Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
Thromb Haemost. 2011 Dec;106(6):1215-23. doi: 10.1160/TH11-04-0240. Epub 2011 Nov 10.
Prothrombin complex concentrates (PCCs) and fresh-frozen plasma (FFP) have been clinically used for acute warfarin reversal. The recovery of prothrombin time (PT) or international normalised ratio (INR) is often reported as an endpoint, but haemostatic efficacies of PCCs and FFP may not be fully reflected in static clotting test in platelet-poor plasma. Using various in vitro assays, we compared the effects of two PCC preparations (3-factor PCC; Bebulin and 4-factor PCC; Beriplex) and FFP on warfarin reversal under static and flow conditions. First, we added an aliquot of either PCC (0.3 or 0.72 U/ml) or 20% FFP (v/v) to commercial warfarin plasma (INR 3.2, or 10.3), and then measured PT, factor II, factor VII, and thrombin generation. Subsequently, we collected whole blood samples from six consented warfarin-treated patients with mean INR 3.0 ± 0.5 (range 2.5-3.7), and compared clot formation under flow conditions at 280 s-1 before and after addition of either PCC preparation (0.3 and 0.6 U/ml) or 20% of FFP (v/v). PT/INR were restored by either PCC in plasma with INR 3.0, but they were more effectively corrected by 4-factor PCC than 3-factor PCC in plasma with INR 10.3. Effects of FFP were similar to 0.3 U/ml of PCCs in terms of PT, but FFP was less efficacious than PCCs in recovering thrombin generation or factor II levels. In flow experiments, the onset of thrombus formation was shortened by either PCC, but not by FFP, contrary to shortened PT values. For warfarin reversal 20% volume replacement with FFP is inferior to PCCs.
凝血酶原复合物浓缩物（PCC）和新鲜冷冻血浆（FFP）已在临床上用于急性华法林逆转。凝血酶原时间（PT）或国际标准化比值（INR）的恢复通常被报告为终点，但 PCC 和 FFP 的止血效果可能无法完全反映在血小板减少的血浆中的静态凝血试验中。使用各种体外测定法，我们比较了两种 PCC 制剂（3 因子 PCC；Bebulin 和 4 因子 PCC；Beriplex）和 FFP 在静态和流动条件下对华法林逆转的影响。首先，我们向商业华法林血浆（INR 3.2，或 10.3）中加入 PCC（0.3 或 0.72 U/ml）或 20%FFP（v/v）的等分试样，然后测量 PT、因子 II、因子 VII 和凝血酶生成。随后，我们从六名同意接受华法林治疗的患者中收集全血样本，平均 INR 为 3.0±0.5（范围 2.5-3.7），并比较在加入 0.3 和 0.6 U/ml 的 PCC 制剂或 20%FFP（v/v）前后在 280 s-1 下的流动条件下的血块形成。在 INR 为 3.0 的血浆中，任何一种 PCC 都能恢复 PT/INR，但在 INR 为 10.3 的血浆中，4 因子 PCC 比 3 因子 PCC 更有效地纠正。FFP 在 PT 方面的作用与 0.3 U/ml 的 PCC 相似，但在恢复凝血酶生成或因子 II 水平方面，FFP 的效果不如 PCC。在流动实验中，PCC 缩短了血栓形成的开始时间，但 FFP 没有，与缩短的 PT 值相反。对于华法林逆转，20%的容量替代用 FFP 不如 PCC。
