Changes in ADAMTS 13 Activity and Von Willebrand Factor Parameters during Acute Dengue Infection.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1492-1492
Author(s):  
Darintr Sosothikul ◽  
Panya Seksarn ◽  
Sureeporn Pongsawaluk ◽  
Jeanne M. Lusher
Keyword(s):  
Von Willebrand Factor ◽  
Cell Activation ◽  
Dengue Infection ◽  
Plasma Concentrations ◽  
Endothelial Activation ◽  
Healthy Children ◽  
Endothelial Cell Activation ◽  
Convalescent Phase ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Dengue virus causes febrile illnesses: Dengue Fever (DF) and less frequently a life-threatening illness, Dengue Hemorrhagic Fever (DHF). The pathophysiology of hemostatic defect in dengue infection is thought to relate to the direct effect of virus or cytokines on endothelial activation. To study the state of endothelial activation during dengue infection, we measured plasma levels of von Willebrand factor antigen (vWF:Ag), vWF-collagen binding assay (vWF:CBA), and ADAMTS 13 activity in 42 children (20 with DF and 22 with DHF) during 3 phases of illness: febrile, toxic, and convalescent phase. 38 healthy children comprised as controls. Our data shows that both VWF:Ag and vWF:CBA levels were significantly higher in dengue patients (p ≤ 0.001 in both DF and DHF patients) versus controls. DHF patients had significantly higher of VWF: Ag (p = 0.01, versus DF). ADAMTS 13 activity levels were significantly decreased only in DHF patients during 3 phases of the illness (febrile; mean 78%; p = 0.016, toxic; mean 68%; p<0.001 and convalescent; mean 69%; p<0.001 compared to mean 104% of the controls). Compared to DF patients, DHF patients had significantly lower plasma concentrations of ADAMTS 13 activity during the febrile, toxic and convalescent phase (p = 0.039, p = 0.002 and p =0.003, respectively). Endothelial cell activation is a hallmark of dengue infection especially in DHF patients; indicated by a significant rise in VWF:Ag and vWF:CBA and a reciprocal decline in ADAMTS 13 activity.

Von Willebrand Factor Propeptide in Vascular Disorders

2001 ◽  
Vol 86 (07) ◽  
pp. 164-171 ◽  
Author(s):  
Thalia Romani de Wit ◽  
Jan van Mourik
Keyword(s):  
Vascular Disease ◽  
Von Willebrand Factor ◽  
Time Course ◽  
Cell Activation ◽  
Cellular Adhesion ◽  
Endothelial Cell Activation ◽  
Diagnostic Significance ◽  
Vascular Disorders ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) is a multifunctional plasma protein that plays a prominent role in haemostasis. In endothelial cells, processing of its precursor pro-VWF results in the formation of two large polypeptides, mature VWF and a propeptide. These proteins are co-secreted on an equimolar basis but are cleared from the circulation at different rates. VWF levels are frequently elevated in response to vascular disorders. Similarly, propeptide levels are increased under these conditions, although primarily in fulminant vascular disease, such as thrombotic thrombocytopenic purpura and septicemia. In chronic vascular disease, e.g. diabetes or peripheral vascular disease, propeptide levels are much less elevated. The differential response of VWF and propeptide levels to vascular disease could provide a means to assess the extent and time course of endothelial cell activation. After secretion, the propeptide may play a role in modulating cellular adhesion processes. Thus, enhanced propeptide secretion seems not to be of merely diagnostic significance.

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and P-selectin in mediating accelerated platelet clearance

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2832-2839 ◽  
Author(s):  
Maha Othman ◽  
Andrea Labelle ◽  
Ian Mazzetti ◽  
Hisham S. Elbatarny ◽  
David Lillicrap
Keyword(s):  
Von Willebrand Factor ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Platelet Surface ◽  
Adenoviral Gene Transfer ◽  
Coxsackie Adenovirus Receptor ◽  
Transfer Vectors ◽  
Adenovirus Receptor ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThrombocytopenia has been consistently reported following the administration of adenoviral gene transfer vectors. The mechanism underlying this phenomenon is currently unknown. In this study, we have assessed the influence of von Willebrand Factor (VWF) and P-selectin on the clearance of platelets following adenovirus administration. In mice, thrombocytopenia occurs between 5 and 24 hours after adenovirus delivery. The virus activates platelets and induces platelet-leukocyte aggregate formation. There is an associated increase in platelet and leukocyte-derived microparticles. Adenovirus-induced endothelial cell activation was shown by VCAM-1 expression on virus-treated, cultured endothelial cells and by the release of ultra-large molecular weight multimers of VWF within 1 to 2 hours of virus administration with an accompanying elevation of endothelial microparticles. In contrast, VWF knockout (KO) mice did not show significant thrombocytopenia after adenovirus administration. We have also shown that adenovirus interferes with adhesion of platelets to a fibronectin-coated surface and flow cytometry revealed the presence of the Coxsackie adenovirus receptor on the platelet surface. We conclude that VWF and P-selectin are critically involved in a complex platelet-leukocyte-endothelial interplay, resulting in platelet activation and accelerated platelet clearance following adenovirus administration.

Persistently Elevated Levels of von Willebrand Factor Antigen in HIV Infection

2000 ◽  
Vol 84 (08) ◽  
pp. 183-187 ◽  
Author(s):  
S. Bjørnsen ◽  
B. Lunden ◽  
K. Otterdal ◽  
E. C. Ng ◽  
W. Ameln ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Von Willebrand Factor ◽  
Cell Activation ◽  
High Viral Load ◽  
Endothelial Cell Activation ◽  
Cross Sectional ◽  
Hiv Rna ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryLevels of circulating von Willebrand factor (vWf) antigen are thought to reflect endothelial involvement in various disorders. In the present study we found markedly elevated plasma levels of vWf in HIV-infected patients demonstrated on both cross-sectional and longitudinal testing. Notably, we found that a persistent rise in vWf antigen was associated with progression of HIV-related disease. This elevation of vWf antigen represented functionally normal vWf as evaluated by plasma FVIII, ristocetin cofactor assay and vWf multimer analyses. While HIV-infected patients showed enhanced platelet activation, platelets did not contribute substantially to the increased vWf levels. The high vWf levels were significantly correlated with high viral load, and during HAART, the pronounced decline in HIV RNA levels was accompanied by a corresponding decrease in vWf. The persistent elevation of functionally normal vWf during HIV infection, most probably reflecting a persistent endothelial cell activation, may have an important role in the pathogenesis of HIV infection.

The Role of von Willebrand Factor in Pre-Eclampsia

1991 ◽  
Vol 66 (05) ◽  
pp. 525-528 ◽  
Author(s):  
Frauke Bergmann ◽  
Siegfried Rotmensch ◽  
Bruce Rosenzweig ◽  
Helen How ◽  
Juan Chediak
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Activation ◽  
Hematological Parameters ◽  
Disease Process ◽  
Clinical Severity ◽  
Endothelial Cell Activation ◽  
Laboratory Findings ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe von Willebrand factor (vWF) has gained considerable interest in recent years as a marker of endothelial cell activation or insult and by virtue of its interactions with platelets and vessel walls. Altered patterns of vWF multimers were found to occur frequently in patients with thrombotic thrombocytopenic purpura in the acute and chronic stages. This disorder shares some clinical and laboratory findings with pre-eclampsia, including thrombocytopenia. Recent studies have also suggested that abnormalities of endothelial cell metabolism play a central role in the pathophysiology of pre-eclampsia. In order to determine if vWF could be instrumental in the disease process and the thrombocytopenia of pre-eclampsia we analyzed the ante- and postpartum structural and functional distribution of vWF. This data was correlated with hematological parameters such as platelet counts and the clinical severity of the disease. We found no consistent changes of vWF in association with thrombocytopenia or clinical severity. However, functional vWF was lower in postpartum samples of severely affected pre-eclamptics as compared to normal controls. This finding may reflect endothelial cell exhaustion after stimulation or cellular injury. Elevated titers of fibrin split products and thrombocytopenia were evident in severe pre-eclampsia, as seen in DIC, despite factor VIII coagulant levels within the normal range. Our data is consistent with the hypothesis of endothelial cell dysfunction in pre-eclampsia. However, the mechanism of thrombocytopenia in this disorder does not appear to be related to alterations in the structure or biological function of vWF.

scholarly journals Acute von Willebrand Factor Secretion from the Endothelium In Vivo: Assessment through Plasma Propeptide (vWf:AgII) Levels

1997 ◽  
Vol 77 (02) ◽  
pp. 387-393 ◽  
Author(s):  
Ulrich M Vischer ◽  
Jørgen Ingerslev ◽  
Claes B Wollheim ◽  
Jean-Claude Mestries ◽  
Dimitrios A Tsakiris ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Time Course ◽  
Plasma Concentrations ◽  
Vascular Wall ◽  
Endothelial Activation ◽  
Relative Increase ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryElevated plasma concentrations of von Willebrand factor (vWf) are increasingly recognized as a cardiovascular risk factor, and are used as a marker of endothelial activation. However, the factors which determine the rate of vWf release from the endothelium in vivo have not been defined clearly. In addition, vWf plasma levels may also be influenced by adhesion of vWf to the vascular wall or to platelets, and by its rate of degradation. The propeptide of vWf (also called vWf:AgII) is stored and released in equimolar amounts with vWf. In the present study we attempted to determine whether this propeptide could be a more reliable marker of endothelial secretion than vWf itself. To accomplish this we developed an ELISA based on monoclonal antibodies. The propeptide levels in normal plasma were found to be 0.7 µg/ml, more than 10 times lower than vWf itself. Administration of desmopressin (DDAVP) induced a rapid relative increase in propeptide (from 106 to 879%) and in vWf (from 112 to 272%). However, the increases in vWf and propeptide were equivalent when expressed in molar units. A time course study indicated a half-life of the propeptide of 3 h or less. In a baboon model of disseminated intravascular coagulation (DIC) induced by FXa, vWf increased by less than 100%, whereas the propeptide concentrations increased by up to 450%. In view of the massive thrombin generation (as assessed by fibrinogen depletion), the increases in vWf are small, compared to the strong secretory response to thrombin and fibrin previously observed in vitro. Our results suggest that due to its rapid turnover, the propeptide could provide a sensitive plasma marker of acute endothelial secretion.

von Willebrand Factor Propeptide in Vascular Disorders: A Tool to Distinguish Between Acute and Chronic Endothelial Cell Perturbation

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 179-185 ◽  
Author(s):  
Jan A. van Mourik ◽  
Ria Boertjes ◽  
Inge A. Huisveld ◽  
Karin Fijnvandraat ◽  
Dasja Pajkrt ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Cell Activation ◽  
Molar Ratio ◽  
Low Grade ◽  
Endothelial Cell Activation ◽  
Endoproteolytic Cleavage ◽  
Von Willebrand ◽  
Willebrand Factor

Before de novo synthesized von Willebrand factor (vWF) leaves the endothelial cell, it undergoes endoproteolytic cleavage of its propeptide (vW antigen II). The processed vWF and propeptide are either released constitutively or, following activation of the endothelium, released through the regulated pathway. In a recent study (Borchiellini et al, Blood 88:2951, 1996), we showed that the half-life of mature vWF and of its propeptide differ fourfold to fivefold. We postulated that the molar ratio of the propeptide to mature vWF could serve as a tool to assess the extent of endothelial cell activation under physiologic and clinical conditions. To test this hypothesis, we measured mature vWF and propeptide in patients with documented acute and chronic vascular disease, including patients with thrombotic thrombocytopenic purpura (TTP), acute septicemia, and diabetes mellitus. These data were compared with experimental conditions in healthy subjects in which perturbation of the endothelium was simulated by physical exercise or by administration of 1-deamino-8-D-arginine vasopressin (DDAVP) or endotoxin. In all individuals of the latter study group, both vWF and propeptide levels were elevated during the acute phase of the experimentally induced vascular perturbation; at later time points after stimulation, only vWF levels remained elevated. In patients with sepsis and TTP, both vWF and propeptide were elevated several-fold. Thus, this pattern can readily be explained in terms of acute perturbation of the endothelium. In contrast, in patients with diabetes mellitus propeptide levels were only slightly elevated, whereas vWF levels were elevated twofold to threefold. This pattern is a typical feature of chronic, low-grade activation of the endothelium. These observations support our hypothesis that measurement of both propeptide and vWF levels allows to discriminate between chronic and acute phases of endothelial cell activation in vivo. Measurement of only vWF is less indicative in this respect.

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