OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag) were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity). The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years). The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001). An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081), was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029) and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004). Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group), preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79), 1.096 (95% CI 1.016 to 1.183), and 37.43 (95% CI 1.79 to 782.73). CONCLUSION: Low plasma ADAMTS-13 activity is a risk factor for postoperative bleeding in children with cyanotic congenital heart disease, particularly in children undergoing cardiopulmonary bypass.

Células-tronco são células indiferenciadas. Como tal, apresentam uma série de características que as tornam candidatas à utilização terapêutica. As principais características das células-tronco são a capacidade de autorrenovação e de se diferenciarem em diversos tipos celulares. Desta forma, acredita-se que células-tronco presentes nos diferentes tecidos tenham papel regenerativo quando estes sofrem uma lesão ou injúria. Entre os tecidos conhecidos por apresentarem células-tronco após a vida pós-natal, a medula óssea foi a mais estudada, por muitos anos, como fonte tanto de células-tronco hematopoéticas quanto de células-tronco mesenquimais, também denominadas de células mesenquimais estromais da medula óssea ou células estromais mesenquimais multipotentes. Estas células são um grupo de células clonogênicas, presentes no estroma da medula óssea, que, quando submetidas a diferentes estímulos apropriados, são capazes de se diferenciarem em várias linhagens de células, como a osteogênica, a condrogênica e a adipogênica e, possivelmente, em outros tipos celulares não mesodérmicos, como células neurais ou hepatócitos. Nesta revisão, as principais características das células-tronco mesenquimais serão abordadas, incluindo os marcadores moleculares e de membrana, as características de divisão e de diferenciação, a heterogeneidade e as aplicações clínicas potenciais.

Stem cells are undifferentiated cells. They show various characteristics that make them suitable for clinical applications. The main stem cell characteristics are their capacity of autorenewal and of differentiation into different cell lines so it is quite possible that stem cells in different tissues exhibit a regenerative role when these tissues are injured. Bone marrow is the best studied tissue as a source of hematopoietic stem cells as well as mesenchymal stem cells (also known as mesenchymal stromal cells or mesenchymal stromal multipotent cells); clonogenic cells in the bone marrow stroma. They are able to differentiate under specific stimuli in several cell lines including osteogenic, chondrogenic and adipogenic cells, and probably in other nonmesodermic cell lines such as neural cells or hepatocytes. Here the main characteristics of mesenchymal stem cells will be discussed, including the molecular and membrane markers, the division and differentiation properties, the heterogeneity, and the potential clinical applications.

Desde o primeiro isolamento e cultivo de células-tronco embrionárias humanas, há mais de 10 anos, seu uso na pesquisa e terapia foi inibida por considerações éticas complexas e pelo risco de transformação maligna destas células indiferenciadas após transplante no paciente. As células-tronco adultas são eticamente aceitas e o risco de transformação maligna é muito baixo. Entretanto, seu potencial de diferenciação e sua capacidade proliferativa são limitados. Cerca de 6 anos atrás, a descoberta de célulastronco no líquido amniótico que expressavam Oct-4, um marcador específico de pluripotencialidade, com alta capacidade de proliferação e diferenciação, iniciou um novo campo promissor na área das células-tronco. Estas células têm potencial de se diferenciar em células dos três folhetos germinativos. Não formam tumores in vivo e não levantam os questionamentos éticos associados com as células-tronco embrionárias humanas. Futuras investigações revelarão se as células-tronco do líquido amniótico realmente irão representar um tipo intermediário com vantagens em relação tanto às células-tronco embrionárias quanto às adultas. Este artigo faz uma revisão acerca destes tópicos e das características biológicas das células-tronco do líquido amniótico.

Since the first successful isolation and cultivation of human embryonic stem cells about 10 years ago, their use for research and therapy has been constrained by complex ethical considerations as well as by the risk of development of malignancies of undifferentiated embryonic stem cells after transplantation into the patient. Adult stem cells are ethically acceptable and the risk of tumor development is low. However, their differentiation potential and proliferative capacity are limited. About 6 years ago, the discovery of Oct-4 expressing amniotic fluid stem cells, a specific marker of pluripotency, with a high proliferative capacity, and multilineage differentiation potential, initiated a promising field of research. These cells, indeed, have the potential to differentiate into cells of all three embryonic germ layers. They do not form tumors in vivo and do not raise ethical concerns. Further investigation will reveal whether these cells really are an intermediate cell type with advantages over both embryonic and adult stem cells. This article reviews the biological characteristics of amniotic fluid stem cells.