Clinical Significance of a Marker of Thrombin Activity-fibrin Monomer after Surgery
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摘要:
目的 探讨凝血酶活化标记物-纤维蛋白单体（FM）在外科术后的影响因素和临床意义。 方法 回顾性分析2021年12月至2022年5月昆明医科大学第二附属医院重症医学科收治的93例Ⅲ～Ⅳ级手术术后患者，收集患者临床资料和围术期出血量。记录手术前（T0）纤维蛋白原（Fib）、术后当日（T1）纤维蛋白原（Fib）和术后24 h（T2）血浆纤维蛋白单体（FM）、抗凝血酶Ⅲ（AT-Ⅲ）、血管性血友病因子（vWF）及纤维蛋白降解产物（DD二聚体）等指标。根据FM检测值的正常参考范围，将患者分为正常组、低水平组、中水平组、高水平组。统计描述患者临床资料；等级Logistic回归分析影响FM的因素；双变量相关性分析FM与Fib及DD的关系；方差分析不同疾病组FM的差异。 结果 （1）共纳入Ⅲ～Ⅳ级手术术后患者93例，平均年龄（59±13）岁，男性49例，女性44例。其中61例是恶性肿瘤患者（66%），32例是非肿瘤患者（34%）；（2）纤维蛋白单体（FM）正常水平组（≤5 µg/mL）9例（9.7%），FM（4.32±1.07） µg/mL；低水平组（6～54 µg/mL）39例（41.9%），FM（20.67±13.25） μg/mL；中水平组（55～103 µg/mL）11例（11.8%），FM（73.96±13.38） µg/mL；高水平组（≥104 µg/mL）34例（36.6%），FM（172.30±26.78）μg/L，方差分析（ANOVA）显示正常水平组和低水平组间差异有统计学意义（P < 0.05），其余各组间差异有统计学意义（P < 0.001）。等级Logistic回归分析显示：出血量达600～1000 mL和胃肠道手术会影响FM的浓度（P < 0.05）。vWF、AT-Ⅲ、肝脏恶性肿瘤、肾脏恶性肿瘤、其他非肿瘤性疾病、年龄、性别均对纤维蛋白单体（FM）浓度无明显影响（P > 0.05）；（3）双变量相关分析显示FM与T0、T1时间Fib无相关性，但是与T2时间Fib呈负相关（r = -0.258，P < 0.05），T2时间DD与FM呈正相关（r = 0.536，P < 0.001）；（4）肝脏恶性肿瘤患者术后血浆纤维蛋白单体（FM）（76.4 µg/mL）浓度明显高于胃肠道肿瘤术后患者（25.7 μgmL），DunnettT3检验显示两者间差异有统计学意义（P < 0.05）。 结论 纤维蛋白单体（FM）反应凝血酶的激活，与DD二聚体成正相关性，术后监测纤维蛋白单体（FM）有助于判断血栓事件。外科术后凝血酶大量活化（即FM升高）与纤维蛋白原（Fib）呈负相关性，即凝血酶大量活化会水解纤维蛋白原（Fib）导致纤维蛋白原降低，外科术后应关注纤维蛋白原浓度，以免发生出血。 Abstract:Objective To investigate the clinical significance and monitoring value of fibrin monomer （FM）after surgery. Methods A total of 93 patients after surgery admitted to the Department of Critical Care Medicine, the Second Affiliated Hospital of Kunming Medical University from December 2021 to May 2022 were retrospectively analyzed. Plasma fibrin monomer （FM）, antithrombinⅢ （AT-Ⅲ）, von willebrand factor （vWF） and fibrin degradation products （DD ） were collected before operation （T0）, on the day after operation （T1） and 24 hours after operation （T2）. According to the normal reference range of FM value, patients were divided into normal group, low level group, medium level group and high level group. The clinical data of patients were statistically analyzed, the influencing factors of FM were analyzed by ordinal logistic regression, the correlation between vWF, AT-Ⅲ, DD dimer and FM was analyzed by multivariate regression, and the correlation between Fib and FM was analyzed by univariate regression. Results （1） A total of 93 patients were enrolled, with an average age of 59±13 years, including 49 males and 44 females. Of these, 61 were malignant （66%） and 32 were non-tumor （34%）. （2） The patients were divided into normal group （≤5 μg/mL, n = 9 （9.7%）, FM （4.32±1.07） μg/mL. The low level group was 6-54 μg/mL, 39 cases （41.9%）, FM （20.67±13.25） μg/mL; Medium level group （55～103 μg/mL, 11 cases （11.8%）, FM （73.96±13.38） μg/mL; High level group ≥104 μg/mL, 34 cases （36.6%）, FM （172.30±26.78） μg/mL.Analysis of variance （ANOVA） showed that the difference between the normal level group and the low level group was statistically significant （P < 0.05）, and the difference between the other groups was significant （P < 0.0010.00）. Ordinal logistic regression analysis showed that blood loss volume, vWF, primary disease, age and gender had no significant effect on fibrin monomer （FM） （P > 0.05）. （3） Bivariate correlation analysis showed that FM was not correlated with Fib at T0 and T1, but was negatively correlated with Fib at T2 （r = -0.258, P < 0.05）. DD at T2 was positively correlated with FM （r = 0.536, P = 0.000）. （4） The plasma fibrin monomer （FM） concentration of patients with liver malignant tumor after surgery （76.4 μg/mL） was significantly higher than that of patients with gastrointestinal tumor after surgery （25.7 μg/mL）. DunnettT3 test showed that the difference was statistically significant （P < 0.05）. Conclusions Monitoring of thrombin activation marker fibrin monomer （FM） in patients after surgery has certain clinical significance, which is expected to be an early marker for predicting thrombosis or guiding anticoagulant therapy. A large amount of thrombin activation after surgery can consume fibrinogen （Fib）, and attention should be paid to the concentration of fibrinogen to avoid postoperative bleeding. -
Key words:
- Fibrin monomer /
- Thrombin /
- Markers /
- Postoperative surgery
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表 1 93例外科术后患者基础资料与凝血指标[n（%）/
$\bar x \pm s $ ]Table 1. Basic data and coagulation indexes of 93 patients postoperation [n（%）/
$\bar x \pm s $ ]变量 数值 性别 男性 49（52.7） 女性 44（47.3） 年龄（岁） 59.00 ± 8.62 原发疾病 肝脏恶性肿瘤 29（31.2） 胃肠道恶性肿瘤 23（24.7） 肾脏恶性肿瘤 9（9.7） 其他非肿瘤性疾病 32（34.4） 出血量 < 300 mL 56（60.2） 300～600 mL 21（22.6） 600～1000 mL 9（9.7） ≥1000 mL 7（7.5） FM 正常组（≤5 µg/mL） 9（9.7） 低水平组（6～54 µg/mL） 39（41.9） 中水平组（55～103 µg/mL） 11（11.8） 高水平组（≥104 µg/mL） 34（36.6） DD（µg/mL） 4.57 ± 4.15 术前Fib（g/L） 3.74 ± 1.34 术后Fib（g/L） 3.45 ± 7.57 vWF（µg/mL） 232.81 ± 70.96 AT-Ⅲ（%） 60.95 ± 15.91 
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表 2 影响FM浓度的多因素Ordinal Logistic回归分析
Table 2. Ordinal logistic regression analysis of multiple factors affecting FM
参数 单因素分析 Chi-Square Estimate P 95%CI 整体模型拟合 92.046 0.001* 拟合优度检验 Deviance 133.164 1.000 平行线检验 112.043 0.325 vWF −0.002 0.366 −0.08～0.03 AT-Ⅲ 0.18 0.844 −0.07～0.042 肝脏恶性肿瘤 0.776 0.020* −2，5～1.782 胃肠道恶性肿瘤 0.463 0.020* 1.80～4.46 肾脏恶性肿瘤 −0.336 0.180 −1.8～1.07 出血量 < 300 mL −0.724 0.578 −2.29～0.85 出血量300～600 mL −0.544 0.408 −2.21～1.12 出血量600～1000 mL 0.472 0.005* 1.27～4.68 年龄 −0.15 0.030* −0.05～0.15 性别 −0.009 0.998 −0.86～0.78 变量 多因素分析 参数估计 P 95%CI 胃肠道恶性肿瘤 −0.442 0.038* 1.50～6.21 出血量600～1000 mL 0.269 0.017* 0.89～1.68 注：*P < 0.05，代表该参数对因变量（FM）有影响。
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表 3 FM与纤维蛋白原（Fib）、DD双变量相关性分析
Table 3. Bivariate correlation analysis of FM with fibrinogen （Fib） and DD
FM 样本量（N） 相关系数（R） Sig（P值） Fib（术前） 93 −0.100 0.371 Fib（术后24 h） 93 −0.258 0.012* DD（术后24 h） 93 0.536 < 0.001* 注：*P < 0.05，代表该参数与FM有相关性。
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