Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Thromb Res. 2010 Jun;125(6):e285-93. doi: 10.1016/j.thromres.2010.01.046. Epub 2010 Feb 24.
Hepatocyte growth factor (HGF), a pleiotropic factor regulating development and wound healing, is secreted as inactive pro-HGF and is converted into active HGF by coagulation serine proteases. HGF receptor overexpression can cause massive venous thrombi, and factor Xa is reported to release soluble HGF from granulocytes. We hypothesized that a hypercoagulable condition, such as disseminated intravascular coagulation (DIC), may increase circulating HGF through active cleavage by coagulation serine proteases.
In 172 DIC-suspected patients, plasma levels of total and active HGF, thrombin-antithrombin complex (TAT), plasmin-antiplasmin complex (PAP), and interleukin (IL)-6 were measured by ELISA. Active HGF release in granulocytes was examined in patients with and without overt-DIC. HGF-induced tissue factor expression in peripheral monocytes was measured by flow cytometry.
Circulating levels of total and active HGF correlated well with coagulopathy severity, including DIC score, D-dimer, TAT and PAP levels. HGF positively correlated with IL-6 and absolute neutrophil count. In contrast to the cancer group, HGF levels were significantly increased in accordance with increased DIC scores in non-cancer group. Elevated circulating HGF was an independent prognostic marker in the non-cancer group, while HGF level failed to predict mortality in the cancer group. Amounts of HGF released from stimulated granulocytes were not significantly different between overt-DIC and no overt-DIC patients. HGF potentiated endotoxin-induced tissue factor expression of monocytes in vitro.
These findings suggest that circulating HGF is a potential laboratory marker reflecting coagulation activity and DIC prognosis in non-cancer patients and that HGF may play a role in a vicious cycle of hypercoagulability.
肝细胞生长因子（HGF）是一种调节发育和创伤愈合的多效因子，以无活性的前 HGF 形式分泌，并被凝血丝氨酸蛋白酶转化为有活性的 HGF。HGF 受体过表达可导致大量静脉血栓形成，据报道，因子 Xa 可从粒细胞中释放可溶性 HGF。我们假设，弥漫性血管内凝血（DIC）等高凝状态可能通过凝血丝氨酸蛋白酶的活性裂解增加循环 HGF。
在 172 例疑似 DIC 的患者中，通过 ELISA 测定总 HGF 和活性 HGF、凝血酶-抗凝血酶复合物（TAT）、纤溶酶-抗纤溶酶复合物（PAP）和白细胞介素（IL）-6 的血浆水平。检查有无显性 DIC 的患者粒细胞中活性 HGF 的释放。通过流式细胞术测量外周单核细胞中 HGF 诱导的组织因子表达。
循环总 HGF 和活性 HGF 水平与凝血功能障碍严重程度（包括 DIC 评分、D-二聚体、TAT 和 PAP 水平）密切相关。HGF 与 IL-6 和中性粒细胞绝对值呈正相关。与癌症组不同，非癌症组 HGF 水平随着 DIC 评分的增加而显著升高。在非癌症组中，升高的循环 HGF 是独立的预后标志物，而在癌症组中 HGF 水平未能预测死亡率。从显性 DIC 和无显性 DIC 患者中刺激的粒细胞释放的 HGF 量无显著差异。HGF 增强了单核细胞中内毒素诱导的组织因子表达。
这些发现表明，循环 HGF 是反映非癌症患者凝血活性和 DIC 预后的潜在实验室标志物，HGF 可能在高凝的恶性循环中发挥作用。
