Precision-guided, Personalized Intrapleural Fibrinolytic Therapy for Empyema and Complicated Parapneumonic Pleural Effusions: The Case for the Fibrinolytic Potential.
Precision-guided, Personalized Intrapleural Fibrinolytic Therapy for Empyema and Complicated Parapneumonic Pleural Effusions: The Case for the Fibrinolytic Potential.
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DOI：
10.1097/cpm.0000000000000216
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发表时间：
2017-07
影响因子：
--
通讯作者：
Komissarov A
中科院分区：
文献类型：
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作者：
Idell S;Florova G;Shetty S;Tucker T;Idell R;Koenig K;Azghani A;Rahman NM;Komissarov A
复杂性胸腔积液和脓胸伴分叶状囊形成和引流失败是常见的临床问题。在成人中，胸膜内纤溶治疗是常用的，结果不一，治疗仍然是经验性的。尽管胸腔内使用各种纤溶酶原激活剂，纤溶酶，约60年来，没有明确的共识，哪一种药物是最有效的。新出现的证据表明，胸膜内给予纤溶酶原激活物受到纤溶酶原激活物抑制剂-1的快速抑制，并且纤溶酶的加工受到其他因素的重要影响，包括胸腔液DNA的水平和质量。目前对伴随胸膜感染的分室的治疗还包括手术，这是侵入性的，并且患者的选择可能是有问题的。迄今为止发表的大多数临床文献都在所有受试者中使用了胸膜内纤溶治疗的平坦剂量，但关于该策略如何影响所施用的纤溶酶的处理或这如何影响结果却知之甚少。我们开发了一种新的离体胸腔积液测试，称为纤溶潜能或FP，其中将一定剂量的纤溶酶加入离体胸腔积液中，然后测量纤溶活性并标准化至基线水平。临床前和临床脓胸液中的测试揭示了广泛的反应，表明个体患者可能对纤维蛋白溶解酶的平坦剂量有不同的反应。该测试仍在开发中，但被设想为这些药物的给药指南，代表了个性化胸膜内纤溶治疗的新候选方法。
Complicated pleural effusions and empyema with loculation and failed drainage are common clinical problems. In adults, intrapleural fibrinolytic therapy is commonly used with variable results and therapy remains empiric. Despite the intrapleural use of various plasminogen activators; fibrinolysins, for about sixty years, there is no clear consensus about which agent is most effective. Emerging evidence demonstrates that intrapleural administration of plasminogen activators is subject to rapid inhibition by plasminogen activator inhibitor-1 and that processing of fibrinolysins is importantly influenced by other factors including the levels and quality of pleural fluid DNA. Current therapy for loculation that accompanies pleural infections also includes surgery, which is invasive and for which patient selection can be problematic. Most of the clinical literature published to date has used flat dosing of intrapleural fibrinolytic therapy in all subjects but little is known about how that strategy influences the processing of the administered fibrinolysin or how this influences outcomes. We developed a new test of pleural fluids ex vivo, which is called the Fibrinolytic Potential or FP, in which a dose of a fibrinolysin is added to pleural fluids ex vivo after which the fibrinolytic activity is measured and normalized to baseline levels. Testing in preclinical and clinical empyema fluids reveals a wide range of responses, indicating that individual patients will likely respond differently to flat dosing of fibrinolysins. The test remains under development but is envisioned as a guide for dosing of these agents, representing a novel candidate approach to personalization of intrapleural fibrinolytic therapy.