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预测接受治疗性依诺肝素的脑肿瘤患者颅内出血发生率更高。

Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin.

机构信息

Department of Medicine and.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

出版信息

Blood. 2017 Jun 22;129(25):3379-3385. doi: 10.1182/blood-2017-02-767285. Epub 2017 May 3.

Abstract

Venous thromboembolism occurs in up to one-third of patients with primary brain tumors. Spontaneous intracranial hemorrhage (ICH) is also a frequent occurrence in these patients, but there is limited data on the safety of therapeutic anticoagulation. To determine the rate of ICH in patients treated with enoxaparin, we performed a matched, retrospective cohort study with blinded radiology review for 133 patients with high-grade glioma. After diagnosis of glioma, the cohort that received enoxaparin was 3 times more likely to develop a major ICH than those not treated with anticoagulation (14.7% vs 2.5%; = .036; hazard ratio [HR], 3.37; 95% confidence interval [CI], 1.02-11.14). When enoxaparin was analyzed as a time-varying covariate, anticoagulation was associated with a >13-fold increased risk of hemorrhage (HR, 13.26; 95% CI, 3.33-52.85; < .0001). Overall survival was significantly shorter for patients who suffered a major ICH on enoxaparin compared with patients not receiving anticoagulation (3.3 vs 10.2 months; log-rank = .012). We applied a validated ICH prediction risk score PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke), and observed that all major ICHs on enoxaparin occurred in the setting of a PANWARDS score ≥25, corresponding with a sensitivity of 100% (95% CI, 63% to 100%) and a specificity of 40% (95% CI, 25% to 56%). We conclude that caution is warranted when considering therapeutic anticoagulation in patients with high-grade gliomas given the increased risk of ICH and poor prognosis after a major hemorrhage on anticoagulation. The PANWARDS score may assist clinicians in identifying the patients at greatest risk of suffering a major intracranial hemorrhage with anticoagulation.

摘要

静脉血栓栓塞症在原发性脑肿瘤患者中发生率高达三分之一。自发性颅内出血(ICH)在这些患者中也很常见,但关于治疗性抗凝的安全性数据有限。为了确定接受依诺肝素治疗的患者ICH 的发生率,我们对 133 例高级别脑胶质瘤患者进行了匹配的回顾性队列研究,并对影像学结果进行了盲法评估。在诊断出脑胶质瘤后,接受依诺肝素治疗的队列发生重大 ICH 的可能性是未接受抗凝治疗的患者的 3 倍(14.7%比 2.5%; =.036;风险比[HR],3.37;95%置信区间[CI],1.02-11.14)。当依诺肝素作为时变协变量进行分析时,抗凝与出血风险增加超过 13 倍相关(HR,13.26;95%CI,3.33-52.85; <.0001)。与未接受抗凝治疗的患者相比,依诺肝素发生重大 ICH 的患者的总生存期明显缩短(3.3 比 10.2 个月;对数秩检验 =.012)。我们应用了经过验证的 ICH 预测风险评分 PANWARDS(血小板、白蛋白、无充血性心力衰竭、华法林、年龄、种族、舒张压、中风),并观察到依诺肝素引起的所有重大 ICH 均发生在 PANWARDS 评分≥25 的情况下,其敏感性为 100%(95%CI,63%至 100%),特异性为 40%(95%CI,25%至 56%)。我们得出结论,鉴于抗凝治疗后颅内出血风险增加和预后不良,在考虑对高级别脑胶质瘤患者进行治疗性抗凝时应谨慎。PANWARDS 评分可帮助临床医生识别在抗凝治疗时发生重大颅内出血风险最高的患者。

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