Department of Pharmacy, Intermountain Medical Center, 5121 South Cottonwood St, Murray, UT, 84107, USA.
Department of Pharmacy, Nebraska Medicine, Omaha, NE, 68198, USA.
J Thromb Thrombolysis. 2022 Aug;54(2):268-275. doi: 10.1007/s11239-022-02646-0. Epub 2022 Apr 4.
Dosing of 4-factor prothrombin complex concentrate (4FPCC) in warfarin treated patients generally utilizes international normalized ratio (INR) and patient weight. The recommended maximum dosing for all INR categories is capped at 100 kg weight. Whether this affects INR reversal is unknown. Furthermore, characteristics associated with adequate INR reversal need to be further elucidated. This was a multi-center, retrospective cohort study of 186 patients who received 4FPCC for INR reversal in the setting of warfarin-associated hemorrhage or need for emergent INR reversal. Utilizing multiple regression analysis, we evaluated INR reversal, achievement of hemostasis, and 28-day all-cause mortality. A target INR < 1.4 was achieved in 132 of 186 patients (71%). Factors significantly affecting the odds of achieving target INR were age in years (OR 1.03; 95% CI 1.01-1.06; P = 0.01), weight-based 4FPCC dose (units/kg) (OR 1.04; 95% CI 1.00-1.08; P = 0.03), and 4FPCC dosing normalized to INR (units/kg/INR) (OR 1.18; 95% CI 1.03-1.35; P = 0.02). Hemostasis was achieved in 109 of 148 bleeding patients (73.6%). Blood transfusions were associated with not achieving hemostasis (OR 0.44; 95% CI 0.21-0.93; P = 0.03). All-cause 28-day mortality was 21.5% and was associated with intracranial hemorrhage (OR 2.83; 95% CI 1.38-5.8; P = 0.01). Adequate INR reversal was associated with age, weight-based 4FPCC dose, and dosing normalized to INR (units/kg/INR). Future studies should evaluate the appropriateness of current INR targets for warfarin reversal and alternative 4FPCC dosing strategies such as utilizing a 4FPCC dosing ratio of units/kg/INR.
在接受华法林治疗的患者中，使用 4 因子凝血酶原复合物浓缩物（4FPCC）的剂量通常采用国际标准化比值（INR）和患者体重。所有 INR 类别中推荐的最大剂量上限为 100kg 体重。但这是否会影响 INR 逆转尚不清楚。此外，还需要进一步阐明与适当 INR 逆转相关的特征。这是一项多中心、回顾性队列研究，共纳入 186 例因华法林相关性出血或需要紧急 INR 逆转而接受 4FPCC 逆转 INR 的患者。我们采用多因素回归分析，评估 INR 逆转、止血效果和 28 天全因死亡率。186 例患者中，有 132 例（71%）达到目标 INR＜1.4。显著影响达到目标 INR 比值的因素包括年龄（OR 1.03；95%CI 1.01-1.06；P=0.01）、体重校正的 4FPCC 剂量（单位/kg）（OR 1.04；95%CI 1.00-1.08；P=0.03）和 INR 标准化的 4FPCC 剂量（单位/kg/INR）（OR 1.18；95%CI 1.03-1.35；P=0.02）。148 例出血患者中，有 109 例（73.6%）止血。输血与未止血相关（OR 0.44；95%CI 0.21-0.93；P=0.03）。28 天全因死亡率为 21.5%，与颅内出血相关（OR 2.83；95%CI 1.38-5.8；P=0.01）。适当的 INR 逆转与年龄、体重校正的 4FPCC 剂量和 INR 标准化的剂量（单位/kg/INR）相关。未来的研究应评估当前华法林逆转的 INR 目标和替代 4FPCC 剂量策略（如使用单位/kg/INR 的 4FPCC 剂量比）的适宜性。
