Genetics in thrombophilia

P. H. Reitsma

doi:10.5482/HAMO-14-11-0062

Hämostaseologie, Table of Contents

Hamostaseologie 2015; 35(01): 47-51
DOI: 10.5482/HAMO-14-11-0062

Review

Schattauer GmbH

Genetics in thrombophilia

An updateGenetik der ThrombophilieEin Update

Authors

P. H. Reitsma

¹Department of Thrombosis and Haemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

Abstract

Summary

Venous thromboembolism (VTE) poses a worldwide health burden affecting millions of people each year. The annual incidence of symptomatic VTE, the collective term used here for deep venous thrombosis, pulmonary embolism or both, is 2–3 per thousand inhabitants. The one-year mortality is 20% after a first VTE. Of the surviving patients 15–25% will experience a recurrent episode of VTE in the three years after the first event. Primary and secondary prevention is key to reducing death and disability from VTE. How to make use of our current knowledge of inherited risk of VTE for primary and secondary disease prevention is not straightforward. This despite the fact that in the past two or three decades we have made major strides in enlarging our understanding of inherited VTE risk, and that new inherited risk factors continue to be identified.

For primary prevention of VTE genetic testing is not likely to play a role in the future. Genetic variations also determine recurrence risk, albeit that the effect sizes for individual genetic variations are invariably lower than those for first VTE events. Multilocus genetic risk scores improve risk classification, and it is now possible to stratify patients who have had a first venous thrombosis, into subgroups with a high and low risk of recurrence. Whether this approach can be used to tailor intensity and duration of treatment remains to be established.

Zusammenfassung

Venöse Thromboembolien (VTE) stellen weltweit eine gesundheitliche Belastung für Millionen Menschen dar. Die jährliche Inzidenz symptomatischer VTE, ein Sammelbegriff für tiefe Venenthrombosen, Lungenembolien oder beides, beträgt 2–3 je 1000 Einwohner. Die Ein-Jahres-Mortalität liegt bei 20% nach einer ersten VTE. Bei 15–25% der Überlebenden tritt innerhalb von drei Jahren nach dem ersten Ereignis eine VTE-Rezidivepisode auf. Primär- und Sekundärprophylaxe haben zentrale Bedeutung für die Reduktion der Mortalität und Behinderung durch VTE. Unser aktuelles Wissen zu angeborene VTE-Risiken kann nicht direkt für die Primärund Sekundärprophylaxe genutzt werden, obgleich wir diesen in den vergangenen zwei oder drei Jahrzehnten viel besser verstanden haben und ständig neue erbliche Risikofaktoren identifiziert werden. Für die VTE-Primärprophylaxe werden Gentests künftig vermutlich keine Rolle spielen. Genvariationen bestimmen das Rezidivrisiko, wenn auch die Effektgrößen bei individuellen Varianten grundsätzlich geringer sind als für erstmalige VTE-Ereignisse. Genetische Multilokus-Risiko-Scores verbessern die Klassifizierung und es ist möglich, Patienten nach der ersten Venenthrombose in Subgruppen mit hohem und niedrigem Rezidivrisiko zu stratifizieren. Ob dies dazu dienen kann, Intensität und Dauer der Behandlung zu individualisieren, ist noch zu klären.

Keywords

Venous thrombosis - thrombophilia - genetics - mutations

Schlüsselwörter

Venenthrombose - Thrombophilie - Genetik - Mutationen

Full Text

References

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