Genetische Thrombosedisposition:

Zusammenfassung

Mit der Beschreibung der Faktor-V-Mutation (Typ Leiden), die sich phänotypisch in einer APC-Resistenz zeigt, konnte erstmals bei zahlreichen betroffenen Thrombosepatienten eine identische Punktmutation identifiziert werden. Dies steht im Gegensatz zu den hereditären Defekten bei anderen Gerinnungsfaktoren oder -inhibitoren, die in nahezu jeder betroffenen Familie unterschiedlich gefunden werden. Dementsprechend zeigt sich eine deutliche Heterogenität, die sich phänotypisch sowohl in den Laborwerten als auch in der klinischen Ausprägung widerspiegelt. Neben der Faktor-V-Leiden-Mutation sind erworbene Ursachen einer APC-Resistenz in der Diskussion. Es konnte gezeigt werden, daß sich angeborene und erworbene Ursachen wie Protein-C-oder -S-Mangel oder Fibrinogen-und Faktor-VllI-Erhöhung unterschiedlich stark in einer APC-Resistenz äußern. Die identische Punktmutation Faktor V Leiden wird eine schärfere Aussage zur individuellen Prognose betroffener Patienten erlauben als heterogene Defekte, da prospektive Studien mit ausreichenden Kohorten durchgeführt werden können. Insgesamt liegen viele Erkenntnisse zur Auswirkung von genetischen Veränderungen auf die Struktur und Funktion der Proteine des Hämostasesystems vor. Deren Bedeutung für den einzelnen Patienten muß unter Berücksichtigung der anamnestischen, klinischen und laborchemischen Befunde festgelegt werden.

Schlüsselwörter

Thrombophilie - APC-Resistenz - Labormethoden

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