Liu Junfeng, Wang Yanan, Li Jing, Zhang Shanshan, Wu Qian, Wei Chenchen, Cui Ting, Wu Bo, Willey Joshua Z, Liu Ming
Department of Neurology, Center of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China.
Department of Neurology, The First People's Hospital of Ziyang, Ziyang, China.
Front Aging Neurosci. 2022 Apr 7;14:847648. doi: 10.3389/fnagi.2022.847648. eCollection 2022.
To investigate the current management of thrombolysis related hemorrhagic transformation (HT) in real-world practice, and whether these treatments would reduce the risk of 3-month death and hematoma expansion after HT.
A multicenter retrospective study was performed in three comprehensive stroke centers in China (West China Hospital, The First People's Hospital of Ziyang, and Mianyang Central Hospital) between January 1st 2012 and December 31th 2020. Participants were patients diagnosed with HT after intravenous thrombolytics on brain computed tomography (CT) within 36 h after stroke onset. The treatment after thrombolysis related HT included aggressive therapy (procoagulant, neurosurgical treatment) and dehydration therapy (mannitol or glycerin and fructose). The primary clinical outcome was 3-month death. The primary radiographic outcome was hematoma expansion, defined as a 33% increase in the hematoma volume using the (A × B × C)/2 method on follow-up imaging.
Of 538 patients with ischemic stroke receiving thrombolysis included during the study period, 94 patients (17.4%) were diagnosed with HT, 50% (47/94) of whom were symptomatic HT. The 3-month death was 31.5% (29/92), with two patients having been lost to follow up. A total of 68 patients (72.3%) had follow-up brain CT scans after HT detection for evaluating hematoma expansion, of whom 14.7% (10/68) had hematoma expansion. Among the 10 patients with hematoma expansion, 7 patients were from symptomatic HT group, and 3 patients were from the asymptomatic hematoma group. In regard to escalation in therapy, six patients received neurosurgical treatment and three patients had a fresh frozen plasma infusion. In addition, dehydration therapy was the most common management after HT diagnosis [87.2% (82 of 94)]. In the multivariable models, refusing any treatment after HT diagnosis was the sole factor associated with increased 3-month death (odds ratio, 13.6; 95% CI, 3.98-56.9) and hematoma expansion risk (odds ratio, 8.54; 95% CI, 1.33-70.1). In regard to the effects of aggressive therapy, a non-significant association of receiving hemostatic/neurosurgery therapy with a lower 3-month death and hematoma expansion risk was observed (all > 0.05).
Refusing any treatment after HT detection had a significant trend of increasing 3-month death and hematoma expansion risk after HT. Our finding of hematoma expansion among patients with asymptomatic HT in non-western populations suggests an opportunity for intervention. Very few patients after thrombolysis related HT diagnosis received procoagulant or neurosurgical therapies. Large multicenter studies enrolling diverse populations are needed to examine the efficacy of these therapies on different HT subtypes.
探讨在实际临床实践中溶栓相关出血转化（HT）的当前管理方式，以及这些治疗方法是否会降低HT后3个月死亡和血肿扩大的风险。
2012年1月1日至2020年12月31日期间，在中国的三个综合性卒中中心（四川大学华西医院、资阳市第一人民医院和绵阳市中心医院）进行了一项多中心回顾性研究。研究对象为卒中发作后36小时内接受静脉溶栓治疗且在脑部计算机断层扫描（CT）上被诊断为HT的患者。溶栓相关HT后的治疗包括积极治疗（促凝血剂、神经外科治疗）和脱水治疗（甘露醇或甘油果糖）。主要临床结局为3个月死亡。主要影像学结局为血肿扩大，定义为在随访影像学检查中使用（A×B×C）/2方法测得血肿体积增加33%。
在研究期间纳入的538例接受溶栓治疗的缺血性卒中患者中，94例（17.4%）被诊断为HT，其中50%（47/94）为症状性HT。3个月死亡率为31.5%（29/92），有2例患者失访。共有68例患者（72.3%）在检测到HT后进行了随访脑部CT扫描以评估血肿扩大情况，其中14.7%（10/68）有血肿扩大。在10例有血肿扩大的患者中，7例来自症状性HT组，3例来自无症状血肿组。在治疗升级方面，6例患者接受了神经外科治疗，3例患者输注了新鲜冰冻血浆。此外，脱水治疗是HT诊断后最常见的管理方式[87.2%（94例中的82例）]。在多变量模型中，HT诊断后拒绝任何治疗是与3个月死亡风险增加（比值比，13.6；95%CI，3.98 - 56.9）和血肿扩大风险增加（比值比，8.54；95%CI，1.33 - 70.1）相关的唯一因素。关于积极治疗的效果，观察到接受止血/神经外科治疗与较低的3个月死亡和血肿扩大风险之间无显著关联（均>0.05）。
HT检测后拒绝任何治疗有显著增加HT后3个月死亡和血肿扩大风险的趋势。我们在非西方人群无症状HT患者中发现血肿扩大提示了干预的机会。溶栓相关HT诊断后很少有患者接受促凝血剂或神经外科治疗。需要开展纳入不同人群的大型多中心研究来检验这些治疗方法对不同HT亚型的疗效。
