Department of Medicine, University of Western Ontario, London, Ontario, Canada.
Thromb Haemost. 2012 Feb;107(2):248-52. doi: 10.1160/TH11-09-0610. Epub 2011 Dec 21.
Prothrombin complex concentrates (PCC) are recommended for urgent warfarin reversal. However, disagreement exists regarding the proper dosing strategy (i.e. fixed vs. weight-based). We measured the in vitro effect of PCC dosing on international normalised ratio (INR) and factor activity. Plasma from warfarin-anticoagulated patients with stable INRs was collected. PCC doses of 1,000, 2,000 and 3,000 IU were added to the samples, and INR and factor activity were analysed before and after PCC. Twenty-three of thirty subjects enrolled had complete data for analysis. INRs were below 1.5 in all samples post-1,000 IU, and decreased further with subsequent doses (p<0.001). Factors II, VII, and X increased with consecutive doses (p<0.01). Linear correlation was seen between INR and factors II, VII and X. Factor IX did not increase consistently nor show correlation with INR reversal. Weight-based dosing was then estimated; INRs were all <1.2 (0.9-1.2) and activity >0.50 IU for factors II, VII and X (0.96-1.52, 0.51-1.45 and 0.81-1.38, respectively). Factor IX did not uniformly correct above 0.50 IU (0.31-1.31). We confirm in vitro that 1,000 IU of Octaplex(®) is able to correct INR to <1.5 but factors were not uniformly >0.50 IU until 2,000 IU, and not >1.00 IU until 3,000 IU. This suggests that INR correction alone may not accurately reflect factor activity, and lends support for weight-based dosing.
凝血酶原复合物浓缩物（PCC）被推荐用于紧急华法林逆转。然而，对于适当的给药策略（即固定剂量与体重剂量）存在分歧。我们测量了 PCC 给药对国际标准化比值（INR）和因子活性的体外影响。从 INR 稳定的华法林抗凝患者中采集血浆。将 1,000、2,000 和 3,000 IU 的 PCC 剂量添加到样品中，并在添加 PCC 前后分析 INR 和因子活性。在 30 名入组的受试者中，有 23 名的完整数据可用于分析。所有样本在 1,000 IU 后 INR 均低于 1.5，并且随着后续剂量的增加而进一步降低（p<0.001）。因子 II、VII 和 X 随着连续剂量的增加而增加（p<0.01）。INR 与因子 II、VII 和 X 之间存在线性相关性。因子 IX 没有一致增加，也没有与 INR 逆转相关。然后估计了基于体重的剂量；INR 均<1.2（0.9-1.2），因子 II、VII 和 X 的活性均>0.50 IU（0.96-1.52、0.51-1.45 和 0.81-1.38，分别）。因子 IX 没有一致增加到 0.50 IU 以上（0.31-1.31）。我们在体外证实，1,000 IU 的 Octaplex(®) 能够将 INR 校正至<1.5，但直到 2,000 IU 因子才没有一致地>0.50 IU，直到 3,000 IU 才>1.00 IU。这表明 INR 校正本身可能无法准确反映因子活性，并为基于体重的给药提供支持。
