVT)发生风险,为抗凝药物的合理使用提供参考依据。     

Increased level of fibrinogen chains in the proteome of blood platelets in secondary progressive multiple sclerosis patients

Epidemiological studies indicate a high risk of stroke, heart failure and myocardial infarction in patients with multiple sclerosis, especially in its secondary progressive (SPMS) phase. Some ischaemic events are directly associated with abnormal platelet functions and their prothrombotic activity. Recent reports, including this study, confirm the increased activation of circulating platelets in SPMS, and also show increased platelet reactivity, among other responses, as well as strong aggregation. In this current study, we conducted a comparative analysis of the platelet proteome in SPMS patients and in healthy controls, to demonstrate the quantitative and qualitative differences likely to affect functional changes observed in SPMS. During densitometry evaluation of 2‐D fluorescence difference gel electrophoresis, we observed differences between the electrophoretic patterns of SPMS platelets and the control samples. To determine a detailed characterisation of the proteome changes in the SPMS patients’ blood platelets, in the next stage, we performed mass spectrometry of selected spots and indicated the increased presence of four proteins (fibrinogen, α‐2 macroglobulin, septin‐14 and tubulin β‐1 chain). The most important of these is the increased amount of prothrombotic protein, fibrinogen, which seems to confirm the accuracy of the imaging and potentially explains the increased risk of platelet‐origin thrombotic events. This study provides new knowledge of the potential existence of the molecular mechanisms responsible for the acceleration of the platelet pro‐coagulant function in SPMS. This can help to identify new targets for therapy, which can then be used not only in the second stage of the disease.     

In vivo monitoring of thrombosis in mice by optical coherence tomography

The objective of this study is to establish a novel method for continuously monitoring thrombus progression with various outcome measures and to assess the efficacy of antithrombotic drugs in murine thrombosis model in mice. In the study, thrombus was induced in the femoral vein of mice by FeCl₃ and monitored over time by spectral‐domain optical coherence tomography (OCT). Three‐dimensional images of thrombi with or without heparin as an antithrombotic agent were obtained from OCT angiography. In addition, several parameters of thrombi were analyzed and compared between control and anticoagulant groups. By using OCT, we were able to trace thrombus generation in the same mouse in real time. We found that in our model heparin reduced thrombus size by ~60% and thrombus cross‐sectional area by 50%. OCT results also show that both time to thrombus size (>0.02mm³) and time to occlusion (>30%) were significantly reduced after heparin addition. This study demonstrates that OCT reliably monitors thrombus generation and progression from various aspects including thrombus size. This enables us to measure the kinetic of thrombosis more accurately, and effectively evaluate the efficacy and activities of antithrombotic drugs. This model may represent a useful tool in antithrombotic drug discoveries in preclinical studies.      

The Blood Platelet as a Model for Regulating Blood Coagulation on Cell Surfaces and Its Consequences

Platelets actively participate in regulating thrombin production following physical or chemical injury to blood vessels. Injury to blood vessels initiates activation of the large numbers of platelets that appear in the subendothelium where they become exposed to tissue factor and to molecules adhesive for platelets and normally found in the extracellular matrix. The complex of plasma factor VIIa with extravascular tissue factor both initiates and localizes thrombin production on platelets and on extravascular cells. Thrombin production at these sites in turn enhances platelet activation and the subsequent hemostatic plug formation to minimize bleeding. Thrombin production and platelet activation also initiate the process of wound healing requiring thrombin-dependent cell activation and platelet-dependent formation of new blood vessels (angiogenesis). Activated platelets release from their storage granules several proteins and other factors that regulate local thrombin formation and the responses of blood vessel cells to injury to assure hemostasis and effective wound healing. Failure to localize and adequately regulate thrombin production and/or platelet activation can have pathological consequences, including the development and propagation of atherosclerosis and enhancement of tumor development. The primary basis for the pathological consequences of the failure to adequately regulate thrombin production is that the multi-functional thrombin activates several types of cells to initiate their mitogenesis. Mitogenesis precedes many of the undesirable consequences of poorly regulated thrombin production and platelet activation. In addition, activated platelets release a variety of products which influence the functions of several cell types to the extent that inadequate regulation of platelet activation (by excessive thrombin production) could contribute to the pathogenesis of acute and chronic arterial thrombosis and to tumor development. Activated platelets participate in tumor development by releasing several factors that positively (and negatively) regulate blood vessel formation.     

Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.     

Epidemiology of venous thromboembolism (VTE) associated with pregnancy

This review is focused on the epidemiology of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), associated with pregnancy. Superficial vein thrombosis, a less hazardous and less studied type of thrombosis in pregnant women, is beyond the scope of this review. This study discusses the VTE incidence rate in women from developed countries for both antepartum and postpartum periods and for subpopulations of women affected by additional risk factors, such as thrombophilias, circulatory diseases, preeclampsia of varying degrees of severity, and Caesarean section. To minimize bias due to historical changes in medical and obstetric practices, lifestyle, diet, etc., this review is generally limited to relatively recent studies, i.e., those that cover the last 35 years. The absolute risk or incidence rate was used to ascertain risk of VTE associated with pregnancy. For the studies where the direct incidence rates of VTE were not reported, we calculated an estimate of the observed but not reported absolute incidence rates using the data presented in respective articles. Birth Defects Research (Part C) 105:167–184, 2015. © 2015 Wiley Periodicals, Inc.     

Inhibition of oxidative-stress-induced platelet aggregation by androgen at physiological levels via its receptor is associated with the reduction of thromboxane A2 release from platelets

BACKGROUND: Platelets play a crucial role in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis. The purposes of our study are to assess the effect of androgen at physiological concentration via its receptor on oxidative-stress-induced platelet aggregation and to further elucidate the possible mechanism. METHODS AND RESULTS: Plasma dihydrotestosterone (DHT) was determined by ELISA using a commercially available kit. Platelet aggregometer was used to measure platelet aggregation. The contents of thromboxane B(2) (TXB(2)) were assayed with radio-immunoassay. Our results showed that addition of DHT (2 nM) significantly inhibited platelet aggregation induced by hydrogen peroxide (H(2)O(2)) (10 mM, 25 mM) in PRP diluted with Tyrode's buffer. Moreover, H(2)O(2)-induced platelet aggregation decreased in sham-operated rats. However, H(2)O(2)-induced platelet aggregation significantly increased in castrated rats. Replacement of DHT inhibited H(2)O(2)-induced platelet aggregation in castrated rats. After PRP was pretreated with flutamide, H(2)O(2)-induced platelet aggregation increased in castrated rats again. Presence of DHT (2 nM) obviously inhibited H(2)O(2)-induced thromboxane A(2) (TXA(2)) release in castrated rats. Pretreatment of DHT and flutamide increased H(2)O(2)-stimulated TXA(2) release from platelet in castrated rats again. Castration caused a significant reduction in plasma testosterone and DHT levels, whereas DHT replaced at a dose of 0.25 mg/rat restored the circulating DHT to physiological levels, without being altered by treatment with flutamide. The plasma TXB(2) increased in castrated rats as compared with that in sham-operated rats. Replacement with DHT reduced plasma TXB(2) contents in castrated rats. However, flutamide supplementation increased plasma contents of TXB(2) in castrated rats again. CONCLUSION: Androgen at physiological doses via its receptor inhibits oxidative-stress-induced platelet aggregation, which is associated with the reduction of TXA(2) release from platelets.     

间歇性充气加压疗法对下肢深静脉血栓患者血液流变学的影响

目的:观察间歇性充气加压疗法(intermittent pneumatic compression,IPC)对下肢深静脉血栓形成(deep vein thrombosis of lower limbs,DVT)患者的治疗效果,并从血液流变学方面探讨间歇性充气加压的作用机理.方法:2003年3月-2010年9月我科收治的243例下肢深静脉血栓患者,将其中42例IPC治疗病例定为B组实验组,145例单纯药物治疗病例中选取60例定为A组对照组.观察两组患者血液流变学指标和小腿肿胀消退情况的对比.结果:两组患者全血粘度、红细胞聚集指数、红细胞电泳时间、红细胞变形性,在治疗第1天较入院时无差异,组间无差异(P＞0.05),第3天较入院时有差异(P＜0.05),组间第3天有差异(P＜0.05),两组患者下肢肿胀度均明显消退,但B组肿胀消退速度明显快于对照组(P＜0.05).结论:间歇性充气加压治疗仪可有效改变血液流变学状态,改善血液高凝状态,有效缓解肢体肿胀症状,缩短住院时间.且不增加治疗难度,使用简单,治疗依从性好.     

颅内静脉系统血栓形成6 例临床分析

目的:探讨颅内静脉系统血栓形成(CVT)的临床表现、影像学特征以及治疗方法对临床诊断的意义。方法:回顾性分析首都医科大学宣武医院收治的6例CVT患者的临床表现及影像学特征与治疗方法。结果:6例临床表现无特殊,4例经MRI+MRV确诊,3例DSA检查确诊,1例介入治疗,4例抗凝治疗,2例保守,无死亡患者。结论:静脉系统血栓形成临床症状缺乏特异性,临床遇到急性起病的头痛、呕吐,伴或不伴有局灶性神经功能缺损或癫痫发作、意识障碍的青中年人,应高度怀疑CVT。早期应用抗凝、溶栓等治疗方法,对改善预后具有较高的临床应用价值。     

Complicaciones de la otitis media con parálisis del sexto par craneal contralateral en pediatría

Otitis media is a frequent infection during childhood. Complications may be present in up to 4 of 100 children including serious neurological complications, particularly in developing countries.We report the case of a 9-year-old girl with no disease history who presented with otitis media, otorrhea, intracranial hypertension syndrome, and paralysis of the VI cranial nerve contralateral to the lesion. A computed tomography scan of the skull and a brain magnetic resonance imaging revealed chronic otomastoiditis, petrous apicitis, and thrombosis of the transverse and sigmoid sinus, the jugular bulb, and the right internal jugular vein. She received antibiotics and surgical treatment.This case shows the spectrum of intra and extracranial complications associated with acute otitis media in the antibiotic era. The physical examination allows early identification of intracranial hypertension with signs such as papilledema and sixth contralateral nerve palsy as an unusual finding.