Department of Anaesthesiology and Intensive Care, Aarhus University Hospital; Aarhus, Denmark.
Thrombosis and Hemostasis Research Unit, Department of Clinical Biochemistry; Aarhus University Hospital, Aarhus, Denmark.
Thromb Res. 2020 May;189:42-47. doi: 10.1016/j.thromres.2020.02.012. Epub 2020 Feb 26.
Rebleeding and hematoma growth are serious complications in subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). As treatment options are sparse, a mechanistic approach may reveal new therapeutic targets.
Firstly, to evaluate hemostasis using a sensitive low tissue factor thromboelastometry (ROTEM®) assay in patients with SAH or ICH and compare them with healthy controls. Secondly, to investigate the ex vivo effect of hemostatic or antifibrinolytic medications in blood from patients with SAH or ICH.
Blood was drawn on admission to hospital in patients with SAH (n = 39) or ICH (n = 35). We included 41 sex and age matched healthy controls for comparison. A low tissue factor (diluted 1:100,000) ROTEM® assay was run in patients and healthy controls. In parallel, coagulation factor XIII, fibrinogen concentrate, prothrombin complex concentrate, and recombinant soluble thrombomodulin were added in concentrations equivalent to doses used in clinical practice.
Patients with SAH or ICH demonstrated a hypercoagulable profile indicated by significantly shorter clotting time, faster maximum velocity, shorter time to maximum velocity, and higher maximum clot firmness than healthy controls (all p-values <.0001). Ex vivo addition of coagulation factor XIII, fibrinogen concentrate, prothrombin complex concentrate, and recombinant soluble thrombomodulin, respectively, did not improve the hemostatic potential in patients with SAH or ICH.
Patients with SAH or ICH demonstrated a hypercoagulable state in the systemic circulation as evaluated by a sensitive low tissue factor assay. Ex vivo addition of hemostatic medication did not further improve coagulation.
再出血和血肿增大是蛛网膜下腔出血（SAH）和脑出血（ICH）的严重并发症。由于治疗选择有限，因此采用机制方法可能会揭示新的治疗靶点。
首先，使用敏感的低组织因子血栓弹性测定法（ROTEM®）评估 SAH 或 ICH 患者的止血情况，并将其与健康对照组进行比较。其次，研究止血或抗纤维蛋白溶解药物对 SAH 或 ICH 患者血液的体外作用。
在 SAH（n=39）或 ICH（n=35）患者入院时抽取血液。我们纳入了 41 名性别和年龄匹配的健康对照者进行比较。在患者和健康对照者中进行低组织因子（稀释 1:100,000）ROTEM®测定。同时，以临床实践中使用的剂量等效的浓度加入凝血因子 XIII、纤维蛋白原浓缩物、凝血酶原复合物浓缩物和重组可溶性血栓调节蛋白。
SAH 或 ICH 患者表现出明显的高凝状态，表现为凝血时间明显缩短、最大速度更快、达到最大速度的时间更短以及最大血凝块硬度更高，与健康对照组相比，所有 p 值均<0.0001）。分别添加凝血因子 XIII、纤维蛋白原浓缩物、凝血酶原复合物浓缩物和重组可溶性血栓调节蛋白，均不能改善 SAH 或 ICH 患者的止血潜能。
通过敏感的低组织因子测定法评估，SAH 或 ICH 患者的全身循环中表现出高凝状态。体外添加止血药物并不能进一步改善凝血。
