Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance

Terraube, Virginie; O’Donnell, James S.; Jenkins, P. Vincent

doi:10.1111/j.1365-2516.2009.02005.x

Cited by 149 publications

(145 citation statements)

References 118 publications

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“…20 Second, VWF acts as a carrier molecule for procoagulant factor (F) VIII, thereby protecting it from premature proteolytic degradation and clearance. 22 VWF synthesized within ECs is either constitutively secreted into the plasma or, alternatively, stored within intracellular organelles known as Weibel-Palade (WP) bodies. 23,24 This stored VWF is enriched in high-molecular-weight multimers and is secreted together with other WP contents following EC activation.…”

Section: Vwf In Malariamentioning

confidence: 99%

Emerging roles for hemostatic dysfunction in malaria pathogenesis

O’Sullivan

Preston

O’Regan

et al. 2016

Blood

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Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum–infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance.

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Section: Vwf In Malariamentioning

confidence: 99%

Emerging roles for hemostatic dysfunction in malaria pathogenesis

O’Sullivan

Preston

O’Regan

et al. 2016

Blood

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“…This requires sound knowledge of cell types capable of replacing FVIII, especially within proximity of von Willebrand factor (vWF), which protects FVIII from degradation. 2 However, the cell-type origin of FVIII has been controversial. 3 Correction of hemophilia after orthotopic liver transplantation (OLT) but not after kidney transplantation, despite FVIII mRNA expression in both organs, 3,4 indicated that liver was a major site for FVIII production.…”

Section: Introductionmentioning

confidence: 99%

Role of bone marrow transplantation for correcting hemophilia A in mice

Follenzi

Raut

Merlin

et al. 2012

Blood

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To better understand cellular basis of hemophilia, cell types capable of producing FVIII need to be identified. We determined whether bone marrow (BM)-derived cells would produce cells capable of synthesizing and releasing FVIII by transplanting healthy mouse BM into hemophilia A mice. To track donor-derived cells, we used genetic reporters. Use of multiple coagulation assays demonstrated whether FVIII produced by discrete cell populations would correct hemophilia A. We found that animals receiving healthy BM cells survived bleeding challenge with correction of hemophilia, although donor BM-derived hepatocytes or endothelial cells were extremely rare, and these cells did not account for therapeutic benefits. IntroductionHemophilia A is characterized by inability to clot blood because of FVIII gene mutations and deficiency of this coagulation factor. 1 The potential for cell and gene therapy in hemophilia A is highly attractive because even small amounts of FVIII may substantially decrease bleeding risk. This requires sound knowledge of cell types capable of replacing FVIII, especially within proximity of von Willebrand factor (vWF), which protects FVIII from degradation. 2 However, the cell-type origin of FVIII has been controversial. 3 Correction of hemophilia after orthotopic liver transplantation (OLT) but not after kidney transplantation, despite FVIII mRNA expression in both organs, 3,4 indicated that liver was a major site for FVIII production. Recently, the cell transplantation approach established that of various liver cell types, liver sinusoidal endothelial cells (LSECs) replaced FVIII in hemophilia mice. 5,6 Nonetheless, extrahepatic organs probably contributed in FVIII production, as indicated by FVIII synthesis in spleen, lungs, or pancreatic islets. [6][7][8] This was in agreement with lack of plasma FVIII deficiency after OLT with donor liver from dogs or people with hemophilia A because such donor liver cells would not have synthesized or secreted FVIII. 9,10 Therefore, whether nonendothelial cells, and cells in extrahepatic organs, could also produce FVIII was not excluded. For instance, macrophages, which originate in bone marrow (BM), and contained FVIII mRNA, 11 could be such a candidate. Although FVIII was cloned from T cells, 12 and transplantation of lymphatic tissue was thought to correct hemophilia in dogs, 13 whether lymphocytes did express FVIII was uncertain, because correction of hemophilia by transplanted organs (eg, spleen) included other cell types. 7,14,15 Because BM cells may generate multiple lineages, the potential of BM-derived cells in FVIII production seemed relevant to us. Previously, BM transplantation studies in hemophilia A, 40 years ago, were limited to just 3 dogs and 2 persons. [16][17][18][19] BM transplantation in hemophilia dogs was carefully performed, although there were limitations, such as suboptimal allograft tolerance, lack of studies showing engraftment and generation of various BM cell types, absence of FVIII expression analysis in donor BM-derived cells,...

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“…Von Willebrand factor (vWF) is a multimeric glycoprotein produced by the vascular endothelium and megakaryocytes that is crucial for hemostasis, and functions as a carrier protein for factor VIII (FVIII) and as a bridge between the subendothelial matrix and platelets (4). The distinctive properties of the distinct molecular masses of VWF influence its ability to mediate platelet adhesion and aggregation (5).…”

Section: Introductionmentioning

confidence: 99%

Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer

et al. 2017

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Abstract. Coagulative and fibrinolytic disorders appear to be associated with the development of lung cancer. The aim of the present study was to determine plasma levels of von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif 13 (ADAMTS-13), and factor VIII (FVIII) activity, in association with O and non-O blood groups in patients with lung cancer. Plasma levels of VWF and ADAMTS-13, and FVIII activity were measured in 115 patients with lung cancer and 98 healthy subjects. Phenotyping of the ABO blood groups was also performed for the two groups. Significantly increased VWF levels and FVIII activity, as well as significantly decreased ADAMTS-13 levels, were observed in patients with distant metastasis as compared with those without distant metastasis and the healthy controls. Plasma VWF levels and FVIII activity were significantly increased in subjects with non-O type blood compared with those with type O blood in the two groups. However, a significant decrease in ADAMTS-13 levels was observed only in the control group among those with non-O type blood, compared with those with type O blood. The results of the present study indicate that increased VWF and decreased ADAMTS-13 levels facilitate the invasiveness and metastasis of lung cancer. Non-O blood groups constitute a risk factor for increased VWF and FVIII in plasma. Continued monitoring of VWF and ADAMTS-13 levels, and of FVIII activity in patients with lung cancer with distinct blood groups may help to minimize the incidence of thrombotic events and improve assessment of disease progression.

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Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance

Cited by 149 publications

References 118 publications

Emerging roles for hemostatic dysfunction in malaria pathogenesis

Emerging roles for hemostatic dysfunction in malaria pathogenesis

Role of bone marrow transplantation for correcting hemophilia A in mice

Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer

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