Department of Neurosurgery, University Medical Center Mainz, Mainz, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.
PLoS One. 2020 Nov 11;15(11):e0241565. doi: 10.1371/journal.pone.0241565. eCollection 2020.
The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome.
Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH.
Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r2 = 0.73; < 0.005) and 6 months (r2 = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r2 = 0.54; < 0.01) and 6 months (r2 = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01).
In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH.
脑凝血栓酶系统在脑出血（ICH）后早期被激活。凝血酶的表达导致浓度依赖性的继发性神经元损伤和不良的神经功能结局。在这项研究中，我们旨在研究 ICH 患者脑脊液（CSF）中凝血酶浓度和活性对临床结局的影响。
本研究纳入了需要行脑室外引流（EVD）的幕上占位性大脑叶出血的患者。使用酶联免疫吸附测定（ELISA）测量凝血酶、其前体凝血酶原和凝血酶-抗凝血酶复合物（TAT）的 CSF 水平。使用超氧化物歧化酶（SOD）作为氧化应激标志物在 CSF 中进行评估。根据入院时的计算机断层扫描（CT）计算初始凝块大小和脑室内出血（IVH）体积。使用改良Rankin 量表（mRS）在 ICH 后 6 周和 6 个月评估人口统计学数据、入院时的临床状况和神经功能结局。
本研究纳入了 22 例连续的幕上出血患者（9 名女性，11 名男性）。与非出血性 CSF 样本相比，ICH 患者的 CSF 中凝血酶原（p < 0.005）、凝血酶（p = 0.005）和 TAT（p = 0.046）的浓度有统计学显著差异。ICH 后 24 小时 CSF 中凝血酶浓度与出院后 6 周（r2 = 0.73；<0.005）和 6 个月（r2 = 0.63；<0.005）的 mRS 指数相关。作为凝血替代参数的 TAT 测量的凝血酶活性同样与 6 周（r2 = 0.54；<0.01）和 6 个月（r2 = 0.66；<0.04）的 mRS 相关。ICH 后 24 小时高凝血酶浓度与较高的 SOD 水平相关（p = 0.01）。
在这项研究中，我们发现 ICH 患者 CSF 中的初始凝血酶浓度和活性与 ICH 和 IVH 体积无关，但与较差的神经功能结局相关。这些发现支持越来越多的证据表明凝血酶作为 ICH 后继发性损伤形成的一个因素的作用。
