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華法林治療新指南強調避免過高的初始劑量,推薦從5毫克開始,並根據國際標準化比率(INR)調整劑量。此外,對於INR異常升高的病人,應增頻監測和適當使用維生素K1或凍乾血漿,以確保治療的安全性和有效性。
Management and dosing of warfarin therapy
Abstract
When initiating warfarin therapy, clinicians should avoid loading doses that can raise the International Normalized Ratio (INR) excessively; instead, warfarin should be initiated with a 5-mg dose (or 2 to 4 mg in the very elderly). With a 5-mg initial dose, the INR will not rise appreciably in the first 24 hours, except in rare patients who will ultimately require a very small daily dose (0.5 to 2.0 mg). Adjusting a steady-state warfarin dose depends on the measured INR values and clinical factors: the dose does not need to be adjusted for a single INR that is slightly out of range, and most changes should alter the total weekly dose by 5% to 20%. The INR should be monitored frequently (eg, 2 to 4 times per week) immediately after initiation of warfarin; subsequently, the interval between INR tests can be lengthened gradually (up to a maximum of 4 to 6 weeks) in patients with stable INR values. Patients who have an elevated INR will need more frequent testing and may also require vitamin K1. For example, a nonbleeding patient with an INR of 9 can be given low-dose vitamin K1 (eg, 2.5 mg phytonadione, by mouth). Patients who have an excessive INR with clinically important bleeding require clotting factors (eg, fresh-frozen plasma) as well as vitamin K1.
摘要
在開始華法林治療時,醫師應避免使用可能過度提高國際標準化比值 (INR) 的負荷劑量,而應以 5 毫克劑量開始(非常年長者則應以 2 至 4 毫克劑量開始)。使用 5 毫克初始劑量時,除非極少數患者最終需要非常小的每日劑量(0.5 至 2.0 毫克),否則 INR 在最初 24 小時內不會明顯升高。穩定狀態下的華法林劑量調整取決於 INR 值和臨床因素:單次 INR 略有偏差時無需調整劑量,大部分的劑量改變應該調整總週劑量的 5% 至 20%。在開始華法林治療後,應頻繁監測 INR(例如,每週 2 至 4 次);隨後,可逐步延長 INR 測試間隔(最長可達 4 至 6 週)對於 INR 穩定的患者。INR 升高的患者需要更頻繁的測試,並可能需要維生素 K1。例如,INR 為 9 的無出血患者可以口服低劑量維生素 K1(例如 2.5 毫克的維他命 K1)。INR 過高且出現臨床重要出血的患者需要凝血因子(如新鮮冰凍血漿)和維生素 K1。
章節摘要
華法林的藥理學
口服華法林後可完全吸收,並高度結合於血漿中的白蛋白(表1)。白蛋白與游離華法林濃度的反比關係,是術後或急性病患者需要較低劑量華法林的原因之一。市售華法林(如 Coumadin)為消旋混合物,兩種對映異構物各自有不同的代謝途徑。S 對映異構物由肝臟中的細胞色素 P450 酶(CYP2C9)氧化,然後……
華法林治療的開始
達到穩定的 INR 反應平均需要將近兩週4, 5。這個長期延遲是由於華法林的長半衰期、功能性凝血因子降至低水平所需的時間以及實驗確立正確日劑量所需的時間。
華法林治療的維持
醫師通常必須就門診華法林劑量做出三個重要決策:何時根據觀察到的 INR 調整劑量,改變劑量以達到目標 INR 的程度,以及如何頻繁監測 INR。然而,文獻並未對這些問題提供確定的答案。
無症狀 INR 升高的管理
隨著 INR 升高,出血風險呈指數上升61, 62, 63, 64, 65, 66。降低 INR 的主要方法是停止服用華法林,口服或注射維生素 K1,以及輸注功能性凝血因子(如新鮮冰凍血漿)。INR 升高的常見原因包括劑量錯誤、華法林-藥物相互作用(表2)、使用肝素、測量誤差、急性疾病或維生素 K1 攝取量減少。
出血患者的管理
唯一能快速恢復正常凝血的方法是通過輸注新鮮冰凍血漿或凝血因子濃縮液來提供功能性凝血因子。如果 INR 升高且患者出血,約 800 毫升的新鮮冰凍血漿(劑量取決於患者的體型)靜脈注射可將升高的 INR 降至治療範圍(88)。應在新鮮冰凍血漿輸注後不久測量 INR,如果需要可進一步補充。
抗凝診所與自我監測的使用
隨機試驗發現,專業的多學科診所比通常的護理能達到更好的管理效果。Sawicki 及其同事(95)發現,隨機分配到包含自我管理抗凝治療的強化病人教育計劃中的患者,其 INR 控制改善。在另一項研究中,抗凝診所的登記患者對其華法林治療更為滿意且更了解(96)。Beyth 及其同事(97)報告了較少的不良事件。
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