Fontan手术成年患者血浆凝块的特性：与凝块通透性和溶解时间的关系——多中心研究
Properties of Plasma Clots in Adult Patients Following Fontan Procedure: Relation to Clot Permeability and Lysis Time-Multicenter Study.
作者信息
Skubera Maciej, Gołąb Aleksandra, Plicner Dariusz, Natorska Joanna, Ząbczyk Michał, Trojnarska Olga, Mazurek-Kula Anna, Smaś-Suska Monika, Bartczak-Rutkowska Agnieszka, Podolec Piotr, Tomkiewicz-Pająk Lidia
机构信息
Department of Cardiac and Vascular Diseases, John Paul II Hospital, 31-202 Krakow, Poland.
Institute of Cardiology, Jagiellonian University Medical College, 31-008 Krakow, Poland.
出版信息
J Clin Med. 2021 Dec 20;10(24):5976. doi: 10.3390/jcm10245976.
OBJECTIVES
thromboembolic complications are a major cause of morbidity and mortality following Fontan (FO) surgery. It is also well established that altered FO circulation results in systemic complications, including liver and endothelium damage. We sought to evaluate whether dysfunctions of these sources of hemostatic factors may result in changes of fibrin clot properties.
METHODS
a permeation coefficient (K) and clot lysis time (CLT) were assessed in 66 FO patients, aged 23.0 years [IQR 19.3-27.0], and 59 controls, aged 24.0 years [IQR 19.0-29.0]. K was determined using a pressure-driven system. CLT value was measured according to assay described by Pieters et al. Endothelium and liver-derived hemostatic factors along with liver function parameters were evaluated. The median time between FO operation and investigation was 20.5 years [IQR 16.3-22.0].
RESULTS
FO patients had lower K ( = 0.005) and prolonged CLT ( < 0.001) compared to that of controls. K correlated with CLT (r = -0.28), FVIII (r = -0.30), FIX (r = -0.38), fibrinogen (r = -0.41), ALT (r = -0.25), AST (r = -0.26), GGTP (r = -0.27) and vWF antigen (r = -0.30), (all < 0.05). CLT correlated with the time between FO operation and investigation (r = 0.29) and FIX (r = 0.25), (all < 0.05). After adjustment for potential cofounders, TAFI antigen and GGTP were independent predictors of reduced K (OR 1.041 per 1% increase, 95% CI 1.009-1.081, = 0.011 and OR 1.025 per 1 U/L increase, 95% CI 1.005-1.053, = 0.033, respectively). Protein C and LDL cholesterol predicted prolonged CLT (OR 1.078 per 1% increase, 95% CI 1.027-1.153, = 0.001 and OR 6.360 per 1 μmol/L increase, 95% CI 1.492-39.894, = 0.011, respectively). Whereas elevated tPA was associated with lower risk of prolonged CLT (OR 0.550 per 1 ng/mL, 95% CI 0.314-0.854, = 0.004). GGTP correlated positively with time between FO surgery and investigation (r = 0.25, = 0.045) and patients with abnormal elevated GGTP activity ( = 28, 42.4%) had decreased K, compared to that of the others (5.9 × 10 cm vs. 6.8 × 10 cm, = 0.042).
CONCLUSION
our study shows that cellular liver damage and endothelial injury were associated with prothrombotic clot phenotype reflected by K and CLT.
目的
血栓栓塞并发症是Fontan（FO）手术后发病和死亡的主要原因。同样明确的是，FO循环改变会导致全身并发症，包括肝脏和内皮损伤。我们试图评估这些止血因子来源的功能障碍是否会导致纤维蛋白凝块特性的改变。
方法
对66例年龄为23.0岁[四分位间距19.3 - 27.0]的FO患者和59例年龄为24.0岁[四分位间距19.0 - 29.0]的对照者进行渗透系数（K）和凝块溶解时间（CLT）评估。使用压力驱动系统测定K。根据Pieters等人描述的测定方法测量CLT值。评估内皮和肝脏来源的止血因子以及肝功能参数。FO手术与检查之间的中位时间为20.5年[四分位间距16.3 - 22.0]。
结果
与对照组相比，FO患者的K较低（ = 0.005）且CLT延长（ < 0.001）。K与CLT（r = -0.28）、FVIII（r = -0.30）、FIX（r = -0.38）、纤维蛋白原（r = -0.41）、ALT（r = -0.25）、AST（r = -0.26）、GGTP（r = -0.27）和vWF抗原（r = -0.30）相关，（均 < 0.05）。CLT与FO手术与检查之间的时间（r = 0.29）和FIX（r = 0.25）相关，（均 < 0.05）。在对潜在混杂因素进行调整后，TAFI抗原和GGTP是K降低的独立预测因素（每增加1%，OR为1.041，95%可信区间1.009 - 1.081， = 0.011；每增加1 U/L，OR为1.025，95%可信区间1.005 - 1.053， = 0.033）。蛋白C和低密度脂蛋白胆固醇预测CLT延长（每增加1%，OR为1.078，95%可信区间1.027 - 1.153， = 0.001；每增加1 μmol/L，OR为6.360，95%可信区间1.492 - 39.894， = 0.011）。而tPA升高与CLT延长风险较低相关（每增加1 ng/mL, OR为0.550，95%可信区间0.314 - 0.854， = 0.004）。GGTP与FO手术与检查之间的时间呈正相关（r = 0.25， = 0.045），GGTP活性异常升高的患者（ = 28，42.4%）与其他患者相比K降低（5.9×10 cm对6.8×10 cm， = 0.042）。
结论
我们的研究表明，肝脏细胞损伤和内皮损伤与K和CLT所反映的促血栓凝块表型相关。
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