Bleeding and Thrombosis: Insights into Pathophysiology of Bothrops Venom-Related Hemostasis Disorders

Toxins from Bothrops venoms targeting hemostasis are responsible for a broad range of clinical and biological syndromes including local and systemic bleeding, incoagulability, thrombotic microangiopathy and macrothrombosis. Beyond hemostais disorders, toxins are also involved in the pathogenesis of edema and in most complications such as hypovolemia, cardiovascular collapse, acute kidney injury, myonecrosis, compartmental syndrome and superinfection. These toxins can be classified as enzymatic proteins (snake venom metalloproteinases, snake venom serine proteases, phospholipases A₂ and L-amino acid oxidases) and non-enzymatic proteins (desintegrins and C-type lectin proteins). Bleeding is due to a multifocal toxicity targeting vessels, platelets and coagulation factors. Vessel damage due to the degradation of basement membrane and the subsequent disruption of endothelial cell integrity under hydrostatic pressure and tangential shear stress is primarily responsible for bleeding. Hemorrhage is promoted by thrombocytopenia, platelet hypoaggregation, consumption coagulopathy and fibrin(ogen)olysis. Onset of thrombotic microangiopathy is probably due to the switch of endothelium to a prothrombotic phenotype with overexpression of tissue factor and other pro-aggregating biomarkers in association with activation of platelets and coagulation. Thrombosis involving large-caliber vessels in B. lanceolatus envenomation remains a unique entity, which exact pathophysiology remains poorly understood.     

Diagnosing Czech Patients with Inherited Platelet Disorders

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.     

Inherited Platelet Disorders: An Updated Overview

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 10¹¹ platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes. Their clinical relevance is highly variable according to the specific disease and even within the same type, ranging from almost negligible to life-threatening. Mucocutaneous bleeding diathesis (epistaxis, gum bleeding, purpura, menorrhagia), but also multisystemic disorders and/or malignancy comprise the clinical spectrum of IPDs. The early and accurate diagnosis of IPDs and a close patient medical follow-up is of great importance. A genotype–phenotype relationship in many IPDs makes a molecular diagnosis especially relevant to proper clinical management. Genetic diagnosis of IPDs has been greatly facilitated by the introduction of high throughput sequencing (HTS) techniques into mainstream investigation practice in these diseases. However, there are still unsolved ethical concerns on general genetic investigations. Patients should be informed and comprehend the potential implications of their genetic analysis. Unlike the progress in diagnosis, there have been no major advances in the clinical management of IPDs. Educational and preventive measures, few hemostatic drugs, platelet transfusions, thrombopoietin receptor agonists, and in life-threatening IPDs, allogeneic hematopoietic stem cell transplantation are therapeutic possibilities. Gene therapy may be a future option. Regular follow-up by a specialized hematology service with multidisciplinary support especially for syndromic IPDs is mandatory.     

急性上消化道出血的诊治与护理

目的总结急性消化道出血的诊治与护理效果。方法对2006年1月1日至2009年6月1日在我科被诊断为上消化道出血的87例患者诊治和护理过程进行回顾性总结,对胃镜手术前,手术中,手术后的护理方法与经验进行概括。结果胃镜检查过程中积极给予护理配合手术前备好必须器械,药品,注射液并进行检查;手术中积极配合医生,用药迅速;手术后对患者进行精心指导。80例病人在内镜帮助下,确诊后止血成功,成功率为91.95%,再出血2例,比率为2.30%,诊治和护理效果良好。结论积极的手术前准备与手术中的配合,以及手术后的用药,饮食指导,医疗宣传可以大大提高该类病症的诊治成功率。     

上消化道出血214例临床分析

目的探讨分析上消化道出血的临床特点。方法回顾性分析我院2004年1月份至2008年12月214例上消化道出血并经胃镜检查的临床病历资料。结果214例上消化道出血患者均行急诊胃镜检查,胃镜下的诊断率高达98.6%,上消化道出血主要病因为十二指肠球部溃疡、胃溃疡、上消化道急性应激性黏膜病变、胃癌、门脉高压性胃病、食管胃底静脉曲张破裂、复合性溃疡。结论急诊胃镜检查是诊断上消化道出血原因的最好方法;消化道出血主要为消化性溃疡。出血的原因主要是胃酸及蛋白酶、胆酸、非甾体消炎药等破坏因素及胃粘膜保护因子平衡紊乱引起。     

中药治疗功能性子宫出血案例分析

目的观察中药治疗功能性子宫出血的疗效。方法共观察本病45例,急性出血期用自拟固冲1号方止血,出血减少缓解期给予辩证施治,血止后中药人工周期调理以善后。1个月经周期为1个疗程,连续3个疗程。结果痊愈18例(占40.6%),显效14例(占31.2),有效10例(占21.8%),无效3例(占6.2%),总有效率93.8%。     

Regulation of Key Antiplatelet Pathways by Bioactive Compounds with Minimal Bleeding Risk

Cardiovascular disease is strongly influenced by platelet activation. Platelet activation and thrombus formation at atherosclerotic plaque rupture sites is a dynamic process regulated by different signaling networks. Therefore, there are now focused efforts to search for novel bioactive compounds which target receptors and pathways in the platelet activation process while preserving normal hemostatic function. The antiplatelet activity of numerous fruits and vegetables and their multiple mechanisms of action have recently been highlighted. In this review, we review the antiplatelet actions of bioactive compounds via key pathways (protein disulfide isomerase, mitogen-activated protein kinases, mitochondrial function, cyclic adenosine monophosphate, Akt, and shear stress-induced platelet aggregation) with no effects on bleeding time. Therefore, targeting these pathways might lead to the development of effective antiplatelet strategies that do not increase the risk of bleeding.     

B超监测在射频消融术治疗功能失调性子宫出血的价值(附46例分析)

目的回顾性分析射频消融术治疗功能失调性子宫出血中使用B超监测的作用和价值。方法总结B超动态监测在应用国产多功能电子射频治疗仪消融46例功能失调性子宫出血的子宫内膜术中的作用和效果,经验和体会,以及术后随访的满意率。结果46例患者在B超监测下顺利进行手术,术中监测效果满意,术后随访满意率98%。结论在B超动态监测下进行子宫内膜射频消融术治疗功能失调性子宫出血的治疗监测效果好、操作简便、费用低,患者安全、无痛苦,值得临床推广应用。     

一次结构法在应力分析中的应用

介绍了一次结构是在其原始结构解除不利约束的基础上得到的、能承受外加机械载荷的简化结构,并利用一次结构法识别了一次应力和二次应力。     

Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.     

指侧方小切口放血技术在毁损性多指离断伤再植术后的应用体会

目的探讨指侧方小切口放血技术在毁损性多指离断伤再植术成功的护理。方法对107例毁损性多指离断伤再植术指侧方小切口放血护理技术应用进行总结。结果共再植107例278指;成活251指,成活率90.2%。结论毁损性多指离断伤再植术后指侧方小切口放血技术的应用是及时处理血管危象保障手术成功的重要手段。     

Fibrinolysis in Platelet Thrombi

The extent and duration of occlusive thrombus formation following an arterial atherothrombotic plaque disruption may be determined by the effectiveness of endogenous fibrinolysis. The determinants of endogenous fibrinolysis are the subject of much research, and it is now broadly accepted that clot composition as well as the environment in which the thrombus was formed play a significant role. Thrombi with a high platelet content demonstrate significant resistance to fibrinolysis, and this may be attributable to an augmented ability for thrombin generation and the release of fibrinolysis inhibitors, resulting in a fibrin-dense, stable thrombus. Additional platelet activators may augment thrombin generation further, and in the case of coronary stenosis, high shear has been shown to strengthen the attachment of the thrombus to the vessel wall. Neutrophil extracellular traps contribute to fibrinolysis resistance. Additionally, platelet-mediated clot retraction, release of Factor XIII and resultant crosslinking with fibrinolysis inhibitors impart structural stability to the thrombus against dislodgment by flow. Further work is needed in this rapidly evolving field, and efforts to mimic the pathophysiological environment in vitro are essential to further elucidate the mechanism of fibrinolysis resistance and in providing models to assess the effects of pharmacotherapy.     

横管初冷器工艺研究

文章主要介绍了横管初冷器的工艺技术特点和横管初冷器对煤气洗萘的影响,对现有煤气初冷提出观点,分析带断塔盘式初冷器的优点,根据煤气初冷器最新技术资料和实际操作情况提出工艺优化建议,提高初冷器煤气冷却能力和洗萘效果,可为焦化初冷器选型提供良好的建议和意见。     

Emerging Genotype-Phenotype Relationships in Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare inherited condition affecting motile cilia and leading to organ laterality defects, recurrent sino-pulmonary infections, bronchiectasis, and severe lung disease. Research over the past twenty years has revealed variability in clinical presentations, ranging from mild to more severe phenotypes. Genotype and phenotype relationships have emerged. The increasing availability of genetic panels for PCD continue to redefine these genotype-phenotype relationships and reveal milder forms of disease that had previously gone unrecognized.     

对初冷器运行方式的探讨

阐述了马钢焦化厂鼓冷工段初冷系统运行状况及存在问题,对其运行方式进行了探讨并提出了建议。     

一段炉顶烧嘴偏烧原因及对策

应用燃烧理论对一段炉顶烧嘴发生偏烧现象进行分析，找出燃烧不好的原因，并制定相应的防范措施，以确保转化管安全运行。     

The Use of Total Thrombus Formation Analysis System as a Tool to Assess Platelet Function in Bleeding and Thrombosis Risk—A Systematic Review

Background. Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. Methods. An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. Conclusion. Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment.     

一段转化炉反应管套管及猪尾管的修复

分析了一段转化炉反应管套管及猪尾管损坏的原因，详细介绍了炉内修复方案及过程。