Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future
Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future
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DOI：
10.1007/s11239-010-0460-x
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Favaloro, Emmanuel J.
中科院分区：
文献类型：
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作者：
Lippi, Giuseppe;Cervellin, Gianfranco;Favaloro, Emmanuel J.
深静脉血栓形成和肺栓塞代表了传统上称为静脉血栓栓塞的相似临床病理过程的两种表达。几项人群研究证明静脉血栓栓塞是全球主要的医疗保健问题，强调需要早期和可靠的诊断，以便对受影响的患者进行适当的分类并优化结果。然而，关于使用哪些血栓标记物以及它们在诊断算法中的最合适位置仍然存在争议。本文旨在综述血栓形成标志物的过去、现在和未来的病理生理学和临床应用，包括可溶性纤维蛋白单体、纤维蛋白/纤维蛋白原降解产物、凝血酶-抗凝血酶复合物、纤溶酶-抗纤溶酶复合物、纤维蛋白肽A和B、凝血酶原片段1 + 2、血栓前体蛋白、D-二聚体、活化蛋白C-蛋白C抑制剂复合物、髓过氧化物酶、凝血酶生成测定和蛋白质组学分析。几条证据现在证明，一些D-二聚体测定的总体诊断性能大大优于迄今提出的任何其他凝血或纤溶标志物的诊断性能，并且用快速酶联荧光免疫测定法测量的“阴性”D-二聚体现在被认为是排除静脉血栓栓塞的预试验概率低的患者中的静脉血栓栓塞急性发作的生化金标准，因此可以安全地省略额外的测试。然而，为了进一步改善临床结果，将D-二聚体测试与覆盖血栓形成的不同病理生理学方面的其他标志物组合的诊断效率，例如连续和进行性凝血酶生成（例如，活化的蛋白C-蛋白C抑制剂复合物）或嗜中性粒细胞活化（即，髓过氧化物酶）值得进一步研究。蛋白质组学分析有助于表征每种蛋白质的结构和功能以及生理和病理止血中蛋白质-蛋白质相互作用的复杂性，也有望在未来鉴定新的标记物并开发有效的诊断方案。
Deep venous thrombosis and pulmonary embolism represent two expressions of a similar clinical pathological process traditionally referred to as venous thromboembolism. Several population studies evidence venous thromboembolism as a leading healthcare problem worldwide, highlighting the need for early and reliable diagnosis to enable appropriate triage of affected patients and to optimize outcome. There is still debate, however, on which thrombotic markers to use, as well as their most suitable position within diagnostic algorithms. This article aims to review the pathophysiology and clinical usefulness of past, present and future markers of thrombosis, including soluble fibrin monomers, fibrin/fibrinogen degradation products, thrombin-antithrombin complex, plasmin-antiplasmin complex, fibrinopeptide A and B, prothrombin fragments 1 + 2, thrombus precursor protein, D-dimer, activated protein C-protein C inhibitor complex, myeloperoxidase, thrombin generation assays and proteomic analysis. Several lines of evidence now attest that the global diagnostic performances of some D-Dimer assays largely outperform those of any other coagulation or fibrinolytic marker proposed thus far, and a "negative" D-Dimer measured with rapid enzyme linked fluorescent immunoassay is now considered the biochemical gold standard for ruling out an acute episode of venous thromboembolism in a patient with a low pretest probability for venous thromboembolism, so that additional testing can be safely omitted. However, to further improve clinical outcomes, the diagnostic efficiency of combining D-Dimer testing with other markers covering different pathophysiological aspects of thrombosis such as continuous and progressive thrombin generation (e.g., activated protein C-protein C inhibitor complex) or neutrophil activation (i.e., myeloperoxidase) merits further investigation. Proteomic analysis, which would help to characterize the structure and function of each protein and the complexities of protein-protein interactions in physiological and pathological hemostasis, also holds promise for identifying novel markers and developing effective diagnostic protocols in the future.