Klinische Bedeutung und Nachweis der APC-Resistenz

Zusammenfassung

Bis zur Entdeckung und Beschreibung der Resistenz gegenüber aktiviertem Protein C (»APC-Resistenz«) durch Dahlbeck et al. 1993 (1) blieb die Ursache einer familiären thrombophilen Diathese bei einem Großteil der Patienten ungeklärt. Bei weniger als einem Viertel der Patienten mit Häufung thrombembolischer Ereignisse konnten bis dahin vererbare Defekte in den bekannten Inhibitoren der plasmatischen Gerinnung nachgewiesen werden. Heute ist die familiäre APCResistenz aufgrund einer Faktor-V-Mutation mit verminderter Inaktivierbarkeit von Faktor V durch APC mit einer Inzidenz von etwa 5% der Bevölkerung als der wichtigste thrombophile Risikofaktor in der nord- und mitteleuropäischen Bevölkerung anzusehen. Bei familiärer thrombophiler Diathese zeigen bis zu 40% der Patienten diese Störung. Im Gegensatz zur initial von Dahlbeck beschriebenen funktionellen Methodik lassen sich mit modernen, einfach und schnell durchführbaren Gerinnungstesten zuverlässige Aussagen über das Vorliegen der Faktor-V-Punktmutation sowie den heterozygoten oder homozygoten Merkmalträgerstatus machen. Die Erkennung zusätzlicher hereditärer oder erworbener Risikofaktoren und ihrer Gewichtung tragen dazu bei, die Strategie einer primären oder sekundären Thromboseprophylaxe festzulegen.

Summary

Less than twenty-five percent of cases with recurrent thrombotic episodes had been identified to be associated with inherited defects of hemostasis, before Dahlbeck et al. described the congenital resistance towards activated protein C in 1993. With an incidence of about 5% of the population, APC-resistance caused by the Factor V Leiden Mutation is the most important hereditary thrombophilic risc factor in Europe. Of all patients with a familiar trace of thrombophilic tendency, up to 40% are carriers of this defect. In addition to molecular methods and in contrast to the original functional method described by Dahlbeck, nowadays, simple tests allow fast and reliable detection of heterocygous or homocygous mutations of Factor V Leiden. Screening for additional hereditary or acquired thrombophilic risc factors seems to be important for the estimation of an individual patient´s risk and for the establishment of a strategy of primary or secondary antithrombotic prophylaxis in a patient.

Résumé

Jusqu‘à la découverte et la description de la résistance vis-à-vis de la protéine C activée («résistance PCA») par Dahlbeck et al. en 1993, la cause d‘une diathèse thrombophile familiale était non élucidée chez de nombreux patients. Chez moins d‘un quart des patients accumulant des événements thromboemboliques, jusque-là les défauts se transmettant héréditairement pouvaient être décelés dans les inhibiteurs connus de la coagulation plasmatique. En raison d‘une mutation du facteur V accompagnée d‘une diminution de l‘inactivation du facteur V par PCA, la résistance PCA familiale est aujourd‘hui considérée comme le facteur de risque thrombophile le plus important au sein de la population de l‘Europe du Nord et de l‘Europe centrale avec une incidence d‘environ 5%. Dans le cas d‘une diathèse thrombophile familiale, 40% des patients au maximum présentent ce trouble. Contrairement à la méthode fonctionnelle décrite initialement par Dahl-beck, des tests de coagulation modernes d‘application simple et rapide donnent des résultats fiables quant à la présence de la mutation ponctuelle du facteur V et au statut du porteur de caractères hétérozygote ou homozygote. L‘idendité de facteurs de risque supplémentaires héréditaires ou acquis et leur évaluation contribuent à fixer la stratégie d‘une prophylaxie des thromboses primaire ou secondaire.

Schlüsselwörter

APC-Resistenz - Faktor-V-Leiden-Mutation - Thrombophilie

Keywords

APC-resistance - factor V Leiden mutation - thrombophilia

Mots clés

Résistance PCA - mutation du facteur V de Leiden - thrombophilie

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