Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2013, vol. 22, nr 4, July-August, p. 459–467

Publication type: editorial article

Language: English

Protein C and Protein S Deficiency – Practical Diagnostic Issues

Niedobór białka C i białka S – praktyczne problemy diagnostyczne

Ewa Wypasek1,2,A,B,C,D, Anetta Undas1,2,A,C,E,F

1 The John Paul II Hospital, Kraków, Poland

2 Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland

Streszczenie

Białko C (protein C, PC) i białko S (protein S, PS) to zależne od witaminy K glikoproteiny będące naturalnymi inhibitorami krzepnięcia krwi. Proteolityczna aktywacja PC przez trombinę zachodzi na powierzchni komórek śródbłonka w obecności trombomoduliny i śródbłonkowego receptora PC. Aktywne PC (APC) z udziałem kofaktora, którym jest PS, w obecności fosfolipidów i wapnia, degraduje czynnik Va i FVIIIa przez ich cięcie w specyficznych resztach argininowych. Niedobory PC i PS są podłożem występowania i nawrotów żylnej choroby zakrzepowozatorowej (ż.ch.z.z.). Niedobory PC/PS są dziedziczone w sposób autosomalny dominujący i w większości przypadków pochodzą z heterozygotycznych mutacji typu zmiany sensu (odpowiednio: 78 i 63%). Heterozygotyczny niedobór PC występuje u 6% rodzin z trombofilią, u 3% pacjentów, z pierwszym epizodem zakrzepicy żył głębokich oraz u 0,2–0,3% osób zdrowych. Niedobór PS pojawia się częściej niż niedobór PC, a jego występowanie szacuje się na mniej niż 0,5% w zdrowej populacji europejskiej i 2–12% u pacjentów z zakrzepicą. U około 75% pacjentów z niedoborem PC występuje niedobór typu I, a u 95% pacjentów z niedoborem PS rozwija się typ I i typ III niedoboru. Diagnostyka niedoborów PC i PS jest trudna ze względu na występowanie wielu czynników fazy przedi analitycznej wpływających na stężenia PC i PS. Analiza molekularna genów PC i PS (odpowiednio: PROC i PROS1) obejmuje ich bezpośrednie sekwencjonowanie genów, a w przypadku wyniku negatywnego stosuje się metodę multipleksowej amplifikacji sondy zależnej od ligacji (multiplex ligation-dependent probe amplification, MLPA). Pacjenci z małymi stężeniami PC i PS oraz mutacją w genach PROC lub PROS1 w połączeniu z innymi genetycznymi i środowiskowymi czynnikami sprzyjającymi zakrzepicy są narażeni na zwiększone ryzyko nawracających epizodów zakrzepowo-zatorowych, co jest wskazaniem do stosowania przewlekłej antykoagulacji.

Key words

protein C, protein S, deficiency, venous thromboembolism, mutation.

Słowa kluczowe

białko C, białko S, niedobór, zakrzepica żylna, mutacja.

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