CSL Behring, King of Prussia, PA.
Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA.
Blood Adv. 2023 May 23;7(10):2206-2213. doi: 10.1182/bloodadvances.2022009015.
Restoration of the international normalized ratio (INR) to values <1.5 is commonly targeted to achieve hemostasis in patients with major bleeding or undergoing urgent surgery who are treated using vitamin K antagonists (VKAs). However, the relationship between corrected INR and vitamin K-dependent factor (VKDF) levels for hemostasis is uncertain. We aim to examine the impact of 4-factor prothrombin complex concentrate (4F-PCC) or plasma on INR correction and VKDF restoration and evaluate the relationship between INR values and VKDF levels in patients with acute major bleeding or patients requiring an urgent surgical procedure. Adult patients treated with VKA with an elevated INR (≥2.0 within 3 hours before study treatment) who received 4F-PCC or plasma after major bleeding or before an urgent surgery or invasive procedure were included in this retrospective analysis of data from 2 prospective phase 3b randomized controlled trials. Of the 370 patients included in this analysis, 185 received 4F-PCC, and 185 received plasma. In the 4F-PCC group, 159 of 185 (85.9%) had an INR ≤1.5 at 30 minutes after the end of infusion compared with only 72 of 184 (39.1%) in the plasma group. After 4F-PCC treatment, all VKDF levels exceeded 50% activity regardless of the postinfusion INR value. However, after plasma administration, mean activity levels for factors II and X were <50% at all time points assessed within 3 hours after starting the infusion, regardless of the postinfusion INR value. This retrospective analysis demonstrated that treatment with 4F-PCC among patients treated with VKA rapidly restores VKDFs to hemostatic levels irrespective of the postinfusion INR value, whereas treatment with plasma does not.
恢复国际标准化比值（INR）至<1.5 通常是为了实现正在接受维生素 K 拮抗剂（VKA）治疗的大出血或紧急手术患者的止血目标。然而，INR 与维生素 K 依赖因子（VKDF）水平之间的关系尚不确定。我们旨在研究 4 因子凝血酶原复合物浓缩物（4F-PCC）或血浆对 INR 校正和 VKDF 恢复的影响，并评估急性大出血或需要紧急手术的患者的 INR 值与 VKDF 水平之间的关系。
在这项对 2 项前瞻性 3b 期随机对照试验数据的回顾性分析中，纳入了正在接受 VKA 治疗且 INR 升高（研究治疗前 3 小时内 INR≥2.0）且在发生大出血或紧急手术或有创操作后接受 4F-PCC 或血浆治疗的成年患者。在这项分析中，共纳入了 370 例患者，其中 185 例接受了 4F-PCC，185 例接受了血浆。在 4F-PCC 组中，输注结束后 30 分钟时，有 159/185（85.9%）例患者 INR≤1.5，而在血浆组中，仅 72/184（39.1%）例患者 INR≤1.5。接受 4F-PCC 治疗后，所有 VKDF 水平均超过 50%的活性，无论输注后 INR 值如何。然而，在给予血浆后，无论输注后 INR 值如何，在输注开始后 3 小时内评估的所有时间点，因子 II 和 X 的平均活性水平均<50%。
这项回顾性分析表明，在接受 VKA 治疗的患者中，使用 4F-PCC 治疗可迅速将 VKDF 恢复至止血水平，而使用血浆治疗则不能。
