Chowdary Pratima, Hamid Colleen, Slatter David, Morris Richard, Foley Jonathan H, Gomez Keith, Brodkin Edgar, Fox Thomas A, Gatt Alex, McVey John H
Katharine Dormandy Haemophilia and Thrombosis Centre Royal Free Hospital London UK.
Department of Haematology University College London London UK.
Res Pract Thromb Haemost. 2020 Feb 14;4(2):334-342. doi: 10.1002/rth2.12310. eCollection 2020 Feb.
Impaired thrombin generation (TG) in patients with acquired coagulopathy, is due to low coagulation factors and thrombocytopenia. The latter is typically treated with platelet transfusions and the former with plasma and occasionally with prothrombin complex concentrates (PCCs). We hypothesized that manipulating the concentrations of coagulation factors might result in restoration of platelet-dependent TG over and above that of simple replacement therapy.
To investigate the influence of PCCs on impaired TG secondary to thrombocytopenia.
TG was evaluated by thrombin generation assay using a thrombocytopenia model in which normal plasma samples with varying platelet counts (20-300 × 10/L) were spiked with PCCs (25%-150% increase in plasma PCC levels).
PCCs and platelets significantly increased TG in a dose-dependent manner in vitro. Two-way repeated measures of analysis of variance showed variance in peak height, area under the curve, time to peak, and velocity. This variance explained, respectively, by levels of PCC was 47, 59, 25 and 53%; by platelet count was 45, 28, 44, and 14%; by the combination was 80, 67, 70, and 62% variance; and a combination with additional interaction was 91, 84, 76, and 68%. TG at a platelet count 40 × 10/L with an approximate 25% increase in PCC concentration was similar to TG at 150 × 10/L. Similarly, patient samples spiked ex vivo with PCCs also showed highly significant improvements in TG.
Impaired TG of thrombocytopenia is improved by PCCs, supporting the need for additional studies in complex coagulopathies characterized by mild to moderate thrombocytopenia and abnormal coagulation.
获得性凝血病患者的凝血酶生成（TG）受损，是由于凝血因子水平低和血小板减少。后者通常采用血小板输注治疗，前者采用血浆治疗，偶尔使用凝血酶原复合物浓缩剂（PCCs）。我们推测，操纵凝血因子的浓度可能会导致血小板依赖性TG恢复，超过单纯替代治疗的效果。
研究PCCs对血小板减少继发的TG受损的影响。
采用血小板减少模型，通过凝血酶生成试验评估TG，在该模型中，将不同血小板计数（20 - 300×10⁹/L）的正常血浆样本加入PCCs（使血浆PCC水平增加25% - 150%）。
在体外，PCCs和血小板以剂量依赖方式显著增加TG。双向重复测量方差分析显示，峰值高度、曲线下面积、达到峰值的时间和速度存在差异。PCC水平分别解释了该差异的47%、59%、25%和53%；血小板计数分别解释了45%、28%、44%和14%；两者联合解释了80%、67%、70%和62%的差异；联合额外相互作用解释了91%、84%、76%和68%的差异。血小板计数为40×10⁹/L且PCC浓度增加约25%时的TG与血小板计数为150×10⁹/L时的TG相似。同样，离体加入PCCs的患者样本的TG也显示出高度显著的改善。
PCCs可改善血小板减少导致的TG受损，支持对以轻度至中度血小板减少和凝血异常为特征的复杂凝血病进行进一步研究的必要性。
