ингибиторы фибринолиза при лечении геморрагических
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ãÖóÖçàÖ ÉÖåéîàãàà ÄèêÖãú 2007 ‹42 ИНГИБИТОРЫ ФИБРИНОЛИЗА ПРИ ЛЕЧЕНИИ ГЕМОРРАГИЧЕСКИХ РАССТРОЙСТВ Lilian Tengborn Центр тромбоза и гемостаза, .. Больница при университете в Malmo, .. Malmo, Швеция 1 ВСЕМИРНАЯ ФЕДЕРАЦИЯ ГЕМОФИЛИИ Лечение для всех Опубликовано Всемирной Федерацией Гемофилии (ВФГ) Всемирная Федерация Гемофилии, 2007 ВФГ поощряет распространение своих публикаций для образовательных целей некоммерческими организациями, занимающимися вопросами гемофилии. Для получения разрешения на перепечатывание, распространение или перевод этой публикации, пожалуйста, обратитесь в отдел коммуникаций по адресу, прилагаемому ниже. Эта публикация доступна в интернете на сайте Всемирной Федерации Гемофилии по адресу www.wfh.org. Кроме того, можно получить копии публикаций из ВФГ по адресу: Всемирная Федерация Гемофилии 1425 René Lévesque Boulevard West, Suite 1010 Монреаль, Квебек H3G 177 КАНАДА Тел.: (514) 875-7944 Факс: (514) 875-8916 E-mail: wfh@wfh.org Интернет: www.wfh.org Цикл публикаций Лечение гемофилии нацелен на предоставление общей информации по лечению и ведению гемофилии. Всемирная Федерация Гемофилии не занимается медицинской практикой и никоим образом не даёт рекомендации по конкретному лечению отдельных больных. Идёт постоянный поиск новых схем и режимов лечения с учётом новых побочных эффектов. ВФГ не занимается представлением или рекламой препаратов и не утверждает, что дозы препаратов или рекомендации по лечению в этих публикациях являются правильными. По этим причинам строго рекомендуется, чтобы больные обращались за консультацией к медицинскому консультанту и/или к печатным инструкциям, предоставляемым фармацевтическими компаниями, прежде чем принимать какой-либо препарат, на который даётся ссылка в этой монографии. Заявления и мнения, выраженные здесь, могут не совпадать с мнением, политикой или рекомендациями Всемирной Федерации Гемофилии, её рабочей Комиссии или персонала. Редактор цикла монографий по лечению гемофилии доктор Sam Schulman 2 Содержание Введение . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Система фибринолиза . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Активация системы фибринолиза . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Ингибиторы системы фибринолиза . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Фармацевтические ингибиторы фибринолиза . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Апротинин . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 ε-аминокапроновая кислота (ЕАСА) и транексамовая кислота . . . . . . . . . . . . . . . . . . . . . . . . 6 Клиническое применение . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Гинекология . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Желудочно-кишечное кровотечение . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Носовое и ротовое кровотечение . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Стоматологическая хирургия . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Макрохирургия . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Транексамовая кислота как дополнение к рекомбинанту FVIIa . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Вывод . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Сокращения . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Использованная литература . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 4 Ингибиторы фибринолиза при лечении геморрагических расстройств Lilian Tengborn ǂ‰ÂÌË ëËÒÚÂχ ÙË·ËÌÓÎËÁ‡ èË ÔÓ‚ÂʉÂÌËË Ú͇ÌË ÔÓËÒıÓ‰ËÚ ‡Á˚‚ ÒÓÒÛ‰Ó‚, ˜ÚÓ ‚‰fiÚ Í ÌÂωÎÂÌÌÓÏÛ Á‡ÔÛÒÍÛ „ÂÏÓÒÚ‡Ú˘ÂÒÍÓ„Ó ÏÂı‡ÌËÁχ: ̇˜Ë̇ÂÚÒfl ÒÓ͇˘ÂÌË ÒÓÒÛ‰Ó‚, Ó·‡ÁÓ‚‡ÌË ÚÓÏ·ÓˆËÚ‡Ì˚ı ÔÓ·ÓÍ Ë ÍÓ‡„ÛÎflˆËfl, ‚ ÂÁÛθڇÚ ˜Â„Ó ÙÓÏËÛÂÚÒfl ÒÚ‡·Ëθ̇fl ÙË·ËÌÓ‚‡fl ÒÚÛÍÚÛ‡. é‰ÌÓ‚ÂÏÂÌÌÓ ‡ÍÚË‚ËÁËÛÂÚÒfl ÒËÒÚÂχ ÙË·ËÌÓÎËÁ‡. îË·ËÌÓÎËÁ – ˝ÚÓ ÙËÁËÓÎӄ˘ÂÒÍËÈ ÏÂı‡ÌËÁÏ, ÍÓÚÓ˚È ‡ÒÚ‚ÓflÂÚ Ò„ÛÒÚÍË, ÔÓ‰‰ÂÊË‚‡ÂÚ ÒÓÒÛ‰˚ ÓÚÍ˚Ú˚ÏË Ë ÙÓÏËÛÂÚ Á‡ÌÓ‚Ó ÔÓ‚ÂʉfiÌÌÛ˛ Ú̸͇. ëÌËÊÂÌË ÙË·ËÌÓÎËÚ˘ÂÒÍÓÈ ‡ÍÚË‚ÌÓÒÚË Á‡ Ò˜fiÚ ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ fl‚ÎflÂÚÒfl ‚‡ÊÌ˚Ï ‚ ıËÛ„ËË Ë Ú‡‚χÚÓÎÓ„ËË ‰Îfl ÒÌËÊÂÌËfl ÍÓ‚ÓÔÓÚ¸. ã˜ÂÌËÂ Ò ËÒÔÓθÁÓ‚‡ÌËÂÏ ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ ‚ ·Óθ¯ÓÈ ÒÚÂÔÂÌË ÔÓ͇Á‡ÌÓ Ô‡ˆËÂÌÚ‡Ï Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ‰Îfl Û‡‚Ìӂ¯˂‡ÌËfl ÒÌËÊÂÌÌÓ„Ó ÔÓÍÓ‡„ÛÎflÌÚÌÓ„Ó ÒÓÒÚÓflÌËfl. ÉÂÏÓ‡„˘ÂÒÍË ‡ÒÒÚÓÈÒÚ‚‡, ‡ÒÒχÚË‚‡ÂÏ˚ ‚ ˝ÚÓÈ ÏÓÌÓ„‡ÙËË, fl‚Îfl˛ÚÒfl, „·‚Ì˚Ï Ó·‡ÁÓÏ, ‚ÓʉfiÌÌ˚ÏË (̇ÔËÏÂ, ·ÓÎÂÁ̸ ÇËÎη‡Ì‰‡ [VWD], „ÂÏÓÙËÎËfl Ä Ë Ç Ë ÚÓÏ·ÓˆËڇ̇fl ‰ËÒÙÛÌ͈Ëfl). èÓÎÂÁÌÓ ‰ÂÈÒÚ‚Ë ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ ÓÒÌÓ‚˚‚‡ÂÚÒfl ̇ ··Ó‡ÚÓÌ˚ı ËÒÒΉӂ‡ÌËflı, ‰ÂÏÓÌÒÚËÛ˛˘Ëı ÙË·ËÌÓÎËÚ˘ÂÒÍÛ˛ ‡ÍÚË‚ÌÓÒÚ¸ ‚ Ô·ÁÏÂ, ÒÎËÁËÒÚÓÈ Ó·ÓÎÓ˜ÍÂ Ë ÓÔ‰ÂÎfiÌÌ˚ı Ú͇Ìflı, ‡ Ú‡ÍÊ ̇ ÍÓÌÚÓÎËÛÂÏ˚ı ‡Ì‰ÓÏËÁËÓ‚‡ÌÌÌ˚ı ËÒÒΉӂ‡ÌËflı, ÔÓ͇Á˚‚‡˛˘Ëı ÔÓÎÓÊËÚÂθÌÓ ‰ÂÈÒÚ‚Ë ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡. ÅÓθ¯ËÌÒÚ‚Ó ˝ÚËı ËÒÒΉӂ‡ÌËÈ ·˚ÎÓ Ôӂ‰ÂÌÓ Ì‡ Ô‡ˆËÂÌÚ‡ı, Ì Ëϲ˘Ëı „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚. 臈ËÂÌÚ˚ Ò ‰ÓÍÛÏÂÌڇθÌÓ ÔÓ‰Ú‚ÂʉfiÌÌ˚ÏË „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ‚ÒÚ˜‡˛ÚÒfl ÓÚÌÓÒËÚÂθÌÓ Â‰ÍÓ. èÓ˝ÚÓÏÛ ËÒÒΉӂ‡ÌËfl Á‡·Ó΂‡ÌËÈ Û ˝ÚËı Ô‡ˆËÂÌÚÓ‚ ˜‡ÒÚÓ fl‚Îfl˛ÚÒfl ̇·Î˛‰‡ÚÂθÌ˚ÏË, ÂÚÓÒÔÂÍÚË‚Ì˚ÏË Ë ‰Ó‚ÓθÌÓ Ó„‡Ì˘ÂÌÌ˚ÏË ÔÓ ÍÓ΢ÂÒÚ‚Û. åÂÚÓ‰ ΘÂÌËfl Ò ÔËÏÂÌÂÌËÂÏ ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ ‚̉fiÌ ÌÂÒÍÓθÍÓ ‰ÂÒflÚËÎÂÚËÈ Ì‡Á‡‰, Ë ‰Ó ÒËı ÔÓ ËÒÔÓθÁÛ˛ÚÒfl Ú Ê ‚¢ÂÒÚ‚‡. 벉‡ ‚ıÓ‰ËÚ ‡ÔÓÚËÌËÌ Ì‡ÚۇθÌÓ„Ó ÔÓËÒıÓʉÂÌËfl; ÔÓËÁ‚Ӊ̇fl ‡ÏËÌÓÍËÒÎÓÚÌÓ„Ó ÎËÁË̇ – ˝ÔÒËÎÓÌ-‡ÏËÌÓ͇ÔÓÌÓ‚‡fl ÍËÒÎÓÚ‡ (ÖÄëÄ); Ë ·ÓΠ˝ÙÙÂÍÚ˂̇fl Ú‡ÌÂÍÒ‡ÏÓ‚‡fl ÍËÒÎÓÚ‡ (íÄ) (ÄåëÄ). Ç ÙÓÍÛÒ ‰‡ÌÌÓÈ ÏÓÌÓ„‡ÙËË Ì‡ıÓ‰ËÚÒfl íÄ, ÍÓÚÓ‡fl ˝ÙÙÂÍÚË‚Ì ÖÄëÄ. (Ç ‰‡Î¸ÌÂȯÂÏ Ú‡ÌÂÍÒ‡ÏÓ‚‡fl ÍËÒÎÓÚ‡ ·Û‰ÂÚ ËÏÂÌÓ‚‡Ú¸Òfl ÒÓ͇˘fiÌÌÓ íÄ, ıÓÚfl ‚ ÎËÚ‡ÚÛ ËÌÓ„‰‡ ËÒÔÓθÁÛÂÚÒfl ̇Á‚‡ÌË ÄåëÄ.) ÄÔÓÚËÌËÌ ·Û‰ÂÚ ‡ÒÒÏÓÚÂÌ Í‡ÚÍÓ, Ú‡Í Í‡Í ÓÌ, ‚ ÔË̈ËÔÂ, Ì ÔËÏÂÌflÂÚÒfl ‰Îfl Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË, ÔÓ Í‡ÈÌÂÈ ÏÂÂ, ‰Îfl Ô‡ˆËÂÌÚÓ‚ Ò ÒËÒÚÂÏÌ˚ÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË. ÄÍÚË‚‡ˆËfl ÒËÒÚÂÏ˚ ÙË·ËÌÓÎËÁ‡ äβ˜Â‚ÓÈ Â‡ÍˆËÂÈ fl‚ÎflÂÚÒfl ‡ÍÚË‚‡ˆËfl ÔÓ˝ÌÁËÏ-Ô·ÁÏËÌÓ„Â̇ ‚ ÔÓÚ‡ÁÛ ÒÂË̇ – Ô·ÁÏËÌ. è·ÁÏËÌÓ„ÂÌ ˜ÂÂÁ ÎËÁËÌ-Ò‚flÁ˚‚‡˛˘Ë ۘ‡ÒÚÍË (LSB) ‚ Ú‡Í Ì‡Á˚‚‡ÂÏ˚ı kringle-ÒÚÛÍÚÛ‡ı Ó·‡ÁÛÂÚ Ò‚flÁË ÒÓ ÒÔˆËÙ˘ÂÒÍËÏ ÎËÁËÌÓÏ ‚ ÏÓÎÂÍÛ·ı ÙË·Ë̇ (1). ç‡Ë·ÓΠ‚‡ÊÌ˚Ï ÙËÁËÓÎӄ˘ÂÒÍËÏ ‡ÍÚË‚‡ÚÓÓÏ Ô·ÁÏËÌÓ„Â̇ fl‚ÎflÂÚÒfl ‡ÍÚË‚‡ÚÓ Ô·ÁÏËÌÓ„Â̇ Ú͇ÌÂ‚Ó„Ó ÚËÔ‡ (tPA), ÍÓÚÓ˚È ËÏÂÂÚ ÒÔˆËÙ˘ÂÒÍÓ ÒıÓ‰ÒÚ‚Ó Ò ÙË·ËÌÓÏ. èÓÒΠڇ‚Ï˚ tPA ‚˚Ò‚Ó·Óʉ‡ÂÚÒfl ËÁ ÍÎÂÚÓÍ ˝Ì‰ÓÚÂÎËfl ‚ ÒÚÂÌ͇ı ÒÓÒÛ‰Ó‚ Ë ˜ÂÂÁ LSB Ò‚flÁ˚‚‡ÂÚÒfl Ò ÙË·ËÌÓÏ (2). é·‡ÁÓ‚‡‚ Ò‚flÁ¸ Ò ÙË·ËÌÓÏ, ÓÌ ÒÚ‡ÌÓ‚ËÚÒfl ÔÓ˜ÚË ÔÓÎÌÓÒÚ¸˛ ‡ÍÚË‚Ì˚Ï(3). ùÚ‡ ÒÓ‚ÏÂÒÚ̇fl ÎÓ͇ÎËÁ‡ˆËfl Ô·ÁÏËÌÓ„Â̇ Ë tPA ‚ ‰‡Î¸ÌÂȯÂÏ Ó·Î„˜‡ÂÚ ÙË·ËÌÓÎËÁ ̇ Û˜‡ÒÚÍ ҄ÛÒÚ͇ ÙË·Ë̇ (ËÒÛÌÓÍ 1). ÑÛ„ËÏ ‡ÍÚË‚‡ÚÓÓÏ Ô·ÁÏËÌÓ„Â̇ fl‚ÎflÂÚÒfl ÛÓÍË̇Á‡ (uPA), ÔËÒÛÚÒÚ‚Û˛˘‡fl ‚ ÏӘ ‚ ·Óθ¯Ëı ÍÓ̈ÂÌÚ‡ˆËflı. àÌ„Ë·ËÚÓ˚ ‚ ÒËÒÚÂÏ ÙË·ËÌÓÎËÁ‡ àÌ„Ë·ËÚÓ‡ÏË ‡ÍÚË‚‡ÚÓ‡ Ô·ÁÏËÌÓ„Â̇ fl‚Îfl˛ÚÒfl PAI-1, ÍÓÚÓ˚È ÒËÌÚÂÁËÛÂÚÒfl ‚ ÍÎÂÚ͇ı ˝Ì‰ÓÚÂÎËfl, ‡‰ËÔÓˆËÚ‡ı Ë Ô˜ÂÌË; PAI-2, ÍÓÚÓ˚È ÒËÌÚÂÁËÛÂÚÒfl ‚ Ô·ˆÂÌÚÂ, ÏÓÌÓˆËÚ‡ı Ë Ï‡ÍÓÙ‡„‡ı; Ë PAI-3, ÍÓÚÓ˚È fl‚ÎflÂÚÒfl ˉÂÌÚ˘Ì˚Ï ËÌ„Ë·ËÚÓÛ ÔÓÚÂË̇ ë Ë ÔÓÚ‡Á˚ ÌÂÍÒË̇ (4). èÓÒΉÌË ‰‚‡, ‚ÂÓflÚÌÓ, ËÏÂ˛Ú ÏÂ̸¯Â Á̇˜ÂÌË ‰Îfl ÙË·ËÌÓÎËÁ‡. ÑÂÙˈËÚ PAI-1 fl‚ÎflÂÚÒfl ‰ÍÓ ‰Ë‡„ÌÓÒÚËÛÂÏ˚Ï ‚‡Ë‡ÌÚÓÏ Ò ÔÓ‚˚¯ÂÌÌÓÈ ÚẨÂ̈ËÂÈ Í ÍÓ‚ÓÚ˜ÂÌ˲. îËÁËÓÎӄ˘ÂÒÍË ‚‡ÊÌ˚Ï ËÌ„Ë·ËÚÓÓÏ Ô·ÁÏË̇ fl‚ÎflÂÚÒfl ÒËÌÚÂÁËÓ‚‡ÌÌ˚È ‚ Ô˜ÂÌË ‡ÌÚËÔ·ÁÏËÌ. ÄÌÚËÔ·ÁÏËÌ Ò‚flÁ˚‚‡ÂÚÒfl Ò LSB ‚ Ô·ÁÏËÌÂ, ÌÓ ÍÓ„‰‡ Ô·ÁÏËÌ ‡·ÒÓ·ËÛÂÚÒfl ÙË·ËÌÓÏ, ˝ÚÓ Ò‚flÁ˚‚‡ÌË Á‡Ï‰ÎflÂÚÒfl, ‚ ÂÁÛθڇÚ ˜Â„Ó ÔÓˆÂÒÒ ÙË·ËÌÓÎËÁ‡ ÔÓÎÓÌ„ËÛÂÚÒfl Ë ÎÓ͇ÎËÁÛÂÚÒfl (5). ë ‰Û„ÓÈ ÒÚÓÓÌ˚, ÔË ‚˚‡ÊÂÌÌÓÏ ÙË·ËÌÓÎËÁ ҂ӷӉÌ˚È Ô·ÁÏËÌ ÔÓÔ‡‰‡ÂÚ ‚ ÍÓ‚ÓÓ·‡˘ÂÌËÂ Ë ÌÂωÎÂÌÌÓ Ë̇ÍÚË‚ËÛÂÚÒfl ‡ÌÚËÔ·ÁÏËÌÓÏ. î‡Ï‡ˆÂ‚Ú˘ÂÒÍË ËÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ë‚flÁ¸ ÎËÁËÌÔÓËÁ‚Ó‰Ì˚ı ÖÄëÄ Ë íÄ Ò LSB fl‚ÎflÂÚÒfl Ó·‡ÚËÏÓÈ (ËÒÛÌÓÍ 1), ˜ÚÓ ÒÌËʇÂÚ ÒÔÓÒÓ·ÌÓÒÚ¸ Ô·ÁÏËÌÓ„Â̇ Í Ó·‡ÁÓ‚‡Ì˲ Ò‚flÁÂÈ Ò ÙË·ËÌÓÏ. ùÚÓ ÒÌËʇÂÚ ‡ÍÚË‚‡ˆË˛ ÔÂÂıÓ‰‡ Ô·ÁÏËÌÓ„Â̇ ‚ Ô·ÁÏËÌ. í‡ÍËÏ Ó·‡ÁÓÏ, ÎËÁËÌÔÓËÁ‚Ó‰Ì˚ ÖÄëÄ Ë íÄ Ï¯‡˛Ú Ó·‡ÁÓ‚‡Ì˲ Ò‚flÁÂÈ Ò LSB. ÄÔÓÚËÌËÌ, ÒÓ Ò‚ÓÂÈ ÒÚÓ5 àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ Рисунок 1. Слева связь плазминогена с фибрином осуществляется через лизин-связывающие участки. Плазминоген преобразуется в плазмин в присутствии активатора плазминогена тканевого типа. Справа ТА образует обратимый комплекс с плазминогеном. Даже при продолжении преобразования плазминогена в плазмин под влиянием tPA комплекс плазмин-tPA не способен образовать связь и переработать фибрин. Механизм действия ЕАСА является таким же. ÓÌ˚, ‰Â·ÂÚ Ô·ÁÏËÌ Ô‡ÒÒË‚Ì˚Ï. ä‡Í ‡ÔÓÚËÌËÌ, Ú‡Í Ë ‡Ì‡ÎÓ„Ë ÎËÁË̇ ÒÌËʇ˛Ú ÙË·ËÌÓÎËÁ, ÌÓ ËÒÔÓθÁÛ˛Ú ‰Îfl ˝ÚÓ„Ó ‡ÁÌ˚ ÏÂı‡ÌËÁÏ˚. ÄÔÓÚËÌËÌ ÄÔÓÚËÌËÌ fl‚ÎflÂÚÒfl ËÌ„Ë·ËÚÓÓÏ ÔÓÚ‡Á˚ ÒÂË̇ ̇ÚۇθÌÓ„Ó ÔÓËÒıÓʉÂÌËfl, ËÁ‚ÎÂ͇ÂÏ˚Ï ËÁ Ú͇ÌË ·˚˜¸Ëı Îfi„ÍËı. ùÚÓ ÔÓÎËÔÂÔÚˉ, ÒÓÒÚÓfl˘ËÈ ËÁ 58 ‡ÏËÌÓÍËÒÎÓÚ Ò ÏÓÎÂÍÛÎflÌÓÈ Ï‡ÒÒÓÈ ÓÍÓÎÓ 6,500 ‰‡Î¸ÚÓÌÓ‚ (Da). èÂÔ‡‡Ú Ó·‡ÁÛÂÚ ÔflÏÛ˛ Ò‚flÁ¸ Ò Ô·ÁÏËÌÓÏ, Í‡Í Ë ‰Û„Ë ÔÓÚ‡Á˚ ÒÂË̇. Ö„Ó ÔÂËÓ‰ ÔÓÎÛ‚˚‚‰ÂÌËfl ÒÓÒÚ‡‚ÎflÂÚ ÔflÚ¸-‰ÂÒflÚ¸ ˜‡ÒÓ‚, Ë ÓÌ ‚˚‚Ó‰ËÚÒfl Ò ÏÓ˜ÓÈ. èÓ·Ó˜Ì˚ ˝ÙÙÂÍÚ˚: ÄÔÓÚËÌËÌ ËÏÂÂÚ Ï‡ÎÓ ÔÓ·Ó˜Ì˚ı ˝ÙÙÂÍÚÓ‚, ÌÓ ËÌÓ„‰‡ ÏÓÊÂÚ ‚˚Á˚‚‡Ú¸ ‡Î΄˘ÂÒÍË / ‡Ì‡ÙËÎËÍÚ˘ÂÒÍË ‡͈ËË (6). Ä̇ÙË·ÍÚ˘ÂÒÍË ‡͈ËË Ì‡·Î˛‰‡ÎËÒ¸ ‚ 5% ÒÎÛ˜‡Â‚ ÔË ÔÓ‚ÚÓÌÓÏ Î˜ÂÌËË ‚ Ú˜ÂÌË ¯ÂÒÚË ÏÂÒflˆÂ‚. äÎËÌ˘ÂÒÍÓ ÔËÏÂÌÂÌËÂ: ëÔÓÒÓ·˚ ÔËÏÂÌÂÌËfl Ó„‡Ì˘˂‡˛ÚÒfl ‚ÌÛÚË‚ÂÌÌ˚ÏË ËÌ˙Â͈ËflÏË, Ú‡Í Í‡Í ÔÂÔ‡‡Ú ‡ÁÛ¯‡ÂÚÒfl ÔË Ó‡Î¸ÌÓÏ ÔËfiÏÂ. Ç Ì‡ÒÚÓfl˘Â ‚ÂÏfl ÓÌ ¯ËÓÍÓ ËÒÔÓθÁÛÂÚÒfl ‚ ıËÛ„ËË Ò‰ˆ‡ Ë ÔË Ú‡ÌÒÔ·ÌÚ‡ˆËË Ô˜ÂÌË, Ë ÔÓ˝ÚÓÏÛ ÓÌ Ì ·Û‰ÂÚ ‡ÒÒχÚË‚‡Ú¸Òfl ‰‡Î ‚ ˝ÚÓÈ ÏÓÌÓ„‡ÙËË. é‰Ì‡ÍÓ ÒΉÛÂÚ ÛÔÓÏflÌÛÚ¸, ˜ÚÓ ‡ÔÓÚËÌËÌ ËÒÔÓθÁÛÂÚÒfl ‚ ÙË·ËÌÓ‚ÓÏ ÍÎÂÂ. ÖÄëÄ Ë íÄ Ç 1953 „Ó‰Û ·˚ÎÓ ÔÓ͇Á‡ÌÓ, ˜ÚÓ ˝ÔÒËÎÓÌ-‡ÏËÌÓ͇ÔÓÌÓ‚‡fl ÍËÒÎÓÚ‡ (ÖÄëÄ), fl‚Îfl˛˘‡flÒfl ÒËÌÚÂÚ˘ÂÒÍÓÈ ÔÓËÁ‚Ó‰ÌÓÈ ‡ÏËÌÓÍËÒÎÓÚÌÓ„Ó ÎËÁË̇, Ó͇Á˚‚‡ÂÚ ÒËθÌÓ ‰ÂÈÒÚ‚Ë ̇ ÔÓ‰‡‚ÎÂÌË Ô·ÁÏËÌÓ„Â̇. Ç Ò‰ËÌ 1960-ı ·˚Î ÓÚÍ˚Ú ÒıÓ‰Ì˚È ‡„ÂÌÚ, Ú‡ÌÒ-4(‡ÏËÌÓÏÂÚËÎ) ˆËÍÎÓ„ÂÍÒ‡Ì͇·ÓÌÓ‚‡fl ÍËÒÎÓÚ‡, ÍÓÚÓ‡fl ·˚· ‚ 10 ‡Á ˝ÙÙÂÍÚË‚ÌÂÂ Ë ÔÂÂÌÓÒË·Ҹ ÎÛ˜¯Â, ˜ÂÏ ÖÄëÄ (7). ÖÄëÄ – ˝ÚÓ ÒËÌÚÂÚ˘ÂÒ͇fl ‡ÏËÌÓÍËÒÎÓÚ‡ Ò ÏÓÎÂÍÛÎflÌÓÈ Ï‡ÒÒÓÈ 131 Da. èÓÒΠÔËfiχ Ó‰ÌÓÈ Ó‡Î¸ÌÓÈ ‰ÓÁ˚ 5 „ ÔËÍÓ‚‡fl ÍÓ̈ÂÌÚ6 ‡ˆËfl ‚ Ô·ÁÏ ‰ÓÒÚË„‡ÂÚÒfl ˜ÂÂÁ 1,2 ˜‡Ò‡. é̇ ‡ÒÔÓÒÚ‡ÌflÂÚÒfl ˜ÂÂÁ ˝ÍÒÚ‡- Ë ËÌÚ‡‚‡ÒÍÛÎflÌ˚ ÔÓÒÚ‡ÌÒÚ‚‡ Ë ‚˚‚Ó‰ËÚÒfl Ò ÏÓ˜ÓÈ, ÍÓ̘Ì˚È ÔÂËÓ‰ ÔÓÎÛ‚˚‚‰ÂÌËfl – ÓÍÓÎÓ ‰‚Ûı ˜‡ÒÓ‚. íÄ – ˝ÚÓ ÒËÌÚÂÚ˘ÂÒ͇fl ‡ÏËÌÓÍËÒÎÓÚ‡ Ò ÏÓÎÂÍÛÎflÌÓÈ Ï‡ÒÒÓÈ 157 Da. î‡Ï‡ÍÓÍËÌÂÚ˘ÂÒÍË ËÒÒΉӂ‡ÌËfl ̇ Á‰ÓÓ‚˚ı Ë̉˂ˉÛÛχı ÔÓ͇Á‡ÎË, ˜ÚÓ ÔË ‚ÌÛÚË‚ÂÌÌÓÏ ‚‚‰ÂÌËË 10 Ï„ ̇ Í„ χÒÒ˚ Ú· (BW) ÔËÍÓ‚‡fl ÍÓ̈ÂÌÚ‡ˆËfl ‚ Ô·ÁÏ ‰ÓÒÚË„‡Î‡Ò¸ ‚ Ú˜ÂÌË ӉÌÓ„Ó ˜‡Ò‡ ÔÓÒΠËÌ˙Â͈ËË (8, 9). óÂÂÁ Ó‰ËÌ ˜‡Ò 30% ‚‚‰fiÌÌÓÈ ‰ÓÁ˚ ‚˚‚Ó‰ËÎÓÒ¸ Ò ÏÓ˜ÓÈ, ‡ ˜ÂÂÁ 24 ˜‡Ò‡ ‚˚‚Ó‰ËÎÓÒ¸ 90%. èÓÒΠӇθÌÓÈ ‰ÓÁ˚ 10–15 Ï„ ̇ Í„ χÒÒ˚ Ú· χÍÒËχθ̇fl ÍÓ̈ÂÌÚ‡ˆËfl ‚ Ô·ÁÏ ‰ÓÒÚË„‡Î‡Ò¸ ‚ Ú˜ÂÌË Úfiı ˜‡ÒÓ‚ (10). èˢ‡ Ì Ó͇Á˚‚‡Î‡ ‚ÎËflÌËfl ̇ ‡·ÒÓ·ˆË˛ ÔÂÔ‡‡Ú‡ ‚ ÊÂÎÛ‰Ó˜ÌÓ-Í˯˜ÌÓÏ Ú‡ÍÚ (11). èÂËÓ‰ ·ËÓÎӄ˘ÂÒÍÓ„Ó ÔÓÎÛ‡ÒÔ‡‰‡ ÒÓÒÚ‡‚ÎflÎ 80 ÏËÌÛÚ (6). íÄ ‡ÍÍÛÏÛÎËÛÂÚÒfl ‚ Ú͇Ìflı (9). é̇ ÔÓÌË͇ÂÚ ˜ÂÂÁ Ô·ˆÂÌÚÛ ‚ ÔÎÓ‰ (12) Ë ÔËÒÛÚÒÚ‚ÛÂÚ ‚ „Û‰ÌÓÏ ÏÓÎÓÍ – ÌÓ ‚ ÍÓ̈ÂÌÚ‡ˆËflı ‚ 100 ‡Á ÏÂ̸¯Â, ˜ÂÏ ‚ Ò˚‚ÓÓÚÍ (10). ÅÓΠÚÓ„Ó, íÄ ·˚ÒÚÓ ‡ÒÚ‚ÓflÂÚÒfl ‚ ÒËÌӂˇθÌÓÈ ÊˉÍÓÒÚË Ë ÒËÌӂˇθÌÓÈ ÏÂÏ·‡Ì (13). Ç ÚÓÍÒËÍÓÎӄ˘ÂÒÍËı ËÒÒΉӂ‡ÌËflı Ú‡ÚÓ„ÂÌÌÓ ‚ÎËflÌË Ì ·˚ÎÓ Ó·Ì‡ÛÊÂÌÓ (7). ëÔÓÒÓ·˚ ÔËÏÂÌÂÌËfl Ë ‰ÓÁ˚: ÖÄëÄ ÔËÏÂÌflÂÚÒfl ‚ ‚ˉ ËÌÙÛÁËË ÔÓ 4–5 „ (16–20 ÏÎ) ‚ 250 ÏÎ ‡ÒÚ‚Ó‡ ‚ Ú˜ÂÌË ÔÂ‚Ó„Ó ˜‡Ò‡ Ò ÔÓÒÎÂ‰Û˛˘ÂÈ ËÌÙÛÁËÂÈ 1 „ ‚ 50 ÏÎ ‡ÒÚ‚Ó‡ ͇ʉ˚È ˜‡Ò ‰Ó ÚÂı ÔÓ, ÔÓ͇ ÍÓ‚ÓÚ˜ÂÌË Ì ÓÒÚ‡ÌÓ‚ËÚÒfl. é‡Î¸ÌÓ, 5 „ (10 Ú‡·ÎÂÚÓÍ), ËÎË 20 ÏÎ ÒËÓÔ‡ (25%) ÔËÏÂÌfl˛ÚÒfl ‚ Ú˜ÂÌË ÔÂ‚Ó„Ó ˜‡Ò‡ Ò ÔÓÒÎÂ‰Û˛˘ËÏ ÔËÏÂÌÂÌËÂÏ 1 „ ͇ʉ˚È ˜‡Ò, ÔÓ͇ ÍÓ‚ÓÚ˜ÂÌË Ì ÓÒÚ‡ÌÓ‚ËÚÒfl. ùÚË ÂÍÓÏẨÛÂÏ˚ ‰ÓÁ˚ Ô‰̇Á̇˜ÂÌ˚ ‰Îfl ‚ÁÓÒÎ˚ı. íÄ ÏÓÊÂÚ ÔËÏÂÌflÚ¸Òfl ‚ÌÛÚË‚ÂÌÌÓ, ӇθÌÓ ËÎË ÏÂÒÚÌÓ. é·˘‡fl ‚ÌÛÚË‚ÂÌ̇fl ‰ÓÁ‡ ÒÓÒÚ‡‚ÎflÂÚ 10 Ï„ ̇ Í„ χÒÒ˚ Ú·, 3–4 ‡Á‡ ‚ ‰Â̸. é‡Î¸Ì‡fl ‰ÓÁ‡ ÒÓÒÚ‡‚ÎflÂÚ 15–20 Ï„ ̇ Í„ χÒÒ˚ Ú·, àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ 3–4 ‡Á‡ ‚ ‰Â̸. Ç ıËÛ„ËË Ô‚‡fl ‰ÓÁ‡ ÔËÏÂÌflÂÚÒfl ÌÂÔÓÒ‰ÒÚ‚ÂÌÌÓ Ô‰ ̇˜‡ÎÓÏ ÓÔ‡ˆËË. é‰Ì‡ÍÓ ÂÒÎË Ô‚‡fl ‰ÓÁ‡ ÔËÏÂÌflÂÚÒfl ӇθÌÓ, ÚÓ Ó̇ ‰ÓÎÊ̇ ·˚Ú¸ ÔËÌflÚ‡ Á‡ 2 ˜‡Ò‡ ‰Ó Ôӈ‰Û˚. ÖÒÎË íÄ ÔËÏÂÌflÂÚÒfl ÏÂÒÚÌÓ, ‰Îfl ÔÓÎÓÒ͇ÌËfl Ú‡, ÚÓ ËÒÔÓθÁÛÂÚÒfl 5%-È ‚Ó‰Ì˚È ‡ÒÚ‚Ó, 10 ÏÎ, ˜ÚÓ ˝Í‚Ë‚‡ÎÂÌÚÌÓ 0,5 „ ӇθÌÓ. íÄ Ú‡ÍÊ ‚ıÓ‰ËÚ ‚ ÒÓÒÚ‡‚ ÌÂÍÓÚÓ˚ı ÚËÔÓ‚ ÙË·ËÌÓ‚Ó„Ó ÍÎÂfl. í‡Í Í‡Í íÄ ‚˚‚Ó‰ËÚÒfl ˜ÂÂÁ ÔÓ˜ÍË, ÚÓ Û Ô‡ˆËÂÌÚÓ‚ Ò ÔӘ˜ÌÓÈ Ì‰ÓÒÚ‡ÚÓ˜ÌÓÒÚ¸˛ ÒΉÛÂÚ Û‚Â΢ËÚ¸ ËÌÚ‚‡Î˚ ÏÂÊ‰Û ‰ÓÁ‡ÏË. äÓÏ ÚÓ„Ó, ÔË ÚflÊfiÎÓÈ ÙÓÏ ÔӘ˜ÌÓÈ Ì‰ÓÒÚ‡ÚÓ˜ÌÓÒÚË ÒΉÛÂÚ ÛÏÂ̸¯ËÚ¸ ‰ÓÁÛ. èË Ï‡ÍÓÒÍÓÔ˘ÂÒÍÓÈ „ÂχÚÛËË ‚ÒΉÒÚ‚Ë Âfi ÔÓËÒıÓʉÂÌËfl ‚ ÔӘ͇ı Ì ÒΉÛÂÚ ÔËÏÂÌflÚ¸ íÄ ËÁ-Á‡ ËÒ͇ Á‡‰ÂÊÍË Ò„ÛÒÚÍÓ‚ ‚ ÏÓ˜ÂÚÓ˜ÌË͇ı Ë ÏӘ‚ÓÏ ÔÛÁ˚Â. èÂÂÌÓÒËÏÓÒÚ¸ Ë ÔÓ·Ó˜Ì˚ ˝ÙÙÂÍÚ˚: Ç Ó·˘ÂÏ, ÖÄëÄ ÔÂÂÌÓÒËÚÒfl ıÓÓ¯Ó. åÓ„ÛÚ ‚ÓÁÌËÍÌÛÚ¸ ÔÓ·Ó˜Ì˚ ˝ÙÙÂÍÚ˚ ÒÓ ÒÚÓÓÌ˚ ÊÂÎÛ‰Ó˜ÌÓ-Í˯˜ÌÓ„Ó Ú‡ÍÚ‡, Í‡Í ÚÓ¯ÌÓÚ‡ Ë ‚ÓÚ‡ ̇fl‰Û Ò „ÓÎÓ‚ÓÍÛÊÂÌËÂÏ Ë „ËÔÓÚÓÌËÂÈ. íÄ Ú‡ÍÊÂ, ‚ Ó·˘ÂÏ, ıÓÓ¯Ó ÔÂÂÌÓÒËÚÒfl. ç‡Ë·ÓΠ˜‡ÒÚÓ ÓÚϘ‡˛ÚÒfl ÔÓ·Ó˜Ì˚ ˝ÙÙÂÍÚ˚ ÒÓ ÒÚÓÓÌ˚ ÊÂÎÛ‰Ó˜ÌÓ-Í˯˜ÌÓ„Ó Ú‡ÍÚ‡. Ç ‰‚ÓÈÌÓÏ ÒÎÂÔÓÏ ËÒÒΉӂ‡ÌËË Ó·˘‡fl ˜‡ÒÚÓÚ‡ ‚ÓÁÌËÍÌÓ‚ÂÌËfl ÚÓ¯ÌÓÚ˚, ‚ÓÚ˚, ‰Ë‡ÂË Ë ·ÓÎÂÈ ‚ ÊË‚ÓÚ ÒÓÒÚ‡‚Ë· 12% Û Ô‡ˆËÂÌÚÓ‚, ÔËÌËχ‚¯Ëı 1 „ íÄ ˜ÂÚ˚ ‡Á‡ Ò ÒÛÚÍË ‚ Ú˜ÂÌË ˜ÂÚ˚fiı ‰ÌÂÈ (14). Å˚ÒÚ‡fl ‚ÌÛÚË‚ÂÌ̇fl ËÌ˙Â͈Ëfl ÏÓÊÂÚ ‚˚Á‚‡Ú¸ „ÓÎÓ‚ÓÍÛÊÂÌËÂ Ë „ËÔÓÚÓÌ˲; ÔÓ˝ÚÓÏÛ ÂÍÓÏẨÛÂÚÒfl, ˜ÚÓ·˚ ÒÍÓÓÒÚ¸ ‚‚‰ÂÌËfl íÄ Ì Ô‚˚¯‡Î‡ 100 Ï„ ‚ ÏËÌÛÚÛ. ÇÓ ‚ÂÏfl ΘÂÌËfl Ò ÔËÏÂÌÂÌËÂÏ íÄ ËÌÓ„‰‡ ÓÚϘ‡ÎËÒ¸ ÒÎÛ˜‡Ë ÚÓÏ·ÓÁ‡ (ˆÂ·‡Î¸Ì˚È ÚÓÏ·ÓÁ, ‡Ú¡θÌ˚È ÚÓÏ·ÓÁ, ÓÍÍβÁËfl ÍÓÓ̇ÌÓ„Ó ËÏÔ·ÌÚ‡Ú‡) ̇fl‰Û ÒÓ ÒÎÛ˜‡flÏË ÓÒÚÓÈ ÔӘ˜ÌÓÈ Ì‰ÓÒÚ‡ÚÓ˜ÌÓÒÚË (15). é‰Ì‡ÍÓ, ÔÓ‰Ú‚ÂʉÂÌËfl ÚÓÏÛ, ˜ÚÓ íÄ fl‚ÎflÂÚÒfl ÔÓ‚ÓˆËÛ˛˘ËÏ ‡„ÂÌÚÓÏ, ÌÂÚ. Ç üÔÓÌËË Ë ·Óθ¯ËÌÒÚ‚Â ÒÚ‡Ì Ö‚ÓÔÂÈÒÍÓ„Ó ëÓÓ·˘ÂÒÚ‚‡ ÂÍÓÏẨÛÂÚÒfl Òӷβ‰‡Ú¸ ÓÒÚÓÓÊÌÓÒÚ¸ Ë ÔËÌËχڸ ÏÂ˚ ·ÂÁÓÔ‡ÒÌÓÒÚË ÔË Ì‡Á̇˜ÂÌËË íÄ Ô‡ˆËÂÌÚ‡Ï Ò ÚÓÏ·Ó˝Ï·ÓÎËÂÈ ‚ ‡Ì‡ÏÌÂÁÂ. Ç ëÓ‰ËÌfiÌÌÓÏ äÓÓ΂ÒÚ‚Â íÄ ÔÓÚË‚ÓÔÓ͇Á‡Ì‡ Ú‡ÍËÏ Ô‡ˆËÂÌÚ‡Ï (16). é‰Ì‡ÍÓ, ÚÓÏ·ÓÚ˘ÂÒÍË ̇ۯÂÌËfl fl‚Îfl˛ÚÒfl ÏÌÓ„ÓÙ‡ÍÚÓÌ˚ÏË Ë ‚ÔÓÎÌ ÏÓ„ÛÚ ‚ÓÁÌË͇ڸ Û Ô‡ˆËÂÌÚÓ‚ Ì ‚ Ò‚flÁË Ò íÄ. ÅÓΠÚÓ„Ó, ÌÂÒÍÓθÍÓ ‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ı ËÒÒΉӂ‡ÌËÈ Ì‡ Ô‡ˆËÂÌÚ‡ı, ÔÓ‰‚„¯ËıÒfl ÓÔ‡ˆËË Ì‡ Ò‰ˆÂ Ò Ó·ıÓ‰Ì˚Ï ¯ÛÌÚËÓ‚‡ÌËÂÏ ÍÓÓ̇ÌÓÈ ‡ÚÂËË, ‡ Ú‡ÍÊ ËÒÒΉӂ‡ÌËfl ̇ Ô‡ˆËÂÌÚ‡ı Ò ÔÓÎÌÓÈ ‡ÚÓÔ·ÒÚËÍÓÈ ÍÓÎÂÌÌÓ„Ó Ë Ú‡Áӷ‰ÂÌÌÓ„Ó ÒÛÒÚ‡‚Ó‚ Ì ÔÓ͇Á‡ÎË ˜ÂÁÏÂÌÛ˛ ˜‡ÒÚÓÚÛ ‚ÓÁÌËÍÌÓ‚ÂÌËfl ÚÓÏ·ÓÚ˘ÂÒÍËı Á‡·Ó΂‡ÌËÈ Û Ô‡ˆËÂÌÚÓ‚, ÔËÌËχ‚¯Ëı íÄ (15, 17). Ç ÂÚÓÒÔÂÍÚË‚ÌÓÏ ‡Ì‡ÎËÁ ËÒÚÓËÈ ·ÓÎÂÁÌÂÈ 256 ÊÂÌ˘ËÌ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ‚Ó ‚ÂÏfl ·ÂÂÏÂÌÌÓÒÚË, Û 168 ËÁ ÍÓÚÓ˚ı ·˚ÎÓ ÍÂÒ‡Â‚Ó Ò˜ÂÌËÂ, ÚÓÏ·Ó„ÂÌÌ˚È ˝ÙÙÂÍÚ íÄ Ì ·˚Î ‚˚fl‚ÎÂÌ. (18). ë ̇˜‡Î‡ 1970-ı „Ó‰Ó‚ íÄ ¯ËÓÍÓ ËÒÔÓθÁÛÂÚÒfl ‚ ò‚ˆËË, Í‡Í ÓÒÌÓ‚ÌӠΘÂÌË ÔË ÏÂÌÓ‡„Ëflı. ì 238000 Ô‡ˆËÂÌÚÓ‚ ̇ ÔÓÚflÊÂÌËË 19 ÎÂÚ Î˜ÂÌËfl ÓÒÚ ˜‡ÒÚÓÚ˚ ‚ÓÁÌËÍÌÓ‚ÂÌËfl ÚÓÏ·Ó˝Ï·Ó΢ÂÒÍËı Á‡·Ó΂‡ÌËÈ Ì ·˚Î ÓÚϘÂÌ (19). ä‡Í ·˚ÎÓ Ò͇Á‡ÌÓ ‚˚¯Â, íÄ ¯ËÓÍÓ ËÒÔÓθÁÛÂÚÒfl ‚ Ö‚ÓÔÂ, ‡ Ú‡ÍÊ ‚ ä‡Ì‡‰Â, ÌÓ ‚ ̇ÒÚÓfl˘Â ‚ÂÏfl Ú‡·ÎÂÚÍË Ì ÎˈÂÌÁËÓ‚‡Ì˚ ‚ ëÓ‰ËÌfiÌÌ˚ı òÚ‡Ú‡ı, „‰Â íÄ ÔËÏÂÌflÂÚÒfl ÚÓθÍÓ ‚ ‚ˉ ‚ÌÛÚË‚ÂÌÌ˚ı ËÌ˙Â͈ËÈ. èÓÚË‚ÓÔÓ͇Á‡ÌËfl: ÖÄëÄ Ë íÄ ÔÓÚË‚ÓÔÓ͇Á‡Ì˚ Ô‡ˆËÂÌÚ‡Ï Ò ÔӘ˜Ì˚Ï ÍÓ‚ÓÚ˜ÂÌËÂÏ Ë ÚÂÏ, ÍÚÓ ÔÓıÓ‰ËÚ Î˜ÂÌËÂ Ò ÔËÏÂÌÂÌËÂÏ ‡ÌÚËËÌ„Ë·ËÚÓÌÓ„Ó ÍÓ‡„ÛÎflÌÚÌÓ„Ó ÍÓÏÔÎÂÍÒ‡ FEIBA. èÓ‚ÚÓÌ˚ ËÌ˙Â͈ËË ÖÄëÄ ËÎË íÄ Ú‡ÍÊ ÔÓÚË‚ÓÔÓ͇Á‡Ì˚ ‚Ó ‚ÂÏfl ÓÒÚÓÈ Ù‡Á˚ ‰ËÒÒÂÏËÌËÓ‚‡ÌÌÓ„Ó ‚ÌÛÚËÒÓÒÛ‰ËÒÚÓ„Ó Ò‚fiÚ˚‚‡ÌËfl. äÎËÌ˘ÂÒÍÓ ÔËÏÂÌÂÌË ÔÂÔ‡‡Ú‡ ÉËÌÂÍÓÎÓ„Ëfl åÂÌÓ‡„Ëfl: é·ËθÌÓ ÏÂÌÒÚۇθÌÓ ÍÓ‚ÓÚ˜ÂÌË ËÎË ÏÂÌÓ- ‡„ËË ¯ËÓÍÓ ‡ÒÔÓÒÚ‡ÌÂÌ˚ Û ÊÂÌ˘ËÌ. èÓ ÓÔ‰ÂÎÂÌ˲ ÏÂÌÓ‡„Ëfl – ˝ÚÓ ÔÓÚÂfl ÏÂÌÒÚۇθÌÓÈ ÍÓ‚Ë, ‡‚̇fl 80 ÏÎ ‚ Ú˜ÂÌË ӉÌÓ„Ó ˆËÍ·. ôfiÎÓ˜ÌÓ-„ÂχÚËÌÓ‚˚È ÏÂÚÓ‰, ÓÔËÒ‡ÌÌ˚È Hallberg Ë Nilsson, fl‚ÎflÂÚÒfl ÚÓ˜ÌÓÈ Ôӈ‰ÛÓÈ ‰Îfl ÓÔ‰ÂÎÂÌËfl ÍÓ‚ÓÔÓÚÂË (20). Ç ·ÓΠÔÓÁ‰ÌËı ËÒÒΉӂ‡ÌËflı ˝ÚÓÚ ÏÂÚÓ‰ ·˚Î Á‡ÏÂÌfiÌ ÛÔÓ˘fiÌÌÓÈ ËÎβÒÚËÓ‚‡ÌÌÓÈ ÒıÂÏÓÈ ÓˆÂÌÍË ÍÓ‚ÓÚ˜ÂÌËfl (21). éÒÌÓ‚‡ÌËÂÏ ‰Îfl ΘÂÌËfl ˉËÓÔ‡Ú˘ÂÒÍÓÈ ÏÂÌÓ‡„ËË ÔÛÚfiÏ ÔËÏÂÌÂÌËfl ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ fl‚ÎflÂÚÒfl ÚÓ, ˜ÚÓ Û ˝ÚËı ÊÂÌ˘ËÌ ÒÓ‰ÂʇÌË ‡ÍÚË‚‡ÚÓÓ‚ Ô·ÁÏËÌÓ„Â̇ ‚ ˝Ì‰ÓÏÂÚËË ‚ Ô‚˚È ‰Â̸ ˆËÍ· ‚˚¯Â, ˜ÂÏ Û ‰Û„Ëı ÊÂÌ˘ËÌ Ò ÌÓχθÌÓÈ ÍÓ‚ÓÔÓÚÂÂÈ (22). çÂÒÍÓθÍÓ ÍÓÌÚÓÎËÛÂÏ˚ı ÍÎËÌ˘ÂÒÍËı ËÒÒΉӂ‡ÌËÈ ÔÓ͇Á‡ÎË, ˜ÚÓ íÄ, ÔËÌËχÂχfl ‚Ó ‚ÂÏfl ÏÂÌÒÚÛ‡ˆËË, ÒÌËʇÂÚ ÍÓ‚ÓÔÓÚ² ̇ 34–59% ÔÓ Ò‡‚ÌÂÌ˲ Ò Ô·ˆÂ·Ó ËÎË ÍÓÌÚÓθÌ˚ÏË Ô‡ˆËÂÌÚ‡ÏË (23–28). èÓ ÏÌÂÌ˲ Winkoff Ò ÒÓ‡‚Ú. (29) Ó·ËθÌÓ ÏÂÌÒÚۇθÌÓ ÍÓ‚ÓÚ˜ÂÌËÂ, ̇˜Ë̇fl Ò ÏÂ̇ıÂ, fl‚ÎflÂÚÒfl Ó·˘ËÏ ÒËÏÔÚÓÏÓÏ ‰Îfl ÊÂÌ˘ËÌ Ò Ú‡ÍËÏË „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË Í‡Í VWD (·ÓÎÂÁ̸ ÇËÎη‡Ì‰‡), ÚÓÏ·ÓˆËڇ̇fl ‰ËÒÙÛÌ͈Ëfl, ‰ÂÙˈËÚ Ù‡ÍÚÓ‡ VII, X Ë XI Ë ‰Îfl ÚÂı, ÍÚÓ ÒÚ‡‰‡ÂÚ „ÂÏÓÙËÎËÂÈ Ä ËÎË Ç. ê‡ÒÔÓÒÚ‡ÌfiÌÌÓÒÚ¸ VWD Û ÊÂÌ˘ËÌ Ò ÏÂÌÓ‡„ËflÏË ‚ ̇ÒÚÓfl˘Â ‚ÂÏfl ÒÓÒÚ‡‚ÎflÂÚ ÓÚ 5 ‰Ó 20% (30). åÂÌÓ‡„Ëfl fl‚ÎflÂÚÒfl Ó‰ÌËÏ ËÁ ̇˷ÓΠ‡ÒÔÓÒÚ‡ÌfiÌÌ˚ı „ÂÏÓ‡„˘ÂÒÍËı ÔËÁ̇ÍÓ‚ VWD, ÓÚϘÂÌÌ˚Ï Û 60–95% ÊÂÌ˘ËÌ Ò ˝ÚËÏ „ÂÏÓ‡„˘ÂÒÍËÏ ‡ÒÒÚÓÈÒÚ‚ÓÏ (30). ä‡Í Ô‰ÔÓ·„‡ÂÚÒfl, Ó·ËθÌ˚ ÏÂÌÒÚۇθÌ˚ ÍÓ‚ÓÚ˜ÂÌËfl Ó͇Á˚‚‡˛Ú ÓÚˈ‡ÚÂθÌÓ ‚ÎËflÌË ̇ Ôӂ҉̂ÌÛ˛ ‡ÍÚË‚ÌÓÒÚ¸ ÊÂÌ˘ËÌ, ˜ÚÓ ‰ÓÍÛÏÂÌڇθÌÓ ÔӉڂ‰ËÎË Kirtaeva Ò ÒÓ‡‚Ú.‚ Ò‚ÓfiÏ ËÌÚ‚¸˛ËÓ‚‡ÌÌÓÏ ËÒÒΉӂ‡ÌËË ÊÂÌ˘ËÌ Ò VWD (31). ÑÎfl Ô‡ˆËÂÌÚÓ‚ Ò VWD Ë ÏÂÌÓ‡„ËflÏË Ì ÔÓ‚Ó‰ËÎËÒ¸ ËÒÒΉӂ‡ÌËfl, Ò‡‚ÌË‚‡˛˘Ë ÓÚÌÓÒËÚÂθÌÛ˛ ˝ÙÙÂÍÚË‚ÌÓÒÚ¸ Ë ·ÂÁÓÔ‡ÒÌÓÒÚ¸ Ëϲ˘ÂÈÒfl ωË͇ÏÂÌÚÓÁÌÓÈ Ú‡ÔËË. é‰Ì‡ÍÓ Demers Ò ÒÓ‡‚Ú. ‡Á‡·ÓÚ‡ÎË Òӄ·ÒËÚÂθÌ˚È ‰ÓÍÛÏÂÌÚ ÔÓ ‚‰ÂÌ˲ ‚ÓʉfiÌÌ˚ı „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚, ÓÒÓ·ÂÌÌÓVWD, ‰Îfl é·˘ÂÒÚ‚‡ ÄÍÛ¯ÂÓ‚ Ë ÉËÌÂÍÓÎÓ„Ó‚ ä‡Ì‡‰˚ (32). éÌ ·˚Î ÓÒÌÓ‚‡Ì ̇ ‰‡ÌÌ˚ı ‡Ì„ÎËÈÒÍÓÈ ÎËÚ‡ÚÛ˚ ÔÓ ‰‡ÌÌÓÏÛ Ô‰ÏÂÚÛ Ì‡ Ò‡ÈÚ Medline, ÓÔÛ·ÎËÍÓ‚‡ÌÌ˚ı ÏÂÊ‰Û 1975 Ë 2003 „Ó‰‡ÏË, Ë ÂÍÓÏẨ‡ˆËflı ËÁ ‰Û„Ëı ÒÔ‡‚Ó˜ÌËÍÓ‚. Ç ˝ÚÓÏ Ó·ÁÓ ‚˚fl‚ÎÂÌÓ, ˜ÚÓ “‚ÓʉfiÌÌÓ „ÂÏÓ‡„˘ÂÒÍÓ ‡ÒÒÚÓÈÒÚ‚Ó Ì fl‚ÎflÂÚÒfl ÔÓÚË‚ÓÔÓ͇Á‡ÌËÂÏ ‰Îfl „ÓÏÓ̇θÌÓÈ Ú‡ÔËË… Ë Ì„ÓÏÓ̇θÌÓÈ Ú‡ÔËË (‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍËÈ ÔÂÔ‡‡Ú íÄ, ‡ Ú‡ÍÊ ‰ÂÒÏÓÔÂÒÒËÌ). ùÚË ‚ˉ˚ ΘÂÌËfl fl‚Îfl˛ÚÒfl Ú‡ÔËÂÈ Ô‚ÓÈ ÎËÌËË”. ëÂ‰Ë ÊÂÌ˘ËÌ Ò Ô‡ÚÓÎӄ˘ÂÒÍËÏ ÏÂÌÒÚۇθÌ˚Ï ÍÓ‚ÓÚ˜ÂÌËÂÏ 20–30% ËÏÂ˛Ú Ì‰ÓÒÚ‡ÚÓ˜ÌÛ˛ ÚÓÏ·ÓˆËÚ‡ÌÛ˛ ÙÛÌÍˆË˛ Ë ÙË·ËÌÓÎËÚ˘ÂÒÍË ‡ÒÒÚÓÈÒÚ‚‡, ˜ÚÓ ÏÓÊÂÚ ·˚Ú¸ ‰ÓÔÓÎÌËÚÂθÌÓÈ Ô˘ËÌÓÈ ÏÂÌÓ‡„ËË, Í‡Í Ô‰ÔÓ·„‡˛Ú ‚ Ò‚ÓfiÏ Ó·ÁÓ Kouides Ò ÒÓ‡‚Ú. (33). ÇÓ ‚ÒÂı ˝ÚËı ÒÎÛ˜‡flı ÏÓÊÌÓ Ô‰ÔÓÎÓÊËÚ¸, ˜ÚÓ íÄ fl‚ÎflÂÚÒfl ÒÓÓÚ‚ÂÚÒÚ‚Û˛˘ËÏ ÔÂÔ‡‡ÚÓÏ ‰Îfl ÒÌËÊÂÌËfl ÍÓ‚ÓÔÓÚÂË Ì‡ ÓÒÌÓ‚‡ÌËË ‚˚¯ÂÛÔÓÏflÌÛÚ˚ı ÓÚÍ˚ÚËÈ. êÂÍÓÏẨÛÂχfl Ӈθ̇fl ‰ÓÁ‡ íÄ ÒÓÒÚ‡‚ÎflÂÚ ÓÍÓÎÓ 15 Ï„ ̇ Í„ χÒÒ˚ Ú· ͇ʉ˚ ¯ÂÒÚ¸-‚ÓÒÂϸ ˜‡ÒÓ‚; ‚ Ó·˘ÂÏ ‚ˉÂ, 1–1,5 „ ÚË ‡Á‡ ‚ ÒÛÚÍË ÔË Ì‡ÒÚÛÔÎÂÌËË ÍÓ‚ÓÚ˜ÂÌËfl ‰Ó Â„Ó ÓÒÚ‡ÌÓ‚ÍË. çÂÍÓÚÓ˚ ԇˆËÂÌÚ˚ Ò VWD Ó·˘Û˛ ÒÛÚÓ˜ÌÛ˛ ‰ÓÁÛ 3–4 „ ÔËÌËχÎË Á‡ Ó‰ËÌ ÔËfiÏ. ùÚ‡ ‚˚ÒÓ͇fl ‰ÓÁ‡ ÔÂÂÌÓÒË·Ҹ ıÓÓ¯Ó Ë ·˚· Û‰Ó·ÌÓÈ Ë ˝ÙÙÂÍÚË‚ÌÓÈ ÔË Î˜ÂÌËË ÏÂÌÓ‡„ËË (34–36). èË ˝ÚÓÏ Ò¸fiÁÌ˚ ÔÓ·Ó˜Ì˚ fl‚ÎÂÌËfl, Ò‚flÁ‡ÌÌ˚Â Ò íÄ, Á‡ ËÒÍβ˜ÂÌËÂÏ Â‰ÍËı ̇ۯÂÌËÈ ‚ Îfi„ÍÓÈ ÙÓÏ ÒÓ ÒÚÓÓÌ˚ ÊÂÎÛ‰Ó˜ÌÓ-Í˯˜ÌÓ„Ó Ú‡ÍÚ‡, Ì ÓÚϘ‡ÎËÒ¸. ëÛ·˙ÂÍÚ˚ ÓÚ‚‡ÊË‚‡ÎËÒ¸ Ò‡ÏÓÒÚÓflÚÂθÌÓ ËÁÏÂÌflÚ¸ ‰ÓÁÛ ‚ ÒÚÓÓÌÛ Û‚Â΢ÂÌËfl Ë ÛÏÂ̸¯ÂÌËfl, ˜ÚÓ·˚ ̇ÈÚË ÒÓ·ÒÚ‚ÂÌÌ˚È ÓÔÚËχθÌ˚È ÂÊËÏ. 7 àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ ТА для лечения меноррагии у женщин с геморрагическими расстройствами. ТА для орального применения: 15–20 мг на кг массы тела три-четыре раза в сутки от начала менструального цикла до остановки кровотечения. При недостаточном эффекте доза увеличивается. Если побочные эффекты со стороны кишечника не приемлемы, доза уменьшается. ÅÂÂÏÂÌÌÓÒÚ¸: ã˯¸ ÌÂÍÓÚÓ˚ ÊÂÌ˘ËÌ˚ Ò ‚ÓʉfiÌÌ˚ÏË „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ËÏÂ˛Ú ÔÓ·ÎÂÏ˚ ÍÓ‚ÓÚ˜ÂÌËfl ‚Ó ‚ÂÏfl ÌÓχθÌÓÈ ·ÂÂÏÂÌÌÓÒÚË. чÊÂ Û ÊÂÌ˘ËÌ Ò ÚflÊfiÎ˚ÏË „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË, Ú‡ÍËÏË Í‡Í VWD, ÚËÔ 3, ·ÂÂÏÂÌÌÓÒÚË ·˚ÎË, ‚ Ó·˘ÂÏ, ·ÂÁ ÔˆẨÂÌÚÓ‚ (37). é‰Ì‡ÍÓ, ‚ Ó‰ÌÓÏ Í‡Ú‡ÏÌÂÒÚ˘ÂÒÍÓÏ ËÒÒΉӂ‡ÌËË ÓÚϘ‡Î‡Ò¸ ‚˚ÒÓ͇fl ˜‡ÒÚÓÚ‡ ‚ÓÁÌËÍÌÓ‚ÂÌËfl ‚‡„Ë̇θÌ˚ı ÍÓ‚ÓÚ˜ÂÌËÈ Û ·ÂÂÏÂÌÌ˚ı ÊÂÌ˘ËÌ Ò VWD Ë ‰ÂÙˈËÚÓÏ Ù‡ÍÚÓ‡ XI ÔÓ Ò‡‚ÌÂÌ˲ Ò ÊÂÌ˘Ë̇ÏË Ò ÌÓχθÌ˚Ï „ÂÏÓÒÚ‡ÁÓÏ, ıÓÚfl ÔÓ͇Á‡ÚÂθ ‚˚Íˉ˚¯ÂÈ Ì ·˚Î ‚˚¯Â (38). çÂÒÏÓÚfl ̇ ÓÚÒÛÚÒÚ‚Ë ‰‡ÌÌ˚ı ÔÓ Ú‡ÚÓ„ÂÌÌÓÒÚË ËÎË ‰Û„ËÏ ÔÓ·Ó˜Ì˚Ï ˝ÙÙÂÍÚ‡Ï Í‡Í Ì‡ ÔÎÓ‰, Ú‡Í Ë Ì‡ χڸ (18), ˝ÍÒÔÂÚ˚ ÔÓ ‰ÂÙˈËÚÛ ËÌ„Ë·ËÚÓ‡ ë1 ÂÍÓÏẨӂ‡ÎË Ì ÔËÏÂÌflÚ¸ íÄ ‚Ó ‚ÂÏfl ·ÂÂÏÂÌÌÓÒÚË, ÂÒÎË ‚ÓÁÏÓÊÌÓ (39). êÓ‰˚: ëΉÛÂÚ Ó͇Á˚‚‡Ú¸ ÒÓÓÚ‚ÂÚÒÚ‚Û˛˘Û˛ ÔÓÏÓ˘¸ ÊÂÌ˘Ë̇Ï, ÒÚ‡‰‡˛˘ËÏ „ÂÏÓÒÚ‡Ú˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË, ÒÓ‚ÏÂÒÚÌÓ Ò ˆÂÌÚ‡ÏË ÔÓ Î˜ÂÌ˲ „ÂÏÓÙËÎËË. ã˜ÂÌË ÔË ‚‡„Ë̇θÌ˚ı Ó‰‡ı ËÎË ÔË ÍÂ҇‚ÓÏ Ò˜ÂÌËË ‰ÓÎÊÌÓ ÔÓ‚Ó‰ËÚ¸Òfl Ë̉˂ˉۇθÌÓ Ë ‚Íβ˜‡Ú¸ ËÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡. çÂÒÏÓÚfl ̇ ÚÓ, ˜ÚÓ ËÌÚÂÌÒË‚ÌÓ ÍÓ‚ÓÚ˜ÂÌË ÔÓÒΠӉӂ ÏÓÊÂÚ ·˚Ú¸ ÒΉÒÚ‚ËÂÏ ‡ÁÌ˚ı Ô˘ËÌ, flÒÌÓ, ˜ÚÓ ÔË ˝ÚÓÏ ÔËÒÛÚÒÚ‚ÛÂÚ ‚˚ÒÓÍËÈ ÛÓ‚Â̸ ÙË·ËÌÓÎËÚ˘ÂÒÍÓÈ ‡ÍÚË‚ÌÓÒÚË. èË ÓÚ‰ÂÎÂÌËË Ô·ˆÂÌÚ˚ ÔÓËÒıÓ‰ËÚ ÂÁÍÓ ÒÌËÊÂÌË ÒÓ‰ÂʇÌËfl PAI-2 ËÌ„Ë·ËÚÓ‡ ‡ÍÚË‚‡ÚÓ‡ Ô·ÁÏËÌÓ„Â̇, Ë Ï‡Ú͇ ‚ ˝ÚÓ ‚ÂÏfl ÒÚ‡ÌÓ‚ËÚÒfl ͇ÈÌ ·Ó„‡ÚÓÈ ‡ÍÚË‚‡ÚÓ‡ÏË Ô·ÁÏËÌÓ„Â̇. ì Ô‡ˆËÂÌÚÓ‚ Ò VWD Ù‡ÍÚÓ ÇËÎη‡Ì‰‡ (VWF) ÒÌËʇÂÚÒfl ÔÓÒΠӉӂ ‚ Ú˜ÂÌË ÌÂÒÍÓθÍËı ̉Âθ, Í‡Í ÔÓËÒıÓ‰ËÚ Ò Ù‡ÍÚÓ‡ÏË VIII Ë IX ‚ ÒÎÛ˜‡Â „ÂÏÓÙËÎËË Ä Ë Ç. ùÚÓ Û‚Â΢˂‡ÂÚ ËÒÍ ÔÓÒÎÂÓ‰Ó‚Ó„Ó ÍÓ‚ÓÚ˜ÂÌËfl Òӄ·ÒÌÓ Kadir Ë Aledort (40). ì ÊÂÌ˘ËÌ Ò VWD, ÚËÔ 3 (ÚflÊfi·fl ÙÓχ), ̇·Î˛‰‡ÎÓÒ¸ ÛÒËÎÂÌË ÍÓ‚ÓÚ˜ÂÌËfl ÔË Î˜ÂÌËË ˝ÚËı ÊÂÌ˘ËÌ ÍÓ̈ÂÌÚ‡ÚÓÏ Ù‡ÍÚÓ‡ ‚ Ú˜ÂÌË ÏÂÌ Úfiı-˜ÂÚ˚fiı ‰ÌÂÈ ÔÓÒΠӉӂ (37). ÇÒÔÓÏÓ„‡ÚÂθ̇fl Ú‡ÔËfl Ò ÔËÏÂÌÂÌËÂÏ íÄ ÏÓÊÂÚ ·˚Ú¸ ÔÓÎÂÁÌÓÈ ‰Îfl ˝ÚËı ÊÂÌ˘ËÌ. ê‰ÍÓ ÓÚϘ‡ÂÚÒfl ‡Á‚ËÚË „ÂÏÓÙËÎËË ÔÓÒΠӉӂ. Ç Ú‡ÍËı ÒÎÛ˜‡flı íÄ ÏÓÊÂÚ ËÒÔÓθÁÓ‚‡Ú¸Òfl Í‡Í ÔÓ‰‰ÂÊË‚‡˛˘‡fl Ú‡ÔËfl ‰Îfl ÛÏÂ̸¯ÂÌËfl ÍÓ‚ÓÚ˜ÂÌËfl. é‰ÌÓ ‚‡ÊÌÓ ËÒÍβ˜ÂÌËÂ: ÂÒÎË Ô‡ˆËÂÌÚ ÔÓıÓ‰ËÚ Î˜ÂÌË ÍÓ̈ÂÌÚ‡Ú‡ÏË ‡ÍÚË‚ËÓ‚‡ÌÌÓ„Ó ÍÓÏÔÎÂÍÒ‡ ÔÓÚÓÏ·Ë̇ (Äêëë), Ú‡ÍËÏË Í‡Í FEIBA, ÚÓ íÄ ˜‡ÒÚÓ ÔÓÚË‚ÓÔÓ͇Á‡Ì‡ ËÁ-Á‡ ËÒ͇ ‡Á‚ËÚËfl ÚÓÏ·ÓÚ˘ÂÒÍËı ÓÒÎÓÊÌÂÌËÈ. èÓ Í‡ÈÌÂÈ ÏÂÂ, Âfi ÒΉÛÂÚ ËÒÔÓθÁÓ‚‡Ú¸ Ò ·Óθ¯ÓÈ ÓÒÚÓÓÊÌÓÒÚ¸˛ (41). äÓÏÎÂÌË „Û‰¸˛ Ò˜ËÚ‡ÂÚÒfl ·ÂÁÓÔ‡ÒÌ˚Ï, Ú‡Í Í‡Í ÍÓ̈ÂÌÚ‡ˆËfl íÄ ‚ „Û‰ÌÓÏ ÏÓÎÓÍ ‚ 100 ‡Á ÏÂ̸¯Â, ˜ÂÏ ‚ Ò˚‚ÓÓÚÍ (10). ÉËÌÂÍÓÎӄ˘ÂÒ͇fl ıËÛ„Ëfl: í̸͇ ¯ÂÈÍË Ï‡ÚÍË, Í‡Í Ë Ú̸͇ Ú· χÚÍË, ÒÓ‰ÂÊËÚ ·Óθ¯Ó ÍÓ΢ÂÒÚ‚Ó ‡ÍÚË‚‡ÚÓÓ‚ Ô·ÁÏËÌÓ„Â̇, ˜ÂÏ Ë Ó·˙flÒÌflÂÚÒfl ÔÓÎÓÊËÚÂθÌÓ ‚ÎËflÌË íÄ ‚ ËÒÒΉӂ‡ÌËflı ÔÓ ÍÓÌËÁ‡ˆËË ¯ÂÈÍË Ï‡ÚÍË (42, 43). Ä̇Îӄ˘Ì˚Ï Ó·‡ÁÓÏ, ‡„ÂÌÚ˚ ‡ÌÚËÙË·ËÌÓÎËÁ‡ ÏÓ„ÛÚ Ë„‡Ú¸ ‚‡ÊÌÛ˛ Óθ ÔË Ú‡ÍËı Ôӈ‰ۇı, Í‡Í Í˛ÂÚ‡Ê Ë „ËÒÚ½ÍÚÓÏËfl. ùÚÓ ÎÂÊËÚ ‚ ÓÒÌÓ‚Â íÄ/ÖÄëÄ Ú‡ÔËË ‰Îfl Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË, ÔÓ‰‚„‡˛˘ËıÒfl „ËÌÂÍÓÎӄ˘ÂÒÍËÏ ÓÔ‡ˆËflÏ. 8 ÜÂÎÛ‰Ó˜ÌÓ-Í˯˜Ì˚ ÍÓ‚ÓÚ˜ÂÌËfl Ç˚ÒÓ͇fl ÏÂÒÚ̇fl ‡ÍÚË‚ÌÓÒÚ¸ ÙË·ËÌÓÎËÚ˘ÂÒÍËı ˝ÌÁËÏÓ‚ ‚ ‚ÂıÌÂÏ ÓÚ‰ÂΠÊÂÎÛ‰Ó˜ÌÓ-Í˯˜ÌÓ„Ó Ú‡ÍÚ‡ ÙÓÏËÛÂÚ ·‡ÁÛ ‰Îfl Ó·˙flÒÌÂÌËfl ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍÓÈ Ú‡ÔËË ÔË ÍÓ‚ÓÚ˜ÂÌËflı Üäí, Í‡Í ˝ÚÓ ÔÓ‰ÂÏÓÌÒÚËÓ‚‡ÎË Cox Ò ÒÓ‡‚Ú. (44). åÂÚ‡-‡Ì‡ÎËÁ ¯ÂÒÚË ‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ı, ‰‚ÓÈÌ˚ı-ÒÎÂÔ˚ı, Ô·ˆÂ·Ó-ÍÓÌÚÓÎËÛÂÏ˚ı ËÒÒΉӂ‡ÌËÈ ÔÓ͇Á‡Î, ˜ÚÓ íÄ ËÏÂÂÚ ÓÚÌÓ¯ÂÌËÂ Í ÒÌËÊÂÌ˲ ˜‡ÒÚÓÚ˚ ̇ 20–30% ÔÓ‚ÚÓÌ˚ı ÍÓ‚ÓÚ˜ÂÌËÈ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÓÚÒÛÚÒÚ‚ËÂÏ Î˜ÂÌËfl, Í ÒÌËÊÂÌ˲ ̇ 30–40% ÌÂÓ·ıÓ‰ËÏÓÒÚË ÓÔ‡ˆËÈ Ë Í ÒÌËÊÂÌ˲ ÒÏÂÚÌÓÒÚË Ì‡ 40% (45). ÄÌ„ËÓ‰ËÒÔ·ÁËfl Í˯˜ÌË͇ ÏÓÊÂÚ ·˚Ú¸ ¢fi Ó‰ÌËÏ ËÒÚÓ˜ÌËÍÓÏ ÍÓ‚ÓÚ˜ÂÌËfl. ÑÓ 6% Ô‡ˆËÂÌÚÓ‚ Ò VWD ËÏÂ˛Ú ˝ÚÓ ‡ÒÒÚÓÈÒÚ‚Ó (46, 47), ˜ÚÓ ÏÓÊÂÚ Û͇Á˚‚‡Ú¸ ̇ ÚÓ, ˜ÚÓ VWD ‰ÂχÒÍËÛÂÚ Ô‡ÚÓÎӄ˲ ÒÓÒÛ‰Ó‚. ÑÎfl ΘÂÌËfl ˝ÚËı ÒÓÒÚÓflÌËÈ – ÔË Ì‡Î˘ËË ËÎË ÔË ÓÚÒÛÚÒÚ‚ËË VWD – íÄ ÏÓÊÂÚ ·˚Ú¸ ÔÓ‰‰ÂÊË‚‡˛˘ËÏ ‡„ÂÌÚÓÏ. ТА для пациентов с геморрагическими расстройствами при кровотечениях из верхнего отдела желудочно-кишечного тракта ТА: 10 мг на кг массы тела 3–6 раз в сутки внутривенно. При эрозивном гастрите: 10 мг на кг массы тела 3–4 раза в сутки вводится в назогастральную трубку до остановки кровотечения. çÓÒÓ‚ÓÂ Ë ÓÚÓ‚Ó ÍÓ‚ÓÚ˜ÂÌË è˘Ë̇ ÌÓÒÓ‚Ó„Ó ÍÓ‚ÓÚ˜ÂÌËfl, ‚ÂÓflÚÌÓ, ÏÌÓ„ÓÙ‡ÍÚÓ̇fl. îË·ËÌÓÎËÚ˘ÂÒ͇fl ‡ÍÚË‚ÌÓÒÚ¸ ·˚· ‚ÒÂÒÚÓÓÌÌ ËÁÛ˜Â̇ Petruson ̇ Ô‡ˆËÂÌÚ‡ı Ò ÂˆË‰Ë‚ËÛ˛˘ËÏË ‰ÎËÚÂθÌ˚ÏË ÌÓÒÓ‚˚ÏË ÍÓ‚ÓÚ˜ÂÌËflÏË Ë ‚ ÍÓÌÚÓθÌÓÈ „ÛÔÔ (48). ëÔÓÌÚ‡Ì̇fl ÙË·ËÌÓÎËÚ˘ÂÒ͇fl ‡ÍÚË‚ÌÓÒÚ¸ ·˚· Á̇˜ËÚÂθÌÓ ‚˚¯Â Û Ô‡ˆËÂÌÚÓ‚ ‚ ÏÓÏÂÌÚ ÍÓ‚ÓÚ˜ÂÌËfl ÔÓ Ò‡‚ÌÂÌ˲ Ò ÒÓÒÚÓflÌËÂÏ ÓÚÒÛÚÒÚ‚Ëfl ÍÓ‚ÓÚ˜ÂÌËfl ˜ÂÂÁ ÌÂÒÍÓθÍÓ Ì‰Âθ. ÇÂÓflÚÌÓ, ÙË·ËÌÓÎËÚ˘ÂÒ͇fl ‡ÍÚË‚ÌÓÒÚ¸ ‚ ÒÎËÁËÒÚÓÈ Ó·ÓÎӘ͠ÌÓÒ‡ ·˚· Á̇˜ËÚÂθÌÓ ‚˚¯Â ‚ ÏÓÏÂÌÚ ÍÓ‚ÓÚ˜ÂÌËfl, ˜ÂÏ ÒÔÛÒÚfl Ó‰ËÌ ÏÂÒflˆ. Ñ‚ÓÈÌÓ ÒÎÂÔÓ ‡Ì‰ÓÏËÁËÓ‚‡ÌÌÓ ËÒÒΉӂ‡ÌËÂ, ‚ ÍÓÚÓÓÏ ÔËÏÂÌflÎË 1 „ íÄ 3 ‡Á‡ Âʉ̂ÌÓ ‚ Ú˜ÂÌË 10 ‰ÌÂÈ, ÔÓ͇Á‡ÎÓ, ˜ÚÓ ÚflÊÂÒÚ¸, ÔÓ‚ÚÓflÂÏÓÒÚ¸ ÍÓ‚ÓÚ˜ÂÌËÈ Ë ‰ÎËÚÂθÌÓÒÚ¸ „ÓÒÔËÚ‡ÎËÁ‡ˆËË Á̇˜ËÚÂθÌÓ ÒÌËʇÎËÒ¸ Û Ô‡ˆËÂÌÚÓ‚, ÔËÌËχ˛˘Ëı íÄ. çÓÒÓ‚Ó ÍÓ‚ÓÚ˜ÂÌË ӘÂ̸ ‡ÒÔÓÒÚ‡ÌÂÌÓ ÒÂ‰Ë ‰ÂÚÂÈ, Ë ˜‡˘Â ‚ÒÂ„Ó ·ÂÁ ÓÒÓ·˚ı Ô˘ËÌ. é‰Ì‡ÍÓ, ÔË ˝ÚÓÏ ÏÓ„ÛÚ ÔËÒÛÚÒÚ‚Ó‚‡Ú¸ „ÂÏÓ‡„˘ÂÒÍË ‡ÒÒÚÓÈÒÚ‚‡, Ú‡ÍËÂ Í‡Í VWD, ÚÓÏ·ÓˆËڇ̇fl ‰ËÒÙÛÌ͈Ëfl Ë, ÂÊÂ, „ÂÏÓÙËÎËfl. Ç Ó‰ÌÓÏ ËÒÒΉӂ‡ÌËË Û ÚÂÚË ‰ÂÚÂÈ Ò ÂˆË‰Ë‚ËÛ˛˘ËÏ ÌÓÒÓ‚˚Ï ÍÓ‚ÓÚ˜ÂÌËÂÏ ‰Ë‡„ÌÓÒÚËÓ‚‡Î‡Ò¸ ÍÓ‡„ÛÎÓÔ‡ÚËfl (49). àÒÒΉӂ‡ÌËfl Û͇Á˚‚‡˛Ú ̇ ÚÓ, ˜ÚÓ 5–10% ‰ÂÚÂÈ Ò ÔÓ‚ÚÓÌ˚ÏË ÌÓÒÓ‚˚ÏË ÍÓ‚ÓÚ˜ÂÌËflÏË ÏÓ„ÛÚ ËÏÂÚ¸ ‡Ì ̠‰Ë‡„ÌÓÒÚËÛÂÏÛ˛ Îfi„ÍÛ˛ ÙÓÏÛ VWD (50, 51). Å˚ÎÓ Ôӂ‰ÂÌÓ ‰‚‡ ËÒÒΉӂ‡ÌËfl ÔÓ ÏÂÒÚÌÓÏÛ ÔËÏÂÌÂÌ˲ ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍËı ‡„ÂÌÚÓ‚ ÔË ÌÓÒÓ‚˚ı ÍÓ‚ÓÚ˜ÂÌËflı: Ó‰ÌÓ ÔÓ ÔËÏÂÌÂÌ˲ ÖÄëÄ (52), Ë Ó‰ÌÓ ÔÓ ÔËÏÂÌÂÌ˲ íÄ (53). íÄ Ì ‰‡Î‡ ÎÛ˜¯Â„Ó ˝ÙÙÂÍÚ‡, ˜ÂÏ Ô·ˆÂ·Ó. çÓ ËÒÒΉӂ‡ÌËfl ·˚ÎË ÒÎ˯ÍÓÏ ÌÂÁ̇˜ËÚÂθÌ˚ÏË ‰Îfl ÚÓ„Ó, ˜ÚÓ·˚ ‰Â·ڸ ͇ÍËÂ-ÎË·Ó ‚˚‚Ó‰˚. äÓÏ ÚÓ„Ó, ·˚Î ËÒÒΉӂ‡Ì ÙË·ËÌÓ‚˚È ÍÎÂÈ, ÒÓ‰Âʇ˘ËÈ ‡ÔÓÚËÌËÌ (54). Ç ÒÓÓÚ‚ÂÚÒÚ‚ËË Ò ‰ËÂÍÚË‚‡ÏË ñÂÌÚ‡ ÉÂÏÓÙËÎËË – 鄇ÌËÁ‡ˆËË ÑÓÍÚÓÓ‚ ëÓ‰ËÌfiÌÌÓ„Ó äÓÓ΂ÒÚ‚‡ – ӇθÌÓ ËÎË ÏÂÒÚÌÓ ÔËÏÂÌÂÌË íÄ ÂÍÓÏẨӂ‡ÌÓ Ô‡ˆËÂÌÚ‡Ï Ò VWD, ÎË·Ó Ò‡ÏÓÒÚÓflÚÂθÌÓ, ÎË·Ó ‚ÏÂÒÚÂ Ò ‰ÂÒÏÓÔÂÒÒËÌÓÏ (DDAVP) ËÎË ÍÓ̈ÂÌÚ‡ÚÓÏ VWF, ‰Îfl ΘÂÌËfl ÍÓ‚ÓÚ˜ÂÌËÈ ‚ ÌÓÒÓ‚ÓÈ Ë ÓÚÓ‚ÓÈ ÔÓÎÓÒÚË (55). íÄ Ú‡ÍÊ ÔÓ͇Á‡Ì‡ Ô‡ˆËÂÌÚ‡Ï Ò ‰Û„ËÏË „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË. äÓ‚ÓÚ˜ÂÌËfl ‚ ÓÚÓ‚ÓÈ ÔÓÎÓÒÚË, Ú‡ÍËÂ Í‡Í ÔË ‡Á˚‚‡ı ÛÁ‰Â˜ÍË Ë ÛÍÛÒ‡ı ̇ „Û·‡ı Ë ˘Â͇ı ˜‡ÒÚÓ Ì‡·Î˛‰‡˛ÚÒfl Û Ï‡ÎÂ̸ÍËı ‰ÂÚÂÈ Ë ÏÓ„ÛÚ ÍÓÌÚÓÎËÓ‚‡Ú¸Òfl ӇθÌ˚Ï Ë ÏÂÒÚÌ˚Ï ÔËÏÂÌÂÌËÂÏ íÄ. Jiménez-Yuste Ò ÒÓ‡‚Ú. fl‚Îfl˛ÚÒfl ÒÚÓÓÌÌË͇ÏË ÔËÏÂÌÂÌËfl DDAVP ËÎË ÍÓ̈ÂÌÚ‡Ú‡ VWF ÔË ÓÚÓ·ËÌ„ÓÎӄ˘ÂÒÍËı ÓÔ‡ˆËflı Û Ô‡ˆËÂÌÚÓ‚ Ò VWD (56). àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ ТА при носовых кровотечениях у пациентов геморрагическими расстройствами Формируется жгут из большого куска хлопковой ваты и закладывается в ноздрю. Один конец погружается в растительное масло или вазелин, смешанный с раздробленной таблеткой ТА. Перед закладыванием ваты в ноздрю следует продуть нос. Можно также применять ТА орально. ëÚÓχÚÓÎӄ˘ÂÒ͇fl ıËÛ„Ëfl .. Ç Ì‡˜‡Î 1960-ı „Ó‰Ó‚ Bjorlin ̇˜‡Î ËÁÛ˜‡Ú¸ ÙË·ËÌÓÎËÁ ‚ ÓÚÓ‚ÓÈ ÔÓÎÓÒÚË (57). éÌ Ò˜ËÚ‡Î, ˜ÚÓ ÏÂÒÚÌ˚È ÙË·ËÌÓÎËÁ ‚ ‡Î¸‚ÂÓ·ı, ‚ÂÓflÚÌÓ, fl‚ÎflÂÚÒfl Ô˘ËÌÓÈ ÍÓ‚ÓÚ˜ÂÌËfl ÔÓÒΠۉ‡ÎÂÌËfl ÁÛ·Ó‚. Å˚ÎË Ôӂ‰ÂÌ˚ ÌÂÒÍÓθÍÓ ËÒÒΉӂ‡ÌËÈ ÔÓ Î˜ÂÌ˲ Ò ÔËÏÂÌÂÌËÂÏ ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Ë VWD, Û ÍÓÚÓ˚ı Û‰‡ÎflÎËÒ¸ ÁÛ·˚, ËÎË ÓÌË ÔÓ‰‚„‡ÎËÒ¸ ӇθÌÓÈ ıËÛ„ËË. ÅÓθ¯ËÌÒÚ‚Ó ËÁ ÌËı Ô‰ÒÚ‡‚Îfl˛Ú ÒÓ·ÓÈ ÓÔËÒ‡ÚÂθÌ˚È ‡Ì‡ÎËÁ, ‚ ÍÓÚÓÓÏ ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍË ‡„ÂÌÚ˚ ÂÍÓÏÂÌ‰Û˛ÚÒfl Ò‡ÏÓÒÚÓflÚÂθÌÓ ËÎË ‚ ÒÓ˜ÂÚ‡ÌËË Ò ÍÓ̈ÂÌÚ‡Ú‡ÏË Ù‡ÍÚÓ‡ ÍÓ‡„ÛÎflˆËË ËÎË DDAVP (58-63). Ç ÌÂÍÓÚÓ˚ı ËÁ ˝ÚËı ËÒÒΉӂ‡ÌËÈ ·˚ÎÓ ‡Ì‰ÓÏËÁËÓ‚‡ÌÓ Ó„‡Ì˘ÂÌÌÓ ˜ËÒÎÓ Ô‡ˆËÂÌÚÓ‚. Forbes Ò ÒÓ‡‚Ú. ÔÓ͇Á‡ÎË, ˜ÚÓ Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Ú‡ÔËfl ‚ Ú˜ÂÌË ÔflÚË ‰ÌÂÈ Ò ÔËÏÂÌÂÌËÂÏ 1 „ íÄ ÚË ‡Á‡ ‚ ÒÛÚÍË, ̇˜Ë̇fl Á‡ ‰‚‡ ˜‡Ò‡ ‰Ó ÓÔ‡ˆËË, ‡ÒÒÓˆËËÓ‚‡Î‡Ò¸ ÒÓ Á̇˜ËÚÂθÌÓ ÏÂ̸¯ËÏ ÔÓ͇Á‡ÚÂÎÂÏ ÔÓÒÎÂÓÔ‡ˆËÓÌÌ˚ı ÍÓ‚ÓÚ˜ÂÌËÈ, ˜ÂÏ ‚ „ÛÔÔ Ô·ˆÂ·Ó (64). ÑÎfl ‰ÓÒÚËÊÂÌËfl Ó‰ÌËı Ë ÚÂı Ê ÔÓ͇Á‡ÚÂÎÂÈ ‚ Ó·ÂËı „ÛÔÔ‡ı Ô‰ ÓÔ‡ˆËÂÈ Ô‡ˆËÂÌÚ‡Ï ‰‡‚‡ÎË ÍÓ̈ÂÌÚ‡Ú .. .. Ù‡ÍÚÓ‡ VIII ËÎË IX. Ramstrom Ë Blomba ck ÔÓ͇Á‡ÎË, ˜ÚÓ ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚ ÍÓ̈ÂÌÚ‡Ú هÍÚÓ‡ Ë ÍÓ΢ÂÒÚ‚Ó ‰ÌÂÈ, Ôӂ‰fiÌÌ˚ı ‚ „ÓÒÔËÚ‡ÎÂ, ÏÓ„ÎË ·˚ ÒÌËÁËÚ¸Òfl ÔË ‚Íβ˜ÂÌËË íÄ Ë ‡ÌÚË·ËÓÚËÍÓ‚ ‚ ÂÊËÏ Î˜ÂÌËfl (65). Å·„ÓÔËflÚÌ˚È ˝ÙÙÂÍÚ ÓÚ ÏÂÒÚÌÓ„Ó ÔËÏÂÌÂÌËfl ÖÄëÄ ‚ ‚ˉ ÊˉÍÓÒÚË ‰Îfl ÔÓÏ˚‚‡ÌËfl Ú‡ ‚Ô‚˚ ·˚Î ÔÓ‰ÂÏÓÌÒÚËÓ‚‡Ì Berry Ò ÒÓ‡‚Ú. (66). Sindet-Pedersen ÂÍÓÏẨÛÂÚ ‰Ó·‡‚ÎflÚ¸ íÄ ‚ ÊˉÍÓÒÚ¸ ‰Îfl ÔÓÏ˚‚‡ÌËfl ÓÚÓ‚ÓÈ ÔÓÎÓÒÚË, Ú‡Í Í‡Í ÔÓÒΠÒËÒÚÂÏÓ„Ó ÔËÏÂÌÂÌËfl íÄ Ì ·˚· ӷ̇ÛÊÂ̇ ‚ ÒβÌÂ Û Á‰ÓÓ‚˚ı ‰Ó·Ó‚ÓθˆÂ‚, ÔËÌËχ‚¯Ëı 1 „ ӇθÌÓ Á‡ Ó‰ËÌ ÔËfiÏ (67). å‡ÍÒËχθ̇fl ÍÓ̈ÂÌÚ‡ˆËfl ‚ Ô·ÁÏ ‰ÓÒÚË„‡Î‡Ò¸ ÔË·ÎËÁËÚÂθÌÓ ˜ÂÂÁ 120 ÏËÌÛÚ. ë ‰Û„ÓÈ ÒÚÓÓÌ˚, ̇·Î˛‰‡Î‡Ò¸ ‚˚ÒÓ͇fl ÍÓ̈ÂÌÚ‡ˆËfl ‚ ÒβÌÂ Û Ô‡ˆËÂÌÚÓ‚ ÔÓÒΠÔÓÎÓÒ͇ÌËfl Ú‡ 5%-Ì˚Ï ‚Ó‰Ì˚Ï ‡ÒÚ‚ÓÓÏ ‚ Ú˜ÂÌË ‰‚Ûı ÏËÌÛÚ ‚ Ó·˙fiÏ 10 ÏÎ, ‚ ÚÓ ‚ÂÏfl Í‡Í ‚ Ô·ÁÏ íÄ Ì ӷ̇ÛÊË‚‡Î‡Ò¸. í‡Ô‚Ú˘ÂÒ͇fl ÍÓ̈ÂÌÚ‡ˆËfl íÄ ÒÓı‡Ìfl·Ҹ ‚ ÒβÌ ·ÓΠ‰‚Ûı ˜‡ÒÓ‚. ì Ô‡ˆËÂÌÚÓ‚ Ò Îfi„ÍÓÈ ÙÓÏÓÈ „ÂÏÓÙËÎËË Ë ÛÓ‚ÌÂÏ Ù‡ÍÚÓ‡, ‡‚Ì˚Ï, ÔÓ Í‡ÈÌÂÈ ÏÂÂ, 10%, ÔËÌËχ‚¯Ëı íÄ ÒËÒÚÂÏÌÓ Ë ÏÂÒÚÌÓ (10 ÏÎ 5%-„Ó ‡ÒÚ‚Ó‡ ‚ Ú˜ÂÌË ‰‚Ûı ÏËÌÛÚ ˜ÂÚ˚ ‡Á‡ ‚ ÒÛÚÍË) ÔË ÒÚÓχÚÓÎӄ˘ÂÒÍËı ÓÔ‡ˆËflı Ì ·˚ÎÓ „ÂÏÓ‡„˘ÂÒÍËı ÓÒÎÓÊÌÂÌËÈ, ‰‡Ê ÂÒÎË ÓÌË Ì ÔÓÎÛ˜‡ÎË Á‡ÏÂÒÚËÚÂθÌÛ˛ Ú‡Ô˲ (68). Waly ÔÓ͇Á‡Î, ˜ÚÓ Û ‰ÂÚÂÈ Ò „ÂÏÓÙËÎËÂÈ, ÔÓÎÛ˜‡‚¯Ëı Á‡ÏÂÒÚËÚÂθÌ˚ ÔÂÔ‡‡Ú˚ Ô‰ Û‰‡ÎÂÌËÂÏ ÁÛ·Ó‚ ÔÎ˛Ò ‡ÒÚ‚Ó íÄ ‰Îfl ÔÓÏ˚‚‡ÌËfl Ú‡, Í‡Í ‰ÓÔÓÎÌÂÌËÂ Í ÒËÒÚÂÏÌÓÈ Ú‡ÔËË, ÂÊ ‡Á‚Ë‚‡ÎÓÒ¸ ÍÓ‚ÓÚ˜ÂÌË ÔÓÒΠۉ‡ÎÂÌËfl ÁÛ·Ó‚ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÚÂÏË, ÍÚÓ Ì ÔËÌËχΠíÄ ÏÂÒÚÌÓ(69). Ç Ò‚ÓfiÏ ÂÚÓÒÔÂÍÚË‚ÌÓÏ ‡Ì‡ÎËÁ ÔË Û˜‡ÒÚËË 63 Ô‡ˆËÂÌÚÓ‚ Ò VWD, Û ÍÓÚÓ˚ı Û‰‡ÎflÎËÒ¸ ÁÛ·˚, ËÎË ÔÓ‚Ó‰ËÎËÒ¸ ‰Û„Ë ÔÂËÓ‰ÓÌڇθÌ˚ ÓÔ‡ˆËË, Federici Ò ÒÓ‡‚Ú. ÓÚÏÂÚËÎË, ˜ÚÓ ÔË ÒËÒÚÂÏÌÓÏ ÔËÏÂÌÂÌËË íÄ ‚ ‚ˉ ÊˉÍÓÒÚË ‰Îfl ÔÓÎÓÒ͇ÌËfl Ú‡ Ë ÓÓ¯ÂÌËfl Ú‡ ̇fl‰Û Ò ÙË·ËÌÓ‚˚Ï ÍÎÂÂÏ ‚Ó ‚ÂÏfl Ôӂ‰ÂÌËfl Ó·¯ËÌ˚ı ÓÔ‡ˆËÈ Á̇˜ËÚÂθÌÓ ÒÌËÁË·Ҹ ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚ ÍÓ̈ÂÌÚ‡Ú VWF (61). ç‡ ÓÒÌÓ‚‡ÌËË Ò‚ÓÂ„Ó ÓÔ˚Ú‡ ‚‰ÂÌËfl Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Zanon Ò ÒÓ‡‚Ú. Ô‰ÎÓÊËÎË ÒÎÂ‰Û˛˘ËÈ ÔÓÚÓÍÓÎ ÔËÏÂÌÂÌËfl: 20 Ï„ íÄ Ì‡ Í„ χÒÒ˚ Ú· Ë Ó‰Ì‡ ËÌÙÛÁËfl Ù‡ÍÚÓ‡ VIII ËÎË IX ‰Îfl ‰ÓÒÚËÊÂÌËfl ÔËÍÓ‚ÓÈ ÍÓ̈ÂÌÚ‡ˆËË ÓÍÓÎÓ 30% ÓÚ ÌÓχθÌÓ„Ó Ù‡ÍÚÓ‡ VIII ËÎË IX Ô‰ Û‰‡ÎÂÌËÂÏ ÁÛ·Ó‚ (70). 20Ï„ íÄ Ì‡ Í„ χÒÒ˚ Ú· ̇Á̇˜‡ÎËÒ¸ ӇθÌÓ ˜ÂÂÁ 8 Ë 16 ˜‡ÒÓ‚, ‡ Á‡ÚÂÏ 3 ‡Á‡ ‚ ÒÛÚÍË ‚ Ú˜ÂÌË ÒÎÂ‰Û˛˘Ëı 7 ‰ÌÂÈ. ÑÓÔÓÎÌËÚÂθÌÓ ËÒÔÓθÁÓ‚‡Î‡Ò¸ χÎfl, ̇Ò˚˘ÂÌ̇fl ‡ÒÚ‚ÓÓÏ íÄ, ÔËÏÂÌfl·Ҹ ÏÂÒÚÌÓ ‚ Ú˜ÂÌË 30–60 ÏËÌÛÚ ÔÓÒΠۉ‡ÎÂÌËfl ÁÛ·‡. ëӄ·ÒÌÓ ÔÓÚÓÍÓÎÛ, ËÒÔÓθÁÛÂÏÓÏÛ Piot Ò ÒÓ‡‚Ú., Ô‰ Û‰‡ÎÂÌËÂÏ ÁÛ·Ó‚ Ë ˜ÂÂÁ 24 ˜‡Ò‡ ÔÓÒΠۉ‡ÎÂÌËfl (ÍÓÏ ÚÓ„Ó, ˜ÂÂÁ 12 ˜‡ÒÓ‚ ÔË ÚflÊfiÎÓÈ ÙÓÏ „ÂÏÓÙËÎËË Ä Ë VWD) ̇Á̇˜‡ÎÒfl ÍÓ̈ÂÌÚ‡Ú Ù‡ÍÚÓ‡ ˜ÚÓ·˚ ‰ÓÒÚ˘¸ 50 % ÓÚ ÌÓχθÌÓ„Ó ÛÓ‚Ìfl ‚ÏÂÒÚÂ Ò ÒËÒÚÂÏÌ˚Ï Ë ÏÂÒÚÌ˚Ï ÔËÏÂÌÂÌËÂÏ íÄ ‚ ‚ˉ ÔÓÎÓÒ͇ÌËfl Ú‡ (71). Rakocz Ò ÒÓ‡‚Ú. ӷ̇ÛÊËÎË, ˜ÚÓ ÙË·ËÌÓ‚˚È ÍÎÂÈ “‰Óχ¯ÌÂ„Ó ÔÓËÁ‚Ó‰ÒÚ‚‡” Ò ‚˚ÒÓÍÓÈ ÍÓ̈ÂÌÚ‡ˆËÂÈ ‡ÔÓÚËÌË̇, ‡‚ÌÓÈ 10000 ‰ËÌˈ‡Ï ËÌ„Ë·ËÚÓ‡ ͇ÎÎËÍÂË̇ (KIU), ̇ ÏÎ (ÔÓ Ò‡‚ÌÂÌ˲ Ò Ëϲ˘ËÏÒfl ‚ ÔÓ‰‡Ê ÍÎÂÂÏ Ò Ó·˚˜ÌÓÈ ÍÓ̈ÂÌÚ‡ˆËÂÈ 1000 KIU ̇ ÏÎ) ÔÎ˛Ò ÔÓÎÓÒ͇ÌË ÒÓ “Ò‚ËÒÚÓÏ Ë „ÎÓÚ‡ÌËÂÏ” ‡ÒÚ‚ÓÓÏ íÄ ·ÂÁ Ô‚ÂÌÚË‚ÌÓÈ Á‡ÏÂÒÚËÚÂθÌÓÈ Ú‡ÔËË ·˚ÎÓ ·ÂÁÓÔ‡ÒÌ˚Ï Ë ˝ÙÙÂÍÚË‚Ì˚Ï ÔË Û‰‡ÎÂÌËË ÁÛ·Ó‚ Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË (72). Ç Ô·ˆÂ·Ó-ÍÓÌÚÓÎËÛÂÏÓÏ ËÒÒΉӂ‡ÌËË Lee Ò ÒÓ‡‚Ú. ÔÓ͇Á‡ÎË, ˜ÚÓ ÊˉÍÓÒÚ¸ ‰Îfl ÔÓÏ˚‚‡ÌËfl Ú‡ Ò ÒÓ‰ÂʇÌËÂÏ íÄ, ÔËÏÂÌflÂχfl Ò‡ÏÓÒÚÓflÚÂθÌÓ, ·˚· Ú‡Í Ê ˝ÙÙÂÍÚ˂̇ ‰Îfl ΘÂÌËfl ‰ÂÒÌ‚˚ı ÍÓ‚ÓÚ˜ÂÌËÈ ÔÓÒΠۉ‡ÎÂÌËfl ÁÛ·ÌÓ„Ó Í‡ÏÌfl, Í‡Í Ë Ô‰‚‡ËÚÂθÌÓ Á‡Ï¢ÂÌË هÍÚÓ‡ Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ (73). àÚ‡Í, ÔË ÒÚÓχÚÓÎӄ˘ÂÒÍËı ÓÔ‡ˆËflı Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Ë VWD ËÒÔÓθÁÛ˛ÚÒfl ‡ÁÌÓÓ·‡ÁÌ˚ ÂÊËÏ˚, ÌÓ Ó˜Â‚Ë‰ÌÓ, ˜ÚÓ ‡„ÂÌÚ˚ ÙË·ËÌÓÎËÁ‡ ÒÓÒÚ‡‚Îfl˛Ú ÓÒÌÓ‚ÌÛ˛ Ú‡Ô˲, Í‡Í ÔË Ò‡ÏÓÒÚÓflÚÂθÌÓÏ ÔËÏÂÌÂÌËË, Ú‡Í Ë ‚ ÒÓ˜ÂÚ‡ÌËË Ò Á‡ÏÂÒÚËÚÂθÌ˚ÏË ÔÂÔ‡‡Ú‡ÏË ËÎË DDAVP. ëӄ·ÒÌÓ Ó·ÁÓ‡Ï ‚‡˜ÂÈ ‚ ç‡Û˜ÌÓ-ËÒÒΉӂ‡ÚÂθÒÍÓÏ é·˙‰ËÌÂÌËË ÔÓ ÉÂÏÓÙËÎËË ‚ ë‚ÂÌÓÈ ÄÏÂËÍ (74), ˝ÚÓ ÒÚ‡ÎÓ ÛÊ Òڇ̉‡ÚÌÓÈ Ôӈ‰ÛÓÈ. Ä̇Îӄ˘Ì˚ ÔÓÚÓÍÓÎ˚ ÓÔËÒ‡Ì˚ Stubbs Ë Lloyd ‚ Ä‚ÒÚ‡ÎËÈÒÍÓÏ ëÚÓχÚÓÎӄ˘ÂÒÍÓÏ ÜÛ̇Π(75) Ë ‚ ‰ËÂÍÚË‚‡ı ëÓ‰ËÌfiÌÌÓ„Ó äÓÓ΂ÒÚ‚‡, ÛÔÓÏflÌÛÚ˚ı ‚˚¯Â (55). á‡Ï¢ÂÌË ÍÓ̈ÂÌÚ‡Ú‡ Ù‡ÍÚÓ‡ ÏÓÊÂÚ ·˚Ú¸ Á̇˜ËÚÂθÌÓ ÒÌËÊÂÌÓ ÔË Ú˘‡ÚÂθÌÓÏ ‚˚ÔÓÎÌÂÌËË ıËۄ˘ÂÒÍÓÈ Ôӈ‰Û˚ ·Ë„‡‰ÓÈ ÓÔ˚ÚÌ˚ı ÒÚÓχÚÓÎÓ„Ó‚, ËÒÔÓθÁÛ˛˘Ëı Ëϲ˘ËÂÒfl „ÂÏÓÒÚ‡Ú˘ÂÒÍË χÚ¡Î˚, Ú‡ÍËÂ Í‡Í íÄ Ë ÙË·ËÌÓ‚˚È ÍÎÂÈ. ä‡Í ÓÚÏÂÚËÎ Schulman, ÌÂËÁ‚ÂÒÚÌÓ, ͇ÍÓÈ ÏËÌËχθÌ˚È ÛÓ‚Â̸ Ù‡ÍÚÓ‡ Ó·ÂÒÔ˜˂‡ÂÚ ‰ÓÒÚ‡ÚÓ˜Ì˚È „ÂÏÓÒÚ‡Ú˘ÂÒÍËÈ ˝ÙÙÂÍÚ ÔË Ôӂ‰ÂÌËË ÓÔ‡ˆËÈ ‡Á΢ÌÓ„Ó ÚËÔ‡ (76). é‡Î¸Ì‡fl ıËÛ„Ëfl ÒÓ Ò‚ÓËÏË Òڇ̉‡ÚËÁËÓ‚‡ÌÌ˚ÏË Ôӈ‰ۇÏË, Ә‚ˉÌÓ, fl‚ÎflÂÚÒfl ÚÓÈ Ó·Î‡ÒÚ¸˛, „‰Â ÔÂÒÔÂÍÚË‚Ì˚ ËÒÒΉӂ‡ÌËfl ÓÔ‡‚‰‡Ì˚. ТА в стоматологической хирургии или для удаления зубов у пациентов с геморрагическими расстройствами В стоматологической хирургии для сужения стенок сосудов рекомендуется использовать местные анестетики с адреналином. Оральное применение ТА: 15–20 мг на кг массы тела перед операцией/удалением зуба, затем три раза в сутки в течение 8–10 дней. Можно полоскать рот 10 мл 5%-го раствора ТА в течение двух минут четыре раза в сутки в течение двух дней. • После удаления зубов и корней в десневые карманы вводится коллагеноподобный TissueFleece® и осторожно накладываются швы. • На область швов можно нанести фибриновый клей. • Местный компресс с давящей повязкой, смоченной в растворе ТА в течение 60 минут. • Холодная мягкая пища в течение двух дней. Одна инфузия концентрата FVIII или IX для достижения пиковой концентрации 30–50 % от нормального уровня назначается пациентам с базальным уровнем ниже 10–15%. 9 àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ å‡ÍÓıËÛ„Ëfl éÚÓÔ‰˘ÂÒ͇fl ıËÛ„Ëfl: ê‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ Ô·ˆÂ·Ó-ÍÓÌÚÓÎËÛÂÏ˚ ËÒÒΉӂ‡ÌËfl ÔÓ Ôӂ‰ÂÌ˲ ÓÔ‡ˆËÈ Ò ÔÓÎÌ˚Ï Á‡Ï¢ÂÌËÂÏ ÍÓÎÂÌÌÓ„Ó ÒÛÒÚ‡‚‡ Û Ô‡ˆËÂÌÚÓ‚ ·ÂÁ „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ ÔÓ͇Á‡ÎË, ˜ÚÓ ÔËÏÂÌÂÌË 10–15 Ï„ íÄ Ì‡ Í„ χÒÒ˚ Ú· Ô‰ ÒÌflÚËÂÏ ÍÓ‚ÓÓÒڇ̇‚ÎË‚‡˛˘Â„Ó Ê„ÛÚ‡ Ò ÔËÏÂÌÂÌËÂÏ ËÎË ·ÂÁ ÔËÏÂÌÂÌËfl ‰ÓÔÓÎÌËÚÂθÌ˚ı ‰ÓÁ ‚ ‰Â̸ Ôӂ‰ÂÌËfl ÓÔ‡ˆËË ÒÌËÁËÎÓ Ó·˘Û˛ ÍÓ‚ÓÔÓÚ² ÔËÏÂÌÓ Ì‡ 50% Ë Á̇˜ËÚÂθÌÓ ÒÓ͇ÚËÎÓ ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚ ÔÂÂÎË‚‡ÌËË ÍÓ‚Ë (77–79). åÂÚ‡-‡Ì‡ÎËÁ ‰Â‚flÚË ‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ı ÍÓÌÚÓÎËÛÂÏ˚ı ËÒÒΉӂ‡ÌËÈ Ì‡ Ô‡ˆËÂÌÚ‡ı Ò ÔÓÎÌÓÈ Á‡ÏÂÌÓÈ ÍÓÎÂÌÌÓ„Ó ÒÛÒÚ‡‚‡ ÔÓ͇Á‡Î, ˜ÚÓ íÄ Á̇˜ËÚÂθÌÓ ÒÌËÁË· ÔÓÔÓˆË˛ Ô‡ˆËÂÌÚÓ‚, ÌÛʉ‡˛˘ËıÒfl ‚ ÔÂÂÎË‚‡ÌËË ÍÓ‚Ë (80). èÂÒÔÂÍÚË‚Ì˚ ‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ ÍÓÌÚÓÎËÛÂÏ˚ ËÒÒΉӂ‡ÌËfl ÔÓ ÔÓÎÌÓÈ Á‡ÏÂÌ ڇÁӷ‰ÂÌÌÓ„Ó ÒÛÒÚ‡‚‡ (81, 82) ÔÓ͇Á‡ÎË, ˜ÚÓ ‰ÓÁ‡ íÄ (10–15 Ï„ ̇ Í„ χÒÒ˚ Ú·), ÔËÏÂÌflÂχfl ÌÂÔÓÒ‰ÒÚ‚ÂÌÌÓ Ô‰ ÓÔ‡ˆËÂÈ, ÒÓ͇ÚË· Ó·˘Û˛ ÍÓ‚ÓÔÓÚ² ÔË·ÎËÁËÚÂθÌÓ Ì‡ 25% ‚ „ÛÔÔ‡ı íÄ ÔÓ Ò‡‚ÌÂÌ˲ Ò „ÛÔÔ‡ÏË Ô·ˆÂ·Ó. í‡ÍÓÈ ÔÓÎÓÊËÚÂθÌ˚È ˝ÙÙÂÍÚ íÄ ÔË Ô‚˘ÌÓÏ ÔÓÎÌÓÏ Á‡Ï¢ÂÌËË Ú‡Áӷ‰ÂÌÌÓ„Ó ÒÛÒÚ‡‚‡ ·˚Î Ú‡ÍÊ ÔÓ‰ÂÏÓÌÒÚËÓ‚‡Ì ‚ ÏÂÚ‡-‡Ì‡ÎËÁ (83). ç‡ÒÍÓθÍÓ ËÁ‚ÂÒÚÌÓ ‡‚ÚÓÛ, ‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ ÍÓÌÚÓÎËÛÂÏ˚ ËÒÒΉӂ‡ÌËfl ÔÓ ÔËÏÂÌÂÌ˲ ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ ‚ χÍÓıËÛ„ËË Ì ÔÓ‚Ó‰ËÎËÒ¸ ̇ Ô‡ˆËÂÌÚ‡ı Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË. Lofquist Ò ÒÓ‡‚Ú. ÓÔÛ·ÎËÍÓ‚‡ÎË ÂÚÓÒÔÂÍÚË‚ÌÓ ËÒÒΉӂ‡ÌË ËÒÚÓËÈ ·ÓÎÂÁÌË 11 Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ (‚ÓÒÂϸ Ô‡ˆËÂÌÚÓ‚ Ò ÚflÊfiÎÓÈ ÙÓÏÓÈ, Ó‰ËÌ Ô‡ˆËÂÌÚ Ò ÛÏÂÂÌÌÓÈ ÙÓÏÓÈ Ë ‰‚‡ Ô‡ˆËÂÌÚ‡ Ò Îfi„ÍÓÈ ÙÓÏÓÈ), Û ÍÓÚÓ˚ı ·˚ÎÓ Ôӂ‰ÂÌÓ Á‡Ï¢ÂÌË ڇÁӷ‰ÂÌÌÓ„Ó ÒÛÒÚ‡‚‡ (84). (é‰ËÌ Ô‡ˆËÂÌÚ ·˚Î ËÒÍβ˜fiÌ, Ú‡Í Í‡Í Û ÌÂ„Ó ·˚· ‰‚ÛıÒÚÓÓÌÌflfl ‡ÚÓÓÔ·ÒÚË͇ ‚ Ó·˙fiÏ ӉÌÓÈ ÓÔ‡ˆËË.) ÑÓÔÓÎÌËÚÂθÌÓ Í Á‡Ï¢ÂÌ˲ Ù‡ÍÚÓ‡ Ô‡ˆËÂÌÚ‡Ï ‰‡‚‡ÎË íÄ Ò ¯ÂÒÚË-, ‚ÓÒ¸Ï˘‡ÒÓ‚˚ÏË ËÌÚ‚‡Î‡ÏË ‚ Ú˜ÂÌË ÒÂÏË ‰ÌÂÈ. Å˚ÎÓ ÔÓ‰Ò˜ËÚ‡ÌÓ, ˜ÚÓ Ó·˘ËÈ Ó·˙fiÏ ÍÓ‚ÓÚ˜ÂÌËfl ÒÓÒÚ‡‚ËÎ 740 ± 400 ÏÎ, ˜ÚÓ ÔÓ˜ÚË ÚÓ Ê ҇ÏÓÂ, ˜ÚÓ Û Ô‡ˆËÂÌÚÓ‚, ÔËÌËχ˛˘Ëı íÄ ‚ ‡Ì‰ÓÏËÁËÓ‚‡ÌÌÓÏ ÍÓÌÚÓÎËÛÂÏÓÏ ËÒÒΉӂ‡ÌËË ÔÓ Á‡Ï¢ÂÌ˲ ‚ÒÂ„Ó Ú‡Áӷ‰ÂÌÌÓ„Ó ÒÛÒÚ‡‚‡ Û Ô‡ˆËÂÌÚÓ‚ ·ÂÁ „ÂÏÓÙËÎËË ËÁ ÚÓ„Ó Ê ÓÚ‰ÂÎÂÌËfl ‚ ÚÓÚ Ê ÔÂËÓ‰ ‚ÂÏÂÌË (81). èË Ôӂ‰ÂÌËË Ó·¯ËÌ˚ı ÓÔ‡ˆËÈ, ÔÓ‰Ó·Ì˚ı ‡ÚÓÔ·ÒÚËÍÂ, Ô‡ˆËÂÌÚ‡Ï Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ˜‡ÒÚÓ Ì‡Á̇˜‡˛Ú ÌÂÔÂ˚‚ÌÛ˛ ËÌÙÛÁ˲ ÍÓ̈ÂÌÚ‡ÚÓ‚ Ù‡ÍÚÓ‡. àϲÚÒfl ‰‡ÌÌ˚Â, ıÓÚfl ÓÌË fl‚Îfl˛ÚÒfl ̇ۘÌÓ ÌÂ۷‰ËÚÂθÌ˚ÏË, ˜ÚÓ ÔË ÌÂÔÂ˚‚ÌÓÈ ËÌÙÛÁËË Ú·ÛÂÚÒfl ÏÂ̸¯Â ÍÓ̈ÂÌÚ‡Ú‡ Ù‡ÍÚÓ‡ ÔÓ Ò‡‚ÌÂÌ˲ Ò ÔÂËӉ˘ÂÒÍËÏË ËÌ˙Â͈ËflÏË Û‰‡Ì˚ı ‰ÓÁ (76). LJÊÌÓ Ó‰ÌÓ‚ÂÏÂÌÌÓ ËÒÔÓθÁÓ‚‡Ú¸ ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍË ‡„ÂÌÚ˚. í‡Í ̇ÔËÏÂ, ‚ ‰‚Ûı ÔÓÒΉӂ‡ÚÂθÌ˚ı „ÛÔÔ‡ı Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Ç, ÔÓÎÛ˜‡˛˘Ëı Ó‰Ë̇ÍÓ‚˚È ÍÓ̈ÂÌÚ‡Ú Ù‡ÍÚÓ‡ ‚ ‚ˉ ËÌÙÛÁËË ÔÓ Ó‰ÌÓÏÛ Ë ÚÓÏÛ Ê ÔÓÚÓÍÓÎÛ ‰Îfl Ó·¯ËÌ˚ı ÓÔ‡ˆËÈ – Ò ÔËÏÂÌÂÌËÂÏ íÄ ‚ Ô‚ÓÈ „ÛÔÔÂ Ë ·ÂÁ ÔËÏÂÌÂÌËfl íÄ ‚Ó ‚ÚÓÓÈ „ÛÔÔ – ÍÓ‚ÓÔÓÚÂË, ‚ Ò‰ÌÂÏ, ÒÓÒÚ‡‚ËÎË 379 Ë 625 ÏÎ ÒÓÓÚ‚ÂÚÒÚ‚ÂÌÌÓ (85, 76). Schulman c ÒÓ‡‚Ú. (86) ÔÓ‰˜ÂÍÌÛÎË ‚ÓÁÏÓÊÌÓÒÚ¸ ÒÌËÊÂÌËfl Ó·˙fiχ ‰ÓÓ„ÓÒÚÓfl˘Â„Ó ÍÓ̈ÂÌÚ‡Ú‡ Ù‡ÍÚÓ‡, ÂÒÎË ËÒÔÓθÁÓ‚‡Ú¸ ÌÂÔÂ˚‚ÌÛ˛ ËÌÙÛÁ˲ ‚ ÒÓ˜ÂÚ‡ÌËË Ò ÏÂÒÚÌ˚ÏË „ÂÏÓÒÚ‡Ú˘ÂÒÍËÏË Ë ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍËÏË ‡„ÂÌÚ‡ÏË, ÍÓÚÓ‡fl ÏÓÊÂÚ ÔÓıÓ‰ËÚ¸ ·ÂÁ Ò¸fiÁÌ˚ı „ÂÏÓ‡„˘ÂÒÍËı ÓÒÎÓÊÌÂÌËÈ. äÓÏ ÚÓ„Ó, ÒΉÛÂÚ ÛÔÓÏflÌÛÚ¸, ˜ÚÓ ÙË·ËÌÓ‚˚È ÍÎÂÈ ÏÓÊÌÓ Ì‰ÓÓ„Ó ÔÓËÁ‚Ó‰ËÚ¸ ‚ ‡Á‚Ë‚‡˛˘ËıÒfl Òڇ̇ı (87). ÅÓθÌ˚ „ÂÏÓÙËÎËÂÈ Ò ËÌ„Ë·ËÚÓ‡ÏË Ô‰ÒÚ‡‚Îfl˛Ú ÒÓ·ÓÈ ÓÒÓ·ÂÌÌÓ ÚÛ‰ÌÛ˛ „ÛÔÔÛ Ô‡ˆËÂÌÚÓ‚. ä‡Í ÛÔÓÏË̇ÎÓÒ¸ ‚˚¯Â, ‰Ó ÒËı ÔÓ Ì ̇ȉÂÌ˚ ÏËÌËχθÌ˚ ˝ÙÙÂÍÚË‚Ì˚ ‰ÓÁ˚ ‰Îfl ‰ÓÒÚËÊÂÌËfl „ÂÏÓÒÚ‡Á‡. ùÚÓ Ôˉ‡fiÚ ·Óθ¯ÓÈ ËÌÚÂÂÒ ˝ÍÒÔÂËÏÂÌÚ‡Ï, ÓÔÛ·ÎËÍÓ‚‡ÌÌ˚Ï Ghosh Ò ÒÓ‡‚Ú. (88). éÌË ÔÓ‚Ó‰ËÎË ËÒÒΉӂ‡ÌËfl ̇ 10 Ô‡ˆËÂÌÚ‡ı Ò „ÂÏÓÙËÎËÂÈ Ë ‚˚ÒÓÍËÏ ÚËÚÓÏ ËÌ„Ë·ËÚÓÓ‚. Ghosh Ò ÍÓÎ΄‡ÏË ÍÓÌÚÓÎËÓ‚‡ÎË „ÂÏÓÒÚ‡Á Û Ò‚ÓËı Ô‡ˆËÂÌÚÓ‚, ÔËÏÂÌflfl ÏÂÒÚÌÓ Ë Ó‡Î¸ÌÓ ÏËÌËχθÌ˚ ӷ˙fiÏ˚ Äêëë Ë/ËÎË ÖÄëÄ ‚ÌÛÚË‚ÂÌÌÓ. Ñ‚‡ Ô‡ˆËÂÌÚ‡ ÔËÌËχÎË FEIBA 25–70–140 ‰ËÌˈ ̇ Í„ 10 χÒÒ˚ Ú· Âʉ̂ÌÓ ‚ÏÂÒÚÂ Ò ÖÄëÄ. èË Ì‡Á̇˜ÂÌËË ·ÓΠ‚˚ÒÓÍÓÈ ‰ÓÁ˚ FEIBA (̇ÔËÏÂ, 200 ‰ËÌˈ ̇ Í„ χÒÒ˚ Ú· ‚ ‰Â̸) Ì ÒΉÛÂÚ ÔËÏÂÌflÚ¸ ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍË ‡„ÂÌÚ˚ ËÁ-Á‡ ËÒ͇ ÚÓÏ·Ó˝Ï·Ó΢ÂÒÍËı ÓÒÎÓÊÌÂÌËÈ. Ä‚ÚÓ˚ ÔÓ‰˜fiÍË‚‡˛Ú ÓÒÓ·Û˛ ‚‡ÊÌÓÒÚ¸ ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍÓÈ Ú‡ÔËË ‰Îfl Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Ë ËÌ„Ë·ËÚÓ‡ÏË. àÚ‡Í, ÌÂÒÏÓÚfl ̇ ÚÓ, ˜ÚÓ ‚ ˝ÚËı ‰ÓÍ·‰‡ı ˜¸ ˉfiÚ Ó· ÓÚÌÓÒËÚÂθÌÓ Ì·Óθ¯ÓÏ ÍÓ΢ÂÒÚ‚Â Ô‡ˆËÂÌÚÓ‚ ‚ ̇̉ÓÏËÁËÓ‚‡ÌÌ˚ı ËÒÒΉӂ‡ÌËflı, ÓÌË ‰‡˛Ú ÓÒÌÓ‚‡ÌË ÔÓ·„‡Ú¸, ˜ÚÓ ÔËÏÂÌÂÌË ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍËı ËÌ„Ë·ËÚÓÓ‚ ÒÌËʇÂÚ ÍÓ‚ÓÔÓÚÂË, ÌÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚ ÔÂÂÎË‚‡ÌËË ÍÓ‚Ë Ë „ÂÏÓ‡„˘ÂÒÍË ÓÒÎÓÊÌÂÌËfl Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ, ‡Ì‡Îӄ˘ÌÓ ˝ÙÙÂÍÚÛ, ‰ÓÒÚË„‡ÂÏÓÏÛ Û Ô‡ˆËÂÌÚÓ‚ ·ÂÁ „ÂÏÓÙËÎËË. Ç ¯‚‰ÒÍËı ˆÂÌÚ‡ı „ÂÏÓÙËÎËË ÔËÏÂÌflÂÚÒfl Òڇ̉‡Ú̇fl Ôӈ‰ۇ, Òӄ·ÒÌÓ ÍÓÚÓÓÈ 10 Ï„ íÄ Ì‡ Í„ χÒÒ˚ Ú· ‚‚Ó‰ËÚÒfl ‚ÌÛÚË‚ÂÌÌÓ ÌÂÔÓÒ‰ÒÚ‚ÂÌÌÓ Ô‰ ÓÔ‡ˆËÂÈ, ‡ Á‡ÚÂÏ ˝Ú‡ ‰ÓÁ‡ ÔËÏÂÌflÂÚÒfl ͇ʉ˚ ¯ÂÒÚ¸-‚ÓÒÂϸ ˜‡ÒÓ‚ ̇ ÔÓÚflÊÂÌËË Ô‡ÂÌÚ‡θÌÓ„Ó ÔËÚ‡ÌËfl Ô‡ˆËÂÌÚ‡, ÔÓÒΠ˜Â„Ó Ì‡Á̇˜‡ÂÚÒfl ‰ÓÁ‡ 1–1,5 „ ӇθÌÓ ÚË ‡Á‡ ‚ ÒÛÚÍË ‚ Ú˜ÂÌË 7–10 ‰ÌÂÈ. ТА в макрохирургии для пациентов с геморрагическими расстройствами Макрохирургия: ТА (10 мг на кг массы тела) три раза в сутки внутривенно с первой дозой непосредственно перед операцией. Орально ТА (15–20 мг на кг массы тела) применяется три раза в сутки после операции, когда пациент может принимать таблетки вместе с антифибринолитической терапией в течение 7–10 дней. • При полной замене коленного сустава непосредственно перед снятием кровоостанавливающего жгута применяется дополнительная доза ТА. • При операциях в нижнем отделе мочевых путей применяется доза 2 г ТА три раза в сутки в день проведения операции и в первый день после операции наряду с орошением мочевого пузыря. • При малых операциях ТА применяется только орально максимум в течение одной недели с первой дозой за два часа до операции. éÔ‡ˆËË Ì‡ ÏӘ‚˚ı ÔÛÚflı: èÓÒÍÓθÍÛ ÏÓ˜‡ ÒÓ‰ÂÊËÚ ‡ÍÚË‚‡ÚÓ ÙË·ËÌÓÎËÁ‡ (uPA), ÚÓ ÒÛ˘ÂÒÚ‚ÛÂÚ Ó˜Â‚Ë‰Ì˚È ËÒÍ ÛÒËÎÂÌËfl ÍÓ‚ÓÚ˜ÂÌËfl ÔË Ôӂ‰ÂÌËË ÓÔ‡ˆËÈ Ì‡ ÏӘ‚˚ı ÔÛÚflı. ÅÓΠÚÓ„Ó, Ô‰ÒÚ‡ÚÂθ̇fl ÊÂÎÂÁ‡ ӷ·‰‡ÂÚ ‚˚ÒÓÍÓÈ ÙË·ËÌÓÎËÚ˘ÂÒÍÓÈ ‡ÍÚË‚ÌÓÒÚ¸˛ (89). ê‡Ì‰ÓÏËÁËÓ‚‡ÌÌ˚ ËÒÒΉӂ‡ÌËfl ÔË ÔÓÒÚ‡Ú˝ÍÚÓÏËË Ò ÌÂÁ̇˜ËÚÂθÌÓ ÓÚ΢‡˛˘ËÏËÒfl ÒıÂχÏË ÔÓ͇Á‡ÎË ÒÌËÊÂÌË ÍÓ‚ÓÚ˜ÂÌËfl ‚ „ÛÔÔ‡ı, ÔËÌËχ˛˘Ëı íÄ ËÎË ÖÄëÄ ÔÓ Ò‡‚ÌÂÌ˲ Ò „ÛÔÔ‡ÏË Ô·ˆÂ·Ó (90–93). çÂÓ·ıÓ‰ËÏÓÒÚ¸ ‚ ÛÓÎӄ˘ÂÒÍÓÈ ÓÔ‡ˆËË, Ú‡ÍÓÈ Í‡Í ÔÓÒÚ‡Ú˝ÍÚÓÏËfl, ÔÓ‚˚¯‡ÂÚÒfl Ò ‚ÓÁ‡ÒÚÓÏ Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË. ç‡ Ò‡ÈÚ Medline ÏÓÊÌÓ Ì‡ÈÚË ÓÍÓÎÓ 20 ‰ÓÍ·‰Ó‚ ÓÚÌÓÒËÚÂθÌÓ ÔÓÒÚ‡Ú˝ÍÚÓÏËË Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ ËÎË VWD. Ç ÌÂÍÓÚÓ˚ı ËÁ ÌËı ‚ ͇˜ÂÒÚ‚Â ‰ÓÔÓÎÌËÚÂθÌÓÈ Ú‡ÔËË ËÒÔÓθÁÓ‚‡ÎËÒ¸ ËÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ (94–95). íÄ Í‡Í ‰ÓÔÓÎÌÂÌËÂ Í ÂÍÓÏ·Ë̇ÌÚÛ FVIIa íÄ ˜‡ÒÚÓ ÔËÏÂÌflÂÚÒfl Í‡Í ‰ÓÔÓÎÌÂÌËÂ Í Ú‡ÔËË Ò ÂÍÓÏ·Ë̇ÌÚÓÏ FVIIa (rFVIIa), ‚˚ÔÓÎÌfl˛˘ËÏ Óθ “Ó·ıÓ‰ÌÓ„Ó ‡„ÂÌÚ‡”. îË·ËÌÓ‚˚È ÍÎÂÈ, ÒÓ‰Âʇ˘ËÈ ‡ÔÓÚËÌËÌ, ‡ Ú‡ÍÊ íÄ ‚‚Ó‰ËÎËÒ¸ ÔË Ô‚ÓÈ ÓÔ‡ˆËË Ò ËÒÔÓθÁÓ‚‡ÌËÂÏ rFVIIa Û Ô‡ˆËÂÌÚ‡ Ò ‚ÓʉfiÌÌÓÈ „ÂÏÓÙËÎËÂÈ Ë ‚˚ÒÓÍËÏ ÚËÚÓÏ ËÌ„Ë·ËÚÓÓ‚ (96). ä‡Í ÓÔËÒ‡ÌÓ ‚ ÌÂÒÍÓθÍËı ÓÚ˜fiÚ‡ı ÔÓ ËÒÚÓËflÏ ·ÓÎÂÁÌÂÈ Ô‡ˆËÂÌÚÓ‚ Ò ËÌ„Ë- àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ ·ËÚÓ‡ÏË Ù‡ÍÚÓ‡ (97–103) ËÎË ÚÓÏ·‡ÒÚÂÌËÂÈ É·̈χÌ̇ (104–106), ̇ ·ÓΠÔÓÁ‰ÌÂÏ ˝Ú‡Ô Ú‡ÔËË íÄ ˜‡ÒÚÓ ËÒÔÓθÁÓ‚‡Î‡Ò¸ Í‡Í ‚ÒÔÓÏÓ„‡ÚÂθÌÓ Ò‰ÒÚ‚Ó ‰Îfl rFVIIa. éÚϘ‡ÂÚÒfl, ˜ÚÓ ÌÂÔÂ˚‚̇fl ËÌÙÛÁËfl Ò rFVIIa Ë ‚ÒÔÓÏÓ„‡ÚÂθ̇fl Ú‡ÔËfl Ò íÄ fl‚Îfl˛ÚÒfl ·ÂÁÓÔ‡ÒÌ˚ÏË Ë ˝ÙÙÂÍÚË‚Ì˚ÏË ÔË Ó·¯ËÌ˚ı ÓÔ‡ˆËflı Û Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓÙËÎËÂÈ Ä Ë ËÌ„Ë·ËÚÓ‡ÏË (107, 109, 99), ‰ÂÙˈËÚÓÏ Ù‡ÍÚÓ‡ XI (109) Ë ‚ÓʉfiÌÌ˚Ï ‰ÂÙˈËÚÓÏ Ù‡ÍÚÓ‡ VII (110). àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ÑÎfl ‚ÒÂı Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË ÏÓÊÌÓ ÔËÏÂÌflÚ¸ ËÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ (íÄ, ÖÄëÄ) – ‚ÌÛÚË‚ÂÌÌÓ, ӇθÌÓ ËÎË ÏÂÒÚÌÓ – ‰Îfl ÔÓÙË·ÍÚËÍË Ë Î˜ÂÌËfl Ò ÌÂÍÓÚÓ˚ÏË ËÒÍβ˜ÂÌËflÏË (ÔӘ˜ÌÓ ÍÓ‚ÓÚ˜ÂÌËÂ, ΘÂÌËÂ Ò ÔËÏÂÌÂÌËÂÏ ÔÓÎÌÓÈ ‰ÓÁ˚ Äêëë). ÑÎfl Ô‡ˆËÂÌÚÓ‚ Ò ÔӘ˜ÌÓÈ Ì‰ÓÒÚ‡ÚÓ˜ÌÓÒÚ¸˛ ‰ÓÁ‡ ‰ÓÎÊ̇ ·˚Ú¸ ÒÌËÊÂ̇. Ç˚‚Ó‰ ùÚ‡ ÏÓÌÓ„‡ÙËfl ‚ ·Óθ¯ÂÈ ÒÚÂÔÂÌË ·‡ÁËÛÂÚÒfl ̇ ËÒÒΉӂ‡ÌËflı, ÔÓ͇Á˚‚‡˛˘Ëı ·Î‡„ÓÔËflÚÌÓ ‚ÎËflÌË ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍËı ‡„ÂÌÚÓ‚, ˜‡˘Â ‚ÒÂ„Ó íÄ, ̇ Ô‡ˆËÂÌÚ‡ı ·ÂÁ ‚ÓʉfiÌÌ˚ı ËÎË ÔËÓ·ÂÚfiÌÌ˚ı „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚. íflÊfiÎ˚ ÔÓ·Ó˜Ì˚ ˝ÙÙÂÍÚ˚ Ì ·˚ÎË ‰ÓÍÛÏÂÌڇθÌÓ ÔÓ‰Ú‚ÂʉÂÌ˚. íÄ ÏÓÊÌÓ ÔËÏÂÌflÚ¸ ‚ÌÛÚË‚ÂÌÌÓ, ӇθÌÓ ËÎË ÏÂÒÚÌÓ. ê‡ÒÚÛ˘Â ÓÒÓÁ̇ÌË ÚÓ„Ó, ˜ÚÓ ˜ÂÂÁ ÍÓÏÔÓÌÂÌÚ˚ ÍÓ‚Ë Ô‰‡˛ÚÒfl ·ÓÎÂÁÌË, ÛÒËÎËÎÓ ‡Á‚Ë- ÚË ÒÚ‡Ú„ËÈ ÔÓ ÛÏÂ̸¯ÂÌ˲ ‡ÎÎÓ„ÂÌÌÓ„Ó ÔÂÂÎË‚‡ÌËfl ÍÓ‚Ë ÔË ÓÔ‡ˆËflı, ‚Íβ˜‡˛˘Ëı ÔËÏÂÌÂÌË ‡ÌÚËÙË·ËÌÓÎËÚ˘ÂÒÍËı ‡„ÂÌÚÓ‚. ùÚÓ Ú‡ÍÊ ÏÓÊÂÚ ÒÌËÁËÚ¸ ÔÓÚ·ÌÓÒÚ¸ ‚ ÍÓ̈ÂÌÚ‡Ú‡ı Ù‡ÍÚÓÓ‚ ÍÓ‡„ÛÎflˆËË, ÔÓÁ‚ÓÎflfl ÒÓ͇ÚËÚ¸ Á‡Ú‡Ú˚. èË ‚ÓÁÌËÍÌÓ‚ÂÌËË ÍÓ‚ÓÚ˜ÂÌËfl ‡ÍÚË‚ËÁËÛÂÚÒfl ÔÓˆÂÒÒ „ÂÏÓÒÚ‡Á‡, ‚Íβ˜‡˛˘ËÈ ÙË·ËÌÓÎËÁ. èÓ˝ÚÓÏÛ ÔËÏÂÌÂÌË ËÌ„Ë·ËÚÓÓ‚ ÙË·ËÌÓÎËÁ‡ Ò‡ÏÓÒÚÓflÚÂθÌÓ ËÎË Í‡Í ‰ÓÔÓÎÌÂÌËÂ Í ‰Û„ÓÈ „ÂÏÓÒÚ‡Ú˘ÂÒÍÓÈ Ú‡ÔËË ‰Îfl Ô‡ˆËÂÌÚÓ‚ Ò „ÂÏÓ‡„˘ÂÒÍËÏË ‡ÒÒÚÓÈÒÚ‚‡ÏË, ˜ÚÓ·˚ Û‡‚ÌÓ‚ÂÒËÚ¸ Ëı ̉ÓÒÚ‡ÚÓ˜Ì˚È ÔÓ„ÂÏÓÒÚ‡Ú˘ÂÒÍËÈ ÔÓˆÂÒÒ, Ô‰ÒÚ‡‚ÎflÂÚÒfl ‚˚ÒÓÍÓ ÓÔ‡‚‰‡ÌÌ˚Ï. ëÓ͇˘ÂÌËfl ÄåëÄ Äêëë BW Da DDAVP ÖÄëÄ GI KIU LBS PAI rFVIIa íÄ tPA U uPA VWD VWF í‡ÌÂÍÒ‡ÏÓ‚‡fl ÍËÒÎÓÚ‡ – íÄ äÓ̈ÂÌÚ‡Ú ‡ÍÚË‚ËÓ‚‡ÌÌÓ„Ó ÍÓÏÔÎÂÍÒ‡ ÔÓÚÓÏ·Ë̇ å‡ÒÒ‡ Ú· чθÚÓÌ ÑÂÒÏÓÔÂÒÒËÌ ùÔÒËÎÓÌ-‡ÏËÌÓ͇ÔÓÌÓ‚‡fl ÍËÒÎÓÚ‡ ÜÂÎÛ‰Ó˜ÌÓ-Í˯˜Ì˚È Ú‡ÍÚ Ö‰ËÌˈ‡ ËÌ„Ë·ËÚÓ‡ Kallikrein ãËÁËÌ-Ò‚flÁ˚‚‡˛˘ËÈ Û˜‡ÒÚÓÍ àÌ„Ë·ËÚÓ ‡ÍÚË‚‡ÚÓ‡ Ô·ÁÏËÌÓ„Â̇ ÄÍÚË‚ËÓ‚‡ÌÌ˚È Ù‡ÍÚÓ VII ÂÍÓÏ·Ë̇ÌÚ‡ í‡ÌÂÍÒ‡ÏÓ‚‡fl ÍËÒÎÓÚ‡ ÄÍÚË‚‡ÚÓ Ô·ÁÏËÌÓ„Â̇ Ú͇ÌÂ‚Ó„Ó ÚËÔ‡ Ö‰ËÌˈ‡ ìÓÍË̇Á‡ ÅÓÎÂÁ̸ ÇËÎη‡Ì‰‡ î‡ÍÚÓ ÇËÎη‡Ì‰‡ 11 àÌ„Ë·ËÚÓ˚ ÙË·ËÌÓÎËÁ‡ ÔË Î˜ÂÌËË „ÂÏÓ‡„˘ÂÒÍËı ‡ÒÒÚÓÈÒÚ‚ ãËÚ‡ÚÛ‡ nolytic agent, tranexamic acid (AMCA). 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