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Venous thrombosis

Abstract

Venous thromboembolism (VTE) encompasses deep-vein thrombosis (DVT) and pulmonary embolism. VTE is the leading cause of lost disability-adjusted life years and the third leading cause of cardiovascular death in the world. DVT leads to post-thrombotic syndrome, whereas pulmonary embolism can cause chronic pulmonary hypertension, both of which reduce quality of life. Genetic and acquired risk factors for thrombosis include non-O blood groups, factor V Leiden mutation, oral contraceptive use, hormone replacement therapy, advanced age, surgery, hospitalization and long-haul travel. A combination of blood stasis, plasma hypercoagulability and endothelial dysfunction is thought to trigger thrombosis, which starts most often in the valve pockets of large veins. Animal studies have revealed pathogenic roles for leukocytes, platelets, tissue factor-positive microvesicles, neutrophil extracellular traps and factors XI and XII. Diagnosis of VTE requires testing and exclusion of other pathologies, and typically involves laboratory measures (such as D-dimer) and diagnostic imaging. VTE is treated with anticoagulants and occasionally with thrombolytics to prevent thrombus extension and to reduce thrombus size. Anticoagulants are also used to reduce recurrence. New therapies with improved safety profiles are needed to prevent and treat venous thrombosis. For an illustrated summary of this Primer, visit: http://go.nature.com/8ZyCuY

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Figure 1: Mechanisms that protect from or promote thrombogenesis.
Figure 2: The coagulation cascade and existing and emerging anticoagulant drugs.
Figure 3: Clinical presentation of deep-vein thrombosis.
Figure 4: Management algorithm for suspected venous thromboembolism.
Figure 5: Diagnostic signs of venous thromboembolism.
Figure 6: Anticoagulation regimens.
Figure 7: Long-term consequences of venous thromboembolism.

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Acknowledgements

The authors thank T. Wakefield, P. Henke, D. Myers and R. Kasthuri for reading the manuscript, and A. Conrad for assistance with Figure 1.

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Contributions

Introduction (N.M. and A.S.W); Epidemiology (F.R.R.); Mechanisms/pathophysiology (N.M. and A.S.W.); Diagnosis, screening and prevention (I.H.J. and J.I.W.); Management (G.A.); Quality of life (T.B.); Outlook (N.M. and A.S.W.); and overview of the Primer (N.M.).

Corresponding authors

Correspondence to Alisa S. Wolberg or Nigel Mackman.

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Competing interests

G.A. has received personal fees from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, Sanofi, Pfizer and Bristol–Myers Squibb; all are outside the scope of the submitted work. T.B. has received honoraria for participating in scientific advisory boards for Boehringer Ingelheim and Daiichi Sankyo, and has received an unconditional travel grant from Boehringer Ingelheim. N.M. served as consultant to Merck and Bayer. F.R.R. is listed on several patents for prothrombotic gene variants. J.I.W. served as a consultant to and received honoraria from Boehringer Ingelheim, Bristol–Myers Squibb, Pfizer, Johnson & Johnson, Daiichi Sankyo, ISIS Pharmaceuticals and Portola. A.S.W. served as a consultant to Merck. I.H.J. has no competing financial interests to report.

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Wolberg, A., Rosendaal, F., Weitz, J. et al. Venous thrombosis. Nat Rev Dis Primers 1, 15006 (2015). https://doi.org/10.1038/nrdp.2015.6

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