濃縮凝固因子製剤up-to-date

Concentrated Coagulation Factor Concentrate Up-to-Date

はじめに

　2019年から発生した新型コロナ感染症（COVID-19）はあらゆる既存の医療システムを崩壊させた。輸血もまたしかりで，若年献血者の激減により，深刻な輸血不足が生じた^1）。COVID-19は5類への移行に伴い，わが国の輸血不足はほぼ解消されたが，オーストラリア発祥のpatient blood managementなど^2），国家を挙げての輸血削減プログラムの重要性が再認識された。一方，超高齢化社会を迎える日本にとって心房細動（atrial fibrillation：AF）患者は2050年に全人口の1.09％に達するといわれている^3）。それに伴う脳血管障害患者数の増加など，副次的疾患も増加し集中治療や周術期を担う麻酔科医にとっては出血・凝固に関する知識はますます必要不可欠となっている。本論文では，“濃縮凝固因子製剤up-to-date” と題し，濃縮凝固因子製剤にフォーカスを当て，特に濃縮フィブリノゲン製剤，濃縮プロトロンビン複合体製剤（PCC），遺伝子組み換え活性型第Ⅶ因子製剤の3つをピックアップし，最近の知見や著者らの臨床経験を交えて提示する。

　The focus of this article is concentrated coagulation-factor preparations, particularly concentrated fibrinogen products, prothrombin concentrated complex products, and recombinant activated factor Ⅶ products.

1．Concentrated fibrinogen products

　The currently available concentrated fibrinogen products are human dried fibrinogen and cryoprecipitate. The indications for the use of concentrated fibrinogen products are limited to the goals of “improvement of bleeding tendency in congenital hypofibrinogenemia” and “supplementation of fibrinogen for acquired hypofibrinogenemia associated with obstetric crisis hemorrhage.” The product volume is very small, and thus the risk of the development of a transfusion associated circulatory overload（TACO）is low. In Japan, 30％ of the uses of concentrated fibrinogen products were off-label for cardiac surgery and trauma. When a cryoprecipitate is used, it must match the patient’s blood type, but cryoprecipitate can be used in a wide range of diseases including cardiac surgery and trauma.

2．Prothrombin concentrated complex products, or PCCs

　A three-factor PCC and a four-factor PCC are used as concentrated coagulation-factor preparations. The three-factor PCC is indicated for hemophilia B and contain coagulation factors Ⅱ, Ⅸ, and Ⅹ；it is less effective for warfarin antagonism. The four-factor PCC contains coagulation factors Ⅱ, Ⅶ, Ⅸ, Ⅹ and proteins C and S, and it is an inhibitor of vitamin K antagonists（VKAs）such as warfarin.

3．Recombinant activated factor Ⅶ products

　Recombinant activated factor Ⅶ products are a bypass hemostatic drug for the treatment of bleeding in patients with hemophilia with bleeding inhibitors. There have been reports since 2000 that recombinant activated factor Ⅶ（rFⅦ）is effective in cardiac surgery. Its most commonly reported dosing ranges are around 40-80 μg/kg, but there have been no randomized control trials indicating a benefit of treatment with rFVII. The dosage reported by Hoffman et al. in 2018 was lower than those described in earlier papers, and they said that a very low dose, that is, 20 μg/kg, might be beneficial and reduce the risk of thrombotic complications.