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Monogenetische Risikofaktoren einer Thrombophilie

Monogenetic thrombophilic risk factors

Zusammenfassung

Die hereditären Thrombophilien gehören zu den angeborenen Prädispositionen, die thrombotische Ereignisse begünstigen. Die wichtigsten monogenetischen Ursachen für einen venös-thromboembolischen (VTE) Phänotyp stellen Mutationen innerhalb der Gene für die Inhibitoren Antithrombin (AT), Protein C (PC) und Protein S (PS) dar. Die Mutationsprofile in diesen Genen sind sehr unterschiedlich. Die Frequenz von AT-, PC- und PS-Mängeln wird bei VTE-Patienten jeweils mit 1,9%, 2,3% und 3,7% angegeben. Die VTE-Rezidivrate liegt in dieser Gruppe bei etwa 48%. Sie ist für AT-, PC- und PS-Mängel zusammengefasst 1,5-fach, für den AT-Mangel isoliert betrachtet 1,9-fach höher als bei VTE-Patienten ohne einen dieser Mängel. Die Detektionsrate bei einem Inhibitormangel und VTE-Ereignis liegt bei etwa 70% für AT, bei 60% für PC und bei 30% für PS. Dies unterstreicht das Problem der unterschiedlichen Sicherheit der Diagnose der Phänotypen und der damit zusammenhängenden differentialdiagnostischen Abgrenzung zwischen erworbenem und angeborenem Inhibitormangel.

Abstract

Inherited thrombophilias are a group of hereditary conditions that predispose to thrombotic events. The most important monogenetic causes of the venous thromboembolic (VTE) phenotype are mutations in the genes for the coagulation inhibitors antithrombin (AT), protein C (PC), and protein S (PS). Their mutation profiles show high heterogeneity in loss-of-function defects. The frequencies of AT, PC, and PS deficiencies in VTE patients are estimated at 1.9%, 2.3%, 3.7%, respectively. The rate of recurrence in that group is 48.4%. The composite risk of recurrence for VTE patients with AT, PC or PS deficiency is estimated at 1.5 times that for VTE patients without inhibitor deficiency, for those with AT deficiency alone up to 1.9 times. The detection rates for inhibitor deficiency and symptomatic VTE are about 70% for AT, 60% for PC, and 30% for PS. These results demonstrate the problems with the varying accuracy of phenotype diagnostics and differential diagnosis of inherited and intrinsic inhibitor deficiencies.

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Abbreviations

APC:

aktiviertes Protein C

Ala:

Alanin

Arg:

Arginin

AT:

Antithrombin

CpG:

Cytosin-phosphatidyl-Guanosin

C4b-BP:

C4b-bindendes Protein

DNA:

Desoxyribonukleinsäure (-acid)

ELISA:

„enyme-linked immuno sorbent assay“

FVa:

Gerinnungsfaktor Va

FVIIIa:

Gerinnungsfaktor VIIIa

FXa:

Gerinnungsfaktor Xa

Gln:

Glutamin

Gly:

Glycin

HBS:

Heparinbindungsstelle

HWZ:

Halbwertszeit

Leu:

Leukin

MW:

Molekulargewicht

PC:

Protein C

Pro:

Prolin

PROS1:

Protein-S-Gen 1

PROS2:

Protein-S-Gen 2 (Pseudogen)

PS:

Protein S

RS:

reaktive Seite

Ser:

Serin

TM:

Thrombomodulin

VTE:

venöse Thromboembolie

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Correspondence to A. Pavlova.

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Pavlova, A., Hertfelder, HJ. Monogenetische Risikofaktoren einer Thrombophilie. medgen 20, 211–217 (2008). https://doi.org/10.1007/s11825-008-0097-8

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Schlüsselwörter

  • Venöse Thrombose
  • Thromboembolie
  • Antithrombin
  • Protein C
  • Protein S

Keywords

  • Venous thrombosis
  • Thromboembolism
  • Antithrombin
  • Protein C
  • Protein S