Department of Internal Medicine, Tergooi Medical Center, Hilversum, The Netherlands; Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands.
General Internal Medicine and Thrombotic and Haemorrhagic Disease Unit, Department of Medicine, University of Padova, Padova, Italy.
J Thromb Haemost. 2023 Oct;21(10):2863-2872. doi: 10.1016/j.jtha.2023.06.009. Epub 2023 Jun 16.
Despite high risk of venous thromboembolism (VTE) in patients with pancreatic cancer, there are little data on contact system activation in these patients.
To quantify contact system and intrinsic pathway activation and subsequent VTE risk in patients with pancreatic cancer.
Patients with advanced pancreatic cancer were compared with controls. Blood was drawn at baseline and patients were followed for 6 months. Complexes of proteases with their natural inhibitors, C1-esterase inhibitor (C1-INH), antithrombin (AT), or alpha-1 antitrypsin (α1at), were measured for complexes containing kallikrein (PKa:C1-INH), factor (F)XIIa (FXIIa:C1-INH), and FXIa (FXIa:C1-INH, FXIa:AT, FXIa:α1at). The association of cancer with complex levels was assessed in a linear regression model, adjusted for age, sex, and body mass index. In a competing risk regression model, we assessed associations between complex levels and VTE.
One hundred nine patients with pancreatic cancer and 22 controls were included. The mean age was 66 years (SD, 8.4) in the cancer cohort and 52 years (SD, 10.1) in controls. In the cancer cohort, 18 (16.7%) patients developed VTE during follow-up. In the multivariable regression model, pancreatic cancer was associated with increased complexes of PKa:C1-INH (P < .001), FXIa:C1-INH (P < .001), and FXIa:AT (P < .001). High FXIa:α1at (subdistribution hazard ratio, 1.48 per log increase; 95% CI, 1.02-2.16) and FXIa:AT (subdistribution hazard ratio, 2.78 highest vs lower quartiles; 95% CI, 1.10-7.00) were associated with VTE.
Complexes of proteases with their natural inhibitors were elevated in patients with cancer. These data suggest that the contact system and intrinsic pathway activation are increased in patients with pancreatic cancer.
尽管胰腺癌患者存在静脉血栓栓塞（VTE）的高风险，但关于这些患者接触系统激活的数据很少。
定量检测胰腺癌患者接触系统和内源性途径的激活情况，并评估随后发生 VTE 的风险。
将晚期胰腺癌患者与对照组进行比较。在基线时采集血液样本，并对患者进行为期 6 个月的随访。测量包含激肽释放酶（PKa）与 C1 酯酶抑制剂（C1-INH）、抗凝血酶（AT）或α1 抗胰蛋白酶（α1at）的蛋白酶-天然抑制剂复合物，以及包含因子 XIIa（FXIIa）与 C1-INH、FXIa 与 C1-INH、AT 或α1at 的复合物。采用线性回归模型评估癌症与复合物水平之间的相关性，模型中调整了年龄、性别和体重指数等因素。在竞争风险回归模型中，评估了复合物水平与 VTE 之间的相关性。
共纳入 109 例胰腺癌患者和 22 例对照组。癌症组患者的平均年龄为 66 岁（标准差，8.4），对照组为 52 岁（标准差，10.1）。在癌症组中，18 例（16.7%）患者在随访期间发生了 VTE。在多变量回归模型中，胰腺癌与 PKa：C1-INH 复合物（P<0.001）、FXIa：C1-INH 复合物（P<0.001）和 FXIa：AT 复合物（P<0.001）的升高相关。高 FXIa：α1at（亚分布危险比，每对数增加 1.48；95%CI，1.02-2.16）和 FXIa：AT（亚分布危险比，最高与最低四分位数比值，2.78；95%CI，1.10-7.00）与 VTE 相关。
与天然抑制剂结合的蛋白酶复合物在癌症患者中升高。这些数据表明，接触系统和内源性途径的激活在胰腺癌患者中增加。
