Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
J Cereb Blood Flow Metab. 2011 Aug;31(8):1736-42. doi: 10.1038/jcbfm.2011.22. Epub 2011 Mar 9.
While oral anticoagulants are associated with greater hematoma expansion and higher mortality rates in patients with intracerebral hemorrhage (ICH), there is ongoing discussion whether pretreatment with antiplatelet drugs also worsens prognosis. Using an experimental model of ICH, we investigated the effects of antiplatelet pretreatment on hematoma volume and functional outcome. CD-1 mice were treated with acetyl-salicylic acid (ASA, 60 mg/kg per 24 hours), clopidogrel (22.5 mg/kg per 24 hours), or both (ASA+clopidogrel) through drinking water for 3 days (n=20 per group). Thereafter, platelet aggregation was found to be significantly reduced. Untreated mice and mice pretreated with warfarin served as controls. A stereotactic injection of collagenase into the right striatum was used to induce ICH. Twenty-four hours after ICH induction, hematoma volume was measured to be 15.0 ± 4.4 μL in controls, 14.1 ± 5.3 μL in ASA mice, 16.8 ± 5.1 μL in clopidogrel mice, and 16.4 ± 5.1 μL in ASA+clopidogrel animals. These differences were not statistically significant. However, mice pretreated with warfarin revealed largely increased hematoma volumes (25.0 ± 7.4 μL versus controls, P=0.001). Neurologic outcome was not different between antiplatelet-pretreated animals and untreated controls. Our results suggest that plasmatic coagulation rather than platelet function is the most critical element for preventing hematoma expansion in acute ICH. Future therapeutic strategies may take these findings into account.
虽然口服抗凝剂与脑出血(ICH)患者的血肿扩大和死亡率升高有关,但目前仍在讨论抗血小板药物的预处理是否也会恶化预后。我们使用 ICH 的实验模型研究了抗血小板预处理对血肿体积和功能结果的影响。CD-1 小鼠通过饮用水接受乙酰水杨酸(ASA,24 小时 60mg/kg)、氯吡格雷(24 小时 22.5mg/kg)或两者(ASA+氯吡格雷)预处理 3 天(每组 20 只)。此后,发现血小板聚集显著降低。未处理的小鼠和用华法林预处理的小鼠作为对照。通过立体定向将胶原酶注射到右侧纹状体以诱导 ICH。ICH 诱导后 24 小时,测量血肿体积为对照组 15.0±4.4μL、ASA 组 14.1±5.3μL、氯吡格雷组 16.8±5.1μL 和 ASA+氯吡格雷组 16.4±5.1μL。这些差异没有统计学意义。然而,用华法林预处理的小鼠血肿体积显著增加(与对照组相比,25.0±7.4μL,P=0.001)。抗血小板预处理动物和未处理对照动物的神经功能结果没有差异。我们的结果表明,在急性 ICH 中,防止血肿扩大的最关键因素是血浆凝血而不是血小板功能。未来的治疗策略可能需要考虑这些发现。