Lenzini Petra A, Grice Gloria R, Milligan Paul E, Gatchel Susan K, Deych Elena, Eby Charles S, Burnett R Stephen J, Clohisy John C, Barrack Robert L, Gage Brian F
Washington University in St. Louis, St. Louis, MO 63110, USA.
Ann Pharmacother. 2007 Nov;41(11):1798-804. doi: 10.1345/aph.1K197. Epub 2007 Oct 2.
Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR).
To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors.
We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105).
About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose.
We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.
华法林钠常用于静脉血栓栓塞的预防和治疗。给药算法尚未得到广泛应用，因为它们需要固定的初始华法林剂量（如5毫克），且未根据可能影响国际标准化比值（INR）的其他因素进行调整。
开发一种算法，该算法可根据药物相互作用、初始华法林剂量后的INR反应及其他临床因素预测华法林的治疗剂量。
我们采用逐步回归法来量化在关节置换术前立即开始预防性华法林治疗的患者中这些因素之间的关系。在推导队列（n = 271）中，我们分别对初始2剂和3剂后的治疗剂量进行建模。我们在一个独立队列（n = 105）中对这两个模型进行了前瞻性验证。
治疗3天后，约一半的治疗剂量变异性是可预测的：推导队列中的R2为53%，验证队列中的R2为42%。3剂华法林后的INR反应（INR3）与治疗剂量呈负相关（p < 0.001）。术中失血会使术后INR值短暂但显著升高。其他显著（p < 0.03）的预测因素为第一剂和第二剂华法林（每1毫克分别增加7%和6%）以及他汀类药物的使用（-15.0%）。2剂华法林后得出的模型解释了治疗剂量变异性的32%。
我们开发并验证了基于华法林治疗2 - 3天后的临床因素和INR反应来估算华法林治疗剂量的算法。这些算法可在www.WarfarinDosing.org在线使用。
