Exploration of the changes of early coagulation function in patients with severe burns
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摘要:
目的 探究重症烧伤患者早期（即伤后14 d内）凝血功能变化。 方法 采用回顾性病例系列研究方法。2018年12月—2019年12月，暨南大学附属广州市红十字会医院收治50例符合入选标准的重症烧伤患者，根据烧伤严重程度，将患者分为重度烧伤组（17例，其中男12例、女5例）和特重度烧伤组（33例，其中男26例、女7例）。收集患者入院时、伤后48 h与72 h和伤后7 d与14 d患者的血小板计数（PLT）、常规凝血功能指标和血栓弹力图指标水平。常规凝血指标包括凝血酶原时间（PT）、凝血酶时间（TT）、活化部分凝血活酶时间（APTT）以及纤维蛋白原（FIB）和D-二聚体水平，血栓弹力图指标包括凝固角（即α角）、凝血综合指数（CI）以及MA值、R值和K值（分别反映最大振幅、凝血反应时间、血液凝固时间）。对数据行独立样本 t检验、Wilcoxon秩和检验和 χ 2检验。对2组患者各指标数据进行混合效应模型验证，同时对PLT行重复测量方差分析。对所有患者的血栓弹力图指标数据（除CI外）分别与PLT和常规凝血指标数据之间的相关性进行Pearson相关分析或Spearman相关分析。 结果 入院时、伤后48 h与72 h和伤后7 d与14 d，重度烧伤组患者的PLT分别为（203±91）、（148±70）、（123±63）、（203±62）、（402±140）×10 9/L，特重度烧伤组患者的PLT分别为（235±116）、（145±71）、（109±52）、（235±106）、（455±138）×10 9/L，总体比较，仅时间因素主效应差异有统计学意义（ F=92.55， P<0.05），重度烧伤组患者PLT仅伤后7 d与其相邻的2个时间点（伤后72 h及伤后14 d）的比较，差异有统计学意义（ P值均<0.05）；特重度烧伤组患者PLT各相邻时间点之间的比较，差异均有统计学意义（ P<0.05）。2组患者各时间点的PT、TT、FIB水平总体比较，仅时间因素主效应差异有统计学意义（ F值分别为6.04、8.45、32.90， P值均<0.05），特重度烧伤组患者伤后14 d内的APTT、FIB水平均长于/高于重度烧伤组。2组患者各时间点的MA值、α角、K值、CI总体比较，仅时间因素主效应差异有统计学意义（ F值分别为18.82、11.38、9.11、9.42， P值均<0.05）。MA值与PLT呈中度相关（ r=0.69， P<0.05），与TT、FIB水平均呈弱相关（ r值分别为-0.29、0.30， P<0.05），与D-二聚体水平呈极弱相关（ r=-0.15， P<0.05）；α角与PLT呈中度相关（ r=0.58， P<0.05），与FIB水平和TT均呈弱相关（ r值分别为0.26、-0.29， P<0.05）；R值与APTT、FIB水平均呈弱相关（ r值分别为0.24、0.31， P<0.05），与PT、TT呈极弱相关（ r值分别为0.16、0.14， P<0.05）；K值与PLT呈中度相关（ r=-0.59， P<0.05），与FIB水平、TT均呈弱相关（ r值分别为-0.29、0.32， P<0.05），与D-二聚体水平呈极弱相关（ r=-0.15， P<0.05）。 结论 重症烧伤患者早期即存在凝血功能不全、血小板聚集能力以及FIB功能增强等凝血功能变化的特点。凝血功能指标与血栓弹力图指标有一定的相关性，但不能相互替代。 Abstract:Objective To study the changes of early (i.e., within post injury day (PID) 14) coagulation function in patients with severe burns. Methods A retrospective case series study was conducted. From December 2018 to December 2019, 50 severe burn patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University. According to the severity of burns, the patients were divided into severe burn group (17 cases, including 12 males and 5 females) and extremely severe burn group (33 cases, including 26 males and 7 females). The platelet count (PLT), and conventional coagulation indexe and thromboelastogram index levels of patients were collected at admission, post injury hour (PIH) 48 and 72, and on PID 7 and 14. The conventional coagulation indexes included prothrombin time (PT), thrombin time (TT), activated partial prothrombin time (APTT), and fibrinogen (FIB) and D-dimer levels. The thromboelastogram indexes included coagulation angle (i.e., α angle), coagulation composite index (CI), MA value, R value, and K value (reflecting maximum amplitude, coagulation reaction time, and blood agglutination time, respectively). Data were statistically analyzed with independent sample t-test, Wilcoxon rank sum test, and chi-square test. Verification of the mixed effect model was performed on each index data of patients in the two groups, while the repeated measures analysis of variance was performed on PLT. Pearson correlation analysis or Spearman correlation analysis were performed to analyze the correlation between the thromboelastogram index data (except CI) and the PLT and conventional coagulation index data, respectively. Results At admission, PIH 48 and 72, and on PID 7 and 14, PLT of patients in severe burn group were (203±91), (148±70), (123±63), (203±62), (402±140)×10 9/L, respectively, PLT of patients in extremely severe burn group were (235±116), (145±71), (109±52), (235±106), (455±138)×10 9/L, respectively. In overall comparison, only the difference of the main effect of time factor was statistically significant ( F=92.55, P<0.05). In severe burn group, statistically significant differences were only identified in comparison of patients' PLT between PID 7 and the adjacent two time points (at PIH 72 and on PID 14, with both P values <0.05). The differences in PLT of patients between all the adjacent time points in extremely severe burn group were statistically significant ( P<0.05). In the overall comparison of PT, TT, and FIB level of patients in the two groups at each time point, only the difference of main effect of time factor was statistically significant (with F values of 6.04, 8.45, and 32.90, respectively, all P values <0.05), and APTT and FIB level of patients in extremely severe burn group within PID 14 were higher than those in severe burn group. There were statistically significant differences in MA value, α angle, K value, and CI of patients in the two groups at each time point (with F values of 18.82, 11.38, 9.11, and 9.42, respectively, all P values <0.05). MA value was moderately correlated with PLT ( r=0.69, P<0.05), weakly correlated with TT and FIB level (with r values of -0.29 and 0.30 respectively, P<0.05), and very weakly correlated with D-dimer level ( r=-0.15, P<0.05); α angle was moderately correlated with PLT ( r=0.58, P<0.05), and weakly correlated with FIB level and TT (with r values of 0.26 and -0.29, respectively, P<0.05); R value was weakly correlated with APTT and FIB level (with r values of 0.24 and 0.31, respectively, P<0.05), and very weakly correlated with PT and TT (with r values of 0.16 and 0.14, respectively, P<0.05); K value was moderately correlated with PLT ( r=-0.59, P<0.05), and weakly correlated with FIB and TT (with r values of -0.29 and 0.32, respectively, P<0.05), and very weakly correlated with D-dimer level ( r=-0.15, P<0.05). Conclusions Severe burn patients are already characterized with coagulation function changes in early stage, including insufficiency of coagulation function, enhanced platelet aggregation ability and enhanced FIB function. There is a certain correlation between conventional coagulation indexes and thromboelastogram indexes, but they cannot replace each other. -
Key words:
- Burns /
- Blood platelets /
- Thromboelastography /
- Coagulation /
- Early stage post trauma /
- Critical illness
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参考文献
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表1 2组重症烧伤患者各时间点常规凝血指标变化
表1. Changes of conventional coagulation indexes at different time points in the two groups of patients with severe burns
组别与时间点 例数 APTT（s， PT（s， TT（s， FIB（g/L， D-二聚体［mg/L， M（ Q 1， Q 3）］ 重度烧伤组 17 入院时 25.0±5.7 11.6±1.5 18.7±2.2 3.1±1.4 2.85（0.85，4.76） 伤后48 h 27.5±2.9 11.5±0.9 17.5±4.7 4.8±1.0 4.11（3.05，6.19） 伤后72 h 27.7±3.6 11.5±0.7 16.5±1.7 5.8±1.8 3.81（2.22，6.86） 伤后7 d 27.5±4.2 12.2±1.2 15.7±1.4 5.5±1.2 3.37（1.62，6.24） 伤后14 d 28.0±5.2 12.1±0.9 16.4±1.1 4.7±0.9 2.87（1.70，4.19） 特重度烧伤组 33 入院时 28.8±8.3 11.9±1.5 19.9±4.4 3.6±1.4 3.77（1.62，10.52） 伤后48 h 29.7±7.3 11.7±1.2 17.4±2.9 5.1±1.0 3.31（1.95，6.04） 伤后72 h 28.4±6.9 11.4±1.0 17.2±3.4 5.8±1.2 3.75（2.81，6.82） 伤后7 d 27.6±3.6 12.1±0.8 16.1±1.6 6.1±1.2 3.12（2.50，6.43） 伤后14 d 29.2±4.4 12.5±1.1 16.5±1.8 5.3±0.8 3.64（2.43，4.81） 注：APTT为活化部分凝血活酶时间、PT为凝血酶原时间、TT为凝血酶时间、FIB为纤维蛋白原；APTT、PT、TT、FIB、D-二聚体的分组因素主效应， F值分别为0.35、0.35、1.08、3.44、2.29， P值分别为0.557、0.557、0.303、0.068、0.134；时间因素主效应， F值分别为1.04、6.04、8.45、32.90、0.75， P值分别为0.387、<0.001、<0.001、<0.001、0.558；两者交互作用， F值分别为0.66、0.72、0.50、0.54、1.24， P值分别为0.623、0.580、0.736、0.705、0.290 
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表2 2组重症烧伤患者各时间点血栓弹力图各指标变化
表2. Changes of thromboelastogram indexes at different time points in the two groups of patients with severe burns
组别与时间点 例数 R值（min， K值［min， M（ Q 1， Q 3）］ α角（°， MA值（mm， 凝血综合指数［ M（ Q 1， Q 3）］ 重度烧伤组 17 入院时 5.1±1.4 2.40（1.60，2.75） 63±12 61±7 -1.00（-1.00，1.75） 伤后48 h 6.0±1.7 2.10（1.40，3.50） 60±11 60±8 0（-2.00，1.50） 伤后72 h 6.0±0.9 2.10（1.70，2.60） 63±8 60±8 -1.00（-1.00，0.50） 伤后7 d 6.6±2.4 1.50（1.30，1.90） 67±8 67±6 1.00（1.00，2.45） 伤后14 d 6.0±0.9 1.20（1.00，1.30） 72±4 70±5 2.00（1.85，3.00） 特重度烧伤组 33 入院时 5.6±1.7 2.70（2.15，3.25） 57±11 59±7 0（-1.00，2.00） 伤后48 h 6.2±1.5 2.30（1.80，2.80） 58±9 60±6 -1.00（-2.00，0） 伤后72 h 6.5±3.3 1.90（1.50，2.25） 61±13 61±7 0（-1.50，1.00） 伤后7 d 6.9±1.5 1.50（1.25，1.70） 66±8 67±13 1.00（0，2.00） 伤后14 d 6.4±1.0 1.10（1.00，1.25） 72±7 73±43 2.00（2.00，3.00） 注：R值、K值和MA值分别反映凝血反应时间、血液凝固时间、最大振幅；R值、K值、α角、MA值、凝血综合指数的分组因素主效应， F值分别为2.58、0.74、1.72、0.04、1.23， P值分别为0.111、0.391、0.193、0.844、0.271；时间因素主效应， F值分别为1.04、9.11、11.38、18.82、9.42， P值分别为0.387、<0.001、<0.001、<0.001、<0.001；两者交互作用， F值分别为0.06、0.61、0.57、0.70、0.38， P值分别为0.994、0.657、0.685、0.591、0.819
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