Balendran Clare A, Lövgren Ann, Hansson Kenny M, Nelander Karin, Olsson Marita, Johansson Karin J, Brohi Karim, Fries Dietmar, Berggren Anders
Personalised HealthCare and Biomarkers, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Pepparedsleden 1, Mölndal, 431 83, Sweden.
Scand J Trauma Resusc Emerg Med. 2017 Mar 14;25(1):30. doi: 10.1186/s13049-016-0332-2.
Fibrinogen and prothrombin have been suggested to become rate limiting in trauma associated coagulopathy. Administration of fibrinogen is now recommended, however, the importance of prothrombin to patient outcome is unknown.
We have utilized two trauma patient databases (database 1 n = 358 and database 2 n = 331) to investigate the relationship of plasma prothrombin concentration on clinical outcome and coagulation status. Database 1 has been used to assess the relationship of plasma prothrombin to administered packed red blood cells (PRBC), clinical outcome and coagulation biomarkers (Prothrombin Time (PT), ROTEM EXTEM Coagulation Time (CT) and Maximum Clot Firmness (MCF)). ROC analyses have been performed to investigate the ability of admission coagulation biomarkers to predict low prothrombin concentration (database 1), massive transfusion and 24 h mortality (database 1 and 2). The importance of prothrombin was further investigated in vitro by PT and ROTEM assays in the presence of a prothrombin neutralizing monoclonal antibody and following step-wise dilution.
Patients who survived the first 24 h had higher admission prothrombin levels compared to those who died (94 vs.67 IU/dL). Patients with lower transfusion requirements within the first 24 h (≤10 units of PRBCs) also had higher admission prothrombin levels compared to patients with massive transfusion demands (>10 units of PRBCs) (95 vs.62 IU/dL). Admission PT, in comparison to admission ROTEM EXTEM CT and MCF, was found to be a better predictor of prothrombin concentration <60 IU/dL (AUC 0.94 in database 1), of massive transfusion (AUC 0.92 and 0.81 in database 1 and 2 respectively) and 24 h mortality (AUC 0.90 and 0.78 in database 1 and 2, respectively). In vitro experiments supported a critical role for prothrombin in coagulation and demonstrated that PT and ROTEM EXTEM CT are sensitive methods to measure low prothrombin concentration.
Our analyses suggest that prothrombin concentration at admission is predictive of mortality and transfusion and indicates that prothrombin and fibrinogen are rate limiting in coagulopathy.
Admission PT is predictive of low prothrombin concentration and clinical outcome. PT could therefore be used as a surrogate for prothrombin concentration and further evaluation of point-of-care devices for faster PT analysis is warranted.
纤维蛋白原和凝血酶原被认为在创伤相关凝血病中成为限速因素。目前建议使用纤维蛋白原，然而，凝血酶原对患者预后的重要性尚不清楚。
我们利用两个创伤患者数据库（数据库1，n = 358；数据库2，n = 331）来研究血浆凝血酶原浓度与临床结局及凝血状态之间的关系。数据库1已用于评估血浆凝血酶原与输注的浓缩红细胞（PRBC）、临床结局及凝血生物标志物（凝血酶原时间（PT）、旋转血栓弹力图EXTEM凝血时间（CT）和最大血凝块硬度（MCF））之间的关系。已进行ROC分析以研究入院时凝血生物标志物预测低凝血酶原浓度（数据库1）、大量输血和24小时死亡率（数据库1和2）的能力。通过在存在凝血酶原中和单克隆抗体的情况下进行PT和旋转血栓弹力图测定以及逐步稀释，在体外进一步研究了凝血酶原的重要性。
存活24小时的患者入院时的凝血酶原水平高于死亡患者（94 vs. 67 IU/dL）。与有大量输血需求（>10单位PRBC）的患者相比，在最初24小时内输血需求较低（≤10单位PRBC）的患者入院时的凝血酶原水平也更高（95 vs. 62 IU/dL）。与入院时的旋转血栓弹力图EXTEM CT和MCF相比，入院时的PT被发现是凝血酶原浓度<60 IU/dL（数据库1中AUC为0.94）、大量输血（数据库1和2中AUC分别为0.92和0.81）以及24小时死亡率（数据库1和2中AUC分别为0.90和0.78）的更好预测指标。体外实验支持凝血酶原在凝血中起关键作用，并证明PT和旋转血栓弹力图EXTEM CT是测量低凝血酶原浓度的敏感方法。
我们的分析表明，入院时的凝血酶原浓度可预测死亡率和输血情况，并表明凝血酶原和纤维蛋白原在凝血病中是限速因素。
入院时的PT可预测低凝血酶原浓度和临床结局。因此，PT可作为凝血酶原浓度的替代指标，有必要进一步评估即时检测设备以更快地进行PT分析。
