{"id":958,"date":"2020-02-29T13:11:40","date_gmt":"2020-02-29T10:11:40","guid":{"rendered":"https:\/\/tatd.org.tr\/tatdtoks\/2021\/09\/17\/yaslilarda-af-tedavisinde-kullanilan-antikoagulanlarin-kirik-riski-doak-vs-varfarin\/"},"modified":"2021-11-10T22:35:23","modified_gmt":"2021-11-10T19:35:23","slug":"yaslilarda-af-tedavisinde-kullanilan-antikoagulanlarin-kirik-riski-doak-vs-varfarin","status":"publish","type":"post","link":"https:\/\/tatd.org.tr\/toksikoloji\/2020\/02\/29\/yaslilarda-af-tedavisinde-kullanilan-antikoagulanlarin-kirik-riski-doak-vs-varfarin\/","title":{"rendered":"Ya\u015fl\u0131larda AF Tedavisinde Kullan\u0131lan Antikoag\u00fclanlar\u0131n K\u0131r\u0131k Riski: DOAK vs. Varfarin"},"content":{"rendered":"

<\/h3>\n

G\u00fcn\u00fcm\u00fczde bir\u00e7ok g\u00fcncel k\u0131lavuz; ya\u015fl\u0131 hastalarda, Atrial Fibrillasyon (AF) gibi s\u0131k g\u00f6zlenen klinik durumlarda, kronik antikoagulan kullan\u0131m\u0131n\u0131 \u00f6nermektedir. Antikoag\u00fclan tedavinin esas hedefi iskemik serebrovask\u00fcler olaylar\u0131n engellenmesidir. Tedavisi zor ve maliyetli olan bu hastal\u0131k; gerek hasta gerekse hasta yak\u0131nlar\u0131 i\u00e7in a\u011f\u0131r sonu\u00e7lar yaratabilmektedir. T\u00fcm d\u00fcnyada klinisyenler taraf\u0131ndan kullan\u0131lan bir\u00e7ok ruhsatl\u0131 antikoagulasyon ila\u00e7lar\u0131 aras\u0131nda Varfarin; yan etkileri, en hayati ve en s\u0131k olan\u0131d\u0131r. Varfarin kullanan hastalarda kanama riski oldu\u011fu ak\u0131lda tutulmal\u0131d\u0131r. Bu kanamalar; asemptomatik kanamalar olabilece\u011fi gibi, hayat\u0131 tehdit edici kanamalar da olabilir. Bu sebeple, p\u0131ht\u0131la\u015fma parametrelerinin yak\u0131n takibi gerekmektedir.<\/p>\n

Yeni geli\u015ftirilen ve \u201cnon-vitamin K antagonisti Oral Antikoagulanlar\u201d veya \u201cDirekt Oral Antikoagulan\u201d (DOAK<\/strong>) olarak bilinen grup ise daha az yan etkiye sahip olduklar\u0131n\u0131 kabul etti\u011fimiz ila\u00e7lard\u0131r. \u00a0Yap\u0131lan klinik \u00e7al\u0131\u015fmalarda; DOAK\u2019lar\u0131n, \u00a0serebrovaskuler iskemik olaylar\u0131 \u00f6nlemede en az Varfarin kadar etkili oldu\u011fu kan\u0131tlanm\u0131\u015ft\u0131r. Daha az yan etkiye sahip olan DOAK\u2019lar yayg\u0131n olarak kullan\u0131lmaya ba\u015flanm\u0131\u015ft\u0131r.<\/p>\n

Oral antikoagulanlar\u0131n kanama riskini art\u0131rd\u0131\u011f\u0131n\u0131 hepimiz biliyoruz. Bu ila\u00e7lar\u0131n ba\u015fka \u00f6nemli yan etkileri aras\u0131nda; osteoporoz ve sonras\u0131nda geli\u015fen patolojik k\u0131r\u0131klar say\u0131labilir. Literat\u00fcrde; oral antikoagulan kullan\u0131m\u0131n\u0131n k\u0131r\u0131k riskini artt\u0131\u011f\u0131n\u0131 g\u00f6steren bir\u00e7ok \u00e7al\u0131\u015fma bulunmaktad\u0131r. Gage ve ark. (1), ulusal verileri tarayarak ger\u00e7ekle\u015ftirdikleri \u00e7al\u0131\u015fmada, AF nedeniyle Varfarin alan hastalarda osteoporoz riskinin artt\u0131\u011f\u0131n\u0131 belirtmi\u015flerdir. Yine ba\u015fka 2 \u00e7al\u0131\u015fmada; Rejnmark (2) ve Sugiyama (3), oral antikoagulan kullan\u0131m\u0131n\u0131n k\u0131r\u0131k riskini art\u0131rd\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015flerdir.<\/p>\n

Osteoporoz; ya\u015fl\u0131 hastalarda s\u0131k kar\u015f\u0131la\u015f\u0131lan komorbiditelerden birisidir. Osteoporoz; hem k\u0131r\u0131klara yola a\u00e7arak immobiliteye neden oldu\u011fu i\u00e7in, hem de sosyoekonomik bir y\u00fck yaratt\u0131\u011f\u0131 i\u00e7in, \u00f6nemli bir sa\u011fl\u0131k sorunudur. AF nedeniyle Varfarin kullanan ya\u015fl\u0131 hastalarda, osteoporoz ve k\u0131r\u0131k riskinin artt\u0131\u011f\u0131, literat\u00fcrde belirtilmi\u015ftir. Yeni ku\u015fak antikoagulanlar hakk\u0131nda hem iyi hem k\u00f6t\u00fc farkl\u0131 bulgular ve g\u00f6zlemler yay\u0131nlanm\u0131\u015ft\u0131r. DOAKlar ilk kez kullan\u0131ma sunuldu\u011fu zamandan beri g\u00fcvenilir ve yan etkileri az ila\u00e7lar olarak varfarin ile k\u0131yaslanmaktad\u0131rlar. Yap\u0131lan son ulusal kohort \u00e7al\u0131\u015fmalarda rutin klinik uygulamadan gelen veriler analiz edilmi\u015ftir.<\/p>\n

Antikoag\u00fclanlar\u0131n hangi mekanizma ile k\u0131r\u0131k olu\u015fumuna katk\u0131da bulunduklar\u0131 halen tam olarak a\u00e7\u0131klanamam\u0131\u015ft\u0131r. Sugiyama; bu yan etkiyi, Varfarinin kemik formasyonunu bozmas\u0131 olarak tan\u0131mlam\u0131\u015ft\u0131r. Kemikte nonkollajen proteinler aras\u0131nda en fazla olan\u0131 Osteokalsin\u2019<\/em>dir. Kemik sertli\u011fine katk\u0131da bulunan Osteokalsin<\/em>, tutunmak i\u00e7in vitamin K- ba\u011f\u0131ml\u0131 \u03b3-karboksilasyona ihtiya\u00e7 duyar (\u015eekil 1)<\/strong>. V<\/em>itamin K antagonisti olan Varfarin; bu enzimatik s\u00fcreci bozar, kemikteki osteokalsin miktar\u0131n\u0131 azalt\u0131r, kemik sertli\u011fini bozar. <\/em>Ya\u015fl\u0131 hastalarda kronik olarak vitamin K antagonisti al\u0131nd\u0131\u011f\u0131 zaman dola\u015f\u0131mdaki osteokalsin proteinleri normalden az karboksillenmi\u015f olarak saptan\u0131r.<\/p>\n

\"\"<\/p>\n

\u015eekil 1.<\/strong> \u03b3-Karboksiglutamik asid (Gla)<\/strong> amino asidler i\u00e7inde \u00f6zel olarak, vitamin- K ba\u011f\u0131ml\u0131 Gla i\u00e7eren proteinlerden modifikasyonlar ile olu\u015fturulur. Osteokalsin Gla i\u00e7eren proteinlerden biridir; ancak Varfarin kullanan hastalarda vitamin K antagonizmas\u0131 y\u00fcz\u00fcnden bu \u00f6nemli reaksiyon bask\u0131lan\u0131r (4).<\/p>\n

En son European Heart Journal\u2019 da Aral\u0131k 2019\u2019 da yay\u0131nlanan, Huang ve arkada\u015flar\u0131n\u0131n ger\u00e7ekle\u015ftirdi\u011fi, ulusal veri tabanlar\u0131n\u0131n incelendi\u011fi bir \u00e7al\u0131\u015fmada, oral antikoagulanlar\u0131n yan etkileri b\u00fcy\u00fck bir kohortta kar\u015f\u0131la\u015ft\u0131r\u0131lm\u0131\u015f (5). Toplamda 28776 hastan\u0131n verilerinin incelendi\u011fi ara\u015ft\u0131rmada; Varfarin ve DOAK\u2019lar\u0131n k\u0131r\u0131k riskine etkileri k\u0131yaslanm\u0131\u015ft\u0131r. K<\/em>al\u00e7a, vertebra, humerus, \u00f6nkol veya bilek kemiklerinde k\u0131r\u0131k riski DOAK\u2019larda, varfarine k\u0131yasla, daha d\u00fc\u015f\u00fck tespit edilmi\u015ftir. <\/em>Bu \u00e7al\u0131\u015fmada konu olan DOAK\u2019lar; dabigatran, rivaroxaban ve apixaban\u2019 d\u0131r.<\/p>\n

DOAK\u2019lar, Varfarin\u2019 in aksine, K vitamininden ba\u011f\u0131ms\u0131z etki ederler ve bu sebeple kemikte osteokalsin tutulmas\u0131n\u0131 bozmazlar. Preklinik \u00e7a\u0131l\u015fmalarda DOAK\u2019lar\u0131n kemik \u00fczerindeki etkileri daha net g\u00f6zlenmi\u015ftir. Dabigatran ile tedavi edilen s\u0131\u00e7anlarda, Varfarin ile tedavi edilenlerle kar\u015f\u0131l\u0131\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, daha fazla kemik hacmi, daha az trabek\u00fcler seperasyon ve daha d\u00fc\u015f\u00fck miktarda kemik y\u0131k\u0131m\u0131 g\u00f6zlenmi\u015ftir. Yine rivaroxaban ile yap\u0131lan bir \u00e7al\u0131\u015fmada femur k\u0131r\u0131\u011f\u0131 olan s\u0131\u00e7anlarda iyile\u015fmenin kontrol grubundan daha iyi oldu\u011fu g\u00f6sterilmi\u015ftir. \u0130nsanlarda yap\u0131lan \u00e7al\u0131\u015fmalar ise; dabigatran ve rivaroxaban tedavilerinin, Varfarin ile k\u0131yasland\u0131\u011f\u0131 zaman, s\u0131ras\u0131yla %12 ve %19 oranlar\u0131nda daha az k\u0131r\u0131k riski olu\u015fturdu\u011funu g\u00f6stermi\u015ftir.<\/em><\/p>\n

\"\"<\/p>\n

\u015eekil 2<\/strong>. Yukar\u0131daki \u015fekilde AF nedeniyle kullan\u0131lan Varfarin ve DOAKlar\u0131n k\u0131r\u0131k insidanslar\u0131n\u0131n kar\u015f\u0131la\u015ft\u0131r\u0131lmas\u0131 g\u00f6steriliyor. Bu e\u011frilerin mavi olanlar\u0131 Varfarin sonucu geli\u015fen kemik k\u0131r\u0131k insidans\u0131n\u0131, k\u0131rm\u0131z\u0131 olanlar ise DOAK\u2019lar\u0131n kemik k\u0131r\u0131\u011f\u0131 insidans\u0131n\u0131 k\u00fcm\u00fclatif olarak g\u00f6steriyor. Bu \u015fekillerde frakt\u00fcrlerin k\u00fcm\u00fclatif insidanslar\u0131 s\u0131ras\u0131yla (A)<\/strong> non-vitamin K antagonist oral antikoagulanlar ile Varfarin, (B)<\/strong> dabigatran ile varfarin, (C)<\/strong> rivaroxaban ile varfarin, (D<\/strong>) apixaban ile varfarin k\u0131yaslanarak g\u00f6sterilmi\u015ftir. Toplamda 28776 hasta; 16110 DOAK kohortunda ve 12666 hasta varfarin kohortundad\u0131r.<\/p>\n

\"\"<\/p>\n

\u015eekil 3<\/strong>. DOAK alan hastalarda varfarin alanlara k\u0131yasla ya\u015f ve cinsiyete g\u00f6re katmanlanm\u0131\u015f k\u0131r\u0131k olu\u015fturma riskleri. aHR; d\u00fczeltilmi\u015f hazard ratio.\u00a0 CI; g\u00fcven aral\u0131\u011f\u0131. T\u00fcm gruplarda varfarin referans grup al\u0131narak hesaplama yap\u0131lm\u0131\u015ft\u0131r. Makalenin tamam\u0131nda k\u0131r\u0131klar\u0131n alt grup analizleri de mevcut.<\/p>\n

Sonu\u00e7 olarak;<\/h2>\n
    \n
  1. Varfarin tedavisinin en \u00f6nemli yan etkisi kontrols\u00fcz kanamad\u0131r. Varfarinin patolojik kemik k\u0131r\u0131klar\u0131na katk\u0131 sa\u011flad\u0131\u011f\u0131 da hat\u0131rlanmal\u0131d\u0131r. \u00dcstelik bu hastalar a\u015f\u0131r\u0131 fiziksel aktivitede bulunan hastalar da de\u011fillerdir. Varfarin kullanan ve dolay\u0131s\u0131yla kanama riski olan hastalar kendilerini travmadan sak\u0131nmaktad\u0131rlar.<\/li>\n
  2. AF tedavisi alacak ya\u015fl\u0131 hastalarda, hem kanama hem de k\u0131r\u0131k riski a\u00e7\u0131s\u0131ndan DOAKlar, Varfarinle kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, daha emniyetli tercihlerdir. Farkl\u0131 kaynaklarda, DOAK\u2019lar\u0131n sebep oldu\u011fu kemik k\u0131r\u0131\u011f\u0131 riskinin, Varfarine g\u00f6re, ortalama %20 daha az oldu\u011fu belirtilmekte.<\/li>\n
  3. Ya\u015fl\u0131larda AF tedavisinin bir yan etkisi olarak geli\u015fen k\u0131r\u0131klar, acil opere edilmesi gereken k\u0131r\u0131klar oldu\u011fu zaman, kullan\u0131lan antikoag\u00fclan tercihi morbiditeyi ve mortaliteyi etkilemektedir. Varfarin tercih edilen hastalarda preoperatif \u00a0kanama komplikasyonlar\u0131 daha ciddi seyretmekte ve hasta stabilizasyonu daha zor olmaktad\u0131r.<\/li>\n<\/ol>\n

    Gelecekte DOAK tedavisi yayg\u0131nla\u015ft\u0131k\u00e7a yan etkiler anlam\u0131nda hastalar\u0131n daha konforlu olaca\u011f\u0131 net g\u00f6r\u00fcn\u00fcyor.<\/em><\/strong><\/p>\n

    KAYNAKLAR<\/h2>\n
      \n
    1. Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF. Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2. Arch Intern Med 2006;166:241\u2013246.<\/li>\n
    2. \u00a0Rejnmark L, Vestergaard P, Mosekilde L. Fracture risk in users of oral anticoagulants: a nationwide case-control study. Int J Cardiol 2007;118:338\u2013344.<\/li>\n
    3. Sugiyama T, Kugimiya F, Kono S, Kim YT, Oda H. Warfarin use and fracture risk: an evidence-based mechanistic insight. Osteoporos Int 2015;26:1231\u20131232.<\/li>\n
    4. Booth, S., Centi, A., Smith, S.\u00a0et al.<\/em>\u00a0The role of osteocalcin in human glucose metabolism: marker or mediator?.\u00a0Nat Rev Endocrinol<\/em>\u00a09,\u00a0<\/strong>43\u201355 (2013). https:\/\/doi.org\/10.1038\/nrendo.2012.201<\/a><\/li>\n
    5. Huang HK, Liu PP, Hsu JY , Lin SM, Peng CCH , Wang JH , Loh CH. Fracture risks among patients with atrial fibrillation receiving different oral anticoagulants: a real-world nationwide cohort study. European Heart Journal 2020; 0: 1-9. \u00a0https:\/\/doi.org\/10.1093\/eurheartj\/ehz952<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

      G\u00fcn\u00fcm\u00fczde bir\u00e7ok g\u00fcncel k\u0131lavuz; ya\u015fl\u0131 hastalarda, Atrial Fibrillasyon (AF) gibi s\u0131k g\u00f6zlenen klinik durumlarda, kronik antikoagulan kullan\u0131m\u0131n\u0131 \u00f6nermektedir. Antikoag\u00fclan tedavinin esas hedefi…<\/p>\n","protected":false},"author":1538,"featured_media":1893,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[10014],"tags":[124,127,160,322,432],"class_list":["post-958","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-akademik-blog-yazisi","tag-direkt-oral-antikoagulan","tag-doak","tag-geriatrik-kiriklar","tag-osteoporoz","tag-varfarin"],"acf":[],"_links":{"self":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/958","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/users\/1538"}],"replies":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/comments?post=958"}],"version-history":[{"count":0,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/958\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media\/1893"}],"wp:attachment":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media?parent=958"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/categories?post=958"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/tags?post=958"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}