Department of Neurology, University of Erlangen-Nuremberg, Erlangen.
Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin.
Ann Neurol. 2018 Jan;83(1):186-196. doi: 10.1002/ana.25134.
To investigate parameters associated with hematoma enlargement in non-vitamin K antagonist oral anticoagulant (NOAC)-related intracerebral hemorrhage (ICH).
This retrospective cohort study includes individual patient data for 190 patients with NOAC-associated ICH over a 5-year period (2011-2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in-hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale.
The study population for analysis of primary and secondary outcomes consisted of 146 NOAC-ICH patients with available follow-up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC-related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and-in the case of factor Xa inhibitor ICH-anti-Xa levels on admission. PCC administration prior to follow-up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC-related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio [RR] = 1.150, 95% confidence interval [CI] = 0.632-2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565-1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365-0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months.
In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC-related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor-related ICH. Ann Neurol 2018;83:186-196.
探讨非维生素 K 拮抗剂口服抗凝剂（NOAC）相关脑出血（ICH）血肿扩大的相关参数。
本回顾性队列研究纳入了 2011 年至 2015 年德国 19 个神经病学系的 190 例 NOAC 相关 ICH 患者的个体患者数据。主要结局是凝血酶原复合物浓缩物（PCC）给药与血肿扩大的相关性。计算了血压管理及其与主要结局的相关性的亚分析。次要结局包括与住院死亡率和使用改良 Rankin 量表评估的 3 个月时功能结局的相关性。
可进行初级和次级结局分析的研究人群由 146 例有随访影像学资料的 NOAC-ICH 患者组成。49/146（33.6%）例 NOAC 相关 ICH 患者发生血肿扩大。与血肿扩大相关的参数包括 4 小时内血压≥160mmHg，以及因子 Xa 抑制剂 ICH 时入院时的抗-Xa 水平。在随访影像学检查前给予 PCC 治疗，与总体 NOAC 相关 ICH 或接受因子 Xa 抑制剂治疗的患者（NOAC：风险比[RR] = 1.150，95%置信区间[CI] = 0.632-2.090；因子 Xa 抑制剂：RR = 1.057，95% CI = 0.565-1.977）血肿扩大发生率降低均无显著相关性，而与 PCC 剂量、到影像学或治疗的时间间隔无关。入院后 4 小时内收缩压水平<160mmHg 与血肿扩大患者比例降低显著相关（RR = 0.598，95% CI = 0.365-0.978）。PCC 给药对出院时或 3 个月时的死亡率和功能结局均无影响。
与血压控制相反，PCC 给药与 NOAC 相关 ICH 血肿扩大率降低无关。我们的研究结果支持需要进一步研究探索新的止血逆转策略，用于治疗接受因子 Xa 抑制剂治疗的 ICH 患者。Ann Neurol 2018；83：186-196。
