Abnormalities in circulating von Willebrand factor and survival in pulmonary hypertension

Lopes, Antônio Augusto; Maeda, Nair Yukie; Bydlowski, Sérgio Paulo

doi:10.1016/s0002-9343(98)00138-7

Cited by 37 publications

(42 citation statements)

References 27 publications

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“…In PH secondary to congenital heart disease and in PPH, the expression of vWF is increased [34,35]. These patients also exhibit abnormal vWF multimer pattern [36], possibly due to degradation of vWF main subunit [37]. These abnormalities of vWF may be related to endothelial cell injury and may cause a decrease of platelet aggregation to ristocetin, since these multimers of vWF are defective.…”

Section: Injured Endotheliummentioning

confidence: 99%

The role of thrombosis in severe pulmonary hypertension

Chaouat¹,

Weitzenblum²,

Higenbottam³

1996

Eur Respir J

116

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Considering the important surface in pulmonary circulation where blood can interact with the endothelium, the maintenance of blood fluidity through the lung, by antithrombotic pathways and products of the endothelium, is essential. This function appears to be ineffective in primary pulmonary hypertension and in severe secondary pulmonary hypertension. Thrombotic lesions are frequently found in pulmonary arteries in these diseases.Thrombin activity appears to be increased in severe pulmonary hypertension. Antithrombotic pathway disorders may account for this abnormality, particularly in chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. Injured endothelium, a constant feature in severe pulmonary hypertension, either primary or secondary, enhances thrombus formation in pulmonary vessels. This is probably related to thrombomodulin and tissue factor imbalance, impairment of prostacyclin and nitric oxide release, as well as inefficiency of fibrinolysis. Moreover, platelets appear to be activated in the pulmonary circulation of these patients. They release several mediators acting on vascular tone and as mitogenic agents, and may also contribute to thrombin and clot generation. Long-term oral anticoagulant and continuous infusion of prostacyclin, treatments which impede thrombosis, are known to improve the survival rate in patients with primary pulmonary hypertension.These are the strongest arguments, so far, in favour of the role of thrombosis in severe pulmonary hypertension. However, we do not know whether these abnormalities result from a previous vascular injury or represent the primary disturbance.

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Section: Injured Endotheliummentioning

confidence: 99%

The role of thrombosis in severe pulmonary hypertension

Chaouat¹,

Weitzenblum²,

Higenbottam³

1996

Eur Respir J

116

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“…Furthermore, the relative density of high molecular weight multimers which are sometimes poorly individualized in densitometric scans may be estimated for the whole group using the curve equation. Previous studies on the multimeric structure of plasma vWF in pulmonary hypertension, including data from our laboratory, showed the disappearance of the larger multimers, associated with the increased density of the smaller ones (11,20). In this study, we were able to identify the exact region of highest vWF protein concentration in the sequence of multimers.…”

Section: Introductionmentioning

confidence: 54%

“…In some instances, unusually large multimers are present in plasma (7,8). In other conditions, high molecular weight multimers are lacking and this may be associated with increased concentrations of low molecular weight forms (9)(10)(11). Using highresolution gels, changes may also be observed in the structure of individual multimers as reported in variants of von Willebrand's disease (12).…”

Section: Introductionmentioning

confidence: 99%

“…In the present study, we propose a method for quantitative estimation of the relative distribution of vWF multimers in immunoblots based on adjustment of mathematical models following densitometry. As an example of the potential usefulness of the method for group analysis, we studied plasma vWF multimers in a population of patients with advanced pulmonary vascular disease for whom abnormalities in vWF structure have been reported that resemble type II von Willebrand's disease (11). The study protocol was approved by the Scientific Committee of the Heart Institute, São Paulo, Brazil.…”

Section: Introductionmentioning

confidence: 99%

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A mathematical framework for group analysis of von Willebrand factor multimeric composition following luminography

Lopes

Soares

Maeda

2002

Braz J Med Biol Res

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The objective of the present study was to establish a method for quantitative analysis of von Willebrand factor (vWF) multimeric composition using a mathematical framework based on curve fitting. Plasma vWF multimers from 15 healthy subjects and 13 patients with advanced pulmonary vascular disease were analyzed by Western immunoblotting followed by luminography. Quantitative analysis of luminographs was carried out by calculating the relative densities of low, intermediate and high molecular weight fractions using laser densitometry. For each densitometric peak (representing a given fraction of vWF multimers) a mean area value was obtained using data from all group subjects (patients and normal individuals) and plotted against the distance between the peak and IgM (950 kDa). Curves were constructed for each group using nonlinear fitting. Results indicated that highly accurate curves could be obtained for healthy controls and patients, with respective coefficients of determination (r 2 ) of 0.9898 and 0.9778. Differences were observed between patients and normal subjects regarding curve shape, coefficients and the region of highest protein concentration. We conclude that the method provides accurate quantitative information on the composition of vWF multimers and may be useful for comparisons between groups and possibly treatments.

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“…3). Sequential studies on this subject [21][22][23][24][25][26] 24,25 More recent data of ours suggest that heightened circulating levels of VWF are associated with decreased medium-term survival in the specific subgroup of patients with PAH-CHD (Fig. 4).…”

Section: Research Activities: Possibilities and Limitationsmentioning

confidence: 91%

Congenital Heart Disease and Pulmonary Arterial Hypertension in South America (2013 Grover Conference Series)

Lopes

Flores

Díaz³

et al. 2014

Pulm. circ.

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South America is a territory of 17,819,100 km 2 , where ∼388 million people live in 13 countries. In the region, access to medical assistance (e.g., for treatment of cardiovascular disorders) is relatively easy in metropolitan areas but difficult in remote places such as the Andes and the Amazon. Altitudes up to ∼6,700 m influence the prevalence of congenital heart disease (CHD) and pulmonary arterial hypertension (PAH). In tertiary centers, CHD is now treated earlier in life but remains an important etiology of PAH. In adolescents and adults with PAH assisted at institutions devoted to treatment of cardiovascular disorders, the relative frequency of PAH-CHD (∼50%-60%) is even higher than that of idiopathic PAH. In one big tertiary center in São Paulo, Brazil, the prevalence of advanced PAH in children and adults with CHD is 1.2% and 4.2%, respectively. In young patients with cardiac septal defects (aged up to 2 years), pulmonary vascular abnormalities are a matter of concern in the decision about operability in 4.9% of cases. Access to specific PAH drugs is not uniform in South America, being unrealistic in remote places. In big cities, there are real possibilities for management of complex CHD, neonatal disorders, and even cardiac transplantation. Research activities have been implemented at clinical, translational, and basic levels. However, because of social and economic inequalities and political issues, access to best standards of medical care remains a problem in the region as a whole.

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Abnormalities in circulating von Willebrand factor and survival in pulmonary hypertension

Cited by 37 publications

References 27 publications

The role of thrombosis in severe pulmonary hypertension

The role of thrombosis in severe pulmonary hypertension

A mathematical framework for group analysis of von Willebrand factor multimeric composition following luminography

Congenital Heart Disease and Pulmonary Arterial Hypertension in South America (2013 Grover Conference Series)

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