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Plasma Factor VIII Levels as a Biomarker for Venous Thromboembolism

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Abstract

Venous thromboembolism (VTE) is a multicausal disease. Multiple genetic, acquired, and environmental factors contribute to the development of the disease, and most of these factors are related to changes in flow and composition of the blood, leading to a hypercoagulable state. Increasing data support the hypothesis that high levels of factor VIII (FVIII) in plasma may play a role in hypercoagulability. An association between increased plasma FVIII levels and VTE was first described in the Leiden Thrombophilia Study. Subsequently, these findings have been supported by several independent case-control studies. Cumulatively, these studies have clearly demonstrated that high FVIII levels constitute a prevalent, independent, and dose-dependent risk factor for the first episode of VTE. Furthermore, subsequent studies have shown that the risk of a recurrent episode is also significantly increased in patients with high FVIII levels. However, the molecular basis of high plasma FVIII levels is incompletely known. In this chapter, we discuss the biological mechanisms that may underlie persistently elevated FVIII levels and the pathways through which high FVIII may increase the thrombotic risk. In addition, we present and review evidences supporting the hypothesis that elevated plasma FVIII levels constitute an important biomarker for VTE risk.

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Abbreviations

APTT:

Activated partial thromboplastin time

Ca2+ :

Calcium

CHARGE:

Cohorts for Heart and Aging Research in Genomic Epidemiology

CRP:

C-reactive protein

DVT:

Deep venous thrombosis

ESR:

Erythrocyte sedimentation rate

FII:

Prothrombin

FIIa:

Thrombin

FIX:

Factor IX

FV:

Factor V

FVII:

Factor VII

FVIII:

Factor VIII

FX:

Factor X

FXI:

Factor XI

FXII:

Factor XII

LETS:

The Leiden Thrombophilia Study

LRP1:

Low-density lipoprotein receptor-related protein 1

mRNA:

Messenger ribonucleic acid

NE:

Not evaluated

PE:

Pulmonary embolism

PTS:

Post-thrombotic syndrome

TF:

Tissue factor

VTE:

Venous thromboembolism

VWF:

von Willebrand factor

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Authors and Affiliations

  1. Hematology and Hemotherapy Center, University of Campinas, Campinas, São Paulo, Brazil

    Luis F. Bittar, Erich V. De Paula, Aline Barnabé, Bruna M. Mazetto, Kiara C. S. Zapponi, Silmara A. L. Montalvão, Marina P. Colella & Joyce M. Annichino-Bizzacchi

  2. Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

    Fernanda A. Orsi

Authors
  1. Luis F. Bittar
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  2. Erich V. De Paula
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  3. Aline Barnabé
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  4. Bruna M. Mazetto
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  5. Kiara C. S. Zapponi
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  6. Silmara A. L. Montalvão
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  7. Marina P. Colella
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  8. Fernanda A. Orsi
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  9. Joyce M. Annichino-Bizzacchi
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Corresponding author

Correspondence to Luis F. Bittar .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Sciences Division, King's College, London, United Kingdom

    Victor R. Preedy

Definitions

Acute phase response

It is a response of the body to a tissue injury.

Coagulation cascade

It is a complex sequence of chemical reactions resulting in the formation of a fibrin clot.

Deep venous thrombosis

It is a condition in which blood clot forms in one or more deep veins of the body, mainly in legs.

Factor VIII

It is a key protein for the coagulation cascade.

Post-thrombotic syndrome

It is a common and chronic complication of deep venous thrombosis of the legs.

Pulmonary embolism

It is a condition in which blood clot forms in a pulmonary vein.

Recurrent thrombosis

It is novel episodes of thrombosis after an initial thrombotic event.

Thrombophilia

It is the tendency to develop thrombosis blood clots due to an abnormality in the coagulation system.

Tissue factor

It is the trigger for the coagulation cascade.

Venous thromboembolism

It is a condition in which a blood clot forms in one or more veins and comprises deep venous thrombosis (DVT) and pulmonary embolism (PE).

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Bittar, L.F. et al. (2015). Plasma Factor VIII Levels as a Biomarker for Venous Thromboembolism. In: Patel, V., Preedy, V. (eds) Biomarkers in Cardiovascular Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7741-5_22-1

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