Big piece, little piece or: Yes, factor VIII is a protein

Owen, Whyte G.

doi:10.1111/j.1538-7836.2005.01247.x

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…Building on the observation that the clinical platelet function abnormality in von Willebrand disease could be dramatically improved by a plasma factor [32,33,236], Ted Zimmerman in Oscar Ratnoff’s [237] laboratory established that most patients with von Willebrand disease have reduced levels of a protein present in normal plasma and the plasma of patients with haemophilia A. A series of biochemical studies ultimately showed that VWF and factor VIII are separate molecules, but as was suspected from the transfusion studies, they circulate as a complex in plasma [22,238]. The unfortunate choice of the term ‘factor VIII‐related antigen’ for VWF created considerable confusion, some of which remains for those new to the field to this day.…”

Section: The Mechanistic Periodmentioning

confidence: 99%

Historical perspective and future directions in platelet research

Coller

2011

Journal of Thrombosis and Haemostasis

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Platelets are a remarkable mammalian adaptation that are required for human survival by virtue of their ability to prevent and arrest bleeding. Ironically, however, in the past century, the platelets’ hemostatic activity became maladaptive for the increasingly large percentage of individuals who develop age-dependent progressive atherosclerosis. As a result, platelets also make a major contribution to ischemic thrombotic vascular disease, the leading cause of death worldwide. In this brief review, I provide historical descriptions of a highly selected group of topics to provide a framework for understanding our current knowledge and the trends that are likely to continue into the future of platelet research. For convenience, I separate the eras of platelet research into the “Descriptive Period” extending from ~1880-1960 and the “Mechanistic Period” encompassing the past ~50 years since 1960. We currently are reaching yet another inflection point, as there is a major shift from a focus on traditional biochemistry and cell and molecular biology to an era of single molecule biophysics, single cell biology, single cell molecular biology, structural biology, computational simulations, and the high-throughput, data-dense techniques collectively named with the “omics” postfix. Given the progress made in understanding, diagnosing, and treating many rare and common platelet disorders during the past 50 years, I think it appropriate to consider it a Golden Age of Platelet Research and to recognize all of the investigators who have made important contributions to this remarkable achievement.

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Section: The Mechanistic Periodmentioning

confidence: 99%

Historical perspective and future directions in platelet research

Coller

2011

Journal of Thrombosis and Haemostasis

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“…Immunological evidence that FVIII activity and FVIII-like antigen (VWF antigen) were independent molecular entities was presented by Rick and Hoyer [36] and by Zimmerman and Edgington [37]. The reader is referred to a recent historical sketch by Owen [38] for more details on this topic. These data strongly suggested that FVIII and VWF (FVIII-related antigen) were two independent entities forming a complex.…”

Section: Factor VIII Coagulant Activity and Fviii-like Antigen: Indepmentioning

confidence: 99%

Unraveling the mystery of von Willebrand factor

Bouma

Mourik

2006

Journal of Thrombosis and Haemostasis

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“…Indeed, it was complicated by the multimeric nature of VWF and the notion that VWF circulates in complex with coagulation factor VIII (FVIII), the protein that is associated with hemophilia A. The technical difficulties that needed to be addressed have nicely been put in context in several personal anecdotes describing the events that led to the discovery in the early 1970s that VWF and FVIII are separate proteins and that VWF is a multimeric protein 3–5. The identification of VWF as a plasma component that is associated with VWD provided the basis for numerous additional studies.…”

Section: Introductionmentioning

confidence: 99%

On the Versatility of Von Willebrand Factor

Lenting¹

2013

Mediterr J Hematol Infect Dis

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Von Willebrand factor (VWF) is a large multimeric protein, the function of which has been demonstrated to be pivotal to the haemostatic system. Indeed, quantitative and/or qualitative abnormalities of VWF are associated with the bleeding disorder Von Willebrand disease (VWD). Moreover, increased plasma concentrations of VWF have been linked to an increased risk for thrombotic complications. In the previous decades, many studies have contributed to our understanding of how VWF is connected to the haemostatic system, particularly with regard to structure-function relationships. Interactive sites for important ligands of VWF (such as factor VIII, collagen, glycoprotein Ibα, integrin αIIbβ3 and protease ADAMTS13) have been identified, and mutagenesis studies have confirmed the physiological relevance of the interactions between VWF and these ligands. However, we have also become aware that VWF has a more versatile character than previously thought, given its potential role in various non-hemostatic processes, like intimal thickening, tumor cell apoptosis and inflammatory processes. In the presence review, a summary of our knowledge on VWF structure-function relationships is provided in the context of the “classical” haemostatic task of VWF and in perspective of pathological processes beyond haemostasis.

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Big piece, little piece or: Yes, factor VIII is a protein

Cited by 5 publications

References 26 publications

Historical perspective and future directions in platelet research

Historical perspective and future directions in platelet research

Unraveling the mystery of von Willebrand factor

On the Versatility of Von Willebrand Factor

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