Pabinger Ingrid, Tiede Andreas, Kalina Uwe, Knaub Sigurd, Germann Reinhard, Ostermann Helmut
Department of Internal Medicine, Division of Haematology and Haemostaseology, Medical University Vienna, Vienna, Austria.
Ann Hematol. 2010 Mar;89(3):309-16. doi: 10.1007/s00277-009-0830-7. Epub 2009 Sep 29.
Prothrombin complex concentrate (PCC) infusion is preferred for emergency reversal of coumarin therapy. Rapid infusion can potentially save crucial time; however, the possible impact of high infusion speed on PCC safety and effectiveness has not been delineated. In a prospective multinational clinical trial with 43 patients receiving PCC (Beriplex P/N) for emergency reversal of coumarin therapy, infusion speeds were selected by the investigators. In a two-phase statistical analysis, the influence of baseline patient variables and dose on selected infusion speed was assessed. Then, the effect of infusion speed on reduction in international normalized ratio (INR) and on thrombogenicity marker pharmacokinetics was evaluated. Infusion speed ranged widely from 2.0 to 40.0 mL min(-1) with a median of 7.5 mL min(-1). Selection of infusion speed was not significantly influenced by gender, age, body mass index, presence of acute bleeding, indication for coumarin therapy, baseline INR, or PCC dose. Infusion speed was higher by a median of 2.2 mL min(-1) (95% confidence interval, 1.0-4.3 mL min(-1)) among patients receiving Beriplex P/N volumes > or =80 mL compared with smaller infusion volumes. Infusion speed did not affect INR attained 30 min following PCC infusion. None of the evaluated thrombogenicity marker pharmacokinetic parameters was affected by infusion speed. Infusions in one patient with questionable hemostatic efficacy and another with a possibly PCC-related thromboembolic event were at moderate and slow speeds, respectively. This study provides the first direct evidence that Beriplex P/N can be rapidly infused for emergency coumarin therapy reversal without altering safety or effectiveness.
凝血酶原复合物浓缩剂（PCC）输注是香豆素类药物治疗紧急逆转的首选方法。快速输注有可能节省关键时间；然而，高输注速度对PCC安全性和有效性的潜在影响尚未明确。在一项前瞻性跨国临床试验中，43例接受PCC（贝林妥欧P/N）进行香豆素类药物治疗紧急逆转的患者，输注速度由研究者选择。在两阶段统计分析中，评估了患者基线变量和剂量对所选输注速度的影响。然后，评估输注速度对国际标准化比值（INR）降低以及血栓形成标志物药代动力学的影响。输注速度范围广泛，从2.0至40.0 mL·min⁻¹，中位数为7.5 mL·min⁻¹。输注速度的选择不受性别、年龄、体重指数、急性出血的存在、香豆素类药物治疗的适应证、基线INR或PCC剂量的显著影响。与较小输注量相比，接受贝林妥欧P/N量≥80 mL的患者输注速度中位数高2.2 mL·min⁻¹（95%置信区间，1.0 - 4.3 mL·min⁻¹）。输注速度不影响PCC输注后30分钟时达到的INR。评估的血栓形成标志物药代动力学参数均不受输注速度影响。一名止血效果存疑的患者和另一名可能发生与PCC相关血栓栓塞事件患者的输注速度分别为中等速度和慢速。本研究提供了首个直接证据，表明贝林妥欧P/N可快速输注用于紧急逆转香豆素类药物治疗，而不改变安全性或有效性。
