Felli Alessia, Zeidler Petra, Jilma Bernd, Opfermann Philipp, Holaubek Caroline, Zimpfer Daniel, Wadowski Patricia P, Steinlechner Barbara
Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
Department of Clinical Pharmacology, Vienna, Austria.
J Cardiothorac Vasc Anesth. 2016 Jan;30(1):96-101. doi: 10.1053/j.jvca.2015.08.012. Epub 2015 Aug 14.
Prothrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs' specific heparin content may compromise the hemostatic effect.
Prospective ex-vivo investigation.
University hospital.
Venous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon.
Four different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments.
Clotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01).
Physicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.
凝血酶原复合物浓缩剂（PCCs）用于快速逆转口服维生素K拮抗剂引起的抗凝作用。它们在凝血因子、内源性抗凝剂和肝素的含量上有所不同。作者推测PCCs中特定的肝素含量可能会损害止血效果。
前瞻性体外研究。
大学医院。
从8名植入心室辅助装置且正在接受苯丙香豆素治疗的患者中采集静脉血样本。
在配对实验中，将四种不同的四因子PCCs添加到患者血液中，以使凝血酶原时间比基线计算增加20%、40%和60%。
使用血栓弹力图和内源性凝血酶潜力来测量凝血情况。与基线相比（p<0.01），以及与肝素含量显著较低或不含肝素的PCCs相比（p<0.01），两种含肝素的PCCs以浓度依赖的方式延长了凝血时间。相对于含肝素的PCCs，低肝素或无肝素的PCCs使凝血酶生成曲线下面积和凝血酶峰值增加了几倍（p<0.01）。其中一种含肝素的PCC与基线相比，甚至使凝血酶峰值生成降低了约90%（p<0.01）。低肝素或无肝素的PCC缩短了延迟期（p<0.01），而一种含肝素的PCC使延迟期延长了66%（p<0.01）。
医生应了解肝素含量的差异。将一种药物的结果外推到其他PCC制剂可能很困难。植入左心室辅助装置并使用维生素K拮抗剂抗凝的患者，在手术或出血需要紧急逆转时，使用低肝素含量的PCC可能会受益。有必要进行进一步的临床研究。
